UPF3B

UniProt ID: Q9BZI7
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

UPF3B (Regulator of nonsense transcripts 3B; also called UPF3X, hUpf3b, RENT3B) is a core factor of the nonsense-mediated mRNA decay (NMD) pathway, the surveillance mechanism that degrades mRNAs bearing premature termination codons. UPF3B is a peripheral component of the exon-junction complex (EJC) that is deposited upstream of exon-exon junctions after splicing. It acts as a molecular adaptor that bridges the EJC core to the central NMD machinery, binding the EJC (through its C-terminal region that contacts EIF4A3 and the MAGOH-RBM8A heterodimer) and recruiting UPF2, which in turn links to the RNA helicase/ATPase UPF1 at the terminating ribosome; together UPF2 and UPF3B stimulate the ATPase and helicase activities of UPF1 to activate NMD. UPF3B binds spliced mRNA upstream of exon-exon junctions, shuttles between nucleus and cytoplasm, and can also stimulate translation in vitro. The gene is X-linked, and loss-of-function mutations cause X-linked syndromic and non-syndromic intellectual disability (including Lujan-Fryns syndrome), reflecting an important role of NMD in neurodevelopment.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		ACCEPT
Summary: UPF3B shuttles between nucleus and cytoplasm and acts in cytoplasmic NMD at the terminating ribosome.
Reason: Cytoplasmic activity is consistent with UPF3B's role in cytoplasmic NMD; it shuttles between compartments.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Shuttling between the nucleus and the cytoplasm
GO:0003729 mRNA binding
IBA
GO_REF:0000033 		ACCEPT
Summary: UPF3B binds spliced mRNA upstream of exon-exon junctions; mRNA binding is a core molecular activity supporting its EJC-associated adaptor role.
Reason: Direct mRNA binding is documented and integral to UPF3B's function on spliced transcripts.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Binds spliced mRNA upstream of exon-exon junctions
GO:0045727 positive regulation of translation
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: In vitro, UPF3B stimulates translation independently of UPF2 and the EJC core.
Reason: A documented in vitro activity, but secondary to UPF3B's core NMD/adaptor role; the in vivo significance is less established.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
In vitro, stimulates translation
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IEA
GO_REF:0000002 		ACCEPT
Summary: NMD is the core biological process of UPF3B; this electronic annotation is strongly corroborated by direct experimental evidence.
Reason: UPF3B is a core NMD factor; this is its central process.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: A generic nucleic-acid-binding term; UPF3B's relevant activity is the more specific mRNA/RNA binding.
Reason: Uninformative parent term; the specific and supported activity is mRNA binding (GO:0003729).
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Binds spliced mRNA upstream of exon-exon junctions
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: UPF3B localizes to the nucleus, where it associates with the EJC after splicing.
Reason: Nuclear localization is well documented and integral to EJC loading.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Cytoplasmic localization, consistent with UPF3B shuttling and cytoplasmic NMD.
Reason: Correct localization; corroborated by experimental evidence.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0035145 exon-exon junction complex
IEA
GO_REF:0000117 		ACCEPT
Summary: UPF3B is a peripheral component of the EJC, a core aspect of its function.
Reason: UPF3B associates with the EJC core; well supported electronically and experimentally.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Core component of the mRNA splicing-dependent exon junction complex
GO:0045727 positive regulation of translation
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Electronic annotation of translation stimulation, also shown in vitro.
Reason: Secondary in vitro activity; non-core relative to NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
In vitro, stimulates translation
GO:0005515 protein binding
IPI
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		KEEP AS NON CORE
Summary: Interaction with UPF1 and UPF2 (founding NMD-targeting study). Bare protein binding is uninformative; the informative function is the UPF2-EJC bridging adaptor role.
Reason: Real, functionally central interactions (UPF1, UPF2) but the generic term is uninformative; the core MF is the molecular adaptor activity.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Recruits UPF2 at the cytoplasmic side of the nuclear envelope
GO:0005515 protein binding
IPI
PMID:11546873
Role of the nonsense-mediated decay factor hUpf3 in the spli... 		KEEP AS NON CORE
Summary: Interaction with RBM8A/Y14 and association with the EJC. Bare term uninformative.
Reason: Real EJC-relevant interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11546873
GO:0005515 protein binding
IPI
PMID:11546874
Communication of the position of exon-exon junctions to the ... 		KEEP AS NON CORE
Summary: EJC-association study interaction. Bare term uninformative.
Reason: Real EJC-relevant interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11546874
GO:0005515 protein binding
IPI
PMID:12417715
Identification of a human decapping complex associated with ... 		KEEP AS NON CORE
Summary: Interaction within a decapping complex associated with hUpf proteins. Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:12417715
GO:0005515 protein binding
IPI
PMID:15231747
A protein interaction framework for human mRNA degradation. 		KEEP AS NON CORE
Summary: mRNA-degradation interaction-framework study. Bare term uninformative.
Reason: Real interaction record; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15231747
GO:0005515 protein binding
IPI
PMID:15361857
eIF4G is required for the pioneer round of translation in ma... 		KEEP AS NON CORE
Summary: Pioneer-round-of-translation study interaction. Bare term uninformative.
Reason: Real interaction record; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15361857
GO:0005515 protein binding
IPI
PMID:15680326
Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so ... 		KEEP AS NON CORE
Summary: Staufen1/UPF1 study interaction. Bare term uninformative.
Reason: Real interaction record; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15680326
GO:0005515 protein binding
IPI
PMID:16209946
Exon-junction complex components specify distinct routes of ... 		KEEP AS NON CORE
Summary: Interaction in study of EJC-dependent NMD routes (UPF2/RNPS1). Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16209946
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: SURF/EJC complex study interaction. Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16452507
GO:0005515 protein binding
IPI
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		KEEP AS NON CORE
Summary: Interaction in study of hUpf3a/hUpf3b in NMD and translation. Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16601204
GO:0005515 protein binding
IPI
PMID:19410547
Disassembly of exon junction complexes by PYM. 		KEEP AS NON CORE
Summary: EJC-disassembly (PYM) study interaction. Bare term uninformative.
Reason: Real EJC-relevant interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19410547
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: SMG-1 complex (SMG-8/SMG-9) study interaction. Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19417104
GO:0005515 protein binding
IPI
PMID:19478851
The hierarchy of exon-junction complex assembly by the splic... 		KEEP AS NON CORE
Summary: EJC-assembly-hierarchy study interaction. Bare term uninformative.
Reason: Real EJC-relevant interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19478851
GO:0005515 protein binding
IPI
PMID:19503078
A UPF3-mediated regulatory switch that maintains RNA surveil... 		KEEP AS NON CORE
Summary: UPF3-mediated RNA-surveillance switch study interaction. Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19503078
GO:0005515 protein binding
IPI
PMID:23084401
The cellular EJC interactome reveals higher-order mRNP struc... 		KEEP AS NON CORE
Summary: Cellular EJC interactome study interaction. Bare term uninformative.
Reason: Real EJC-relevant interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23084401
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz... 		KEEP AS NON CORE
Summary: Quantitative interactome study interaction. Bare term uninformative.
Reason: Real interaction record; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:26496610
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		KEEP AS NON CORE
Summary: OpenCell endogenous-tagging interactome study interaction. Bare term uninformative.
Reason: Real interaction record; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311
GO:0043025 neuronal cell body
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Neuronal cell body localization inferred from the ortholog; relevant to UPF3B's role in neurodevelopment.
Reason: Electronically inferred localization; peripheral to the core NMD function.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0043025 neuronal cell body cellular_component
GO:0071025 RNA surveillance
NAS
PMID:31131562
Nonsense-mediated mRNA decay: The challenge of telling right... 		KEEP AS NON CORE
Summary: UPF3B functions in RNA surveillance (NMD is the principal surveillance pathway it serves).
Reason: A correct but more general process term; the specific core process is nonsense-mediated decay.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
serving as link between the EJC core and NMD machinery
GO:0170010 nonsense-mediated decay complex
NAS
PMID:35640974
Structures of nonsense-mediated mRNA decay factors UPF3B and... 		ACCEPT
Summary: UPF3B is part of the NMD complex (UPF1-UPF2-UPF3 surveillance complex).
Reason: UPF3B is a defined component of the NMD/UPF surveillance complex.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
formation of an UPF1-UPF2-UPF3 surveillance complex
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... 		ACCEPT
Summary: UPF3B positively regulates/activates NMD by bridging the EJC to UPF1/UPF2.
Reason: UPF3B is an activator of NMD; this regulatory term accurately reflects its role.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
is believed to activate NMD
GO:0005654 nucleoplasm
IDA
GO_REF:0000052 		ACCEPT
Summary: Direct (HPA) nucleoplasmic localization.
Reason: IDA-supported nuclear localization consistent with EJC loading.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005730 nucleolus
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: Direct (HPA) nucleolar localization; a secondary localization of uncertain functional relevance to NMD.
Reason: Documented IDA localization but peripheral to the core cytoplasmic/nuclear NMD function.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005730 nucleolus cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Direct (HPA) cytosolic localization, consistent with cytoplasmic NMD.
Reason: IDA-supported cytosolic localization consistent with site of action.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005634 nucleus
EXP
PMID:11113196
Identification and characterization of human orthologues to ... 		ACCEPT
Summary: Experimental nuclear localization.
Reason: Direct evidence for nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0003729 mRNA binding
IDA
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		ACCEPT
Summary: Direct demonstration of UPF3B mRNA binding.
Reason: Direct support for the core mRNA-binding molecular function.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Binds spliced mRNA upstream of exon-exon junctions
GO:0005515 protein binding
IPI
PMID:25220460
The RNA helicase DHX34 activates NMD by promoting a transiti... 		KEEP AS NON CORE
Summary: Interaction with DHX34 (NMD-activating helicase). Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25220460
GO:0035145 exon-exon junction complex
IDA
PMID:11546873
Role of the nonsense-mediated decay factor hUpf3 in the spli... 		ACCEPT
Summary: Direct demonstration that UPF3B associates with the EJC.
Reason: Direct evidence for EJC membership.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Core component of the mRNA splicing-dependent exon junction complex
GO:0035145 exon-exon junction complex
IDA
PMID:12718880
Y14 and hUpf3b form an NMD-activating complex. 		ACCEPT
Summary: UPF3B and Y14/RBM8A form an NMD-activating complex within the EJC context.
Reason: Direct evidence for EJC membership.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Core component of the mRNA splicing-dependent exon junction complex
GO:0005515 protein binding
IPI
PMID:19864460
Mammalian pre-mRNA 3' end processing factor CF I m 68 functi... 		KEEP AS NON CORE
Summary: Interaction with CPSF6. Bare term uninformative.
Reason: Real interaction record; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19864460
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 with the RNA helicase DDX5/p68 that enhances NMD. Bare term uninformative.
Reason: Real NMD-relevant interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23788676
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi... 		KEEP AS NON CORE
Summary: High-throughput identification of UPF3B as an mRNA-binding protein.
Reason: A more general term than the specific mRNA binding; corroborates the RNA-binding activity.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22658674
GO:0003723 RNA binding
HDA
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on ... 		KEEP AS NON CORE
Summary: High-throughput identification of UPF3B in the mRNA-bound proteome.
Reason: General term corroborating RNA-binding activity; the specific term is mRNA binding.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22681889
GO:0005515 protein binding
IPI
PMID:20930030
SMG6 interacts with the exon junction complex via two conser... 		KEEP AS NON CORE
Summary: Interaction with SMG6 (EJC-binding NMD factor). Bare term uninformative.
Reason: Real NMD-pathway interaction; non-core under generic term.
Supporting Evidence:
file:human/UPF3B/UPF3B-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20930030
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-159101 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-75096 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-75097 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8849157 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9770131 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9770141 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9770236 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9770847 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9794542 		ACCEPT
Summary: Reactome-curated nucleoplasmic localization.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005829 cytosol
TAS
Reactome:R-HSA-75097 		ACCEPT
Summary: Reactome-curated cytosolic localization.
Reason: Consistent with cytoplasmic NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-75098 		ACCEPT
Summary: Reactome-curated cytosolic localization.
Reason: Consistent with cytoplasmic NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927813 		ACCEPT
Summary: Reactome-curated cytosolic localization.
Reason: Consistent with cytoplasmic NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927832 		ACCEPT
Summary: Reactome-curated cytosolic localization.
Reason: Consistent with cytoplasmic NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927836 		ACCEPT
Summary: Reactome-curated cytosolic localization.
Reason: Consistent with cytoplasmic NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-927889 		ACCEPT
Summary: Reactome-curated cytosolic localization.
Reason: Consistent with cytoplasmic NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm
GO:0035145 exon-exon junction complex
IDA
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		ACCEPT
Summary: UPF3B associates with the EJC core (hUpf3b NMD/translation study).
Reason: Direct evidence for EJC membership.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Core component of the mRNA splicing-dependent exon junction complex
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IDA
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		ACCEPT
Summary: Direct evidence that UPF3B functions in NMD.
Reason: Direct support for the core NMD process.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
GO:0045727 positive regulation of translation
IDA
PMID:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA dec... 		KEEP AS NON CORE
Summary: UPF3B stimulates translation in vitro, independently of UPF2 and the EJC core.
Reason: Documented in vitro activity; non-core relative to NMD.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
In vitro, stimulates translation
GO:0003729 mRNA binding
IDA
PMID:11546873
Role of the nonsense-mediated decay factor hUpf3 in the spli... 		ACCEPT
Summary: Direct demonstration of UPF3B RNA/mRNA binding within the post-splicing mRNP.
Reason: Direct support for the core mRNA-binding molecular function.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Binds spliced mRNA upstream of exon-exon junctions
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
IMP
PMID:18369367
NMD resulting from encephalomyocarditis virus IRES-directed ... 		ACCEPT
Summary: Functional (knockdown) evidence that UPF3B is required for NMD.
Reason: Functional support for the core NMD process.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
NAS
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		ACCEPT
Summary: UPF3B functions in NMD of premature-stop-codon-containing mRNAs (founding study).
Reason: Supports the core NMD process.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
GO:0005634 nucleus
NAS
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		ACCEPT
Summary: Nuclear localization asserted in the founding study.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Nucleus
GO:0005737 cytoplasm
NAS
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated deca... 		ACCEPT
Summary: Cytoplasmic localization asserted in the founding study.
Reason: Consistent with cytoplasmic NMD and shuttling.
Supporting Evidence:
file:human/UPF3B/UPF3B-uniprot.txt
Cytoplasm

Core Functions

Core nonsense-mediated mRNA decay (NMD) factor that acts as a molecular adaptor bridging the exon-junction complex to the UPF surveillance machinery - UPF3B associates with the EJC core and recruits UPF2, which links to the RNA helicase/ATPase UPF1 at the terminating ribosome, and together UPF2/UPF3B stimulate UPF1 to activate NMD.

Molecular Function:
mRNA binding
In Complex:
exon-exon junction complex
Supporting Evidence:
  • file:human/UPF3B/UPF3B-uniprot.txt
    serving as link between the EJC core and NMD machinery
  • PMID:18066079
    UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity

Peripheral component of the exon-junction complex that binds spliced mRNA upstream of exon-exon junctions, positioning the NMD machinery on premature-termination-codon-containing transcripts.

Molecular Function:
mRNA binding
In Complex:
exon-exon junction complex
Supporting Evidence:
  • file:human/UPF3B/UPF3B-uniprot.txt
    Binds spliced mRNA upstream of exon-exon junctions

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:11113196
Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4).
  • UPF3B interacts with UPF2 and localizes to the nucleus.
PMID:11163187
Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon.
  • UPF3B (with UPF1 and UPF2) targets mRNAs for nonsense-mediated decay when bound downstream of a termination codon; it shuttles between nucleus and cytoplasm.
PMID:11546873
Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex.
  • hUpf3 (UPF3B) associates with the splicing-dependent exon-exon junction complex and binds RBM8A.
PMID:11546874
Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1.
PMID:12417715
Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay.
PMID:12718880
Y14 and hUpf3b form an NMD-activating complex.
  • UPF3B and Y14/RBM8A form an NMD-activating complex.
PMID:15231747
A protein interaction framework for human mRNA degradation.
PMID:15361857
eIF4G is required for the pioneer round of translation in mammalian cells.
PMID:15680326
Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
PMID:16209946
Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements.
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:16601204
Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation.
  • UPF3B functions in nonsense-mediated mRNA decay and stimulates translation; it associates with the EJC core.
PMID:18066079
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity.
  • UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate UPF1 RNA helicase activity.
PMID:18369367
NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
  • UPF3B is required for NMD (knockdown reduces NMD).
PMID:19410547
Disassembly of exon junction complexes by PYM.
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:19864460
Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export.
PMID:20930030
SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay.
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
PMID:23084401
The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus.
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: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.
  • UPF3B functions in RNA surveillance/NMD as part of the UPF surveillance machinery.
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.
  • UPF3B (and UPF3A) bind UPF2 within the NMD complex.
Reactome:R-HSA-159101
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-75096
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-75097
Reactome: NMD/mRNA processing pathway step
Reactome:R-HSA-75098
Reactome: NMD/mRNA processing pathway step (cytosol localization)
Reactome:R-HSA-8849157
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-927813
Reactome: NMD/mRNA processing pathway step (cytosol localization)
Reactome:R-HSA-927832
Reactome: NMD/mRNA processing pathway step (cytosol localization)
Reactome:R-HSA-927836
Reactome: NMD/mRNA processing pathway step (cytosol localization)
Reactome:R-HSA-927889
Reactome: NMD/mRNA processing pathway step (cytosol localization)
Reactome:R-HSA-9770131
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-9770141
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-9770236
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-9770847
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)
Reactome:R-HSA-9794542
Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)

Suggested Questions for Experts

Q: How do UPF3B and its paralog UPF3A differ functionally - is UPF3A an antagonist/buffer of UPF3B-dependent NMD, and how does this balance affect neurodevelopment?

Q: Which neuronal transcripts are the key physiological NMD substrates whose dysregulation underlies UPF3B-associated intellectual disability?

Suggested Experiments

Experiment: Reconstitute the EJC-UPF3B-UPF2-UPF1 assembly in vitro with purified components to quantify how UPF3B (and disease mutants such as Y160D) contribute to UPF1 ATPase/helicase stimulation.

Experiment: Transcriptome-wide NMD-substrate profiling (e.g. RNA-seq with UPF3B knockdown/rescue) in neuronal models to define the UPF3B-dependent NMD regulon and its disease relevance.

📚 Additional Documentation

Notes

(UPF3B-notes.md)

UPF3B / UPF3X (Regulator of nonsense transcripts 3B) — research notes

UniProt: Q9BZI7 (REN3B_HUMAN), 483 aa. HGNC:20439. X chromosome. Synonyms: UPF3X, hUpf3b, RENT3B.

Core function

UPF3B is a core nonsense-mediated mRNA decay (NMD) factor and a peripheral component of the
exon-junction complex (EJC). It is a molecular adaptor that bridges the EJC core to the UPF
surveillance machinery.
- UniProt FUNCTION: "Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 ... formation of an UPF1-UPF2-UPF3 surveillance complex ... is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1."
- PMID:18066079
- Binds the EJC core via C-terminal region (424–483; contacts EIF4A3 and the MAGOH–RBM8A dimer).
- Binds spliced mRNA upstream of exon-exon junctions → MF GO:0003729 mRNA binding.
- In vitro also stimulates translation (independent of UPF2/EJC) — secondary/non-core.

Localization

Nucleus and cytoplasm; shuttles between them. HPA: nucleoplasm, nucleolus, cytosol. Many Reactome TAS
nucleoplasm/cytosol annotations reflect NMD pathway steps.

Interactions

Functionally central: UPF1, UPF2, RBM8A/Y14, EIF4A3, MAGOH (EJC); DHX34, DDX5/p68, SMG6, SMG-1 complex
(NMD). Most GOA IPI entries are bare "protein binding" from EJC/NMD interactome studies → KEEP_AS_NON_CORE.

Disease

X-linked; LoF mutations cause X-linked syndromic/non-syndromic intellectual disability incl. Lujan-Fryns
syndrome (MRXS14) PMID:17704778. Variant Y160D.

Core function conclusion

Core MF: GO:0003729 mRNA binding plus molecular-adaptor activity bridging UPF2/EJC to UPF1.
Core BP: GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay.
Core CC: GO:0035145 exon-exon junction complex / GO:0170010 nonsense-mediated decay complex.
GO:0003676 nucleic acid binding is over-general (mark as over-annotated).

Pn Notes

(UPF3B-pn-notes.md)

UPF3B PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9BZI7
  • 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: UPF3B (Regulator of nonsense transcripts 3B; also called UPF3X, hUpf3b, RENT3B) is a core factor of the nonsense-mediated mRNA decay (NMD) pathway, the surveillance mechanism that degrades mRNAs bearing premature termination codons. UPF3B is a peripheral component of the exon-junction complex (EJC) that is deposited upstream of exon-exon junctions after splicing. It acts as a molecular adaptor that bridges the EJC core to the central NMD machinery, binding the EJC (through its C-terminal region that contacts EIF4A3 and the MAGOH-RBM8A heterodimer) and recruiting UPF2, which in turn links to the RNA helicase/ATPase UPF1 at the terminating ribosome; together UPF2 and UPF3B stimulate the ATPase and helicase activities of UPF1 to activate NMD. UPF3B binds spliced mRNA upstream of exon-exon junctions, shuttles between nucleus and cytoplasm, and can also stimulate translation in vitro. The gene is X-linked, and loss-of-function mutations cause X-linked syndromic and non-syndromic intellectual disability (including Lujan-Fryns syndrome), reflecting an important role of NMD in neurodevelopment.
  • Existing/core annotation action counts: ACCEPT: 36; KEEP_AS_NON_CORE: 29; MARK_AS_OVER_ANNOTATED: 1

PN Consistency Summary

  • Consistency: Gene-level consistent. Deep-research/notes, review YAML and GOA agree UPF3B is the principal active UPF3 paralog: EJC-associated NMD adaptor that recruits UPF2 and links to UPF1, stimulating NMD. Core: GO:0003729 mRNA binding, GO:0035145 EJC, GO:0170010 NMD complex, GO:0000184 NMD (ACCEPT, multiple), and notably GO:2000624 positive regulation of NMD — the correct opposite directionality to its antagonist paralog UPF3A. No internal contradictions; the UPF3A/UPF3B directionality is handled correctly across the pair.
  • PN story / NEW pressure: PN groups UPF3B under "Modulation of termination," projecting GO:0006415 as new_to_goa. UPF3B's biology (positive NMD adaptor) is fully captured by GO:0000184 + GO:2000624 + EJC/complex terms. No NEW term is defensible; the termination link is indirect (acts after termination, via the surveillance complex).
  • Evidence alignment: PN row carries no reference titles; review well-evidenced (PMID:18066079 UPF2/UPF3 bridge UPF1 / stimulate helicase; UniProt EJC-link FUNCTION; NMD/complex terms). No competing PN citations.
  • Verdict: Consistent gene biology with correct positive directionality (mirror of UPF3A); PN group→GO:0006415 over-reaches — UPF3B's role is NMD adaptor (GO:0000184 / GO:2000624), not translational termination.

Full Consistency Review

  • UniProt: Q9BZI7 · 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 UPF3B is the principal active UPF3 paralog: EJC-associated NMD adaptor that recruits UPF2 and links to UPF1, stimulating NMD. Core: GO:0003729 mRNA binding, GO:0035145 EJC, GO:0170010 NMD complex, GO:0000184 NMD (ACCEPT, multiple), and notably GO:2000624 positive regulation of NMD — the correct opposite directionality to its antagonist paralog UPF3A. No internal contradictions; the UPF3A/UPF3B directionality is handled correctly across the pair.
  • PN story / NEW pressure: PN groups UPF3B under "Modulation of termination," projecting GO:0006415 as new_to_goa. UPF3B's biology (positive NMD adaptor) is fully captured by GO:0000184 + GO:2000624 + EJC/complex terms. No NEW term is defensible; the termination link is indirect (acts after termination, via the surveillance complex).
  • Mapping strategy: As with the other UPF genes, GROUP→GO:0006415 (translational termination, = peptide release) over-reaches — UPF3B is an EJC/NMD adaptor, not a release factor — and would be an unsupported new GOA assertion. Type-level no_mapping should govern; UPF3B is already correctly anchored on GO:0000184 and positively-directed GO:2000624.
  • Evidence alignment: PN row carries no reference titles; review well-evidenced (PMID:18066079 UPF2/UPF3 bridge UPF1 / stimulate helicase; UniProt EJC-link FUNCTION; NMD/complex terms). No competing PN citations.
  • Verdict: Consistent gene biology with correct positive directionality (mirror of UPF3A); PN group→GO:0006415 over-reaches — UPF3B's role is NMD adaptor (GO:0000184 / GO:2000624), not translational termination.

Recommended edits: [MAP] do NOT project GO:0006415 (translational termination) onto UPF3B — it is an EJC/NMD adaptor acting downstream of termination, already correctly anchored on GO:0000184 and GO:2000624 (positive regulation of NMD). Type-level no_mapping should win.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/UPF3B/UPF3B-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9BZI7
  • 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: Q9BZI7
gene_symbol: UPF3B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: UPF3B (Regulator of nonsense transcripts 3B; also called UPF3X, hUpf3b, RENT3B) is a core factor of the nonsense-mediated mRNA decay (NMD) pathway, the surveillance mechanism that degrades mRNAs bearing premature termination codons. UPF3B is a peripheral component of the exon-junction complex (EJC) that is deposited upstream of exon-exon junctions after splicing. It acts as a molecular adaptor that bridges the EJC core to the central NMD machinery, binding the EJC (through its C-terminal region that contacts EIF4A3 and the MAGOH-RBM8A heterodimer) and recruiting UPF2, which in turn links to the RNA helicase/ATPase UPF1 at the terminating ribosome; together UPF2 and UPF3B stimulate the ATPase and helicase activities of UPF1 to activate NMD. UPF3B binds spliced mRNA upstream of exon-exon junctions, shuttles between nucleus and cytoplasm, and can also stimulate translation in vitro. The gene is X-linked, and loss-of-function mutations cause X-linked syndromic and non-syndromic intellectual disability (including Lujan-Fryns syndrome), reflecting an important role of NMD in neurodevelopment.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: UPF3B shuttles between nucleus and cytoplasm and acts in cytoplasmic NMD at the terminating ribosome.
    action: ACCEPT
    reason: Cytoplasmic activity is consistent with UPF3B's role in cytoplasmic NMD; it shuttles between compartments.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Shuttling between the nucleus and the cytoplasm
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: UPF3B binds spliced mRNA upstream of exon-exon junctions; mRNA binding is a core molecular activity supporting its EJC-associated adaptor role.
    action: ACCEPT
    reason: Direct mRNA binding is documented and integral to UPF3B's function on spliced transcripts.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Binds spliced mRNA upstream of exon-exon junctions
- term:
    id: GO:0045727
    label: positive regulation of translation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: In vitro, UPF3B stimulates translation independently of UPF2 and the EJC core.
    action: KEEP_AS_NON_CORE
    reason: A documented in vitro activity, but secondary to UPF3B's core NMD/adaptor role; the in vivo significance is less established.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: In vitro, stimulates translation
- 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: NMD is the core biological process of UPF3B; this electronic annotation is strongly corroborated by direct experimental evidence.
    action: ACCEPT
    reason: UPF3B is a core NMD factor; this is its central process.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: A generic nucleic-acid-binding term; UPF3B's relevant activity is the more specific mRNA/RNA binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative parent term; the specific and supported activity is mRNA binding (GO:0003729).
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Binds spliced mRNA upstream of exon-exon junctions
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: UPF3B localizes to the nucleus, where it associates with the EJC after splicing.
    action: ACCEPT
    reason: Nuclear localization is well documented and integral to EJC loading.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, consistent with UPF3B shuttling and cytoplasmic NMD.
    action: ACCEPT
    reason: Correct localization; corroborated by experimental evidence.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0035145
    label: exon-exon junction complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: UPF3B is a peripheral component of the EJC, a core aspect of its function.
    action: ACCEPT
    reason: UPF3B associates with the EJC core; well supported electronically and experimentally.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Core component of the mRNA splicing-dependent exon junction complex
- term:
    id: GO:0045727
    label: positive regulation of translation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Electronic annotation of translation stimulation, also shown in vitro.
    action: KEEP_AS_NON_CORE
    reason: Secondary in vitro activity; non-core relative to NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: In vitro, stimulates translation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11163187
  qualifier: enables
  review:
    summary: Interaction with UPF1 and UPF2 (founding NMD-targeting study). Bare protein binding is uninformative; the informative function is the UPF2-EJC bridging adaptor role.
    action: KEEP_AS_NON_CORE
    reason: Real, functionally central interactions (UPF1, UPF2) but the generic term is uninformative; the core MF is the molecular adaptor activity.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Recruits UPF2 at the cytoplasmic side of the nuclear envelope
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11546873
  qualifier: enables
  review:
    summary: Interaction with RBM8A/Y14 and association with the EJC. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real EJC-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11546873
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11546874
  qualifier: enables
  review:
    summary: EJC-association study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real EJC-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11546874
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12417715
  qualifier: enables
  review:
    summary: Interaction within a decapping complex associated with hUpf proteins. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:12417715
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15231747
  qualifier: enables
  review:
    summary: mRNA-degradation interaction-framework study. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15231747
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15361857
  qualifier: enables
  review:
    summary: Pioneer-round-of-translation study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15361857
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15680326
  qualifier: enables
  review:
    summary: Staufen1/UPF1 study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:15680326
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16209946
  qualifier: enables
  review:
    summary: Interaction in study of EJC-dependent NMD routes (UPF2/RNPS1). Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16209946
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16452507
  qualifier: enables
  review:
    summary: SURF/EJC complex study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16452507
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16601204
  qualifier: enables
  review:
    summary: Interaction in study of hUpf3a/hUpf3b in NMD and translation. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16601204
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19410547
  qualifier: enables
  review:
    summary: EJC-disassembly (PYM) study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real EJC-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19410547
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19417104
  qualifier: enables
  review:
    summary: SMG-1 complex (SMG-8/SMG-9) study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19417104
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19478851
  qualifier: enables
  review:
    summary: EJC-assembly-hierarchy study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real EJC-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19478851
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19503078
  qualifier: enables
  review:
    summary: UPF3-mediated RNA-surveillance switch study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19503078
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23084401
  qualifier: enables
  review:
    summary: Cellular EJC interactome study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real EJC-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23084401
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Quantitative interactome study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:26496610
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome study interaction. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Neuronal cell body localization inferred from the ortholog; relevant to UPF3B's role in neurodevelopment.
    action: KEEP_AS_NON_CORE
    reason: Electronically inferred localization; peripheral to the core NMD function.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0043025 neuronal cell body cellular_component
- term:
    id: GO:0071025
    label: RNA surveillance
  evidence_type: NAS
  original_reference_id: PMID:31131562
  qualifier: involved_in
  review:
    summary: UPF3B functions in RNA surveillance (NMD is the principal surveillance pathway it serves).
    action: KEEP_AS_NON_CORE
    reason: A correct but more general process term; the specific core process is nonsense-mediated decay.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: serving as link between the EJC core and NMD machinery
- term:
    id: GO:0170010
    label: nonsense-mediated decay complex
  evidence_type: NAS
  original_reference_id: PMID:35640974
  qualifier: part_of
  review:
    summary: UPF3B is part of the NMD complex (UPF1-UPF2-UPF3 surveillance complex).
    action: ACCEPT
    reason: UPF3B is a defined component of the NMD/UPF surveillance complex.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: formation of an UPF1-UPF2-UPF3 surveillance complex
- 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: UPF3B positively regulates/activates NMD by bridging the EJC to UPF1/UPF2.
    action: ACCEPT
    reason: UPF3B is an activator of NMD; this regulatory term accurately reflects its role.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: is believed to activate NMD
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct (HPA) nucleoplasmic localization.
    action: ACCEPT
    reason: IDA-supported nuclear localization consistent with EJC loading.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct (HPA) nucleolar localization; a secondary localization of uncertain functional relevance to NMD.
    action: KEEP_AS_NON_CORE
    reason: Documented IDA localization but peripheral to the core cytoplasmic/nuclear NMD function.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005730 nucleolus cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct (HPA) cytosolic localization, consistent with cytoplasmic NMD.
    action: ACCEPT
    reason: IDA-supported cytosolic localization consistent with site of action.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:11113196
  qualifier: located_in
  review:
    summary: Experimental nuclear localization.
    action: ACCEPT
    reason: Direct evidence for nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IDA
  original_reference_id: PMID:11163187
  qualifier: enables
  review:
    summary: Direct demonstration of UPF3B mRNA binding.
    action: ACCEPT
    reason: Direct support for the core mRNA-binding molecular function.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Binds spliced mRNA upstream of exon-exon junctions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25220460
  qualifier: enables
  review:
    summary: Interaction with DHX34 (NMD-activating helicase). Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25220460
- term:
    id: GO:0035145
    label: exon-exon junction complex
  evidence_type: IDA
  original_reference_id: PMID:11546873
  qualifier: part_of
  review:
    summary: Direct demonstration that UPF3B associates with the EJC.
    action: ACCEPT
    reason: Direct evidence for EJC membership.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Core component of the mRNA splicing-dependent exon junction complex
- term:
    id: GO:0035145
    label: exon-exon junction complex
  evidence_type: IDA
  original_reference_id: PMID:12718880
  qualifier: part_of
  review:
    summary: UPF3B and Y14/RBM8A form an NMD-activating complex within the EJC context.
    action: ACCEPT
    reason: Direct evidence for EJC membership.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Core component of the mRNA splicing-dependent exon junction complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19864460
  qualifier: enables
  review:
    summary: Interaction with CPSF6. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction record; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19864460
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23788676
  qualifier: enables
  review:
    summary: Interaction with the RNA helicase DDX5/p68 that enhances NMD. Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-relevant interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23788676
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: High-throughput identification of UPF3B as an mRNA-binding protein.
    action: KEEP_AS_NON_CORE
    reason: A more general term than the specific mRNA binding; corroborates the RNA-binding activity.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22658674
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: High-throughput identification of UPF3B in the mRNA-bound proteome.
    action: KEEP_AS_NON_CORE
    reason: General term corroborating RNA-binding activity; the specific term is mRNA binding.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22681889
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20930030
  qualifier: enables
  review:
    summary: Interaction with SMG6 (EJC-binding NMD factor). Bare term uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real NMD-pathway interaction; non-core under generic term.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20930030
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-159101
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75096
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75097
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8849157
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770131
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770141
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770236
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9770847
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9794542
  qualifier: located_in
  review:
    summary: Reactome-curated nucleoplasmic localization.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75097
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75098
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927813
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927832
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927836
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927889
  qualifier: located_in
  review:
    summary: Reactome-curated cytosolic localization.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
- term:
    id: GO:0035145
    label: exon-exon junction complex
  evidence_type: IDA
  original_reference_id: PMID:16601204
  qualifier: part_of
  review:
    summary: UPF3B associates with the EJC core (hUpf3b NMD/translation study).
    action: ACCEPT
    reason: Direct evidence for EJC membership.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Core component of the mRNA splicing-dependent exon junction complex
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: IDA
  original_reference_id: PMID:16601204
  qualifier: involved_in
  review:
    summary: Direct evidence that UPF3B functions in NMD.
    action: ACCEPT
    reason: Direct support for the core NMD process.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
- term:
    id: GO:0045727
    label: positive regulation of translation
  evidence_type: IDA
  original_reference_id: PMID:16601204
  qualifier: involved_in
  review:
    summary: UPF3B stimulates translation in vitro, independently of UPF2 and the EJC core.
    action: KEEP_AS_NON_CORE
    reason: Documented in vitro activity; non-core relative to NMD.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: In vitro, stimulates translation
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IDA
  original_reference_id: PMID:11546873
  qualifier: enables
  review:
    summary: Direct demonstration of UPF3B RNA/mRNA binding within the post-splicing mRNP.
    action: ACCEPT
    reason: Direct support for the core mRNA-binding molecular function.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Binds spliced mRNA upstream of exon-exon junctions
- 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: Functional (knockdown) evidence that UPF3B is required for NMD.
    action: ACCEPT
    reason: Functional support for the core NMD process.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
- term:
    id: GO:0000184
    label: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  evidence_type: NAS
  original_reference_id: PMID:11163187
  qualifier: involved_in
  review:
    summary: UPF3B functions in NMD of premature-stop-codon-containing mRNAs (founding study).
    action: ACCEPT
    reason: Supports the core NMD process.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:11163187
  qualifier: located_in
  review:
    summary: Nuclear localization asserted in the founding study.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:11163187
  qualifier: located_in
  review:
    summary: Cytoplasmic localization asserted in the founding study.
    action: ACCEPT
    reason: Consistent with cytoplasmic NMD and shuttling.
    supported_by:
    - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
      supporting_text: Cytoplasm
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11113196
  title: Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4).
  findings:
  - statement: UPF3B interacts with UPF2 and localizes to the nucleus.
    reference_section_type: ABSTRACT
- id: PMID:11163187
  title: Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon.
  findings:
  - statement: UPF3B (with UPF1 and UPF2) targets mRNAs for nonsense-mediated decay when bound downstream of a termination codon; it shuttles between nucleus and cytoplasm.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Founding study of human UPF3B in NMD.
- id: PMID:11546873
  title: Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex.
  findings:
  - statement: hUpf3 (UPF3B) associates with the splicing-dependent exon-exon junction complex and binds RBM8A.
    reference_section_type: ABSTRACT
- id: PMID:11546874
  title: Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1.
  findings: []
- id: PMID:12417715
  title: Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay.
  findings: []
- id: PMID:12718880
  title: Y14 and hUpf3b form an NMD-activating complex.
  findings:
  - statement: UPF3B and Y14/RBM8A form an NMD-activating complex.
    reference_section_type: ABSTRACT
- id: PMID:15231747
  title: A protein interaction framework for human mRNA degradation.
  findings: []
- id: PMID:15361857
  title: eIF4G is required for the pioneer round of translation in mammalian cells.
  findings: []
- id: PMID:15680326
  title: Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
  findings: []
- id: PMID:16209946
  title: Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements.
  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:16601204
  title: Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation.
  findings:
  - statement: UPF3B functions in nonsense-mediated mRNA decay and stimulates translation; it associates with the EJC core.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes UPF3B NMD and translation activities.
- id: PMID:18066079
  title: NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity.
  findings:
  - statement: UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate UPF1 RNA helicase activity.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the UPF3 adaptor/bridging role and UPF1 stimulation.
- id: PMID:18369367
  title: NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
  findings:
  - statement: UPF3B is required for NMD (knockdown reduces NMD).
    reference_section_type: RESULTS
- id: PMID:19410547
  title: Disassembly of exon junction complexes by PYM.
  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:19864460
  title: Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export.
  findings: []
- id: PMID:20930030
  title: SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
  findings: []
- id: PMID:23084401
  title: The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus.
  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: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:
  - statement: UPF3B functions in RNA surveillance/NMD as part of the UPF surveillance machinery.
    reference_section_type: ABSTRACT
- 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:
  - statement: UPF3B (and UPF3A) bind UPF2 within the NMD complex.
    reference_section_type: ABSTRACT
- id: Reactome:R-HSA-159101
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-75096
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-75097
  title: 'Reactome: NMD/mRNA processing pathway step'
  findings: []
- id: Reactome:R-HSA-75098
  title: 'Reactome: NMD/mRNA processing pathway step (cytosol localization)'
  findings: []
- id: Reactome:R-HSA-8849157
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-927813
  title: 'Reactome: NMD/mRNA processing pathway step (cytosol localization)'
  findings: []
- id: Reactome:R-HSA-927832
  title: 'Reactome: NMD/mRNA processing pathway step (cytosol localization)'
  findings: []
- id: Reactome:R-HSA-927836
  title: 'Reactome: NMD/mRNA processing pathway step (cytosol localization)'
  findings: []
- id: Reactome:R-HSA-927889
  title: 'Reactome: NMD/mRNA processing pathway step (cytosol localization)'
  findings: []
- id: Reactome:R-HSA-9770131
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-9770141
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-9770236
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-9770847
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
- id: Reactome:R-HSA-9794542
  title: 'Reactome: NMD/mRNA processing pathway step (nucleoplasm localization)'
  findings: []
core_functions:
- description: Core nonsense-mediated mRNA decay (NMD) factor that acts as a molecular adaptor bridging the exon-junction complex to the UPF surveillance machinery - UPF3B associates with the EJC core and recruits UPF2, which links to the RNA helicase/ATPase UPF1 at the terminating ribosome, and together UPF2/UPF3B stimulate UPF1 to activate NMD.
  molecular_function:
    id: GO:0003729
    label: mRNA binding
  in_complex:
    id: GO:0035145
    label: exon-exon junction complex
  supported_by:
  - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
    supporting_text: serving as link between the EJC core and NMD machinery
  - reference_id: PMID:18066079
    supporting_text: UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity
- description: Peripheral component of the exon-junction complex that binds spliced mRNA upstream of exon-exon junctions, positioning the NMD machinery on premature-termination-codon-containing transcripts.
  molecular_function:
    id: GO:0003729
    label: mRNA binding
  in_complex:
    id: GO:0035145
    label: exon-exon junction complex
  supported_by:
  - reference_id: file:human/UPF3B/UPF3B-uniprot.txt
    supporting_text: Binds spliced mRNA upstream of exon-exon junctions
proposed_new_terms: []
suggested_questions:
- question: How do UPF3B and its paralog UPF3A differ functionally - is UPF3A an antagonist/buffer of UPF3B-dependent NMD, and how does this balance affect neurodevelopment?
- question: Which neuronal transcripts are the key physiological NMD substrates whose dysregulation underlies UPF3B-associated intellectual disability?
suggested_experiments:
- description: Reconstitute the EJC-UPF3B-UPF2-UPF1 assembly in vitro with purified components to quantify how UPF3B (and disease mutants such as Y160D) contribute to UPF1 ATPase/helicase stimulation.
- description: Transcriptome-wide NMD-substrate profiling (e.g. RNA-seq with UPF3B knockdown/rescue) in neuronal models to define the UPF3B-dependent NMD regulon and its disease relevance.