id: O76094
gene_symbol: SRP72
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  SRP72 is the largest protein subunit of the mammalian signal recognition
  particle (SRP), a cytosolic ribonucleoprotein composed of a 300-nucleotide 7SL
  RNA and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72). SRP72 forms
  a stable heterodimer with SRP68 and, together, they bind a regulatory region of
  the 7SL RNA to constitute part of the SRP S-domain. SRP72 is an RNA-binding
  scaffolding subunit rather than a GTPase: its N-terminal tetratricopeptide-repeat
  (TPR) region binds an extended linear motif of SRP68, while its C-terminal
  RNA-binding region threads along the 5e/5f loops of the 7SL RNA, remodeling the
  RNA into a state competent for SRP54 binding and modulating ribosome contacts.
  Through these interactions SRP72 contributes to assembly and architecture of SRP
  and to its core biological role, the co-translational targeting of secretory and
  membrane proteins to the endoplasmic reticulum: SRP recognizes the signal
  sequence of nascent chains emerging from the ribosome and delivers the
  ribosome-nascent chain complex to the membrane-anchored SRP receptor, where
  translocation into the ER ensues. SRP72 is broadly expressed, acts in the cytosol
  and at the ER membrane, and heterozygous mutations in the gene cause
  autosomal-dominant bone marrow failure (aplastic anemia/myelodysplasia, BMFS1).
alternative_products:
- name: '1'
  id: O76094-1
- name: '2'
  id: O76094-2
  sequence_note: VSP_045576
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: SRP72 is an SRP subunit and participates in the defining SRP biological process, co-translational targeting of secretory/membrane proteins to the ER membrane. Phylogenetic (IBA) inference is consistent with experimental evidence on the SRP complex.
    action: ACCEPT
    reason: Core biological process of SRP and of SRP72 as one of its subunits; consistent with UniProt FUNCTION and structural studies.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: mediates the cotranslational targeting
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: SRP72 binds the 7SL (7S) RNA, threading along the 5e/5f loops of the SRP RNA; this RNA-binding scaffold activity is a core molecular function. Phylogenetic inference matches experimental IMP evidence (PMID:27899666).
    action: ACCEPT
    reason: Core molecular function; SRP72 directly contacts the 7SL RNA (RNA-binding region 545-617) and binds it in presence of SRP68.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA) in presence of
    - reference_id: PMID:27899666
      supporting_text: flexible peptide crawling along the 5e- and 5f-loops of SRP RNA
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: contributes_to
  review:
    summary: SRP72 (within SRP68/72) makes multiple contacts with the ribosome, and SRP72-mediated remodeling of the 5f-loop affects ribosome binding. The contributes_to qualifier appropriately reflects that ribosome binding is a property of the assembled SRP to which SRP72 contributes.
    action: ACCEPT
    reason: Supported by structural evidence that SRP68/72 contacts the ribosome and that SRP72 remodels the ribosome-binding 5f-loop; contributes_to qualifier is correct for a subunit-level contribution.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: reveals multiple contact sites between SRP68/72 and the ribosome
- 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: SRP72 is a constitutive subunit of the ER-targeting SRP. This is a core cellular component annotation, corroborated by direct (IDA) evidence.
    action: ACCEPT
    reason: SRP72 is part of the SRP complex; phylogenetic assignment agrees with experimental IDA annotations.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'six protein subunits: SRP72, SRP68, SRP54,'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: SRP72 is cytoplasmic, consistent with the cytosolic SRP. Electronic transfer from the UniProt subcellular location, redundant with experimental EXP evidence (PMID:22541560).
    action: ACCEPT
    reason: Correct compartment; SRP operates in the cytosol. The more specific cytosol/SRP terms better localize the function but cytoplasm is accurate.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-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: SRP delivers nascent chains to the ER membrane and SRP72 localizes to the ER; the BMFS1 R207H variant disrupts ER localization. Electronic transfer from UniProt subcellular location, redundant with IDA/EXP evidence.
    action: ACCEPT
    reason: Correct compartment for SRP72 during co-translational targeting; consistent with experimental IDA (PMID:22541560) and EXP (PMID:28369529).
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Endoplasmic reticulum
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Cytosol is a core compartment for the SRP, where it scans translating ribosomes. ARBA machine-learning electronic annotation, consistent with TAS (Reactome) cytosol annotation.
    action: ACCEPT
    reason: Correct and core compartment; SRP is cytosolic. Redundant with Reactome TAS.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-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: InterPro-based electronic assignment of the core SRP-dependent targeting process, consistent with the IBA/experimental evidence.
    action: ACCEPT
    reason: Correct core biological process; redundant with IBA annotation.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: mediates the cotranslational targeting
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic assignment of 7S RNA binding (the SRP72 RNA-binding domain, IPR013699), consistent with the experimental IMP evidence.
    action: ACCEPT
    reason: Correct core molecular function; redundant with IMP/IBA.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA) in presence of
- term:
    id: GO:0048500
    label: signal recognition particle
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: InterPro-based electronic assignment to the SRP complex, consistent with the experimental IDA annotation (PMID:27899666).
    action: ACCEPT
    reason: Correct core cellular component; SRP72 is a defining SRP subunit.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'six protein subunits: SRP72, SRP68, SRP54,'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16672232
  qualifier: enables
  review:
    summary: IntAct capture of the physiological SRP72-SRP68 heterodimer interaction. The bare protein binding term is uninformative; the informative version is captured by signal recognition particle binding (GO:0005047) and the SUBUNIT description.
    action: KEEP_AS_NON_CORE
    reason: Records the real SRP68-SRP72 heterodimer interaction, but bare protein binding is uninformative per curation guidelines; the heterodimer scaffolding role is captured by more specific terms.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Heterodimer with SRP68
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: High-throughput binary interactome (HuRI) capture; the recorded partner is SULT2B1 (O00204). Bare protein binding is uninformative and the partner does not reflect SRP72's core SRP function.
    action: KEEP_AS_NON_CORE
    reason: Real high-throughput interaction record, but bare protein binding is uninformative and not elevated to core per guidelines.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'O76094; O00204: SULT2B1'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: High-throughput affinity-purification interactome (BioPlex) capturing the SRP72-SRP68 (Q9UHB9) interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Captures the SRP68 partner via high-throughput screen, but bare protein binding is uninformative; the heterodimer is better described by specific terms.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Heterodimer with SRP68
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome capturing the SRP72-SRP68 (Q9UHB9) interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real interactome capture of the SRP68 partner, but bare protein binding is uninformative; not core per guidelines.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Heterodimer with SRP68
- 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 (ComplexPortal NAS) assertion of SRP72 as a component of the ER-targeting SRP, consistent with experimental IDA evidence.
    action: ACCEPT
    reason: Correct core cellular component; consistent with the SRP review and IDA annotations.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'six protein subunits: SRP72, SRP68, SRP54,'
- 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: ComplexPortal NAS annotation for the signal-sequence-recognition step of SRP-dependent targeting. SRP recognizes the signal sequence of nascent chains; SRP72 participates as a complex subunit, though signal-sequence binding itself is performed by SRP54.
    action: KEEP_AS_NON_CORE
    reason: Accurate at the complex level (SRP recognizes signal sequences) but the actual signal-sequence recognition is mediated by SRP54, not SRP72; kept as a non-core process-level annotation for SRP72.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:22541560
  qualifier: located_in
  review:
    summary: Experimental (EXP) cytoplasmic localization from the BMFS1 disease study, which examined SRP72 localization in transfected cells. Consistent with the cytosolic SRP.
    action: ACCEPT
    reason: Correct compartment; experimentally supported localization consistent with SRP biology.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: EXP
  original_reference_id: PMID:28369529
  qualifier: located_in
  review:
    summary: Experimental ER localization from the SRP68/72 structural study, which showed cancer-associated mutations disrupt co-localization with the ER. Consistent with SRP's site of action.
    action: ACCEPT
    reason: Correct compartment for SRP72 during co-translational targeting; experimentally supported.
    supported_by:
    - reference_id: PMID:28369529
      supporting_text: disrupt the SRP68-SRP72 interaction and their co-localization with ER in
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IMP
  original_reference_id: PMID:27899666
  qualifier: enables
  review:
    summary: Direct experimental (IMP) evidence that SRP72 binds the 7SL RNA; the SRP72-RBD crawls along the 5e/5f loops and a conserved tryptophan forms an RNA kink-turn. This is a core molecular function.
    action: ACCEPT
    reason: Core molecular function with direct experimental and structural support (PDB 5M73; RNA-binding mutagenesis).
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: flexible peptide crawling along the 5e- and 5f-loops of SRP RNA
- term:
    id: GO:0030911
    label: TPR domain binding
  evidence_type: IPI
  original_reference_id: PMID:27899666
  qualifier: enables
  review:
    summary: The SRP72 protein-binding domain is a TPR that binds an extended linear motif of SRP68 with high affinity. The annotation records that SRP72's TPR mediates the SRP68 interaction; the WITH/FROM partner is SRP68 (Q9UHB9).
    action: KEEP_AS_NON_CORE
    reason: Mechanistically accurate (SRP72 TPR-PBD binds SRP68), but this is the structural means by which the SRP68-SRP72 heterodimer forms; the heterodimer/scaffold role is better captured by signal recognition particle binding and complex membership.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: The SRP72-PBD is a tetratricopeptide repeat, which binds an
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IMP
  original_reference_id: PMID:27899666
  qualifier: contributes_to
  review:
    summary: SRP72 remodels the 5f-loop of the 7SL RNA involved in ribosome binding, and SRP68/72 makes multiple contacts with the ribosome. The contributes_to qualifier reflects SRP72's subunit-level contribution to SRP-ribosome interaction.
    action: ACCEPT
    reason: Supported by structural/functional evidence; contributes_to is the appropriate qualifier for a subunit contributing to a complex-level binding activity.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: SRP72-RBD remodels the 5f-loop involved in ribosome binding
- term:
    id: GO:0048500
    label: signal recognition particle
  evidence_type: IDA
  original_reference_id: PMID:27899666
  qualifier: part_of
  review:
    summary: Direct experimental demonstration that SRP72 is part of the SRP S-domain (crystal structures of SRP72 bound to SRP RNA, SRP19 and SRP68). Core cellular component.
    action: ACCEPT
    reason: Core cellular component; SRP72 is a defining SRP subunit, directly demonstrated structurally.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: 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: SRP72 co-purified with the pestivirus N-terminal protease (Npro) in an interactome of ribosomal/ribonucleoprotein components. Bare protein binding is uninformative and the viral partner does not reflect SRP72's core function.
    action: KEEP_AS_NON_CORE
    reason: Records a real (host-virus) interaction capture, but bare protein binding is uninformative and the partner is unrelated to SRP72's core SRP role.
    supported_by:
    - reference_id: PMID:24965446
      supporting_text: components of the ribonucleoprotein complex
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: High-throughput mRNA-interactome capture (HeLa) identifying SRP72 as an RNA-binding protein. Consistent with SRP72's bona fide RNA-binding activity, though this assay reports general mRNA crosslinking rather than the specific 7SL RNA interaction.
    action: ACCEPT
    reason: SRP72 is a genuine RNA-binding protein; the general term is correct, with the more specific 7S RNA binding (GO:0008312) capturing the core physiological function.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA) in presence of
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: Second high-throughput mRNA-bound proteome study identifying SRP72 as RNA-binding. Consistent with its RNA-binding scaffold role in SRP.
    action: ACCEPT
    reason: Correct general molecular function; the specific 7S RNA binding term better captures the core function.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: Binds the signal recognition particle RNA (7SL RNA) in presence of
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1799332
  qualifier: located_in
  review:
    summary: Reactome curation of SRP72 cytosolic localization within the SRP-targeting reaction. Core compartment.
    action: ACCEPT
    reason: Correct and core compartment; SRP scans translating ribosomes in the cytosol.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:22541560
  qualifier: located_in
  review:
    summary: Direct (IDA) ER localization of SRP72 from the BMFS1 study; the disease-associated R207H variant affects protein localization to the ER. Consistent with SRP's ER-targeting role.
    action: ACCEPT
    reason: Correct compartment; experimentally supported and mechanistically relevant (variant disrupts ER localization).
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: affects protein localization to
- term:
    id: GO:0005047
    label: signal recognition particle binding
  evidence_type: IPI
  original_reference_id: PMID:17254600
  qualifier: enables
  review:
    summary: SRP72 (with SRP68) binds the assembling SRP and the 7SL RNA, rearranging it into an SRP54-binding-competent state. This is the informative molecular function capturing SRP72's association with the particle.
    action: ACCEPT
    reason: Informative molecular function for SRP72's role in SRP assembly/binding; supported by the RNA conformational-change assembly study and the heterodimer/RNA interactions.
    supported_by:
    - reference_id: PMID:17254600
      supporting_text: SRP68/72, together with SRP19, rearranges the 7SL RNA in an SRP54 binding
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: IDA
  original_reference_id: PMID:18089836
  qualifier: part_of
  review:
    summary: SRP72 annotated as part of the ER-targeting SRP based on a study identifying SRP as the cellular target of TAS-103. The abstract foregrounds SRP54, but the work assays the intact SRP complex of which SRP72 is a subunit; the CC localization is accurate.
    action: ACCEPT
    reason: SRP72 is a constitutive SRP subunit; the SRP complex localization is correct. Per guidelines, an experimental annotation is not removed because the abstract emphasizes another subunit.
    supported_by:
    - reference_id: file:human/SRP72/SRP72-uniprot.txt
      supporting_text: 'six protein subunits: SRP72, SRP68, SRP54,'
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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:16672232
  title: 'Protein SRP68 of human signal recognition particle: identification of the RNA and SRP72 binding domains.'
  findings:
  - statement: SRP68 and SRP72 form a heterodimer; ~150 N-terminal residues of SRP72, within a predicted tandem array of four TPR-like motifs, mediate binding to SRP68.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; defines the SRP72 N-terminal TPR region as the SRP68-binding domain. Source of the SRP68 IPI protein-binding annotation.
- id: PMID:17254600
  title: Protein-induced conformational changes of RNA during the assembly of human signal recognition particle.
  findings:
  - statement: SRP68/72, together with SRP19, rearranges the 7SL RNA into an SRP54-binding-competent state, demonstrating SRP72's role in SRP assembly.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; supports the signal recognition particle binding (GO:0005047) annotation and SRP72's RNA-remodeling/assembly function.
- 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:
  - statement: Identifies the signal recognition particle (SRP) as the cellular target of TAS-103; primarily characterizes SRP54 but assays the intact SRP complex.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Abstract foregrounds SRP54; cited in GOA only for the SRP (ER targeting) CC of SRP72 as an SRP subunit. Not removed for subunit-naming reasons per guidelines.
- id: PMID:22541560
  title: Exome sequencing identifies autosomal-dominant SRP72 mutations associated with familial aplasia and myelodysplasia.
  findings:
  - statement: Heterozygous SRP72 mutations cause autosomal-dominant aplastic anemia/myelodysplasia (BMFS1); variants mislocalize the protein and the R207H variant affects ER localization.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified disease study; source of the EXP cytoplasm and IDA ER localization annotations and the BMFS1 disease association.
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings:
  - statement: Interactome-capture identifies SRP72 among HeLa mRNA-binding proteins, supporting general RNA-binding activity.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-throughput RBP atlas; supports the HDA RNA binding annotation but does not distinguish 7SL RNA binding.
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
  findings:
  - statement: Genome-wide mRNA-interactome study identifying SRP72 as an RNA-binding protein.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-throughput RBP study; corroborates the HDA RNA binding annotation.
- id: PMID:24965446
  title: Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.
  findings:
  - statement: SRP72 co-purifies with the pestivirus Npro protease among ribosomal/ribonucleoprotein components.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Host-virus interactome; source of a bare protein binding IPI (partner is the viral Npro protease). Not core to SRP72 function.
- id: PMID:27899666
  title: Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction.
  findings:
  - statement: The SRP72-PBD is a TPR that binds an extended linear SRP68 motif with high affinity; the SRP72-RBD is a flexible peptide crawling along the 5e/5f loops of SRP RNA, forming an RNA kink-turn and remodeling the ribosome-binding 5f-loop.
    reference_section_type: ABSTRACT
  - statement: Docking into cryo-EM density reveals multiple contact sites between SRP68/72 and the ribosome, explaining SRP72's role in the SRP pathway.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive structural study of SRP72; basis for the 7S RNA binding (IMP), TPR domain binding (IPI), ribosome binding (IMP) and SRP membership (IDA) annotations.
- id: PMID:28369529
  title: Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation.
  findings:
  - statement: Crystal structures of human apo-SRP72 and the SRP68/72 complex; the SRP68-binding domain of SRP72 contains four atypical TPRs and a flexible C-terminal cap, and cancer-associated mutations disrupt the SRP68-SRP72 interaction and ER co-localization.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified structural study; supports the SRP68 interaction region and the EXP ER localization annotation.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: HuRI high-throughput binary interactome; source of a bare protein binding IPI (partner SULT2B1). Not core.
- 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 AP-MS interactome; source of a bare protein binding IPI (partner SRP68). Not core.
- id: PMID:34208095
  title: 'SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection.'
  findings:
  - statement: Review of SRP function in co-translational protein targeting and signal-sequence recognition; basis for the ComplexPortal NAS annotations.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: SRP review used by ComplexPortal for NAS annotations of SRP membership and signal-sequence recognition.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: OpenCell endogenous-tagging interactome; source of a bare protein binding IPI (partner SRP68). Not core.
- id: Reactome:R-HSA-1799332
  title: Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)
  findings: []
- id: file:human/SRP72/SRP72-uniprot.txt
  title: UniProt entry O76094 (SRP72_HUMAN), Signal recognition particle subunit SRP72
  findings:
  - statement: SRP72 is the largest subunit of the SRP (7SL RNA + SRP9/14/19/54/68/72); forms a heterodimer with SRP68; binds 7SL RNA in presence of SRP68; cytoplasmic and ER-localized; heterozygous mutations cause BMFS1.
    reference_section_type: OTHER
- id: PMID:38858088
  title: The nucleolar phase of signal recognition particle assembly.
  findings:
  - statement: GFP-SRP72 co-immunoprecipitates other SRP subunits (RNase-sensitive S-domain/Alu-domain contacts) and localizes to the nucleolus (periphery of the dense fibrillar component) and to Cajal bodies; five SRP proteins including SRP72 assemble with 7SL RNA in the nucleolus before SRP54 joins in the cytoplasm.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:38858088; Life Sci Alliance 2024). Primary data localizing SRP72 to the nucleolus (PDFC) and Cajal bodies and defining a nucleolar phase of SRP assembly; new localization/biogenesis evidence not previously in the review. Not cached; no verbatim supporting_text added.
- id: PMID:30670445
  title: 'Genetic predisposition to MDS: clinical features and clonal evolution.'
  findings:
  - statement: Review summarizing germline predisposition syndromes to MDS/bone marrow failure, including heterozygous SRP72 mutations described in two autosomal-dominant families with aplastic anemia/myelodysplasia.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:30670445; Blood 2019). Expert review reinforcing SRP72 as a germline MDS/bone-marrow-failure (BMFS1) predisposition gene. Not cached; no verbatim supporting_text added.
- id: PMID:39621795
  title: Flaviviruses induce ER-specific remodelling of protein synthesis.
  findings:
  - statement: Zika virus bypasses the SRP receptor via interactions between viral non-structural proteins and the host translational machinery, with NS3 engaging SRP54 and the translocon; SRP72 is implicated in the SRP machinery engaged during ER-translation remodeling.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:39621795; PLoS Pathog 2024). Host-pathogen context in which SRP machinery (including SRP72) is co-opted; peripheral to SRP72 core function. Not cached; no verbatim supporting_text added.
- id: PMID:39952919
  title: 7SL RNA and signal recognition particle orchestrate a global cellular response
    to acute thermal stress.
  findings:
  - statement: Under acute heat shock, 7SL RNA and SRP (independent of signal peptides) selectively arrest transcription and translation; SRP binds ribosomes and inhibits new protein synthesis, revealing an SRP function in the acute thermal-stress response beyond protein secretion.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:39952919; Nat Commun 2025). Describes a non-canonical 7SL/SRP role in acute thermal stress; SRP72-specific mechanistic contribution not established. Not cached; no verbatim supporting_text added.
core_functions:
- description: RNA-binding scaffold subunit of the signal recognition particle that binds the 7SL (7S) RNA, threading along its 5e/5f loops to remodel the RNA and modulate ribosome contacts.
  molecular_function:
    id: GO:0008312
    label: 7S RNA binding
  in_complex:
    id: GO:0048500
    label: signal recognition particle
  supported_by:
  - reference_id: PMID:27899666
    supporting_text: flexible peptide crawling along the 5e- and 5f-loops of SRP RNA
  - reference_id: file:human/SRP72/SRP72-uniprot.txt
    supporting_text: Binds the signal recognition particle RNA (7SL RNA) in presence of
- description: Structural subunit of the SRP that forms a heterodimer with SRP68 (via its N-terminal TPR region) and binds/assembles into the signal recognition particle, contributing to its architecture and ribosome interaction.
  molecular_function:
    id: GO:0005047
    label: signal recognition particle binding
  in_complex:
    id: GO:0048500
    label: signal recognition particle
  supported_by:
  - reference_id: file:human/SRP72/SRP72-uniprot.txt
    supporting_text: Heterodimer with SRP68
  - reference_id: PMID:17254600
    supporting_text: SRP68/72, together with SRP19, rearranges the 7SL RNA in an SRP54 binding
- description: As an integral SRP subunit, participates in SRP-dependent co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum membrane.
  molecular_function:
    id: GO:0008312
    label: 7S RNA binding
  in_complex:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  supported_by:
  - reference_id: file:human/SRP72/SRP72-uniprot.txt
    supporting_text: mediates the cotranslational targeting
  directly_involved_in:
  - id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
proposed_new_terms: []
suggested_questions:
- question: Beyond its structural/RNA-binding role in SRP, does SRP72 have any SRP-independent function that explains the hematopoietic specificity of BMFS1 (bone marrow failure)?
- question: How do the BMFS1 SRP72 variants (e.g. R207H) mechanistically impair SRP assembly or ER targeting, and why is the phenotype dominant rather than recessive?
suggested_experiments:
- description: Reconstitute SRP assembly in vitro with purified SRP68, wild-type vs BMFS1-variant SRP72 and 7SL RNA to quantify effects on heterodimer formation, RNA binding, and SRP54-binding competence.
- description: Use a cell model (e.g. CRISPR knock-in of R207H) with proximity labeling and ribosome profiling to test whether the variant alters co-translational ER targeting efficiency and the secretome, particularly in hematopoietic lineages.