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.