UPF2

UniProt ID: Q9HAU5
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

UPF2 (regulator of nonsense transcripts 2; RENT2) is a core adaptor of the nonsense-mediated mRNA decay (NMD) pathway. Built around tandem MIF4G domains with a C-terminal UPF1-binding region, UPF2 bridges UPF1 (bound to the release factors eRF1/eRF3 at a terminating ribosome) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex that activates NMD. Binding of UPF2 (together with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, committing premature-termination-codon and certain long-3'UTR transcripts to decay. UPF2 acts mainly at the cytoplasmic/perinuclear face of the nuclear envelope and in the cytoplasm, binds spliced mRNA, and has additional reported associations (e.g. telomere/TERRA, mRNA export) peripheral to its core NMD adaptor role.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0035145 exon-exon junction complex
IBA
GO_REF:0000033 		ACCEPT
Summary: UPF2 is functionally associated with the exon-junction complex; it is recruited by EJC-bound UPF3B and bridges the EJC to UPF1 during NMD.
Reason: Central to UPF2 function as the EJC-UPF1 bridging adaptor in EJC-dependent NMD.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Recruited by UPF3B associated with the EJC core
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IEA
GO_REF:0000002 		ACCEPT
Summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
Reason: Core NMD process; UPF2 is an essential NMD factor.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Involved in nonsense-mediated decay (NMD)
GO:0003723 RNA binding
IEA
GO_REF:0000002 		ACCEPT
Summary: UPF2 binds spliced mRNA, consistent with its association with mRNP/EJC during NMD.
Reason: RNA (spliced mRNA) binding is part of UPF2 engagement with target mRNPs.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Binds spliced mRNA
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Cytoplasmic localization, where NMD occurs; UPF2 acts at the cytoplasmic face of the nuclear envelope and in the cytoplasm.
Reason: Well-supported cytoplasmic/perinuclear localization.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Perinuclear region of cytoplasm; UPF2 concentrates at the cytoplasmic side of the nuclear envelope where it meets EJC-bound mRNPs.
Reason: Directly documented perinuclear localization for UPF2.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0005515 protein binding
IPI
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:15231747
A protein interaction framework for human mRNA degradation. 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:16086026
Regulated degradation of replication-dependent histone mRNAs... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:16452507
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to th... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:18066079
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction c... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:20371770
AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:20479275
Insights into the recruitment of the NMD machinery from the ... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:21145460
Upf1 ATPase-dependent mRNP disassembly is required for compl... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:22522823
The cryo-EM structure of the UPF-EJC complex shows UPF1 pois... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
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 UPF2 is an essential adaptor.
Reason: Accurate high-level descriptor; the specific NMD term is the core annotation.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0071025
GO:0170010 nonsense-mediated decay complex
NAS
PMID:35640974
Structures of nonsense-mediated mRNA decay factors UPF3B and... 		ACCEPT
Summary: UPF2 is a component of the nonsense-mediated decay (UPF1-UPF2-UPF3) surveillance complex.
Reason: UPF2 is a defining subunit of the NMD effector complex.
Supporting Evidence:
file:human/UPF2/UPF2-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; context-dependent modulation of NMD efficiency.
Reason: NAS regulatory annotation; non-core relative to UPF2 driving NMD.
Supporting Evidence:
file:human/UPF2/UPF2-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; UPF2 promotes NMD by stimulating UPF1 ATPase/helicase activity.
Reason: NAS regulatory annotation consistent with UPF2 function; non-core relative to the direct NMD term.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:2000624
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
Reason: Cytosolic localization agrees with the principal site of UPF2 function.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0005737 cytoplasm
ISS
GO_REF:0000024 		ACCEPT
Summary: Cytoplasmic localization, where NMD occurs; UPF2 acts at the cytoplasmic face of the nuclear envelope and in the cytoplasm.
Reason: Well-supported cytoplasmic/perinuclear localization.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IMP
PMID:19556969
Unusual bipartite mode of interaction between the nonsense-m... 		ACCEPT
Summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
Reason: Core NMD process; UPF2 is an essential NMD factor.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Involved in nonsense-mediated decay (NMD)
GO:0005515 protein binding
IPI
PMID:25220460
The RNA helicase DHX34 activates NMD by promoting a transiti... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005634 nucleus
IDA
PMID:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains t... 		KEEP AS NON CORE
Summary: Nuclear localization (IDA); a minor UPF2 pool / shuttling consistent with EJC association near the nuclear envelope.
Reason: Minor nuclear pool; the core adaptor function acts at the cytoplasmic/perinuclear face.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005634
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 NMD-factor association with telomeres/TERRA.
Reason: Telomere-associated activity (PMID:17916692) is a moonlighting role distinct from core NMD adaptor function.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0042162
GO:0005515 protein binding
IPI
PMID:20930030
SMG6 interacts with the exon junction complex via two conser... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005829 cytosol
TAS
Reactome:R-HSA-927813 		ACCEPT
Summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
Reason: Cytosolic localization agrees with the principal site of UPF2 function.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0005829 cytosol
TAS
Reactome:R-HSA-927832 		ACCEPT
Summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
Reason: Cytosolic localization agrees with the principal site of UPF2 function.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0005829 cytosol
TAS
Reactome:R-HSA-927836 		ACCEPT
Summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
Reason: Cytosolic localization agrees with the principal site of UPF2 function.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0005829 cytosol
TAS
Reactome:R-HSA-927889 		ACCEPT
Summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
Reason: Cytosolic localization agrees with the principal site of UPF2 function.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
GO:0005515 protein binding
IPI
PMID:17468741
Human INT6/eIF3e is required for nonsense-mediated mRNA deca... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0035145 exon-exon junction complex
IDA
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		ACCEPT
Summary: UPF2 is functionally associated with the exon-junction complex; it is recruited by EJC-bound UPF3B and bridges the EJC to UPF1 during NMD.
Reason: Central to UPF2 function as the EJC-UPF1 bridging adaptor in EJC-dependent NMD.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Recruited by UPF3B associated with the EJC core
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 is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
Reason: Core NMD process; UPF2 is an essential NMD factor.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Involved in nonsense-mediated decay (NMD)
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
TAS
PMID:17468741
Human INT6/eIF3e is required for nonsense-mediated mRNA deca... 		ACCEPT
Summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
Reason: Core NMD process; UPF2 is an essential NMD factor.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Involved in nonsense-mediated decay (NMD)
GO:0005515 protein binding
IPI
PMID:11544179
Human SMG-1, a novel phosphatidylinositol 3-kinase-related p... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
TAS
PMID:16488880
The human RNA surveillance factor UPF1 is required for S pha... 		ACCEPT
Summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
Reason: Core NMD process; UPF2 is an essential NMD factor.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
Involved in nonsense-mediated decay (NMD)
GO:0005515 protein binding
IPI
PMID:14636577
Phosphorylation of hUPF1 induces formation of mRNA surveilla... 		KEEP AS NON CORE
Summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
Reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005515
GO:0005634 nucleus
IDA
PMID:14636577
Phosphorylation of hUPF1 induces formation of mRNA surveilla... 		KEEP AS NON CORE
Summary: Nuclear localization (IDA); a minor UPF2 pool / shuttling consistent with EJC association near the nuclear envelope.
Reason: Minor nuclear pool; the core adaptor function acts at the cytoplasmic/perinuclear face.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0005634
GO:0005737 cytoplasm
IDA
PMID:14636577
Phosphorylation of hUPF1 induces formation of mRNA surveilla... 		ACCEPT
Summary: Cytoplasmic localization, where NMD occurs; UPF2 acts at the cytoplasmic face of the nuclear envelope and in the cytoplasm.
Reason: Well-supported cytoplasmic/perinuclear localization.
Supporting Evidence:
file:human/UPF2/UPF2-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
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 linked to UPF2/NMD-factor mRNP metabolism.
Reason: Peripheral mRNA-metabolism role; non-core relative to NMD adaptor function.
Supporting Evidence:
file:human/UPF2/UPF2-goa.tsv
GO:0006406

Core Functions

NMD adaptor that bridges UPF1 (at the terminating ribosome, with eRF1/eRF3) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex.

Cellular Locations:
perinuclear region of cytoplasm
In Complex:
exon-exon junction complex
Supporting Evidence:
  • file:human/UPF2/UPF2-uniprot.txt
    Recruited by UPF3B associated with the EJC core
  • file:human/UPF2/UPF2-uniprot.txt
    Involved in nonsense-mediated decay (NMD)

Activator of UPF1 in NMD: UPF2 (with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, driving decay of target mRNAs.

Cellular Locations:
cytosol
In Complex:
exon-exon junction complex
Supporting Evidence:
  • file:human/UPF2/UPF2-uniprot.txt
    stimulates both ATPase and RNA helicase
  • file:human/UPF2/UPF2-goa.tsv
    GO:0000184

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs using Ensembl Compara
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
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:14636577
Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7.
PMID:15231747
A protein interaction framework for human mRNA degradation.
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: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: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:18369367
NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
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:20371770
AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay.
PMID:20479275
Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex.
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:21829167
Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication.
PMID:22522823
The cryo-EM structure of the UPF-EJC complex shows UPF1 poised toward the RNA 3' end.
PMID:23788676
The RNA helicase Ddx5/p68 binds to hUpf3 and enhances NMD of Ddx17/p72 and Smg5 mRNA.
PMID:25220460
The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:26496610
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
PMID:31131562
Nonsense-mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome.
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.
Reactome:R-HSA-927813
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: How is the competitive binding of UPF3A versus UPF3B to UPF2 regulated, and how does it tune NMD efficiency on different transcripts?

Q: Which UPF2-dependent NMD branches require the EJC versus operating in EJC-independent NMD?

Suggested Experiments

Experiment: Domain-resolved UPF2 mutants (MIF4G vs UPF1-binding vs UPF3-binding) with transcriptome-wide NMD-target profiling to separate bridging from UPF1-activation functions.

Experiment: In vitro reconstitution measuring UPF2/UPF3B stimulation of UPF1 ATPase/helicase activity on EJC-containing substrates to quantify the activation step.

📚 Additional Documentation

Notes

(UPF2-notes.md)

UPF2 (Q9HAU5) research notes

Summary

UPF2 (regulator of nonsense transcripts 2; RENT2) is a core adaptor of the nonsense-mediated mRNA decay (NMD) pathway. Built around tandem MIF4G domains with a C-terminal UPF1-binding region, UPF2 bridges UPF1 (bound to the release factors eRF1/eRF3 at a terminating ribosome) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex that activates NMD. Binding of UPF2 (together with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, committing premature-termination-codon and certain long-3'UTR transcripts to decay. UPF2 acts mainly at the cytoplasmic/perinuclear face of the nuclear envelope and in the cytoplasm, binds spliced mRNA, and has additional reported associations (e.g. telomere/TERRA, mRNA export) peripheral to its core NMD adaptor role.

Core functions (from review)

  • GO:0035145 exon-exon junction complex — NMD adaptor that bridges UPF1 (at the terminating ribosome, with eRF1/eRF3) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex.
  • GO:0035145 exon-exon junction complex — Activator of UPF1 in NMD: UPF2 (with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, driving decay of target mRNAs.

Provenance

Research and verbatim supporting quotes are recorded inline in UPF2-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

(UPF2-pn-notes.md)

UPF2 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9HAU5
  • 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: UPF2 (regulator of nonsense transcripts 2; RENT2) is a core adaptor of the nonsense-mediated mRNA decay (NMD) pathway. Built around tandem MIF4G domains with a C-terminal UPF1-binding region, UPF2 bridges UPF1 (bound to the release factors eRF1/eRF3 at a terminating ribosome) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex that activates NMD. Binding of UPF2 (together with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, committing premature-termination-codon and certain long-3'UTR transcripts to decay. UPF2 acts mainly at the cytoplasmic/perinuclear face of the nuclear envelope and in the cytoplasm, binds spliced mRNA, and has additional reported associations (e.g. telomere/TERRA, mRNA export) peripheral to its core NMD adaptor role.
  • Existing/core annotation action counts: ACCEPT: 18; KEEP_AS_NON_CORE: 36

PN Consistency Summary

  • Consistency: Gene-level: consistent. Deep-research/notes, review YAML and GOA agree UPF2 is the NMD adaptor (tandem MIF4G + C-terminal UPF1-binding region) bridging UPF1 to UPF3B/EJC, relieving UPF1 autoinhibition and stimulating its ATPase/helicase. Core annotations: GO:0000184 NMD (multiple, ACCEPT), GO:0035145 EJC, GO:0170010 NMD complex, GO:0003723 RNA binding. But the PN-node frame (translation termination) is not reflected in the review's account of UPF2.
  • PN story / NEW pressure: PN places UPF2 under "Modulation of termination," projecting GO:0006415 as new_to_goa. GOA cross-check confirms UPF2 has NO translational-termination annotation (and no GO:0006449 either). But UPF2 is an NMD adaptor, not a release/termination factor — its termination link is indirect (acts on UPF1 after termination). The story is already captured by GO:0000184 NMD; no NEW translation-termination term is defensible for UPF2.
  • Evidence alignment: PN row carries no reference titles; review is well-evidenced for the NMD-adaptor role (UniProt FUNCTION; EJC/complex terms). No competing citations to reconcile.
  • Verdict: Gene biology consistent, but PN group→GO:0006415 over-reaches and would create an unsupported new GOA term; UPF2's role is NMD adaptor (GO:0000184), not translational termination.

Full Consistency Review

  • UniProt: Q9HAU5 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: Translation|Cytosolic translation|Translation termination|Modulation of termination ; PN-node mapping: type no_mapping; group mapped, ok_for_propagation → GO:0006415 translational termination; class/branch context_only, too_broad. Projected: GO:0006415 (goa_status=new_to_goa).
  • Consistency: Gene-level: consistent. Deep-research/notes, review YAML and GOA agree UPF2 is the NMD adaptor (tandem MIF4G + C-terminal UPF1-binding region) bridging UPF1 to UPF3B/EJC, relieving UPF1 autoinhibition and stimulating its ATPase/helicase. Core annotations: GO:0000184 NMD (multiple, ACCEPT), GO:0035145 EJC, GO:0170010 NMD complex, GO:0003723 RNA binding. But the PN-node frame (translation termination) is not reflected in the review's account of UPF2.
  • PN story / NEW pressure: PN places UPF2 under "Modulation of termination," projecting GO:0006415 as new_to_goa. GOA cross-check confirms UPF2 has NO translational-termination annotation (and no GO:0006449 either). But UPF2 is an NMD adaptor, not a release/termination factor — its termination link is indirect (acts on UPF1 after termination). The story is already captured by GO:0000184 NMD; no NEW translation-termination term is defensible for UPF2.
  • Mapping strategy: The GROUP→GO:0006415 (translational termination, = polypeptide release) projection is wrong for UPF2 — it would add a peptide-release process the protein does not perform, and would be a genuinely new (unsupported) GOA assertion. This is the clearest over-reach of the UPF set (new_to_goa, no regulatory-term backstop unlike UPF1). The type-level no_mapping is correct and should govern; do not project GO:0006415.
  • Evidence alignment: PN row carries no reference titles; review is well-evidenced for the NMD-adaptor role (UniProt FUNCTION; EJC/complex terms). No competing citations to reconcile.
  • Verdict: Gene biology consistent, but PN group→GO:0006415 over-reaches and would create an unsupported new GOA term; UPF2's role is NMD adaptor (GO:0000184), not translational termination.

Recommended edits: [MAP] do NOT project GO:0006415 (translational termination) onto UPF2 — it is an NMD adaptor recruited downstream of termination, not a peptide-release factor; the type-level no_mapping should win. UPF2 is already correctly anchored on GO:0000184 (NMD).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/UPF2/UPF2-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9HAU5
  • 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=new_to_goa | 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: Q9HAU5
gene_symbol: UPF2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: UPF2 (regulator of nonsense transcripts 2; RENT2) is a core adaptor of the nonsense-mediated mRNA decay (NMD) pathway. Built around tandem MIF4G domains with a C-terminal UPF1-binding region, UPF2 bridges UPF1 (bound to the release factors eRF1/eRF3 at a terminating ribosome) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex that activates NMD. Binding of UPF2 (together with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, committing premature-termination-codon and certain long-3'UTR transcripts to decay. UPF2 acts mainly at the cytoplasmic/perinuclear face of the nuclear envelope and in the cytoplasm, binds spliced mRNA, and has additional reported associations (e.g. telomere/TERRA, mRNA export) peripheral to its core NMD adaptor role.
existing_annotations:
- term:
    id: GO:0035145
    label: exon-exon junction complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: UPF2 is functionally associated with the exon-junction complex; it is recruited by EJC-bound UPF3B and bridges the EJC to UPF1 during NMD.
    action: ACCEPT
    reason: Central to UPF2 function as the EJC-UPF1 bridging adaptor in EJC-dependent NMD.
    supported_by: &id004
    - reference_id: file:human/UPF2/UPF2-uniprot.txt
      supporting_text: Recruited by UPF3B associated with the EJC core
- 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 is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
    action: ACCEPT
    reason: Core NMD process; UPF2 is an essential NMD factor.
    supported_by: &id002
    - reference_id: file:human/UPF2/UPF2-uniprot.txt
      supporting_text: Involved in nonsense-mediated decay (NMD)
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: UPF2 binds spliced mRNA, consistent with its association with mRNP/EJC during NMD.
    action: ACCEPT
    reason: RNA (spliced mRNA) binding is part of UPF2 engagement with target mRNPs.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-uniprot.txt
      supporting_text: Binds spliced mRNA
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, where NMD occurs; UPF2 acts at the cytoplasmic face of the nuclear envelope and in the cytoplasm.
    action: ACCEPT
    reason: Well-supported cytoplasmic/perinuclear localization.
    supported_by: &id001
    - reference_id: file:human/UPF2/UPF2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- 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; UPF2 concentrates at the cytoplasmic side of the nuclear envelope where it meets EJC-bound mRNPs.
    action: ACCEPT
    reason: Directly documented perinuclear localization for UPF2.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11163187
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15231747
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16452507
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18066079
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20371770
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20479275
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21145460
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22522823
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- 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 UPF2 is an essential adaptor.
    action: KEEP_AS_NON_CORE
    reason: Accurate high-level descriptor; the specific NMD term is the core annotation.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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: UPF2 is a component of the nonsense-mediated decay (UPF1-UPF2-UPF3) surveillance complex.
    action: ACCEPT
    reason: UPF2 is a defining subunit of the NMD effector complex.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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; context-dependent modulation of NMD efficiency.
    action: KEEP_AS_NON_CORE
    reason: NAS regulatory annotation; non-core relative to UPF2 driving NMD.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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; UPF2 promotes NMD by stimulating UPF1 ATPase/helicase activity.
    action: KEEP_AS_NON_CORE
    reason: NAS regulatory annotation consistent with UPF2 function; non-core relative to the direct NMD term.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:2000624
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF2 function.
    supported_by: &id003
    - reference_id: file:human/UPF2/UPF2-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, perinuclear region'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, where NMD occurs; UPF2 acts at the cytoplasmic face of the nuclear envelope and in the cytoplasm.
    action: ACCEPT
    reason: Well-supported cytoplasmic/perinuclear localization.
    supported_by: *id001
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: IMP
  original_reference_id: PMID:19556969
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
    action: ACCEPT
    reason: Core NMD process; UPF2 is an essential NMD factor.
    supported_by: *id002
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25220460
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23788676
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21829167
  qualifier: located_in
  review:
    summary: Nuclear localization (IDA); a minor UPF2 pool / shuttling consistent with EJC association near the nuclear envelope.
    action: KEEP_AS_NON_CORE
    reason: Minor nuclear pool; the core adaptor function acts at the cytoplasmic/perinuclear face.
    supported_by: &id005
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005634
- 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 NMD-factor association with telomeres/TERRA.
    action: KEEP_AS_NON_CORE
    reason: Telomere-associated activity (PMID:17916692) is a moonlighting role distinct from core NMD adaptor function.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0042162
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20930030
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927813
  qualifier: located_in
  review:
    summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF2 function.
    supported_by: *id003
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927832
  qualifier: located_in
  review:
    summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF2 function.
    supported_by: *id003
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927836
  qualifier: located_in
  review:
    summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF2 function.
    supported_by: *id003
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927889
  qualifier: located_in
  review:
    summary: Cytosol localization, consistent with cytoplasmic NMD activity of UPF2.
    action: ACCEPT
    reason: Cytosolic localization agrees with the principal site of UPF2 function.
    supported_by: *id003
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17468741
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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: UPF2 is functionally associated with the exon-junction complex; it is recruited by EJC-bound UPF3B and bridges the EJC to UPF1 during NMD.
    action: ACCEPT
    reason: Central to UPF2 function as the EJC-UPF1 bridging adaptor in EJC-dependent NMD.
    supported_by: *id004
- 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 is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
    action: ACCEPT
    reason: Core NMD process; UPF2 is an essential NMD factor.
    supported_by: *id002
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: TAS
  original_reference_id: PMID:17468741
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
    action: ACCEPT
    reason: Core NMD process; UPF2 is an essential NMD factor.
    supported_by: *id002
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11544179
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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:16488880
  qualifier: involved_in
  review:
    summary: Nonsense-mediated mRNA decay is the core biological process of UPF2; it nucleates the UPF1-UPF2-UPF3 surveillance complex that activates NMD.
    action: ACCEPT
    reason: Core NMD process; UPF2 is an essential NMD factor.
    supported_by: *id002
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14636577
  qualifier: enables
  review:
    summary: Interaction captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-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 captured under the uninformative generic protein binding term. UPF2 is a central NMD adaptor with many partners (UPF1, UPF3A/B, EJC, SMG factors); this records a real interaction but does not by itself specify function.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding (GO:0005515) is uninformative per curation guidelines; retained as non-core because the informative function is its adaptor role bridging UPF1 to UPF3-EJC.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0005515
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:14636577
  qualifier: located_in
  review:
    summary: Nuclear localization (IDA); a minor UPF2 pool / shuttling consistent with EJC association near the nuclear envelope.
    action: KEEP_AS_NON_CORE
    reason: Minor nuclear pool; the core adaptor function acts at the cytoplasmic/perinuclear face.
    supported_by: *id005
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14636577
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, where NMD occurs; UPF2 acts at the cytoplasmic face of the nuclear envelope and in the cytoplasm.
    action: ACCEPT
    reason: Well-supported cytoplasmic/perinuclear localization.
    supported_by: *id001
- 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 linked to UPF2/NMD-factor mRNP metabolism.
    action: KEEP_AS_NON_CORE
    reason: Peripheral mRNA-metabolism role; non-core relative to NMD adaptor function.
    supported_by:
    - reference_id: file:human/UPF2/UPF2-goa.tsv
      supporting_text: GO:0006406
core_functions:
- description: NMD adaptor that bridges UPF1 (at the terminating ribosome, with eRF1/eRF3) to UPF3B and the exon-junction complex, nucleating the UPF1-UPF2-UPF3 surveillance complex.
  locations:
  - id: GO:0048471
    label: perinuclear region of cytoplasm
  supported_by:
  - reference_id: file:human/UPF2/UPF2-uniprot.txt
    supporting_text: Recruited by UPF3B associated with the EJC core
  - reference_id: file:human/UPF2/UPF2-uniprot.txt
    supporting_text: Involved in nonsense-mediated decay (NMD)
  in_complex:
    id: GO:0035145
    label: exon-exon junction complex
- description: 'Activator of UPF1 in NMD: UPF2 (with UPF3B) relieves UPF1 autoinhibition and stimulates its ATPase and RNA helicase activities, driving decay of target mRNAs.'
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/UPF2/UPF2-uniprot.txt
    supporting_text: stimulates both ATPase and RNA helicase
  - reference_id: file:human/UPF2/UPF2-goa.tsv
    supporting_text: GO:0000184
  in_complex:
    id: GO:0035145
    label: exon-exon junction complex
proposed_new_terms: []
suggested_questions:
- question: How is the competitive binding of UPF3A versus UPF3B to UPF2 regulated, and how does it tune NMD efficiency on different transcripts?
- question: Which UPF2-dependent NMD branches require the EJC versus operating in EJC-independent NMD?
suggested_experiments:
- description: Domain-resolved UPF2 mutants (MIF4G vs UPF1-binding vs UPF3-binding) with transcriptome-wide NMD-target profiling to separate bridging from UPF1-activation functions.
- description: In vitro reconstitution measuring UPF2/UPF3B stimulation of UPF1 ATPase/helicase activity on EJC-containing substrates to quantify the activation step.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs using Ensembl Compara
  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: PMID:11163187
  title: Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached PMID_11163187 title matches; foundational demonstration that human UPF proteins (including UPF2) target mRNAs for NMD when positioned downstream of a termination codon, supporting the NMD core role."
- 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:14636577
  title: Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7.
  findings: []
- id: PMID:15231747
  title: A protein interaction framework for human mRNA degradation.
  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: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 UPF2 protein binding (IPI) source but the resolved title is a melanoma serum-marker study unrelated to UPF2; 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:18066079
  title: NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached PMID_18066079 title matches; directly establishes both UPF2 core functions - bridging UPF1 to the EJC and stimulating UPF1's RNA helicase activity (supports GO:0000184 NMD role)."
- 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:18369367
  title: NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
  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: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached PMID_19556969 title matches; characterizes the UPF1-UPF2 interaction mode underpinning UPF2's UPF1-activating/bridging function."
- id: PMID:20371770
  title: AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay.
  findings: []
- id: PMID:20479275
  title: Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex.
  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: []
- id: PMID:21829167
  title: Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication.
  findings: []
- id: PMID:22522823
  title: The cryo-EM structure of the UPF-EJC complex shows UPF1 poised toward the RNA 3' end.
  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:25220460
  title: The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
  findings: []
- id: PMID:31131562
  title: 'Nonsense-mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome.'
  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: Reactome:R-HSA-927813
  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: []