id: Q9Y5M8
gene_symbol: SRPRB
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: SRPRB (signal recognition particle receptor subunit beta, SR-beta; also APMCF1) is a 271 aa single-pass ER membrane protein and a small Ras-superfamily GTPase closely related to Arf and Sar1. It is the membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor (SR), assembling with the soluble alpha subunit SRPRA via a Longin-domain interface and tethering SRPRA to the ER membrane. The SRP receptor docks the SRP-ribosome-nascent chain complex at the ER so that signal-sequence-bearing nascent secretory and membrane proteins are delivered to the Sec61 translocon for cotranslational translocation and insertion. SRP-dependent targeting is driven by a GTPase cycle in which the SR (SRPRA and SRPRB) and the SRP54 GTPase reciprocally activate one another; GTP binding and hydrolysis by SRPRB regulate ribosome-nascent chain handover and receptor recycling. SRPRB is broadly expressed and localizes to the ER membrane.
existing_annotations:
- term:
    id: GO:0005785
    label: signal recognition particle receptor complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: SRPRB is the beta subunit of the heterodimeric SRP receptor; phylogenetic assignment of SR-complex membership is consistent with direct structural and biochemical evidence. Core structural identity.
    action: ACCEPT
    reason: SRP receptor complex membership is the core cellular-component identity of SRPRB; SRPRB heterodimerizes with SRPRA.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Component of the signal recognition particle (SRP) complex receptor (SR)
- term:
    id: GO:0045047
    label: protein targeting to ER
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: As part of the SRP receptor, SRPRB participates in targeting nascent secretory/membrane proteins to the ER. Core biological process.
    action: ACCEPT
    reason: Core SR-mediated process; the SRP receptor ensures correct targeting of nascent proteins to the ER membrane.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: the correct targeting of the nascent secretory proteins to the
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: SRPRB is a small GTPase of the Ras superfamily (Arf/Sar1-related) with conserved GTP-binding motifs; GTP binding and hydrolysis drive the SRP-targeting cycle. Core molecular function.
    action: ACCEPT
    reason: Core molecular function; SRPRB binds GTP (structure solved in the Mg2+-GTP-bound state) and its GTPase activity regulates targeting.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: GTP-binding
    - reference_id: PMID:29567807
    - reference_id: PMID:34020957
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of the ER membrane subcellular location from UniProt; the correct and core compartment for the membrane-anchored SR-beta subunit.
    action: ACCEPT
    reason: Correct core location; SRPRB is a single-pass ER membrane protein.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16169070
  qualifier: enables
  review:
    summary: High-throughput protein-protein interaction capture. SRPRB's functionally informative interaction is with SRPRA (the SR heterodimer), but bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real but the bare protein binding term is uninformative per curation guidelines; the SR-complex term captures the informative content.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Heterodimer with SRPRA
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-MS interactome capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Heterodimer with SRPRA
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-map interactome capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Heterodimer with SRPRA
- term:
    id: GO:0005785
    label: signal recognition particle receptor complex
  evidence_type: EXP
  original_reference_id: PMID:16439358
  qualifier: part_of
  review:
    summary: Crystal structure of mammalian SR-beta in complex with the SRalpha (SRPRA) binding domain (SRX); direct experimental evidence that SRPRB is part of the heterodimeric SRP receptor. Core structural identity.
    action: ACCEPT
    reason: Experimentally demonstrated core SR membership; SRPRB-SRPRA heterodimer structure.
    supported_by:
    - reference_id: PMID:16439358
      supporting_text: The SR is a heterodimeric complex assembled by the two GTPases SRalpha and SRbeta
- term:
    id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
  evidence_type: NAS
  original_reference_id: PMID:16439358
  qualifier: involved_in
  review:
    summary: SRPRB, as part of the SR, participates in SRP-dependent cotranslational targeting of nascent chains to the ER membrane. Core biological process.
    action: ACCEPT
    reason: Core SR-mediated process; the SRP receptor mediates SRP-dependent cotranslational targeting at the ER.
    supported_by:
    - reference_id: PMID:16439358
      supporting_text: co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum
- term:
    id: GO:0016020
    label: membrane
  evidence_type: NAS
  original_reference_id: PMID:16439358
  qualifier: located_in
  review:
    summary: The SR is membrane-anchored via SRPRB; a generic membrane localization that is a parent of the specific ER membrane term.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: PMID:16439358
      supporting_text: which is membrane-anchored
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Curator ISS transfer of ER membrane localization from an ortholog; the correct and core compartment for SRPRB.
    action: ACCEPT
    reason: Correct core location; redundant with other ER membrane evidence.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:22375059
  qualifier: located_in
  review:
    summary: Direct evidence of membrane localization from a study of Sec61/Sec62/Sec63-dependent ER translocation; a generic membrane term, parent of ER membrane.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1791060
  qualifier: located_in
  review:
    summary: Reactome TAS annotation of ER membrane localization for SRPRB, consistent with the core compartment.
    action: ACCEPT
    reason: Correct core location; consistent with experimental and ISS evidence.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005881
    label: cytoplasmic microtubule
  evidence_type: IDA
  original_reference_id: PMID:23264731
  qualifier: located_in
  review:
    summary: Wrong-gene citation. PMID:23264731 characterizes MTR120/KIAA1383 as a microtubule-associated protein; the now-cached full text never mentions or assays SRPRB (no occurrence of SRPRB / SR-beta / SRP receptor). SRPRB is an ER-membrane GTPase, for which a cytoplasmic microtubule localization is biologically implausible.
    action: REMOVE
    reason: The full text of PMID:23264731 is now available and confirms the paper is entirely about MTR120/KIAA1383 and does not assay SRPRB, so this GO:0005881 IDA is a wrong-gene mis-attribution. This matches the sibling SERP1 review, where the same PMID:23264731 cytoplasmic-microtubule annotation was REMOVED after full-text confirmation; previously this row was held UNDECIDED only because the full text was unavailable.
    supported_by:
    - reference_id: PMID:23264731
      supporting_text: a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19664239
  qualifier: located_in
  review:
    summary: GFP-APMCF1 (SRPRB) overexpression showed a generally cytoplasmic distribution in COS-7 cells. A diffuse cytoplasmic signal is consistent with an ER-membrane protein (the ER is in the cytoplasm), but cytoplasm is imprecise relative to the ER membrane and the signal derives from overexpression of a GFP fusion.
    action: KEEP_AS_NON_CORE
    reason: Plausible but imprecise (and overexpression-based); the informative core localization is the ER membrane.
    supported_by:
    - reference_id: PMID:19664239
      supporting_text: EGFP-APMCF1 was generally localized in the cytoplasm of COS-7 cell
core_functions:
- description: Membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor; a Ras-superfamily GTPase that, together with SRPRA, docks the SRP-ribosome-nascent chain complex at the ER membrane to enable SRP-dependent cotranslational protein targeting.
  molecular_function:
    id: GO:0005525
    label: GTP binding
  in_complex:
    id: GO:0005785
    label: signal recognition particle receptor complex
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
    supporting_text: Component of the signal recognition particle (SRP) complex receptor (SR)
  - reference_id: PMID:16439358
    supporting_text: The SR is a heterodimeric complex assembled by the two GTPases SRalpha and SRbeta
  - reference_id: PMID:29567807
  - reference_id: PMID:37643813
  directly_involved_in:
  - id: GO:0045047
    label: protein targeting to ER
  - id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
proposed_new_terms: []
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:16169070
  title: 'A human protein-protein interaction network: a resource for annotating the proteome.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of an IPI protein-binding annotation.
- id: PMID:16439358
  title: The structure of the mammalian signal recognition particle (SRP) receptor as prototype for the interaction of small GTPases with Longin domains.
  findings:
  - statement: The SR is a heterodimeric complex of the two GTPases SRalpha and SRbeta, membrane-anchored; crystal structure of mammalian SRbeta in the Mg2+-GTP-bound state in complex with the SRalpha (SRX) binding domain.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis for the SRPRB-SRPRA heterodimer and SRPRB GTPase identity; source of SR-complex membership and targeting annotations.
- id: PMID:19664239
  title: Subcellular localization of APMCF1 and its biological significance of expression pattern in normal and malignant human tissues.
  findings:
  - statement: EGFP-APMCF1 (SRPRB) overexpressed in COS-7 cells localized generally to the cytoplasm.
    reference_section_type: RESULTS
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Overexpression GFP-fusion localization study under the APMCF1 alias; diffuse cytoplasmic signal consistent with an ER-membrane protein.
- id: PMID:22375059
  title: Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Study of Sec61/62/63-dependent ER translocation; source of a generic membrane localization for SRPRB.
- id: PMID:23264731
  title: MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis.
  findings:
  - statement: Characterizes MTR120/KIAA1383 as a microtubule-associated protein promoting microtubule stability and cytokinesis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: NONE
    correctness: WRONG_IDENTIFIER
    review_notes: Full text (now cached, full_text_available) is entirely about MTR120/KIAA1383 and never mentions or assays SRPRB (no occurrence of SRPRB / SR-beta / SRP receptor). The GO:0005881 cytoplasmic-microtubule IDA citing this paper is a wrong-gene mis-attribution and has been REMOVED, consistent with the sibling SERP1 review.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex affinity-MS interactome; source of an IPI protein-binding annotation.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Multimodal cell-map interactome; source of an IPI protein-binding annotation.
- id: Reactome:R-HSA-1791060
  title: Expression of SRPRB (SRP Receptor subunit beta)
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Reactome record; source of a TAS ER membrane localization for SRPRB.
- id: PMID:29567807
  title: "Structure of a prehandover mammalian ribosomal SRP\xB7SRP receptor targeting\
    \ complex."
  findings:
  - statement: Cryo-EM structure of the mammalian translating ribosome with SRP and SRP receptor in a prehandover conformation; GTP-bound SRbeta and eukaryote-specific SRP/SR proteins form a large assembly at the distal SRP RNA site, and SRP/SR GTP hydrolysis is delayed at this stage to allow signal-sequence handover.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:29567807; Science 2018). Structural basis for GTP-bound SRbeta in the targeting complex and delayed GTP hydrolysis during handover; directly informs SRPRB GTPase function and SR-complex role. Not cached; no verbatim supporting_text added.
- id: PMID:34020957
  title: Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational
    protein translocation into the ER.
  findings:
  - statement: Structural, biochemical and single-molecule analyses show eukaryotic SRP-mediated targeting requires sequential GTPase-driven compaction of the SRP receptor (SRalpha/SRbeta) and conformational rearrangements that couple the SRP/SR GTPase cycle to protein translocation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:34020957; Sci Adv 2021). Mechanistic model of SR compaction and GTPase rearrangement during targeting; supports SRPRB GTP-binding/hydrolysis role in the receptor cycle. Not cached; no verbatim supporting_text added.
- id: PMID:37643813
  title: Examining SRP pathway function in mRNA localization to the endoplasmic reticulum.
  findings:
  - statement: CRISPR/Cas9 knockout of SRPRB (SRbeta) in mammalian cells profoundly destabilizes SRalpha (proteasome-sensitive) and redistributes residual SRalpha to the cytosol, yet steady-state ER mRNA localization is largely unaltered, uncoupling ER mRNA localization from SRP receptor expression.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:37643813; RNA 2023). Direct human SRPRB knockout evidence that SRbeta stabilizes SRalpha at the ER; refines models of SR-dependent mRNA localization. Not cached; no verbatim supporting_text added.
- id: PMID:36921042
  title: "Signal recognition particle receptor-β (SR-β) coordinates cotranslational\
    \ N-glycosylation."
  findings:
  - statement: SRbeta (SRPRB) is required for assembly of an N-glycosylation-competent translocon; perturbing the SRbeta GTP-binding site (mutation or guanine-analog probes) causes hypoglycosylation and reduces SRbeta association with the oligosaccharyltransferase (OST) complex without disrupting SRalpha-SRbeta association, revealing a function coordinating ER translation with N-glycosylation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:36921042; Sci Adv 2023). Newly described SRbeta function beyond receptor anchoring (coordinating cotranslational N-glycosylation via OST engagement, GTP-dependent). Not cached; no verbatim supporting_text added.
suggested_questions:
- question: Is the reported cytoplasmic-microtubule localization of SRPRB a genuine secondary localization or a mis-attribution from the MTR120 study, and does SRPRB have any verified function outside the SRP receptor?
- question: How do the GTPase cycles of SRPRB, SRPRA, and SRP54 coordinate ribosome-nascent chain handover to the Sec61 translocon, and what is the specific catalytic contribution of SRPRB GTP hydrolysis?
suggested_experiments:
- description: Use endogenous tagging plus proximity labeling and super-resolution microscopy to test whether SRPRB localizes to microtubules under any condition, distinguishing genuine localization from overexpression or co-purification artifacts.
- description: Reconstitute SRP-dependent targeting with wild-type and GTPase-dead SRPRB to quantify the role of SRPRB GTP hydrolysis in receptor recycling and nascent-chain delivery to Sec61.