UPF1

UniProt ID: Q92900
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

UPF1 (regulator of nonsense transcripts 1; RENT1) is the central ATP-dependent RNA helicase and ATPase of the nonsense-mediated mRNA decay (NMD) pathway. A superfamily-1 (SF1) helicase with an N-terminal cysteine-histidine-rich (CH) zinc-binding regulatory domain, UPF1 is recruited to mRNAs at translation termination, where release factors (eRF1/eRF3) and the SMG1 kinase complex assemble the transient SURF complex. In EJC-dependent NMD the adaptor UPF2 bridges UPF1 to UPF3 and the downstream exon-junction complex, forming the UPF1-UPF2-UPF3 surveillance complex; UPF1 is then phosphorylated by SMG1 and the phospho-form is recognized by SMG5/SMG6/SMG7 to recruit decay enzymes and PP2A. UPF1 ATPase/helicase activity remodels and disassembles target mRNPs, committing premature-termination-codon-containing and certain long-3'UTR or staufen-bound transcripts to degradation, and also mediates replication-dependent histone mRNA decay at the end of S phase. UPF1 acts mainly on cytoplasmic translating mRNAs (with a smaller nuclear pool), concentrates in P-bodies in its hyperphosphorylated state, and has additional reported moonlighting roles at telomeres and in DNA replication; it can unwind both RNA and DNA in vitro.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003724 RNA helicase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central ATP-dependent helicase of nonsense-mediated mRNA decay.
Reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
RNA-dependent helicase required for nonsense-mediated decay
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IEA
GO_REF:0000002 		ACCEPT
Summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological process of UPF1; it is recruited at termination and triggers decay.
Reason: Core biological process; UPF1 is the central NMD factor.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0000932 P-body
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: P-body localization; hyperphosphorylated UPF1 is targeted to P-bodies where mRNA decay factors concentrate.
Reason: Supported by UniProt note that the hyperphosphorylated form is targeted to P-bodies; a functional but non-core localization.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Hyperphosphorylated form is
GO:0003677 DNA binding
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: DNA binding (IEA); UPF1 can act on DNA substrates in vitro and has reported telomere/replication roles.
Reason: Supported in vitro but peripheral to the core RNA/NMD function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Also capable of unwinding double-stranded DNA and
GO:0003723 RNA binding
IEA
GO_REF:0000002 		ACCEPT
Summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part of its helicase function.
Reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays) and is integral to UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0003723
GO:0003724 RNA helicase activity
IEA
GO_REF:0000002 		ACCEPT
Summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central ATP-dependent helicase of nonsense-mediated mRNA decay.
Reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
RNA-dependent helicase required for nonsense-mediated decay
GO:0004386 helicase activity
IEA
GO_REF:0000002 		ACCEPT
Summary: General helicase activity, a parent of the specific RNA helicase activity that is core to UPF1.
Reason: Correct but less specific than RNA helicase activity; retained as a valid parent MF.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
RNA-dependent helicase required for nonsense-mediated decay
GO:0005524 ATP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: ATP binding, required for the ATPase/helicase cycle of UPF1.
Reason: ATP binding is integral to the SF1 helicase catalytic mechanism of UPF1.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
ATPase activity of UPF1 is
GO:0005634 nucleus
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Nuclear localization; a minor UPF1 pool is nuclear (and UPF1 has nuclear/chromatin-associated roles).
Reason: Documented nuclear pool but the core NMD function is cytoplasmic; retained as non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005634
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: Cytoplasmic localization, a principal site of UPF1 action (NMD occurs on cytoplasmic translating mRNAs).
Reason: Well-supported cytoplasmic localization.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0008270 zinc ion binding
IEA
GO_REF:0000002 		ACCEPT
Summary: Zinc ion binding (IEA); UPF1 has a CH (cysteine-histidine-rich) zinc-binding regulatory domain.
Reason: UPF1's N-terminal CH domain coordinates zinc and regulates helicase/UPF2 interaction.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0008270
GO:0010468 regulation of gene expression
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Regulation of gene expression, a very general process annotation reflecting NMD-mediated control of transcript levels.
Reason: Too general to be a core annotation; subsumed by specific mRNA-decay terms.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0010468
GO:0016787 hydrolase activity
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: Generic hydrolase activity, an uninformative high-level parent of the ATPase/helicase activity.
Reason: Too general to be informative; the specific activities (RNA helicase, ATP hydrolysis) already capture this.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
ATPase activity of UPF1 is
GO:0016887 ATP hydrolysis activity
IEA
GO_REF:0000116 		ACCEPT
Summary: ATP hydrolysis (ATPase) activity powers UPF1 translocation/unwinding and mRNP remodeling during NMD.
Reason: UPF1's ATPase activity is directly demonstrated and required for disassembly of mRNPs undergoing NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
ATPase activity of UPF1 is
GO:0032574 5'-3' RNA helicase activity
IEA
GO_REF:0000003 		ACCEPT
Summary: UPF1 unwinds RNA with 5'-3' directionality; a precise statement of its helicase polarity.
Reason: Biochemically demonstrated 5'-3' RNA helicase activity; a useful specific child of RNA helicase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0032574
GO:0043139 5'-3' DNA helicase activity
IEA
GO_REF:0000003 		KEEP AS NON CORE
Summary: 5'-3' DNA helicase activity (IEA/IDA); UPF1 can unwind DNA in vitro.
Reason: In vitro DNA-unwinding activity; non-core relative to RNA helicase/NMD function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Also capable of unwinding double-stranded DNA and
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Perinuclear region of cytoplasm localization (by similarity).
Reason: Localization inferred by similarity; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0048471
GO:1903313 positive regulation of mRNA metabolic process
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Positive regulation of mRNA metabolic process, a high-level process reflecting UPF1 control of mRNA turnover.
Reason: Correct but general; the specific NMD/mRNA-catabolism terms are more informative.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:1903313
GO:0005515 protein binding
IPI
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:12417715
Identification of a human decapping complex associated with ... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:12881429
Interaction between Ski7p and Upf1p is required for nonsense... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:15680326
Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so ... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:16086026
Regulated degradation of replication-dependent histone mRNAs... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:16364915
Multiple processing body factors and the ARE binding protein... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:17469741
Results of the determination of serum markers in patients wi... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:18256688
Interactions between UPF1, eRFs, PABP and the exon junction ... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:18362360
The editing enzyme ADAR1 and the mRNA surveillance protein h... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:18447585
A competition between stimulators and antagonists of Upf com... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:19150429
Human proline-rich nuclear receptor coregulatory protein 2 m... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:19417104
SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, re... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:19478851
The hierarchy of exon-junction complex assembly by the splic... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:19503078
A UPF3-mediated regulatory switch that maintains RNA surveil... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:19556969
Unusual bipartite mode of interaction between the nonsense-m... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains t... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:23348841
An unusual arrangement of two 14-3-3-like domains in the SMG... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:23722113
Non-structural protein 1 of influenza viruses inhibits rapid... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:24267889
Affinity proteomics reveals human host factors implicated in... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
Q92900-2
PMID:16452507
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to th... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
Q92900-2
PMID:18066079
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction c... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
Q92900-2
PMID:18423202
Upf1 phosphorylation triggers translational repression durin... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
Q92900-2
PMID:21145460
Upf1 ATPase-dependent mRNP disassembly is required for compl... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0032574 5'-3' RNA helicase activity
IDA
PMID:26138914
Human Upf1 is a highly processive RNA helicase and transloca... 		ACCEPT
Summary: UPF1 unwinds RNA with 5'-3' directionality; a precise statement of its helicase polarity.
Reason: Biochemically demonstrated 5'-3' RNA helicase activity; a useful specific child of RNA helicase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0032574
GO:0043139 5'-3' DNA helicase activity
IDA
PMID:26138914
Human Upf1 is a highly processive RNA helicase and transloca... 		KEEP AS NON CORE
Summary: 5'-3' DNA helicase activity (IEA/IDA); UPF1 can unwind DNA in vitro.
Reason: In vitro DNA-unwinding activity; non-core relative to RNA helicase/NMD function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Also capable of unwinding double-stranded DNA and
GO:0033678 5'-3' DNA/RNA helicase activity
IDA
PMID:18066079
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction c... 		KEEP AS NON CORE
Summary: 5'-3' DNA/RNA helicase activity; reflects UPF1's ability to translocate/unwind both nucleic acids.
Reason: Captures dual substrate unwinding; the RNA helicase activity is the core function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Also capable of unwinding double-stranded DNA and
GO:0033678 5'-3' DNA/RNA helicase activity
IDA
PMID:21419344
Molecular mechanisms for the RNA-dependent ATPase activity o... 		KEEP AS NON CORE
Summary: 5'-3' DNA/RNA helicase activity; reflects UPF1's ability to translocate/unwind both nucleic acids.
Reason: Captures dual substrate unwinding; the RNA helicase activity is the core function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Also capable of unwinding double-stranded DNA and
GO:0071025 RNA surveillance
NAS
PMID:31131562
Nonsense-mediated mRNA decay: The challenge of telling right... 		KEEP AS NON CORE
Summary: RNA surveillance, the broad quality-control category encompassing NMD in which UPF1 is the central factor.
Reason: Accurate high-level descriptor; the specific NMD term is the core annotation.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0071025
GO:0170010 nonsense-mediated decay complex
NAS
PMID:35640974
Structures of nonsense-mediated mRNA decay factors UPF3B and... 		ACCEPT
Summary: UPF1 is a component of the nonsense-mediated decay (SURF/UPF1-UPF2-UPF3 surveillance) complex.
Reason: UPF1 is a defining subunit of the NMD effector complex.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0170010
GO:2000623 negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
NAS
PMID:31131562
Nonsense-mediated mRNA decay: The challenge of telling right... 		KEEP AS NON CORE
Summary: Negative regulation of NMD; reflects context-dependent modulation of NMD efficiency by UPF1/regulators.
Reason: NAS regulatory annotation; plausible in the context of NMD autoregulation but non-core relative to UPF1 driving NMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:2000623
GO:2000624 positive regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
NAS
PMID:31131562
Nonsense-mediated mRNA decay: The challenge of telling right... 		KEEP AS NON CORE
Summary: Positive regulation of NMD; UPF1 activity promotes NMD of target transcripts.
Reason: NAS regulatory annotation consistent with UPF1 function; non-core relative to the direct NMD term.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:2000624
GO:0005654 nucleoplasm
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: Nucleoplasm localization (IDA), consistent with a nuclear UPF1 pool.
Reason: Minor nuclear localization; non-core relative to cytoplasmic NMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005654
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005634 nucleus
EXP
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		KEEP AS NON CORE
Summary: Nuclear localization; a minor UPF1 pool is nuclear (and UPF1 has nuclear/chromatin-associated roles).
Reason: Documented nuclear pool but the core NMD function is cytoplasmic; retained as non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005634
GO:0005737 cytoplasm
EXP
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		ACCEPT
Summary: Cytoplasmic localization, a principal site of UPF1 action (NMD occurs on cytoplasmic translating mRNAs).
Reason: Well-supported cytoplasmic localization.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
TAS
PMID:26255671
Regnase-1 and Roquin regulate inflammatory mRNAs. 		ACCEPT
Summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological process of UPF1; it is recruited at termination and triggers decay.
Reason: Core biological process; UPF1 is the central NMD factor.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0061158 3'-UTR-mediated mRNA destabilization
TAS
PMID:26255671
Regnase-1 and Roquin regulate inflammatory mRNAs. 		ACCEPT
Summary: 3'-UTR-mediated mRNA destabilization; UPF1 (with UPF2/TDRD6) degrades mRNAs bearing long 3'UTRs, a recognized NMD-related branch.
Reason: Supported NMD-related destabilization function on long-3'UTR transcripts.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0061158
GO:0071222 cellular response to lipopolysaccharide
TAS
PMID:26255671
Regnase-1 and Roquin regulate inflammatory mRNAs. 		KEEP AS NON CORE
Summary: Cellular response to lipopolysaccharide (TAS); UPF1/NMD modulates inflammatory transcript stability.
Reason: Stimulus-response context for NMD targets; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0071222
GO:0071347 cellular response to interleukin-1
TAS
PMID:26255671
Regnase-1 and Roquin regulate inflammatory mRNAs. 		KEEP AS NON CORE
Summary: Cellular response to interleukin-1 (TAS); NMD-related modulation of cytokine-response transcripts.
Reason: Stimulus-response context; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0071347
GO:0016887 ATP hydrolysis activity
IDA
PMID:30218034
UPF1-like helicase grip on nucleic acids dictates processivi... 		ACCEPT
Summary: ATP hydrolysis (ATPase) activity powers UPF1 translocation/unwinding and mRNP remodeling during NMD.
Reason: UPF1's ATPase activity is directly demonstrated and required for disassembly of mRNPs undergoing NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
ATPase activity of UPF1 is
GO:0036121 double-stranded DNA helicase activity
IDA
PMID:30218034
UPF1-like helicase grip on nucleic acids dictates processivi... 		KEEP AS NON CORE
Summary: Double-stranded DNA helicase activity (IDA); UPF1 unwinds dsDNA in vitro.
Reason: In vitro dsDNA helicase activity; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
Also capable of unwinding double-stranded DNA and
GO:0005515 protein binding
IPI
PMID:26841701
The RNA helicase DHX34 functions as a scaffold for SMG1-medi... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0044877 protein-containing complex binding
IPI
PMID:26841701
The RNA helicase DHX34 functions as a scaffold for SMG1-medi... 		KEEP AS NON CORE
Summary: Protein-containing complex binding; UPF1 engages multiprotein assemblies (EJC, SMG complexes).
Reason: Records complex association but is non-specific; the informative facts are the named complexes (EJC, SURF).
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0044877
GO:0005515 protein binding
IPI
PMID:25220460
The RNA helicase DHX34 activates NMD by promoting a transiti... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:27974568
IRAV (FLJ11286), an Interferon-Stimulated Gene with Antivira... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0003723 RNA binding
IDA
PMID:24726324
MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA t... 		ACCEPT
Summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part of its helicase function.
Reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays) and is integral to UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0003723
GO:0005515 protein binding
IPI
PMID:24726324
MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA t... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0061014 positive regulation of mRNA catabolic process
IDA
PMID:24726324
MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA t... 		ACCEPT
Summary: Positive regulation of mRNA catabolic process; UPF1 promotes decay of its target mRNAs.
Reason: Consistent with UPF1 driving mRNA degradation in NMD/SMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0061014
GO:0061158 3'-UTR-mediated mRNA destabilization
IDA
PMID:24726324
MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA t... 		ACCEPT
Summary: 3'-UTR-mediated mRNA destabilization; UPF1 (with UPF2/TDRD6) degrades mRNAs bearing long 3'UTRs, a recognized NMD-related branch.
Reason: Supported NMD-related destabilization function on long-3'UTR transcripts.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0061158
GO:0005515 protein binding
IPI
PMID:19864460
Mammalian pre-mRNA 3' end processing factor CF I m 68 functi... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0032204 regulation of telomere maintenance
IMP
PMID:17916692
Telomeric repeat containing RNA and RNA surveillance factors... 		KEEP AS NON CORE
Summary: Regulation of telomere maintenance (IMP); part of the UPF1 telomere function.
Reason: Moonlighting telomere role; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0032204
GO:0044770 cell cycle phase transition
IMP
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: Cell cycle phase transition (IMP); reflects UPF1 effects on cell-cycle progression (e.g. via histone mRNA decay / replication).
Reason: Downstream/indirect phenotype; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0044770
GO:0005515 protein binding
IPI
PMID:23788676
The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:25225333
Plakophilins 1 and 3 bind to FXR1 and thereby influence the ... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0061014 positive regulation of mRNA catabolic process
IMP
PMID:25225333
Plakophilins 1 and 3 bind to FXR1 and thereby influence the ... 		ACCEPT
Summary: Positive regulation of mRNA catabolic process; UPF1 promotes decay of its target mRNAs.
Reason: Consistent with UPF1 driving mRNA degradation in NMD/SMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0061014
GO:0005515 protein binding
IPI
PMID:26255671
Regnase-1 and Roquin regulate inflammatory mRNAs. 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:24965446
Host factors that interact with the pestivirus N-terminal pr... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:26000482
Regnase-1 and Roquin Regulate a Common Element in Inflammato... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0000781 chromosome, telomeric region
IDA
PMID:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains t... 		KEEP AS NON CORE
Summary: Chromosome telomeric region localization, consistent with UPF1 telomere-associated role.
Reason: Telomere localization; moonlighting, non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0000781
GO:0032201 telomere maintenance via semi-conservative replication
IDA
PMID:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains t... 		KEEP AS NON CORE
Summary: Telomere maintenance via semi-conservative replication; UPF1 supports telomere leading-strand synthesis.
Reason: Telomere-replication role (PMID:21829167); moonlighting, non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0032201
GO:0042162 telomeric repeat DNA binding
IDA
PMID:17916692
Telomeric repeat containing RNA and RNA surveillance factors... 		KEEP AS NON CORE
Summary: Telomeric repeat DNA binding (IDA); part of a reported UPF1 role at telomeres with TPP1/telomerase.
Reason: Documented telomere-associated activity (PMID:21829167) but a moonlighting role distinct from core NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
interacts with TPP1 and telomerase
GO:0042162 telomeric repeat DNA binding
IDA
PMID:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains t... 		KEEP AS NON CORE
Summary: Telomeric repeat DNA binding (IDA); part of a reported UPF1 role at telomeres with TPP1/telomerase.
Reason: Documented telomere-associated activity (PMID:21829167) but a moonlighting role distinct from core NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
interacts with TPP1 and telomerase
GO:0005829 cytosol
TAS
Reactome:R-HSA-927813 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927830 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927836 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927889 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi... 		ACCEPT
Summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part of its helicase function.
Reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays) and is integral to UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0003723
GO:0003723 RNA binding
HDA
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on ... 		ACCEPT
Summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part of its helicase function.
Reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays) and is integral to UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0003723
GO:0000956 nuclear-transcribed mRNA catabolic process
IMP
PMID:23828042
DHX34 and NBAS form part of an autoregulatory NMD circuit th... 		KEEP AS NON CORE
Summary: Nuclear-transcribed mRNA catabolic process, a parent of the NMD process that UPF1 drives.
Reason: Correct but more general than the specific NMD term; retained as a valid parent process.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0000956
GO:0005515 protein binding
IPI
PMID:20930030
SMG6 interacts with the exon junction complex via two conser... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005829 cytosol
TAS
Reactome:R-HSA-927789 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927832 		ACCEPT
Summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
Reason: Cytosolic localization agrees with the principal site of UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005634 nucleus
IDA
PMID:18362360
The editing enzyme ADAR1 and the mRNA surveillance protein h... 		KEEP AS NON CORE
Summary: Nuclear localization; a minor UPF1 pool is nuclear (and UPF1 has nuclear/chromatin-associated roles).
Reason: Documented nuclear pool but the core NMD function is cytoplasmic; retained as non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005634
GO:0044530 supraspliceosomal complex
IDA
PMID:18362360
The editing enzyme ADAR1 and the mRNA surveillance protein h... 		KEEP AS NON CORE
Summary: Supraspliceosomal complex; a nuclear assembly with which UPF1 was found associated.
Reason: Nuclear complex association; peripheral to the core cytoplasmic NMD function.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0044530
GO:0003724 RNA helicase activity
IDA
PMID:21419344
Molecular mechanisms for the RNA-dependent ATPase activity o... 		ACCEPT
Summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central ATP-dependent helicase of nonsense-mediated mRNA decay.
Reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
RNA-dependent helicase required for nonsense-mediated decay
GO:0005515 protein binding
IPI
PMID:17932509
Proteomic and functional analysis of Argonaute-containing mR... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0035145 exon-exon junction complex
IDA
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		KEEP AS NON CORE
Summary: Exon-exon junction complex; UPF1 functionally couples to the EJC during EJC-dependent NMD (via UPF2/UPF3).
Reason: UPF1 associates with the EJC-linked surveillance complex; recorded as a relevant but non-core part_of.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
exon junction complex
GO:0071044 histone mRNA catabolic process
IMP
PMID:16086026
Regulated degradation of replication-dependent histone mRNAs... 		ACCEPT
Summary: Histone mRNA catabolic process; UPF1 mediates replication-dependent histone mRNA degradation at the end of S phase, independent of UPF2.
Reason: Well-documented UPF1 function in histone mRNA decay; a genuine UPF1-dependent decay pathway.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
replication-dependent histone mRNA degradation
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IMP
PMID:18369367
NMD resulting from encephalomyocarditis virus IRES-directed ... 		ACCEPT
Summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological process of UPF1; it is recruited at termination and triggers decay.
Reason: Core biological process; UPF1 is the central NMD factor.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IDA
PMID:17468741
Human INT6/eIF3e is required for nonsense-mediated mRNA deca... 		ACCEPT
Summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological process of UPF1; it is recruited at termination and triggers decay.
Reason: Core biological process; UPF1 is the central NMD factor.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0005515 protein binding
IPI
PMID:17468741
Human INT6/eIF3e is required for nonsense-mediated mRNA deca... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
TAS
PMID:8855285
Mammalian orthologues of a yeast regulator of nonsense trans... 		ACCEPT
Summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological process of UPF1; it is recruited at termination and triggers decay.
Reason: Core biological process; UPF1 is the central NMD factor.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0005515 protein binding
IPI
PMID:11544179
Human SMG-1, a novel phosphatidylinositol 3-kinase-related p... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0000785 chromatin
IDA
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: Chromatin localization (IDA) associated with UPF1 nuclear/replication roles.
Reason: Nuclear chromatin association; non-core relative to cytoplasmic NMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0000785
GO:0003682 chromatin binding
IDA
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: Chromatin binding (IDA), consistent with the chromatin-associated UPF1 pool.
Reason: Chromatin binding; moonlighting/non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0003682
GO:0003724 RNA helicase activity
IDA
PMID:12554878
Characterization of human Smg5/7a: a protein with similariti... 		ACCEPT
Summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central ATP-dependent helicase of nonsense-mediated mRNA decay.
Reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
RNA-dependent helicase required for nonsense-mediated decay
GO:0005515 protein binding
IPI
PMID:14636577
Phosphorylation of hUPF1 induces formation of mRNA surveilla... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0006260 DNA replication
IMP
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: DNA replication (IMP); UPF1 has a reported role in S-phase/replication.
Reason: Reported replication role (also linked to histone mRNA decay timing); non-core relative to NMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0006260
GO:0006281 DNA repair
IDA
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: DNA repair (IDA); reported chromatin/replication-associated UPF1 activity.
Reason: Peripheral genome-maintenance role; non-core.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0006281
GO:0006406 mRNA export from nucleus
TAS
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		KEEP AS NON CORE
Summary: mRNA export from nucleus (TAS); a reported ancillary role in mRNA metabolism.
Reason: Peripheral mRNA-metabolism role; non-core relative to NMD.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0006406
GO:0005515 protein binding
IPI
PMID:9620853
The surveillance complex interacts with the translation rele... 		KEEP AS NON CORE
Summary: Interaction evidence captured under the uninformative generic protein binding term. UPF1 is a hub with many physical partners; this records a real interaction but does not by itself specify a function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept as non-core because it records a genuine interaction but the core molecular function is the RNA helicase/ATPase activity.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0005515
GO:0006449 regulation of translational termination
IMP
PMID:9620853
The surveillance complex interacts with the translation rele... 		ACCEPT
Summary: Regulation of translational termination; UPF1 acts at terminating ribosomes (SURF complex with eRF1/eRF3) to couple termination to decay.
Reason: Supported by UPF1 association with release factors at termination as the trigger for NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
NAS
PMID:10999600
Characterization of the biochemical properties of the human ... 		ACCEPT
Summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological process of UPF1; it is recruited at termination and triggers decay.
Reason: Core biological process; UPF1 is the central NMD factor.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0003723 RNA binding
NAS
PMID:10999600
Characterization of the biochemical properties of the human ... 		ACCEPT
Summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part of its helicase function.
Reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays) and is integral to UPF1 function.
Supporting Evidence:
file:human/UPF1/UPF1-goa.tsv
GO:0003723
GO:0006449 regulation of translational termination
NAS
PMID:10999600
Characterization of the biochemical properties of the human ... 		ACCEPT
Summary: Regulation of translational termination; UPF1 acts at terminating ribosomes (SURF complex with eRF1/eRF3) to couple termination to decay.
Reason: Supported by UPF1 association with release factors at termination as the trigger for NMD.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
recruited to mRNAs upon translation termination
GO:0004386 helicase activity
NAS
PMID:9064659
Cloning and characterization of HUPF1, a human homolog of th... 		ACCEPT
Summary: General helicase activity, a parent of the specific RNA helicase activity that is core to UPF1.
Reason: Correct but less specific than RNA helicase activity; retained as a valid parent MF.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
RNA-dependent helicase required for nonsense-mediated decay
GO:0005737 cytoplasm
NAS
PMID:9064659
Cloning and characterization of HUPF1, a human homolog of th... 		ACCEPT
Summary: Cytoplasmic localization, a principal site of UPF1 action (NMD occurs on cytoplasmic translating mRNAs).
Reason: Well-supported cytoplasmic localization.
Supporting Evidence:
file:human/UPF1/UPF1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm

Core Functions

ATP-dependent RNA helicase / ATPase that, recruited at translation termination, remodels and disassembles target mRNPs to drive nonsense-mediated mRNA decay.

Molecular Function:
RNA helicase activity
Cellular Locations:
cytosol
Supporting Evidence:
  • file:human/UPF1/UPF1-uniprot.txt
    RNA-dependent helicase required for nonsense-mediated decay
  • file:human/UPF1/UPF1-uniprot.txt
    ATPase activity of UPF1 is

Central effector of nonsense-mediated mRNA decay of premature-termination-codon-containing transcripts; recruited at terminating ribosomes and, via SMG1 phosphorylation and the UPF2/UPF3-EJC surveillance complex, commits target mRNAs to degradation.

Molecular Function:
RNA helicase activity
Cellular Locations:
cytosol
Supporting Evidence:
  • file:human/UPF1/UPF1-uniprot.txt
    recruited to mRNAs upon translation termination
  • file:human/UPF1/UPF1-goa.tsv
    GO:0000184

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000003
Gene Ontology annotation based on Enzyme Commission mapping
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation through association of UniProtKB keywords with GO terms
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000116
Gene Ontology annotation based on the InterPro2GO/ARBA mapping
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10999600
Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay.
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon.
PMID:11544179
Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay.
PMID:12417715
Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay.
PMID:12554878
Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1.
PMID:12881429
Interaction between Ski7p and Upf1p is required for nonsense-mediated 3'-to-5' mRNA decay in yeast.
PMID:14636577
Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7.
PMID:15680326
Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
PMID:16086026
Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1.
PMID:16364915
Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping.
PMID:16452507
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.
PMID:16488880
The human RNA surveillance factor UPF1 is required for S phase progression and genome stability.
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation.
PMID:17468741
Human INT6/eIF3e is required for nonsense-mediated mRNA decay.
PMID:17469741
Results of the determination of serum markers in patients with malignant melanoma.
PMID:17916692
Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.
PMID:17932509
Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells.
PMID:18066079
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity.
PMID:18256688
Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways.
PMID:18362360
The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus.
PMID:18369367
NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
PMID:18423202
Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA decay.
PMID:18447585
A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay.
PMID:19150429
Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex.
PMID:19417104
SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay.
PMID:19478851
The hierarchy of exon-junction complex assembly by the spliceosome explains key features of mammalian nonsense-mediated mRNA decay.
PMID:19503078
A UPF3-mediated regulatory switch that maintains RNA surveillance.
PMID:19556969
Unusual bipartite mode of interaction between the nonsense-mediated decay factors, UPF1 and UPF2.
PMID:19864460
Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export.
PMID:20930030
SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay.
PMID:21145460
Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay.
PMID:21419344
Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2.
PMID:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication.
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
PMID:23348841
An unusual arrangement of two 14-3-3-like domains in the SMG5-SMG7 heterodimer is required for efficient nonsense-mediated mRNA decay.
PMID:23722113
Non-structural protein 1 of influenza viruses inhibits rapid mRNA degradation mediated by double-stranded RNA-binding protein, staufen1.
PMID:23788676
The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA.
PMID:23828042
DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous RNA targets in human cells, zebrafish and Caenorhabditis elegans.
PMID:24267889
Affinity proteomics reveals human host factors implicated in discrete stages of LINE-1 retrotransposition.
PMID:24726324
MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs.
PMID:24965446
Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.
PMID:25220460
The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex.
PMID:25225333
Plakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal proteins.
PMID:26000482
Regnase-1 and Roquin Regulate a Common Element in Inflammatory mRNAs by Spatiotemporally Distinct Mechanisms.
PMID:26138914
Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities.
PMID:26255671
Regnase-1 and Roquin regulate inflammatory mRNAs.
PMID:26841701
The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation.
PMID:27974568
IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10.
PMID:30218034
UPF1-like helicase grip on nucleic acids dictates processivity.
PMID:31131562
Nonsense-mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:35640974
Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing mutation.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:8855285
Mammalian orthologues of a yeast regulator of nonsense transcript stability.
PMID:9064659
Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein.
PMID:9620853
The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs.
Reactome:R-HSA-927789
Reactome: Formation of the SURF complex (cytosol)
Reactome:R-HSA-927813
Reactome: nonsense-mediated decay (cytosol)
Reactome:R-HSA-927830
Reactome: nonsense-mediated decay (cytosol)
Reactome:R-HSA-927832
Reactome: nonsense-mediated decay (cytosol)
Reactome:R-HSA-927836
Reactome: nonsense-mediated decay (cytosol)
Reactome:R-HSA-927889
Reactome: nonsense-mediated decay (cytosol)

Suggested Questions for Experts

Q: Which of UPF1’s non-NMD roles (telomere replication, DNA repair, histone mRNA decay) reflect distinct molecular activities versus indirect consequences of perturbing NMD?

Q: How does the phosphorylation/dephosphorylation cycle of UPF1 (SMG1 vs PP2A) quantitatively gate the commitment of a target mRNA to decay?

Suggested Experiments

Experiment: Separation-of-function UPF1 mutants (helicase-dead vs phospho-site vs CH-domain) followed by transcriptome-wide NMD-target profiling to dissect catalytic from scaffolding roles.

Experiment: Single-molecule assays of UPF1 ATPase-driven translocation/mRNP disassembly on reconstituted EJC-containing substrates to quantify the remodeling step that commits mRNAs to decay.

📚 Additional Documentation

Notes

(UPF1-notes.md)

UPF1 (Q92900) research notes

Summary

UPF1 (regulator of nonsense transcripts 1; RENT1) is the central ATP-dependent RNA helicase and ATPase of the nonsense-mediated mRNA decay (NMD) pathway. A superfamily-1 (SF1) helicase with an N-terminal cysteine-histidine-rich (CH) zinc-binding regulatory domain, UPF1 is recruited to mRNAs at translation termination, where release factors (eRF1/eRF3) and the SMG1 kinase complex assemble the transient SURF complex. In EJC-dependent NMD the adaptor UPF2 bridges UPF1 to UPF3 and the downstream exon-junction complex, forming the UPF1-UPF2-UPF3 surveillance complex; UPF1 is then phosphorylated by SMG1 and the phospho-form is recognized by SMG5/SMG6/SMG7 to recruit decay enzymes and PP2A. UPF1 ATPase/helicase activity remodels and disassembles target mRNPs, committing premature-termination-codon-containing and certain long-3'UTR or staufen-bound transcripts to degradation, and also mediates replication-dependent histone mRNA decay at the end of S phase. UPF1 acts mainly on cytoplasmic translating mRNAs (with a smaller nuclear pool), concentrates in P-bodies in its hyperphosphorylated state, and has additional reported moonlighting roles at telomeres and in DNA replication; it can unwind both RNA and DNA in vitro.

Core functions (from review)

  • GO:0003724 RNA helicase activity — ATP-dependent RNA helicase / ATPase that, recruited at translation termination, remodels and disassembles target mRNPs to drive nonsense-mediated mRNA decay.
  • GO:0003724 RNA helicase activity — Central effector of nonsense-mediated mRNA decay of premature-termination-codon-containing transcripts; recruited at terminating ribosomes and, via SMG1 phosphorylation and the UPF2/UPF3-EJC surveillance complex, commits target mRNAs to degradation.

Provenance

Research and verbatim supporting quotes are recorded inline in UPF1-ai-review.yaml (per-annotation supported_by and references findings). This notes file summarizes the completed review; see the YAML for evidence citations.

Pn Notes

(UPF1-pn-notes.md)

UPF1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q92900
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: UPF1 (regulator of nonsense transcripts 1; RENT1) is the central ATP-dependent RNA helicase and ATPase of the nonsense-mediated mRNA decay (NMD) pathway. A superfamily-1 (SF1) helicase with an N-terminal cysteine-histidine-rich (CH) zinc-binding regulatory domain, UPF1 is recruited to mRNAs at translation termination, where release factors (eRF1/eRF3) and the SMG1 kinase complex assemble the transient SURF complex. In EJC-dependent NMD the adaptor UPF2 bridges UPF1 to UPF3 and the downstream exon-junction complex, forming the UPF1-UPF2-UPF3 surveillance complex; UPF1 is then phosphorylated by SMG1 and the phospho-form is recognized by SMG5/SMG6/SMG7 to recruit decay enzymes and PP2A. UPF1 ATPase/helicase activity remodels and disassembles target mRNPs, committing premature-termination-codon-containing and certain long-3'UTR or staufen-bound transcripts to degradation, and also mediates replication-dependent histone mRNA decay at the end of S phase. UPF1 acts mainly on cytoplasmic translating mRNAs (with a smaller nuclear pool), concentrates in P-bodies in its hyperphosphorylated state, and has additional reported moonlighting roles at telomeres and in DNA replication; it can unwind both RNA and DNA in vitro.
  • Existing/core annotation action counts: ACCEPT: 41; KEEP_AS_NON_CORE: 78; MARK_AS_OVER_ANNOTATED: 1

PN Consistency Summary

  • Consistency: Mostly consistent on the gene's biology — deep-research/notes, review YAML and GOA all agree UPF1 is the central ATP-dependent SF1 RNA helicase/ATPase of NMD (core MF GO:0003724; core BP GO:0000184). But there is a framing tension with the PN-node mapping (see below): the review never frames UPF1 as a translation-termination factor; it is recruited at termination but its function is mRNA surveillance/decay, not polypeptide release.
  • PN story / NEW pressure: The PN "modulation of termination" story IS reflected in GOA — UPF1 carries GO:0006449 regulation of translational termination (verified real; 2 records, ECO:0000315/0000303), which the dossier correctly cites as supported_by_goa_regulation. This is the defensible frame and is already captured. No NEW term needed; UPF1's core (RNA helicase, NMD, ATPase) is fully annotated.
  • Evidence alignment: PN row carries no reference titles; the review is heavily evidenced (NMD: PMID:26255671 TAS, GO:0000184 IEA; helicase: PMID:21419344, 26138914, 30218034 IDA; complex GO:0170010). No divergence to reconcile — PN provides no competing citations.
  • Verdict: Gene biology consistent; PN group→GO:0006415 (translational termination) over-reaches — UPF1's termination link is regulatory (GO:0006449), already in GOA.

Full Consistency Review

  • UniProt: Q92900 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: Translation|Cytosolic translation|Translation termination|Modulation of termination ; PN-node mapping: type (Modulation of termination) no_mapping; group (Translation termination) mapped, ok_for_propagation → GO:0006415 translational termination; class/branch context_only, too_broad. Projected: GO:0006415 (goa_status=supported_by_goa_regulation).
  • Consistency: Mostly consistent on the gene's biology — deep-research/notes, review YAML and GOA all agree UPF1 is the central ATP-dependent SF1 RNA helicase/ATPase of NMD (core MF GO:0003724; core BP GO:0000184). But there is a framing tension with the PN-node mapping (see below): the review never frames UPF1 as a translation-termination factor; it is recruited at termination but its function is mRNA surveillance/decay, not polypeptide release.
  • PN story / NEW pressure: The PN "modulation of termination" story IS reflected in GOA — UPF1 carries GO:0006449 regulation of translational termination (verified real; 2 records, ECO:0000315/0000303), which the dossier correctly cites as supported_by_goa_regulation. This is the defensible frame and is already captured. No NEW term needed; UPF1's core (RNA helicase, NMD, ATPase) is fully annotated.
  • Mapping strategy: The GROUP projection onto GO:0006415 translational termination (verified: "release of a polypeptide chain from the ribosome … in response to a termination codon") is the wrong/over-broad term for UPF1 — UPF1 does not catalyze peptide release. UPF1 already has the precise GO:0006449 (regulation of termination) and GO:0000184 (NMD). The type-level no_mapping for "Modulation of termination" is correct; the group-level GO:0006415 projection should be GO:0006449, not GO:0006415, for UPF1 (precedent: TOMM20/HSPA8/RAB7A broader-term rejections).
  • Evidence alignment: PN row carries no reference titles; the review is heavily evidenced (NMD: PMID:26255671 TAS, GO:0000184 IEA; helicase: PMID:21419344, 26138914, 30218034 IDA; complex GO:0170010). No divergence to reconcile — PN provides no competing citations.
  • Verdict: Gene biology consistent; PN group→GO:0006415 (translational termination) over-reaches — UPF1's termination link is regulatory (GO:0006449), already in GOA.

Recommended edits: [MAP] for UPF1, replace/avoid the group projection GO:0006415 (translational termination, = peptide release) with GO:0006449 (regulation of translational termination), which is already in UPF1 GOA and is the accurate frame; UPF1's core remains NMD (GO:0000184) + RNA helicase (GO:0003724).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/UPF1/UPF1-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Translation | Cytosolic translation | Translation termination | Modulation of termination

  • UniProt: Q92900
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Cytosolic translation|Translation termination|Modulation of termination
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a contextual PN bucket. The label is useful for curator triage, but no direct GO mapping is appropriate because propagation would add a process, activity, or localization not shared cleanly by all members.
    • [group] Translation|Cytosolic translation|Translation termination
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006415 translational termination]
      rationale: This PN group denotes cytosolic translation termination and release factors. Translational termination is the shared process target.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (1)

  • GO:0006415 translational termination | scope=ok_for_propagation_to_go | goa_status=supported_by_goa_regulation | from=Translation|Cytosolic translation|Translation termination

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q92900
gene_symbol: UPF1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
alternative_products:
- name: '1'
  id: Q92900-1
- name: '2'
  id: Q92900-2
  sequence_note: VSP_003393
description: UPF1 (regulator of nonsense transcripts 1; RENT1) is the central ATP-dependent
  RNA helicase and ATPase of the nonsense-mediated mRNA decay (NMD) pathway. A superfamily-1
  (SF1) helicase with an N-terminal cysteine-histidine-rich (CH) zinc-binding regulatory domain,
  UPF1 is recruited to mRNAs at translation termination, where release factors (eRF1/eRF3) and
  the SMG1 kinase complex assemble the transient SURF complex. In EJC-dependent NMD the adaptor
  UPF2 bridges UPF1 to UPF3 and the downstream exon-junction complex, forming the UPF1-UPF2-UPF3
  surveillance complex; UPF1 is then phosphorylated by SMG1 and the phospho-form is recognized
  by SMG5/SMG6/SMG7 to recruit decay enzymes and PP2A. UPF1 ATPase/helicase activity remodels
  and disassembles target mRNPs, committing premature-termination-codon-containing and certain
  long-3'UTR or staufen-bound transcripts to degradation, and also mediates replication-dependent
  histone mRNA decay at the end of S phase. UPF1 acts mainly on cytoplasmic translating mRNAs
  (with a smaller nuclear pool), concentrates in P-bodies in its hyperphosphorylated state,
  and has additional reported moonlighting roles at telomeres and in DNA replication; it can
  unwind both RNA and DNA in vitro.
existing_annotations:
- term:
    id: GO:0003724
    label: RNA helicase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central
      ATP-dependent helicase of nonsense-mediated mRNA decay.
    action: ACCEPT
    reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for
      NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: RNA-dependent helicase required for nonsense-mediated decay
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological
      process of UPF1; it is recruited at termination and triggers decay.
    action: ACCEPT
    reason: Core biological process; UPF1 is the central NMD factor.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0000932
    label: P-body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: P-body localization; hyperphosphorylated UPF1 is targeted to P-bodies where mRNA
      decay factors concentrate.
    action: KEEP_AS_NON_CORE
    reason: Supported by UniProt note that the hyperphosphorylated form is targeted to P-bodies;
      a functional but non-core localization.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Hyperphosphorylated form is
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: DNA binding (IEA); UPF1 can act on DNA substrates in vitro and has reported telomere/replication
      roles.
    action: KEEP_AS_NON_CORE
    reason: Supported in vitro but peripheral to the core RNA/NMD function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Also capable of unwinding double-stranded DNA and
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part
      of its helicase function.
    action: ACCEPT
    reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays)
      and is integral to UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0003723
- term:
    id: GO:0003724
    label: RNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central
      ATP-dependent helicase of nonsense-mediated mRNA decay.
    action: ACCEPT
    reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for
      NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: RNA-dependent helicase required for nonsense-mediated decay
- term:
    id: GO:0004386
    label: helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: General helicase activity, a parent of the specific RNA helicase activity that
      is core to UPF1.
    action: ACCEPT
    reason: Correct but less specific than RNA helicase activity; retained as a valid parent
      MF.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: RNA-dependent helicase required for nonsense-mediated decay
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ATP binding, required for the ATPase/helicase cycle of UPF1.
    action: ACCEPT
    reason: ATP binding is integral to the SF1 helicase catalytic mechanism of UPF1.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: ATPase activity of UPF1 is
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear localization; a minor UPF1 pool is nuclear (and UPF1 has nuclear/chromatin-associated
      roles).
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool but the core NMD function is cytoplasmic; retained as non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005634
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, a principal site of UPF1 action (NMD occurs on cytoplasmic
      translating mRNAs).
    action: ACCEPT
    reason: Well-supported cytoplasmic localization.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Zinc ion binding (IEA); UPF1 has a CH (cysteine-histidine-rich) zinc-binding regulatory
      domain.
    action: ACCEPT
    reason: UPF1's N-terminal CH domain coordinates zinc and regulates helicase/UPF2 interaction.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0008270
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Regulation of gene expression, a very general process annotation reflecting NMD-mediated
      control of transcript levels.
    action: KEEP_AS_NON_CORE
    reason: Too general to be a core annotation; subsumed by specific mRNA-decay terms.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0010468
- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Generic hydrolase activity, an uninformative high-level parent of the ATPase/helicase
      activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general to be informative; the specific activities (RNA helicase, ATP hydrolysis)
      already capture this.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: ATPase activity of UPF1 is
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: ATP hydrolysis (ATPase) activity powers UPF1 translocation/unwinding and mRNP remodeling
      during NMD.
    action: ACCEPT
    reason: UPF1's ATPase activity is directly demonstrated and required for disassembly of
      mRNPs undergoing NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: ATPase activity of UPF1 is
- term:
    id: GO:0032574
    label: 5'-3' RNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: UPF1 unwinds RNA with 5'-3' directionality; a precise statement of its helicase
      polarity.
    action: ACCEPT
    reason: Biochemically demonstrated 5'-3' RNA helicase activity; a useful specific child
      of RNA helicase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0032574
- term:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: 5'-3' DNA helicase activity (IEA/IDA); UPF1 can unwind DNA in vitro.
    action: KEEP_AS_NON_CORE
    reason: In vitro DNA-unwinding activity; non-core relative to RNA helicase/NMD function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Also capable of unwinding double-stranded DNA and
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Perinuclear region of cytoplasm localization (by similarity).
    action: KEEP_AS_NON_CORE
    reason: Localization inferred by similarity; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0048471
- term:
    id: GO:1903313
    label: positive regulation of mRNA metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Positive regulation of mRNA metabolic process, a high-level process reflecting
      UPF1 control of mRNA turnover.
    action: KEEP_AS_NON_CORE
    reason: Correct but general; the specific NMD/mRNA-catabolism terms are more informative.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:1903313
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11163187
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12417715
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12881429
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15680326
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16086026
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16364915
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16601204
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17469741
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18256688
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18362360
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18447585
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19150429
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19417104
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19478851
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19503078
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19556969
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21829167
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23348841
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23722113
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24267889
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16452507
  qualifier: enables
  isoform: Q92900-2
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18066079
  qualifier: enables
  isoform: Q92900-2
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18423202
  qualifier: enables
  isoform: Q92900-2
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21145460
  qualifier: enables
  isoform: Q92900-2
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0032574
    label: 5'-3' RNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:26138914
  qualifier: enables
  review:
    summary: UPF1 unwinds RNA with 5'-3' directionality; a precise statement of its helicase
      polarity.
    action: ACCEPT
    reason: Biochemically demonstrated 5'-3' RNA helicase activity; a useful specific child
      of RNA helicase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0032574
- term:
    id: GO:0043139
    label: 5'-3' DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:26138914
  qualifier: enables
  review:
    summary: 5'-3' DNA helicase activity (IEA/IDA); UPF1 can unwind DNA in vitro.
    action: KEEP_AS_NON_CORE
    reason: In vitro DNA-unwinding activity; non-core relative to RNA helicase/NMD function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Also capable of unwinding double-stranded DNA and
- term:
    id: GO:0033678
    label: 5'-3' DNA/RNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:18066079
  qualifier: enables
  review:
    summary: 5'-3' DNA/RNA helicase activity; reflects UPF1's ability to translocate/unwind
      both nucleic acids.
    action: KEEP_AS_NON_CORE
    reason: Captures dual substrate unwinding; the RNA helicase activity is the core function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Also capable of unwinding double-stranded DNA and
- term:
    id: GO:0033678
    label: 5'-3' DNA/RNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:21419344
  qualifier: enables
  review:
    summary: 5'-3' DNA/RNA helicase activity; reflects UPF1's ability to translocate/unwind
      both nucleic acids.
    action: KEEP_AS_NON_CORE
    reason: Captures dual substrate unwinding; the RNA helicase activity is the core function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Also capable of unwinding double-stranded DNA and
- term:
    id: GO:0071025
    label: RNA surveillance
  evidence_type: NAS
  original_reference_id: PMID:31131562
  qualifier: involved_in
  review:
    summary: RNA surveillance, the broad quality-control category encompassing NMD in which
      UPF1 is the central factor.
    action: KEEP_AS_NON_CORE
    reason: Accurate high-level descriptor; the specific NMD term is the core annotation.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0071025
- term:
    id: GO:0170010
    label: nonsense-mediated decay complex
  evidence_type: NAS
  original_reference_id: PMID:35640974
  qualifier: part_of
  review:
    summary: UPF1 is a component of the nonsense-mediated decay (SURF/UPF1-UPF2-UPF3 surveillance)
      complex.
    action: ACCEPT
    reason: UPF1 is a defining subunit of the NMD effector complex.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0170010
- term:
    id: GO:2000623
    label: negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated
      decay
  evidence_type: NAS
  original_reference_id: PMID:31131562
  qualifier: involved_in
  review:
    summary: Negative regulation of NMD; reflects context-dependent modulation of NMD efficiency
      by UPF1/regulators.
    action: KEEP_AS_NON_CORE
    reason: NAS regulatory annotation; plausible in the context of NMD autoregulation but non-core
      relative to UPF1 driving NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:2000623
- term:
    id: GO:2000624
    label: positive regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated
      decay
  evidence_type: NAS
  original_reference_id: PMID:31131562
  qualifier: involved_in
  review:
    summary: Positive regulation of NMD; UPF1 activity promotes NMD of target transcripts.
    action: KEEP_AS_NON_CORE
    reason: NAS regulatory annotation consistent with UPF1 function; non-core relative to the
      direct NMD term.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:2000624
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Nucleoplasm localization (IDA), consistent with a nuclear UPF1 pool.
    action: KEEP_AS_NON_CORE
    reason: Minor nuclear localization; non-core relative to cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005654
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:11163187
  qualifier: located_in
  review:
    summary: Nuclear localization; a minor UPF1 pool is nuclear (and UPF1 has nuclear/chromatin-associated
      roles).
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool but the core NMD function is cytoplasmic; retained as non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005634
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:11163187
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, a principal site of UPF1 action (NMD occurs on cytoplasmic
      translating mRNAs).
    action: ACCEPT
    reason: Well-supported cytoplasmic localization.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: TAS
  original_reference_id: PMID:26255671
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological
      process of UPF1; it is recruited at termination and triggers decay.
    action: ACCEPT
    reason: Core biological process; UPF1 is the central NMD factor.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0061158
    label: 3'-UTR-mediated mRNA destabilization
  evidence_type: TAS
  original_reference_id: PMID:26255671
  qualifier: involved_in
  review:
    summary: 3'-UTR-mediated mRNA destabilization; UPF1 (with UPF2/TDRD6) degrades mRNAs bearing
      long 3'UTRs, a recognized NMD-related branch.
    action: ACCEPT
    reason: Supported NMD-related destabilization function on long-3'UTR transcripts.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0061158
- term:
    id: GO:0071222
    label: cellular response to lipopolysaccharide
  evidence_type: TAS
  original_reference_id: PMID:26255671
  qualifier: involved_in
  review:
    summary: Cellular response to lipopolysaccharide (TAS); UPF1/NMD modulates inflammatory
      transcript stability.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response context for NMD targets; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0071222
- term:
    id: GO:0071347
    label: cellular response to interleukin-1
  evidence_type: TAS
  original_reference_id: PMID:26255671
  qualifier: involved_in
  review:
    summary: Cellular response to interleukin-1 (TAS); NMD-related modulation of cytokine-response
      transcripts.
    action: KEEP_AS_NON_CORE
    reason: Stimulus-response context; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0071347
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:30218034
  qualifier: enables
  review:
    summary: ATP hydrolysis (ATPase) activity powers UPF1 translocation/unwinding and mRNP remodeling
      during NMD.
    action: ACCEPT
    reason: UPF1's ATPase activity is directly demonstrated and required for disassembly of
      mRNPs undergoing NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: ATPase activity of UPF1 is
- term:
    id: GO:0036121
    label: double-stranded DNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:30218034
  qualifier: enables
  review:
    summary: Double-stranded DNA helicase activity (IDA); UPF1 unwinds dsDNA in vitro.
    action: KEEP_AS_NON_CORE
    reason: In vitro dsDNA helicase activity; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: Also capable of unwinding double-stranded DNA and
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26841701
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IPI
  original_reference_id: PMID:26841701
  qualifier: enables
  review:
    summary: Protein-containing complex binding; UPF1 engages multiprotein assemblies (EJC,
      SMG complexes).
    action: KEEP_AS_NON_CORE
    reason: Records complex association but is non-specific; the informative facts are the named
      complexes (EJC, SURF).
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0044877
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25220460
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27974568
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IDA
  original_reference_id: PMID:24726324
  qualifier: enables
  review:
    summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part
      of its helicase function.
    action: ACCEPT
    reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays)
      and is integral to UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0003723
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24726324
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0061014
    label: positive regulation of mRNA catabolic process
  evidence_type: IDA
  original_reference_id: PMID:24726324
  qualifier: involved_in
  review:
    summary: Positive regulation of mRNA catabolic process; UPF1 promotes decay of its target
      mRNAs.
    action: ACCEPT
    reason: Consistent with UPF1 driving mRNA degradation in NMD/SMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0061014
- term:
    id: GO:0061158
    label: 3'-UTR-mediated mRNA destabilization
  evidence_type: IDA
  original_reference_id: PMID:24726324
  qualifier: involved_in
  review:
    summary: 3'-UTR-mediated mRNA destabilization; UPF1 (with UPF2/TDRD6) degrades mRNAs bearing
      long 3'UTRs, a recognized NMD-related branch.
    action: ACCEPT
    reason: Supported NMD-related destabilization function on long-3'UTR transcripts.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0061158
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19864460
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0032204
    label: regulation of telomere maintenance
  evidence_type: IMP
  original_reference_id: PMID:17916692
  qualifier: involved_in
  review:
    summary: Regulation of telomere maintenance (IMP); part of the UPF1 telomere function.
    action: KEEP_AS_NON_CORE
    reason: Moonlighting telomere role; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0032204
- term:
    id: GO:0044770
    label: cell cycle phase transition
  evidence_type: IMP
  original_reference_id: PMID:16488880
  qualifier: involved_in
  review:
    summary: Cell cycle phase transition (IMP); reflects UPF1 effects on cell-cycle progression
      (e.g. via histone mRNA decay / replication).
    action: KEEP_AS_NON_CORE
    reason: Downstream/indirect phenotype; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0044770
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23788676
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25225333
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0061014
    label: positive regulation of mRNA catabolic process
  evidence_type: IMP
  original_reference_id: PMID:25225333
  qualifier: involved_in
  review:
    summary: Positive regulation of mRNA catabolic process; UPF1 promotes decay of its target
      mRNAs.
    action: ACCEPT
    reason: Consistent with UPF1 driving mRNA degradation in NMD/SMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0061014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26255671
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24965446
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26000482
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0000781
    label: chromosome, telomeric region
  evidence_type: IDA
  original_reference_id: PMID:21829167
  qualifier: located_in
  review:
    summary: Chromosome telomeric region localization, consistent with UPF1 telomere-associated
      role.
    action: KEEP_AS_NON_CORE
    reason: Telomere localization; moonlighting, non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0000781
- term:
    id: GO:0032201
    label: telomere maintenance via semi-conservative replication
  evidence_type: IDA
  original_reference_id: PMID:21829167
  qualifier: involved_in
  review:
    summary: Telomere maintenance via semi-conservative replication; UPF1 supports telomere
      leading-strand synthesis.
    action: KEEP_AS_NON_CORE
    reason: Telomere-replication role (PMID:21829167); moonlighting, non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0032201
- term:
    id: GO:0042162
    label: telomeric repeat DNA binding
  evidence_type: IDA
  original_reference_id: PMID:17916692
  qualifier: enables
  review:
    summary: Telomeric repeat DNA binding (IDA); part of a reported UPF1 role at telomeres with
      TPP1/telomerase.
    action: KEEP_AS_NON_CORE
    reason: Documented telomere-associated activity (PMID:21829167) but a moonlighting role
      distinct from core NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: interacts with TPP1 and telomerase
- term:
    id: GO:0042162
    label: telomeric repeat DNA binding
  evidence_type: IDA
  original_reference_id: PMID:21829167
  qualifier: enables
  review:
    summary: Telomeric repeat DNA binding (IDA); part of a reported UPF1 role at telomeres with
      TPP1/telomerase.
    action: KEEP_AS_NON_CORE
    reason: Documented telomere-associated activity (PMID:21829167) but a moonlighting role
      distinct from core NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: interacts with TPP1 and telomerase
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927813
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927830
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927836
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927889
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part
      of its helicase function.
    action: ACCEPT
    reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays)
      and is integral to UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0003723
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part
      of its helicase function.
    action: ACCEPT
    reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays)
      and is integral to UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0003723
- term:
    id: GO:0000956
    label: nuclear-transcribed mRNA catabolic process
  evidence_type: IMP
  original_reference_id: PMID:23828042
  qualifier: involved_in
  review:
    summary: Nuclear-transcribed mRNA catabolic process, a parent of the NMD process that UPF1
      drives.
    action: KEEP_AS_NON_CORE
    reason: Correct but more general than the specific NMD term; retained as a valid parent
      process.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0000956
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20930030
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927789
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927832
  qualifier: located_in
  review:
    summary: Cytosol, consistent with cytoplasmic NMD activity of UPF1.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18362360
  qualifier: located_in
  review:
    summary: Nuclear localization; a minor UPF1 pool is nuclear (and UPF1 has nuclear/chromatin-associated
      roles).
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool but the core NMD function is cytoplasmic; retained as non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005634
- term:
    id: GO:0044530
    label: supraspliceosomal complex
  evidence_type: IDA
  original_reference_id: PMID:18362360
  qualifier: part_of
  review:
    summary: Supraspliceosomal complex; a nuclear assembly with which UPF1 was found associated.
    action: KEEP_AS_NON_CORE
    reason: Nuclear complex association; peripheral to the core cytoplasmic NMD function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0044530
- term:
    id: GO:0003724
    label: RNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:21419344
  qualifier: enables
  review:
    summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central
      ATP-dependent helicase of nonsense-mediated mRNA decay.
    action: ACCEPT
    reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for
      NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: RNA-dependent helicase required for nonsense-mediated decay
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17932509
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0035145
    label: exon-exon junction complex
  evidence_type: IDA
  original_reference_id: PMID:16601204
  qualifier: part_of
  review:
    summary: Exon-exon junction complex; UPF1 functionally couples to the EJC during EJC-dependent
      NMD (via UPF2/UPF3).
    action: KEEP_AS_NON_CORE
    reason: UPF1 associates with the EJC-linked surveillance complex; recorded as a relevant
      but non-core part_of.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: exon junction complex
- term:
    id: GO:0071044
    label: histone mRNA catabolic process
  evidence_type: IMP
  original_reference_id: PMID:16086026
  qualifier: involved_in
  review:
    summary: Histone mRNA catabolic process; UPF1 mediates replication-dependent histone mRNA
      degradation at the end of S phase, independent of UPF2.
    action: ACCEPT
    reason: Well-documented UPF1 function in histone mRNA decay; a genuine UPF1-dependent decay
      pathway.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: replication-dependent histone mRNA degradation
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: IMP
  original_reference_id: PMID:18369367
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological
      process of UPF1; it is recruited at termination and triggers decay.
    action: ACCEPT
    reason: Core biological process; UPF1 is the central NMD factor.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: IDA
  original_reference_id: PMID:17468741
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological
      process of UPF1; it is recruited at termination and triggers decay.
    action: ACCEPT
    reason: Core biological process; UPF1 is the central NMD factor.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17468741
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: TAS
  original_reference_id: PMID:8855285
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological
      process of UPF1; it is recruited at termination and triggers decay.
    action: ACCEPT
    reason: Core biological process; UPF1 is the central NMD factor.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11544179
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:16488880
  qualifier: located_in
  review:
    summary: Chromatin localization (IDA) associated with UPF1 nuclear/replication roles.
    action: KEEP_AS_NON_CORE
    reason: Nuclear chromatin association; non-core relative to cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0000785
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:16488880
  qualifier: enables
  review:
    summary: Chromatin binding (IDA), consistent with the chromatin-associated UPF1 pool.
    action: KEEP_AS_NON_CORE
    reason: Chromatin binding; moonlighting/non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0003682
- term:
    id: GO:0003724
    label: RNA helicase activity
  evidence_type: IDA
  original_reference_id: PMID:12554878
  qualifier: enables
  review:
    summary: RNA helicase activity is the core catalytic molecular function of UPF1, the central
      ATP-dependent helicase of nonsense-mediated mRNA decay.
    action: ACCEPT
    reason: Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for
      NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: RNA-dependent helicase required for nonsense-mediated decay
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14636577
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16488880
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0006260
    label: DNA replication
  evidence_type: IMP
  original_reference_id: PMID:16488880
  qualifier: involved_in
  review:
    summary: DNA replication (IMP); UPF1 has a reported role in S-phase/replication.
    action: KEEP_AS_NON_CORE
    reason: Reported replication role (also linked to histone mRNA decay timing); non-core relative
      to NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0006260
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IDA
  original_reference_id: PMID:16488880
  qualifier: involved_in
  review:
    summary: DNA repair (IDA); reported chromatin/replication-associated UPF1 activity.
    action: KEEP_AS_NON_CORE
    reason: Peripheral genome-maintenance role; non-core.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0006281
- term:
    id: GO:0006406
    label: mRNA export from nucleus
  evidence_type: TAS
  original_reference_id: PMID:16488880
  qualifier: involved_in
  review:
    summary: mRNA export from nucleus (TAS); a reported ancillary role in mRNA metabolism.
    action: KEEP_AS_NON_CORE
    reason: Peripheral mRNA-metabolism role; non-core relative to NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0006406
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9620853
  qualifier: enables
  review:
    summary: Interaction evidence captured under the uninformative generic protein binding term.
      UPF1 is a hub with many physical partners; this records a real interaction but does not
      by itself specify a function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; kept
      as non-core because it records a genuine interaction but the core molecular function is
      the RNA helicase/ATPase activity.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0006449
    label: regulation of translational termination
  evidence_type: IMP
  original_reference_id: PMID:9620853
  qualifier: involved_in
  review:
    summary: Regulation of translational termination; UPF1 acts at terminating ribosomes (SURF
      complex with eRF1/eRF3) to couple termination to decay.
    action: ACCEPT
    reason: Supported by UPF1 association with release factors at termination as the trigger
      for NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: NAS
  original_reference_id: PMID:10999600
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay of PTC-containing transcripts is the central biological
      process of UPF1; it is recruited at termination and triggers decay.
    action: ACCEPT
    reason: Core biological process; UPF1 is the central NMD factor.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: NAS
  original_reference_id: PMID:10999600
  qualifier: enables
  review:
    summary: RNA binding underlies UPF1 recruitment to target mRNAs; UPF1 binds RNA as part
      of its helicase function.
    action: ACCEPT
    reason: RNA binding is well supported (including HTP mRNA-interactome and direct assays)
      and is integral to UPF1 function.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-goa.tsv
      supporting_text: GO:0003723
- term:
    id: GO:0006449
    label: regulation of translational termination
  evidence_type: NAS
  original_reference_id: PMID:10999600
  qualifier: involved_in
  review:
    summary: Regulation of translational termination; UPF1 acts at terminating ribosomes (SURF
      complex with eRF1/eRF3) to couple termination to decay.
    action: ACCEPT
    reason: Supported by UPF1 association with release factors at termination as the trigger
      for NMD.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: recruited to mRNAs upon translation termination
- term:
    id: GO:0004386
    label: helicase activity
  evidence_type: NAS
  original_reference_id: PMID:9064659
  qualifier: enables
  review:
    summary: General helicase activity, a parent of the specific RNA helicase activity that
      is core to UPF1.
    action: ACCEPT
    reason: Correct but less specific than RNA helicase activity; retained as a valid parent
      MF.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: RNA-dependent helicase required for nonsense-mediated decay
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:9064659
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, a principal site of UPF1 action (NMD occurs on cytoplasmic
      translating mRNAs).
    action: ACCEPT
    reason: Well-supported cytoplasmic localization.
    supported_by:
    - reference_id: file:human/UPF1/UPF1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
core_functions:
- description: ATP-dependent RNA helicase / ATPase that, recruited at translation termination,
    remodels and disassembles target mRNPs to drive nonsense-mediated mRNA decay.
  molecular_function:
    id: GO:0003724
    label: RNA helicase activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/UPF1/UPF1-uniprot.txt
    supporting_text: RNA-dependent helicase required for nonsense-mediated decay
  - reference_id: file:human/UPF1/UPF1-uniprot.txt
    supporting_text: ATPase activity of UPF1 is
- description: Central effector of nonsense-mediated mRNA decay of premature-termination-codon-containing
    transcripts; recruited at terminating ribosomes and, via SMG1 phosphorylation and the UPF2/UPF3-EJC
    surveillance complex, commits target mRNAs to degradation.
  molecular_function:
    id: GO:0003724
    label: RNA helicase activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/UPF1/UPF1-uniprot.txt
    supporting_text: recruited to mRNAs upon translation termination
  - reference_id: file:human/UPF1/UPF1-goa.tsv
    supporting_text: GO:0000184
proposed_new_terms: []
suggested_questions:
- question: Which of UPF1’s non-NMD roles (telomere replication, DNA repair, histone mRNA decay)
    reflect distinct molecular activities versus indirect consequences of perturbing NMD?
- question: How does the phosphorylation/dephosphorylation cycle of UPF1 (SMG1 vs PP2A) quantitatively
    gate the commitment of a target mRNA to decay?
suggested_experiments:
- description: Separation-of-function UPF1 mutants (helicase-dead vs phospho-site vs CH-domain)
    followed by transcriptome-wide NMD-target profiling to dissect catalytic from scaffolding
    roles.
- description: Single-molecule assays of UPF1 ATPase-driven translocation/mRNP disassembly on
    reconstituted EJC-containing substrates to quantify the remodeling step that commits mRNAs
    to decay.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation through association of UniProtKB keywords with GO terms
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000116
  title: Gene Ontology annotation based on the InterPro2GO/ARBA mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10999600
  title: Characterization of the biochemical properties of the human Upf1 gene product that
    is involved in nonsense-mediated mRNA decay.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached PMID_10999600 title matches; biochemical characterization of human UPF1's RNA-dependent ATPase/helicase activity, supporting the GO:0003724 helicase core function (consistent with GOA helicase/NMD rows)."
- id: PMID:11163187
  title: Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream
    of a termination codon.
  findings: []
- id: PMID:11544179
  title: Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates
    with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated
    mRNA decay.
  findings: []
- id: PMID:12417715
  title: Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated
    decay.
  findings: []
- id: PMID:12554878
  title: 'Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans
    SMG5 and SMG7 that functions in the dephosphorylation of Upf1.'
  findings: []
- id: PMID:12881429
  title: Interaction between Ski7p and Upf1p is required for nonsense-mediated 3'-to-5' mRNA
    decay in yeast.
  findings: []
- id: PMID:14636577
  title: Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing
    hSMG-5 and hSMG-7.
  findings: []
- id: PMID:15680326
  title: Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
  findings: []
- id: PMID:16086026
  title: Regulated degradation of replication-dependent histone mRNAs requires both ATR and
    Upf1.
  findings: []
- id: PMID:16364915
  title: Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping.
  findings: []
- id: PMID:16452507
  title: Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex
    triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.
  findings: []
- id: PMID:16488880
  title: The human RNA surveillance factor UPF1 is required for S phase progression and genome
    stability.
  findings: []
- id: PMID:16601204
  title: Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation.
  findings: []
- id: PMID:17468741
  title: Human INT6/eIF3e is required for nonsense-mediated mRNA decay.
  findings: []
- id: PMID:17469741
  title: Results of the determination of serum markers in patients with malignant melanoma.
  findings: []
  reference_review:
    relevance: NONE
    correctness: WRONG_IDENTIFIER
    review_notes: Cited as a UPF1 protein binding (IPI) source but the resolved title is a melanoma
      serum-marker study unrelated to UPF1; appears to be an incorrect identifier in the GOA/IntAct
      record.
- id: PMID:17916692
  title: Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome
    ends.
  findings: []
- id: PMID:17932509
  title: Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in
    human cells.
  findings: []
- id: PMID:18066079
  title: NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its
    RNA helicase activity.
  findings: []
- id: PMID:18256688
  title: Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated
    model for mammalian NMD pathways.
  findings: []
- id: PMID:18362360
  title: The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell
    nucleus.
  findings: []
- id: PMID:18369367
  title: NMD resulting from encephalomyocarditis virus IRES-directed translation initiation
    seems to be restricted to CBP80/20-bound mRNA.
  findings: []
- id: PMID:18423202
  title: Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA
    decay.
  findings: []
- id: PMID:18447585
  title: A competition between stimulators and antagonists of Upf complex recruitment governs
    human nonsense-mediated mRNA decay.
  findings: []
- id: PMID:19150429
  title: Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction
    between mRNA surveillance machinery and decapping complex.
  findings: []
- id: PMID:19417104
  title: SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the
    mRNA surveillance complex during nonsense-mediated mRNA decay.
  findings: []
- id: PMID:19478851
  title: The hierarchy of exon-junction complex assembly by the spliceosome explains key features
    of mammalian nonsense-mediated mRNA decay.
  findings: []
- id: PMID:19503078
  title: A UPF3-mediated regulatory switch that maintains RNA surveillance.
  findings: []
- id: PMID:19556969
  title: Unusual bipartite mode of interaction between the nonsense-mediated decay factors,
    UPF1 and UPF2.
  findings: []
- id: PMID:19864460
  title: Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export.
  findings: []
- id: PMID:20930030
  title: SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs
    (EBMs) required for nonsense-mediated mRNA decay.
  findings: []
- id: PMID:21145460
  title: Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated
    mRNA decay.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached PMID_21145460 title matches; demonstrates UPF1 ATPase-driven mRNP disassembly is required to complete NMD, directly supporting the helicase/ATPase effector core function."
- id: PMID:21419344
  title: Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation
    by Upf2.
  findings: []
- id: PMID:21829167
  title: Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand
    replication.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
  findings: []
- id: PMID:23348841
  title: An unusual arrangement of two 14-3-3-like domains in the SMG5-SMG7 heterodimer is required
    for efficient nonsense-mediated mRNA decay.
  findings: []
- id: PMID:23722113
  title: Non-structural protein 1 of influenza viruses inhibits rapid mRNA degradation mediated
    by double-stranded RNA-binding protein, staufen1.
  findings: []
- id: PMID:23788676
  title: The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA.
  findings: []
- id: PMID:23828042
  title: DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous
    RNA targets in human cells, zebrafish and Caenorhabditis elegans.
  findings: []
- id: PMID:24267889
  title: Affinity proteomics reveals human host factors implicated in discrete stages of LINE-1
    retrotransposition.
  findings: []
- id: PMID:24726324
  title: MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation
    along 3' UTRs.
  findings: []
- id: PMID:24965446
  title: Host factors that interact with the pestivirus N-terminal protease, Npro, are components
    of the ribonucleoprotein complex.
  findings: []
- id: PMID:25220460
  title: The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance
    to the decay-inducing complex.
  findings: []
- id: PMID:25225333
  title: Plakophilins 1 and 3 bind to FXR1 and thereby influence the mRNA stability of desmosomal
    proteins.
  findings: []
- id: PMID:26000482
  title: Regnase-1 and Roquin Regulate a Common Element in Inflammatory mRNAs by Spatiotemporally
    Distinct Mechanisms.
  findings: []
- id: PMID:26138914
  title: Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling
    activities.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached PMID_26138914 title matches; characterizes human UPF1 as a processive RNA helicase/translocase with RNP-remodeling activity, supporting GO:0003724."
- id: PMID:26255671
  title: Regnase-1 and Roquin regulate inflammatory mRNAs.
  findings: []
- id: PMID:26841701
  title: The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation.
  findings: []
- id: PMID:27974568
  title: IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue
    Virus, Interacts with MOV10.
  findings: []
- id: PMID:30218034
  title: UPF1-like helicase grip on nucleic acids dictates processivity.
  findings: []
- id: PMID:31131562
  title: 'Nonsense-mediated mRNA decay: The challenge of telling right from wrong in a complex
    transcriptome.'
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:35640974
  title: Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with
    UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing
    mutation.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8855285
  title: Mammalian orthologues of a yeast regulator of nonsense transcript stability.
  findings: []
- id: PMID:9064659
  title: Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae
    nonsense mRNA-reducing UPF1 protein.
  findings: []
- id: PMID:9620853
  title: The surveillance complex interacts with the translation release factors to enhance
    termination and degrade aberrant mRNAs.
  findings: []
- id: Reactome:R-HSA-927789
  title: 'Reactome: Formation of the SURF complex (cytosol)'
  findings: []
- id: Reactome:R-HSA-927813
  title: 'Reactome: nonsense-mediated decay (cytosol)'
  findings: []
- id: Reactome:R-HSA-927830
  title: 'Reactome: nonsense-mediated decay (cytosol)'
  findings: []
- id: Reactome:R-HSA-927832
  title: 'Reactome: nonsense-mediated decay (cytosol)'
  findings: []
- id: Reactome:R-HSA-927836
  title: 'Reactome: nonsense-mediated decay (cytosol)'
  findings: []
- id: Reactome:R-HSA-927889
  title: 'Reactome: nonsense-mediated decay (cytosol)'
  findings: []