id: Q9UHB9
gene_symbol: SRP68
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: SRP68 is the 68 kDa subunit of the signal recognition particle (SRP), a cytosolic ribonucleoprotein composed of the 7SL (7S) RNA and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). SRP68 and SRP72 form the heterodimeric "S-domain" module of SRP; SRP68 binds the large/S-domain of the 7SL RNA through an N-terminal RNA-binding domain (residues ~52-252) and, via its C-terminus, recruits SRP72. SRP68 is an RNA-binding scaffold subunit, not a GTPase. Its RNA-binding domain is a tetratricopeptide-like module that bends the SRP RNA at a three-way junction and remodels the conserved 5f loop, a rearrangement required for SRP function in cotranslational targeting and for productive engagement of the SRP receptor. Within SRP, the particle binds the signal sequence of nascent secretory and membrane proteins emerging from the translating ribosome and delivers the ribosome-nascent chain complex to the ER-anchored SRP receptor, where translocation through the Sec61 channel proceeds. SRP68 is predominantly cytosolic; pools are also detected in the nucleolus (reflecting SRP assembly trafficking) and at the endoplasmic reticulum. Biallelic germline SRP68 variants cause severe congenital neutropenia (SCN10).
alternative_products:
- name: '1'
  id: Q9UHB9-1
- name: '2'
  id: Q9UHB9-2
  sequence_note: VSP_008347
- name: '3'
  id: Q9UHB9-3
  sequence_note: VSP_045132
- name: '4'
  id: Q9UHB9-4
  sequence_note: VSP_046944
existing_annotations:
- term:
    id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: SRP68 is a core SRP subunit and participates directly in SRP-dependent cotranslational targeting of secretory and membrane proteins to the ER. This is the defining biological process of the gene and is conserved across the SRP68 family.
    action: ACCEPT
    reason: Phylogenetically (IBA) and experimentally supported core biological process; SRP68 is an essential S-domain subunit of the targeting SRP complex.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER)
- term:
    id: GO:0005047
    label: signal recognition particle binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: SRP68 binds within the SRP complex, contacting the 7SL RNA and the SRP72/SRP19 components; signal recognition particle binding captures its integral association with the particle.
    action: ACCEPT
    reason: Core molecular function corroborated by structural and biochemical evidence of SRP68 binding SRP RNA and SRP72 within the particle.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: SRP68 is a constitutive subunit of the ER-targeting signal recognition particle. Conserved across the family.
    action: ACCEPT
    reason: Core cellular component; SRP68 is one of the six defining SRP protein subunits.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: SRP68 binds the SRP (7SL) RNA via its N-terminal RNA-binding domain; the general RNA binding term is a correct parent of the more specific 7S RNA binding.
    action: ACCEPT
    reason: Correct general molecular function; the more precise GO:0008312 (7S RNA binding) better captures the specific activity.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: The N-terminus is required for RNA-binding.
- term:
    id: GO:0005047
    label: signal recognition particle binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic assignment of signal recognition particle binding, consistent with the experimental/IBA evidence.
    action: ACCEPT
    reason: Correct core molecular function; redundant with IBA and IPI evidence.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: A pool of SRP68 traffics through the nucleolus, consistent with partial SRP assembly there; this is not its core site of action.
    action: KEEP_AS_NON_CORE
    reason: Real localization (UniProt subcellular location; PMID:10618370) reflecting SRP assembly trafficking, not the core cytosolic/ER targeting function.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Nucleus, nucleolus'
    - reference_id: PMID:10618370
      supporting_text: green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: SRP68 is predominantly cytoplasmic, consistent with the cytosolic SRP targeting cycle.
    action: ACCEPT
    reason: Correct compartment; SRP acts in the cytoplasm to capture nascent chains on translating ribosomes.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: SRP68 accumulates at the ER, consistent with delivery of the SRP-ribosome-nascent chain complex to the ER-bound SRP receptor.
    action: ACCEPT
    reason: Correct; ER association reflects the targeting endpoint where SRP docks the nascent-chain complex.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Endoplasmic reticulum {ECO:0000269|PubMed:28369529}'
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: InterPro-based electronic assignment to the ER-targeting SRP, consistent with experimental evidence.
    action: ACCEPT
    reason: Correct core cellular component; redundant with IBA/IDA.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Component of a signal recognition particle (SRP) complex'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Cytosolic localization consistent with the cytoplasmic SRP targeting cycle.
    action: ACCEPT
    reason: Correct compartment; redundant with the IDA cytosol annotation and the UniProt cytoplasm location.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Electronic (InterPro) assignment of the defining SRP cotranslational targeting process, consistent with IBA/NAS evidence.
    action: ACCEPT
    reason: Correct core biological process; redundant with experimentally supported annotations.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: SRP68 directly binds the 7SL (7S) SRP RNA through its N-terminal RNA-binding domain and remodels it; 7S RNA binding is the core molecular function.
    action: ACCEPT
    reason: Core molecular function with structural support (crystal structures of SRP68-RBD with SRP RNA); also supported by IMP.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA)
    - reference_id: PMID:24700861
      supporting_text: We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19.
- term:
    id: GO:0030942
    label: endoplasmic reticulum signal sequence receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: This activity describes the ER signal-sequence receptor (the SRP receptor / TRAP-type signal sequence receptor), not the 7SL-RNA-binding SRP68 scaffold subunit. The InterPro mapping over-extends a receptor function onto an SRP S-domain protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: SRP68 is an RNA-binding scaffold subunit of the cytosolic SRP, not a membrane signal-sequence receptor; signal-sequence receptor activity belongs to the SRP receptor (SRPR/SRPRB) and the SSR/TRAP complex, not to SRP68.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: The N-terminus is required for RNA-binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16672232
  qualifier: enables
  review:
    summary: SRP68 binds SRP72 (and SRP RNA); this captures the SRP68-SRP72 heterodimer interaction. The informative aspect (SRP/SRP72 binding) is better represented by signal recognition particle binding; bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real SRP68-SRP72 interaction but the bare protein binding term is uninformative; the SRP-binding function is captured by GO:0005047.
    supported_by:
    - reference_id: PMID:16672232
      supporting_text: Human SRP68 was purified from overexpressing Escherichia coli cells and was found to bind to recombinant SRP72
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24700861
  qualifier: enables
  review:
    summary: Structural study of SRP68-RBD in complex with SRP19 and SRP RNA; the interaction captured is with SRP partners. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interaction within SRP (SRP19/RNA) but bare protein binding is uninformative; SRP function is captured by other terms.
    supported_by:
    - reference_id: PMID:24700861
      supporting_text: in complex with SRP RNA and SRP19
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: High-throughput interactome (BioPlex) capture; bare protein binding is uninformative for core function.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome interaction; bare protein binding is uninformative and not elevated to core per guidelines.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Q9UHB9; O76094: SRP72'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35156780
  qualifier: enables
  review:
    summary: CFTR-interactome mammalian membrane two-hybrid screen captured SRP68; the CFTR interaction is consistent with SRP engaging nascent membrane proteins but bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Screen-derived interaction; bare protein binding is uninformative and the CFTR partner reflects SRP substrate capture rather than a distinct core function.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Q9UHB9; P13569: CFTR'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome capture; bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome interaction; uninformative bare term not elevated to core.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Q9UHB9; O76094: SRP72'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: CFTR-interactome proximity-labeling capture; bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Screen-derived interaction; uninformative bare term not elevated to core.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Q9UHB9; P13569: CFTR'
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: NAS
  original_reference_id: PMID:34208095
  qualifier: part_of
  review:
    summary: Review-based assertion that SRP68 is part of the ER-targeting SRP.
    action: ACCEPT
    reason: Consistent with the experimentally supported SRP membership; the cited review summarizes mammalian SRP composition and function.
    supported_by:
    - reference_id: PMID:34208095
      supporting_text: It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals.
- term:
    id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence
      recognition
  evidence_type: NAS
  original_reference_id: PMID:34208095
  qualifier: involved_in
  review:
    summary: SRP, of which SRP68 is a core subunit, recognizes the signal sequence of nascent chains during cotranslational targeting; SRP68 participates in this signal-sequence-recognition step as part of the particle.
    action: ACCEPT
    reason: Consistent with SRP's signal-sequence recognition role; SRP68 is an integral S-domain subunit of the recognizing particle.
    supported_by:
    - reference_id: PMID:34208095
      supporting_text: SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with the cytoplasmic SRP targeting cycle.
    action: ACCEPT
    reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:10618370
  qualifier: located_in
  review:
    summary: Experimental (GFP-fusion) evidence that SRP68 localizes to the cytoplasm.
    action: ACCEPT
    reason: Correct compartment; SRP acts in the cytoplasm.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: EXP
  original_reference_id: PMID:28369529
  qualifier: located_in
  review:
    summary: Experimental evidence for SRP68 ER localization, consistent with SRP docking at the ER-bound receptor.
    action: ACCEPT
    reason: Correct; ER association reflects the targeting endpoint. The F590L mutant (disrupting SRP72 interaction) diminishes ER localization, linking ER targeting to heterodimer formation.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'F->L: Loss of interaction with SRP72. Diminished'
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IMP
  original_reference_id: PMID:27899666
  qualifier: enables
  review:
    summary: SRP68 binds and remodels the SRP (7S/7SL) RNA; structures of SRP68/72-RNA complexes establish the direct RNA-binding/remodeling activity.
    action: ACCEPT
    reason: Core molecular function with direct structural support; SRP68-RBD binds the SRP RNA three-way junction and remodels the 5f loop.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68)
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:27899666
  qualifier: enables
  review:
    summary: SRP68 binds the SRP72 protein-binding domain (a TPR module) via an extended linear motif in its C-terminus; this domain-specific interaction mediates heterodimer formation.
    action: KEEP_AS_NON_CORE
    reason: Captures the structurally defined SRP68-SRP72 PBD interaction; a genuine and informative interaction, but subsidiary to the core RNA-binding and SRP-targeting functions.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: The SRP72-PBD is a tetratricopeptide repeat, which binds an extended linear motif of SRP68 with high affinity.
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IMP
  original_reference_id: PMID:27899666
  qualifier: contributes_to
  review:
    summary: SRP68/72 contribute to SRP-ribosome contacts; SRP72-RBD remodels the 5f loop involved in ribosome binding, and the SRP68/72 module makes multiple ribosome contacts.
    action: ACCEPT
    reason: Supported; the SRP68/72 heterodimer contributes to the particle's interaction with the translating ribosome during targeting.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: SRP72-RBD remodels the 5f-loop involved in ribosome binding
    - reference_id: PMID:30649417
- term:
    id: GO:0048500
    label: signal recognition particle
  evidence_type: IDA
  original_reference_id: PMID:27899666
  qualifier: part_of
  review:
    summary: SRP68 is a structurally demonstrated component of the signal recognition particle S domain.
    action: ACCEPT
    reason: Core cellular component; directly demonstrated by structures of SRP68 within the SRP S domain.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24965446
  qualifier: enables
  review:
    summary: SRP68 was identified as a component of a pestivirus Npro-associated ribonucleoprotein complex; bare protein binding is uninformative for core SRP function.
    action: KEEP_AS_NON_CORE
    reason: Captures a virus-host interactome observation; bare protein binding is uninformative and peripheral to core SRP function.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Q9UHB9; O76094: SRP72'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: SRP68 was captured in a high-throughput mRNA-interactome (RNA-binding proteome) study; consistent with its 7SL-RNA-binding function.
    action: ACCEPT
    reason: Correct general molecular function; SRP68 is an RNA-binding protein (the more specific 7S RNA binding captures its physiological target).
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: The N-terminus is required for RNA-binding.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1799332
  qualifier: located_in
  review:
    summary: Reactome curation of SRP68 cytosolic localization within the SRP targeting reaction.
    action: ACCEPT
    reason: Correct compartment; redundant with experimental cytosol/cytoplasm annotations.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005047
    label: signal recognition particle binding
  evidence_type: IPI
  original_reference_id: PMID:17254600
  qualifier: enables
  review:
    summary: SRP68 interacts with the SRP RNA/particle during assembly, driving protein-induced conformational changes of the SRP RNA.
    action: ACCEPT
    reason: Core molecular function; SRP68 binding within the particle is supported by assembly/conformational-change studies.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: IDA
  original_reference_id: PMID:18089836
  qualifier: part_of
  review:
    summary: SRP68 was identified as part of the SRP via affinity capture; consistent with its established SRP membership.
    action: ACCEPT
    reason: Correct core cellular component; redundant with stronger structural evidence.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Component of a signal recognition particle (SRP) complex'
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IDA
  original_reference_id: PMID:18089836
  qualifier: involved_in
  review:
    summary: SRP68/SRP72 were pulled out as binding targets of the anticancer drug TAS-103 using drug-immobilized affinity beads; this is an affinity-capture observation, peripheral to SRP68's core SRP function.
    action: KEEP_AS_NON_CORE
    reason: Drug target-screening (affinity capture) observation; does not represent a core biological process of SRP68.
    supported_by:
    - reference_id: file:human/SRP68/SRP68-uniprot.txt
      supporting_text: 'Component of a signal recognition particle (SRP) complex'
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: TAS
  original_reference_id: PMID:10618370
  qualifier: located_in
  review:
    summary: SRP68 localizes to the nucleolus (in addition to cytoplasm and ER), consistent with partial SRP assembly there; not the core site of action.
    action: KEEP_AS_NON_CORE
    reason: Genuine localization reflecting SRP assembly trafficking, not the core cytosolic/ER targeting function.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm
    - reference_id: PMID:38858088
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:10618370
  qualifier: located_in
  review:
    summary: SRP68 accumulates at the ER, consistent with its affinity for the ER-bound SRP receptor.
    action: ACCEPT
    reason: Correct; ER association reflects the targeting endpoint where SRP docks the nascent-chain complex.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: SRP68 also accumulated in the ER, consistent with its affinity for the ER-bound SRP receptor.
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: TAS
  original_reference_id: PMID:10618370
  qualifier: part_of
  review:
    summary: SRP68 is a component of the S domain of the ER-targeting SRP.
    action: ACCEPT
    reason: Correct core cellular component.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: 'The S domain contains unique sequence SRP RNA and four SRP proteins: SRP19, SRP54, SRP68, and SRP72.'
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: TAS
  original_reference_id: PMID:10618370
  qualifier: located_in
  review:
    summary: SRP, via the SRP68/72 module, contacts the translating ribosome; the ribosome localization reflects SRP engagement with ribosome-nascent chain complexes rather than SRP68 being a ribosomal protein.
    action: KEEP_AS_NON_CORE
    reason: SRP68 is not a ribosomal subunit; it transiently associates with ribosomes during targeting. The functional ribosome-contact role is better captured by GO:0043022 ribosome binding.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: SRP interacts with ribosomes to bring translating membrane and secreted proteins to the endoplasmic reticulum
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 based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:10618370
  title: Signal recognition particle components in the nucleolus.
  findings:
  - statement: GFP fusions of SRP19, SRP68 and SRP72 localize to the nucleolus and cytoplasm; SRP68 also accumulates in the ER, consistent with partial SRP assembly in the nucleolus.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Source of the nucleolar/cytoplasmic/ER localization annotations; establishes SRP68 as an S-domain SRP protein trafficking through the nucleolus.
- id: PMID:16672232
  title: 'Protein SRP68 of human signal recognition particle: identification of the
    RNA and SRP72 binding domains.'
  findings:
  - statement: Human SRP68 binds recombinant SRP72 and in vitro-transcribed SRP RNA; the RNA-binding domain spans residues 52-252 and ~94 C-terminal residues mediate SRP72 binding.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the SRP68 RNA-binding (52-252) and SRP72-binding (C-terminal) domains; primary biochemical evidence for SRP68 RNA/SRP72 binding.
- id: PMID:17254600
  title: Protein-induced conformational changes of RNA during the assembly of human
    signal recognition particle.
  findings: []
- id: PMID:18089836
  title: A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one
    dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized
    affinity beads.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Source of the response-to-xenobiotic (TAS-103) and SRP-membership annotations via drug-affinity capture; peripheral to core SRP function.
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:24700861
  title: SRP RNA remodeling by SRP68 explains its role in protein translocation.
  findings:
  - statement: Crystal structures of SRP68-RBD alone and with SRP RNA and SRP19; SRP68-RBD is a TPR-like module that binds the RNA three-way junction, bends the RNA, and opens the conserved 5f loop required for translocation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis of SRP68-driven SRP RNA remodeling; key evidence for the 7S RNA-binding/remodeling core function.
- id: PMID:24965446
  title: Host factors that interact with the pestivirus N-terminal protease, Npro,
    are components of the ribonucleoprotein complex.
  findings: []
- id: PMID:27899666
  title: Structures of human SRP72 complexes provide insights into SRP RNA remodeling
    and ribosome interaction.
  findings:
  - statement: Crystal structures of SRP68-PBD/SRP72-PBD and SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19, SRP68); SRP72-RBD remodels the 5f loop involved in ribosome binding and SRP68/72 make multiple ribosome contacts.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines SRP68/72 RNA remodeling and ribosome interaction; supports 7S RNA binding, domain-specific binding, SRP membership, and ribosome binding.
- id: PMID:28369529
  title: Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis
    of protein translocation.
  findings:
  - statement: Crystal structures of apo-SRP72 and the SRP68/72 complex; the SRP68-binding domain of SRP72 contains four TPR motifs; SRP68/72 heterodimer is essential for protein translocation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis of the SRP68/72 heterodimer; source of ER-localization and SRP72-interaction (F590) annotations.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34208095
  title: 'SRPassing Co-translational Targeting: The Role of the Signal Recognition
    Particle in Protein Targeting and mRNA Protection.'
  findings:
  - statement: Mammalian SRP consists of six proteins and one noncoding RNA; SRP co-translationally targets secretory proteins to the ER and additionally protects their mRNAs.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Authoritative SRP review used by ComplexPortal for the NAS SRP-membership and signal-sequence-recognition annotations.
- id: PMID:35156780
  title: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput
    screening system.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment
    in Multiple SLC Transporters.
  findings: []
- id: Reactome:R-HSA-1799332
  title: Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle
    (SRP)
  findings: []
- id: file:human/SRP68/SRP68-uniprot.txt
  title: UniProt entry Q9UHB9 (SRP68_HUMAN), Signal recognition particle subunit SRP68
  findings:
  - statement: SRP68 is an S-domain SRP subunit that binds the 7SL RNA via its N-terminal RNA-binding domain (52-252) and forms a heterodimer with SRP72; SRP mediates cotranslational targeting of secretory/membrane proteins to the ER. Cytoplasm, nucleolus and ER localizations. Biallelic variants cause SCN10.
    reference_section_type: OTHER
- id: PMID:30649417
  title: Reconstitution of the human SRP system and quantitative and systematic analysis
    of its ribosome interactions.
  findings:
  - statement: Reconstitution of recombinant human SRP shows the SRP68/72 heterodimer binds the 80S ribosome with ultrasensitive (avidity-driven, multi-site) nanomolar affinity dominated by the SRP72 C-terminus, quantifying the SRP68/72 contribution to SRP-ribosome engagement.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:30649417; NAR 2019). Reconstituted human SRP system; provides the quantitative biophysical basis (avidity, two-step SRP54 mechanism, SRP68/72 ultrasensitive ribosome binding) for SRP68's contribution to ribosome binding. Not cached; no verbatim supporting_text added.
- id: PMID:38858088
  title: The nucleolar phase of signal recognition particle assembly.
  findings:
  - statement: Quantitative proteomics shows SRP proteins (including SRP68) associate with scores of nucleolar/ribosome-biogenesis factors; an intact nucleolus is required for proper SRP protein localization, and some SRP proteins are detected in Cajal bodies, defining a nucleolar phase of SRP assembly.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:38858088; Life Sci Alliance 2024). Modern evidence for the nucleolar phase of SRP biogenesis; supports the non-core nucleolus localization (GO:0005730). Not cached; no verbatim supporting_text added.
- id: PMID:32273475
  title: Identification of biallelic germline variants of SRP68 in a sporadic case with
    severe congenital neutropenia.
  findings:
  - statement: Biallelic germline SRP68 loss-of-function variants cause severe congenital neutropenia; patient granulocytic cells show reduced SRP68 protein, impaired granulopoiesis, ER-stress (spliced XBP1) and p53-pathway activation.
    reference_section_type: OTHER
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:32273475; Haematologica 2021). Primary clinical/functional evidence for the SRP68 SCN disease association cited in the description. Abstract not available in PubMed; not cached, so no verbatim supporting_text added.
core_functions:
- description: RNA-binding scaffold subunit of the signal recognition particle that binds and remodels the SRP (7SL) RNA, opening the conserved 5f loop required for cotranslational targeting.
  molecular_function:
    id: GO:0008312
    label: 7S RNA binding
  in_complex:
    id: GO:0048500
    label: signal recognition particle
  supported_by:
  - reference_id: PMID:24700861
    supporting_text: We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19.
  - reference_id: file:human/SRP68/SRP68-uniprot.txt
    supporting_text: Binds the signal recognition particle RNA (7SL RNA)
- description: Component of the SRP S-domain that, in heterodimer with SRP72, mediates SRP-dependent cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum.
  molecular_function:
    id: GO:0005047
    label: signal recognition particle binding
  in_complex:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  supported_by:
  - reference_id: file:human/SRP68/SRP68-uniprot.txt
    supporting_text: 'Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9'
  directly_involved_in:
  - id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
proposed_new_terms: []
suggested_questions:
- question: Beyond cotranslational targeting, does the SRP68/72 module contribute to the recently described mRNA-protection function of SRP, and is SRP68 RNA remodeling required for it?
- question: How do the SCN10-causing biallelic SRP68 variants impair SRP assembly or targeting, and why is the neutrophil lineage particularly sensitive?
suggested_experiments:
- description: Reconstitute SRP with wild-type versus RNA-binding-deficient SRP68 and measure SRP RNA 5f-loop remodeling and cotranslational targeting efficiency to a model secretory substrate in vitro.
- description: Introduce patient SCN10 SRP68 variants into a human myeloid differentiation model and quantify SRP assembly, ER targeting, and granulopoiesis to define the disease mechanism.