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.

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:
Supporting Evidence:
  • file:human/UPF2/UPF2-uniprot.txt
    stimulates both ATPase and RNA helicase
  • file:human/UPF2/UPF2-goa.tsv
    GO:0000184

References

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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.

πŸ“š Additional Documentation

Notes

(UPF2-notes.md)

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Pn Notes

(UPF2-pn-notes.md)

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πŸ“„ View Raw YAML

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