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.
| 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: PMID:10999600 human Upf1 is an RNA-binding protein whose RNA-binding activity is modulated by ATP file:human/UPF1/UPF1-uniprot.txt RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons |
| 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-uniprot.txt Cytoplasm, P-body. Nucleus PMID:18362360 the human Upf1 (hUpf1) protein involved in RNA surveillance are found associated within nuclear RNA-splicing complexes |
| 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-uniprot.txt /ligand="Zn(2+)" file:human/UPF1/UPF1-uniprot.txt Upf1 CH-rich PMID:10999600 the amino terminal cysteine/histidine-rich region and the region comprising the domains that define this protein as a superfamily group I helicase have been conserved |
| 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-uniprot.txt modulates the expression level of normal mRNAs |
| 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: PMID:10999600 We demonstrate that human Upf1 protein displays a nucleic-acid-dependent ATPase activity and a 5'--> 3' helicase activity. |
| 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-uniprot.txt Cytoplasm, perinuclear region |
| 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-uniprot.txt RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons |
| GO:0005515 protein binding | IPI PMID:11163187 Human Upf proteins target an mRNA for nonsense-mediated deca... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:12417715 Identification of a human decapping complex associated with ... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:12881429 Interaction between Ski7p and Upf1p is required for nonsense... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:15680326 Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so ... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:16086026 Regulated degradation of replication-dependent histone mRNAs... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:16364915 Multiple processing body factors and the ARE binding protein... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:16601204 Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:17469741 Results of the determination of serum markers in patients wi... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:18256688 Interactions between UPF1, eRFs, PABP and the exon junction ... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:18362360 The editing enzyme ADAR1 and the mRNA surveillance protein h... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:18447585 A competition between stimulators and antagonists of Upf com... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19150429 Human proline-rich nuclear receptor coregulatory protein 2 m... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19417104 SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, re... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19478851 The hierarchy of exon-junction complex assembly by the splic... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19503078 A UPF3-mediated regulatory switch that maintains RNA surveil... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19556969 Unusual bipartite mode of interaction between the nonsense-m... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:21829167 Human UPF1 interacts with TPP1 and telomerase and sustains t... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:23348841 An unusual arrangement of two 14-3-3-like domains in the SMG... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:23722113 Non-structural protein 1 of influenza viruses inhibits rapid... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:24267889 Affinity proteomics reveals human host factors implicated in... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI Q92900-2 PMID:16452507 Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to th... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI Q92900-2 PMID:18066079 NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction c... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI Q92900-2 PMID:18423202 Upf1 phosphorylation triggers translational repression durin... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI Q92900-2 PMID:21145460 Upf1 ATPase-dependent mRNP disassembly is required for compl... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:26138914 Our observation of processive unwinding by an eukaryotic RNA helicase reveals that Upf1, once recruited onto NMD mRNA targets, can scan the entire transcript PMID:26138914 Interestingly, the substrates containing a 5′-overhang long enough to bind one (12 nts) or multiple (54 nts) Upf1 molecules, were unwound with similar efficiencies |
| 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: PMID:31131562 The three most widely conserved NMD pathway components are the up-frameshift proteins UPF1, UPF2, and UPF3 |
| 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: PMID:35640974 The NMD machinery comprises the conserved UP-Frameshift proteins UPF1, UPF2 and UPF3 (paralogs A and B) PMID:35640974 The UPF2–UPF3B complex binds to UPF1, leading to structural rearrangements and stimulation of ATPase and helicase activity of UPF1 |
| 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... | UNDECIDED | 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. Previously KEEP_AS_NON_CORE; set to UNDECIDED because the only cited support was the GOA row for this annotation, which records the annotation rather than evidence for it. |
| 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: PMID:31131562 The UPF1 enzymatic core is specialized for function in NMD through accessory protein features that regulate the helicase activity of UPF1 |
| 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-uniprot.txt Cytoplasm, P-body. Nucleus |
| 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. The cached abstract describes hUpf1 as cytoplasmic in intact cells, but UniProt cites this paper for the nuclear location; this defers to the curator's reading of the full text. Supporting Evidence: file:human/UPF1/UPF1-uniprot.txt Nucleus {ECO:0000269|PubMed:11163187 PMID:11163187 assembly of a dynamic hUpf complex initiates in the nucleus at mRNA exon-exon junctions |
| 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: PMID:26255671 Furthermore, we found that Regnase-1 associated with UPF1, an RNA helicase essential for nonsense-mediated RNA decay (NMD), and UPF1 helicase activity was critical for Regnase-1-mediated mRNA decay. PMID:26255671 Regnase-1 and Roquin recognize overlapping target mRNAs via the same SL structures present in their 3′ UTRs. |
| GO:0071222 cellular response to lipopolysaccharide | TAS PMID:26255671 Regnase-1 and Roquin regulate inflammatory mRNAs. | UNDECIDED | Summary: Cellular response to lipopolysaccharide (TAS); UPF1/NMD modulates inflammatory transcript stability. Reason: Stimulus-response context for NMD targets; non-core. Previously KEEP_AS_NON_CORE; set to UNDECIDED because the only cited support was the GOA row for this annotation, which records the annotation rather than evidence for it. |
| GO:0071347 cellular response to interleukin-1 | TAS PMID:26255671 Regnase-1 and Roquin regulate inflammatory mRNAs. | UNDECIDED | Summary: Cellular response to interleukin-1 (TAS); NMD-related modulation of cytokine-response transcripts. Reason: Stimulus-response context; non-core. Previously KEEP_AS_NON_CORE; set to UNDECIDED because the only cited support was the GOA row for this annotation, which records the annotation rather than evidence for it. |
| 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... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:26841701 these data suggest the existence of a complex comprising SMG1, UPF1 and DHX34, with DHX34 functioning as a scaffold for UPF1 and SMG1 |
| GO:0005515 protein binding | IPI PMID:25220460 The RNA helicase DHX34 activates NMD by promoting a transiti... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:27974568 IRAV (FLJ11286), an Interferon-Stimulated Gene with Antivira... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:24726324 PAR-CLIP of UPF1 reveals that MOV10 and UPF1 bind to RNA in close proximity. |
| GO:0005515 protein binding | IPI PMID:24726324 MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA t... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:24726324 Knockdown of MOV10 resulted in increased mRNA half-lives of MOV10-bound as well as UPF1-regulated transcripts, suggesting that MOV10 functions in UPF1-mediated mRNA degradation |
| 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: PMID:24726324 MOV10 functions in UPF1-mediated mRNA degradation as an RNA clearance factor to resolve structures and displace proteins from 3' UTRs. |
| GO:0005515 protein binding | IPI PMID:19864460 Mammalian pre-mRNA 3' end processing factor CF I m 68 functi... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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. The cached abstract refers to SMG (NMD effector) proteins collectively rather than naming UPF1, so this defers to the curator's reading of the full text. Supporting Evidence: PMID:17916692 suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss |
| 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: PMID:16488880 shRNA-mediated depletion of UPF1 causes human cells to arrest early in S phase, inducing an ATR-dependent DNA-damage response. |
| GO:0005515 protein binding | IPI PMID:23788676 The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:25225333 Plakophilins 1 and 3 bind to FXR1 and thereby influence the ... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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. The claim is supported by the MOV10 study (PMID:24726324) cited on the sibling row; this paper's cached text shows UPF1 in PKP1/3 mRNPs and a UPF1 knockdown assay, and the annotation defers to the curator's reading of it. Supporting Evidence: PMID:24726324 Knockdown of MOV10 resulted in increased mRNA half-lives of MOV10-bound as well as UPF1-regulated transcripts, suggesting that MOV10 functions in UPF1-mediated mRNA degradation PMID:25225333 UPF1-mediated mRNA decay is stimulated by long 3′-UTRs of more than 1,000 nt |
| GO:0005515 protein binding | IPI PMID:26255671 Regnase-1 and Roquin regulate inflammatory mRNAs. | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:26000482 Regnase-1 and Roquin Regulate a Common Element in Inflammato... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:21829167 UPF1 is present at telomeres at least during S and G2/M phases |
| 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: PMID:21829167 these defects stem predominantly from inefficient telomere leading-strand replication PMID:21829167 UPF1 orchestrates crucial aspects of telomere biology, including telomere replication and telomere length homeostasis |
| 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: PMID:22658674 we describe a systematic, unbiased, and comprehensive approach, termed "interactome capture," to define the mRNA interactome of proliferating human HeLa cells |
| 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: PMID:22681889 We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics |
| 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: PMID:23828042 Depletion of UPF1 affected the expression of 1336 genes PMID:23828042 A similar analysis was carried out with this subset of targets to validate their upregulation upon depletion of NBAS and/or UPF1 as seen in the microarray data. |
| GO:0005515 protein binding | IPI PMID:20930030 SMG6 interacts with the exon junction complex via two conser... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:18362360 the human Upf1 (hUpf1) protein involved in RNA surveillance are found associated within nuclear RNA-splicing complexes |
| 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: PMID:18362360 the human Upf1 (hUpf1) protein involved in RNA surveillance are found associated within nuclear RNA-splicing complexes |
| 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... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:16488880 A fraction of hyperphosphorylated UPF1 associates with chromatin of unperturbed cells, and chromatin association increases in S phase and upon gamma irradiation. |
| 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: PMID:16488880 A fraction of hyperphosphorylated UPF1 associates with chromatin of unperturbed cells, and chromatin association increases in S phase and upon gamma irradiation. |
| 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... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:16488880 The human RNA surveillance factor UPF1 is required for S pha... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:16488880 shRNA-mediated depletion of UPF1 causes human cells to arrest early in S phase PMID:16488880 Physical interaction of UPF1 with DNA polymerase delta suggests a role for human UPF1 in DNA synthesis during replication or repair. |
| 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: PMID:16488880 chromatin association increases in S phase and upon gamma irradiation PMID:16488880 Physical interaction of UPF1 with DNA polymerase delta suggests a role for human UPF1 in DNA synthesis during replication or repair. |
| 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: PMID:16488880 The NMD machinery is also thought to coordinate mRNA nuclear export and translation |
| GO:0005515 protein binding | IPI PMID:9620853 The surveillance complex interacts with the translation rele... | REMOVE | 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 GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| 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: PMID:10999600 human Upf1 is an RNA-binding protein whose RNA-binding activity is modulated by ATP |
| 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 |
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Download this section (compressed HTML)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?
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.
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