SRP72

UniProt ID: O76094
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006614 SRP-dependent cotranslational protein targeting to membrane
IBA
GO_REF:0000033 		ACCEPT
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.
Reason: Core biological process of SRP and of SRP72 as one of its subunits; consistent with UniProt FUNCTION and structural studies.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
mediates the cotranslational targeting
GO:0008312 7S RNA binding
IBA
GO_REF:0000033 		ACCEPT
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).
Reason: Core molecular function; SRP72 directly contacts the 7SL RNA (RNA-binding region 545-617) and binds it in presence of SRP68.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Binds the signal recognition particle RNA (7SL RNA) in presence of
PMID:27899666
flexible peptide crawling along the 5e- and 5f-loops of SRP RNA
GO:0043022 ribosome binding
IBA
GO_REF:0000033 		ACCEPT
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.
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.
Supporting Evidence:
PMID:27899666
reveals multiple contact sites between SRP68/72 and the ribosome
GO:0005786 signal recognition particle, endoplasmic reticulum targeting
IBA
GO_REF:0000033 		ACCEPT
Summary: SRP72 is a constitutive subunit of the ER-targeting SRP. This is a core cellular component annotation, corroborated by direct (IDA) evidence.
Reason: SRP72 is part of the SRP complex; phylogenetic assignment agrees with experimental IDA annotations.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
six protein subunits: SRP72, SRP68, SRP54,
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: SRP72 is cytoplasmic, consistent with the cytosolic SRP. Electronic transfer from the UniProt subcellular location, redundant with experimental EXP evidence (PMID:22541560).
Reason: Correct compartment; SRP operates in the cytosol. The more specific cytosol/SRP terms better localize the function but cytoplasm is accurate.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000044 		ACCEPT
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.
Reason: Correct compartment for SRP72 during co-translational targeting; consistent with experimental IDA (PMID:22541560) and EXP (PMID:28369529).
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Endoplasmic reticulum
GO:0005829 cytosol
IEA
GO_REF:0000117 		ACCEPT
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.
Reason: Correct and core compartment; SRP is cytosolic. Redundant with Reactome TAS.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0006614 SRP-dependent cotranslational protein targeting to membrane
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based electronic assignment of the core SRP-dependent targeting process, consistent with the IBA/experimental evidence.
Reason: Correct core biological process; redundant with IBA annotation.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
mediates the cotranslational targeting
GO:0008312 7S RNA binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based electronic assignment of 7S RNA binding (the SRP72 RNA-binding domain, IPR013699), consistent with the experimental IMP evidence.
Reason: Correct core molecular function; redundant with IMP/IBA.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Binds the signal recognition particle RNA (7SL RNA) in presence of
GO:0048500 signal recognition particle
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based electronic assignment to the SRP complex, consistent with the experimental IDA annotation (PMID:27899666).
Reason: Correct core cellular component; SRP72 is a defining SRP subunit.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
six protein subunits: SRP72, SRP68, SRP54,
GO:0005515 protein binding
IPI
PMID:16672232
Protein SRP68 of human signal recognition particle: identifi... 		KEEP AS NON CORE
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.
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.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Heterodimer with SRP68
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
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.
Reason: Real high-throughput interaction record, but bare protein binding is uninformative and not elevated to core per guidelines.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
O76094; O00204: SULT2B1
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		KEEP AS NON CORE
Summary: High-throughput affinity-purification interactome (BioPlex) capturing the SRP72-SRP68 (Q9UHB9) interaction. Bare protein binding is uninformative.
Reason: Captures the SRP68 partner via high-throughput screen, but bare protein binding is uninformative; the heterodimer is better described by specific terms.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Heterodimer with SRP68
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		KEEP AS NON CORE
Summary: OpenCell endogenous-tagging interactome capturing the SRP72-SRP68 (Q9UHB9) interaction. Bare protein binding is uninformative.
Reason: Real interactome capture of the SRP68 partner, but bare protein binding is uninformative; not core per guidelines.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Heterodimer with SRP68
GO:0005786 signal recognition particle, endoplasmic reticulum targeting
NAS
PMID:34208095
SRPassing Co-translational Targeting: The Role of the Signal... 		ACCEPT
Summary: Review-based (ComplexPortal NAS) assertion of SRP72 as a component of the ER-targeting SRP, consistent with experimental IDA evidence.
Reason: Correct core cellular component; consistent with the SRP review and IDA annotations.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
six protein subunits: SRP72, SRP68, SRP54,
GO:0006617 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
NAS
PMID:34208095
SRPassing Co-translational Targeting: The Role of the Signal... 		KEEP AS NON CORE
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.
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.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins
GO:0005737 cytoplasm
EXP
PMID:22541560
Exome sequencing identifies autosomal-dominant SRP72 mutatio... 		ACCEPT
Summary: Experimental (EXP) cytoplasmic localization from the BMFS1 disease study, which examined SRP72 localization in transfected cells. Consistent with the cytosolic SRP.
Reason: Correct compartment; experimentally supported localization consistent with SRP biology.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005783 endoplasmic reticulum
EXP
PMID:28369529
Human apo-SRP72 and SRP68/72 complex structures reveal the m... 		ACCEPT
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.
Reason: Correct compartment for SRP72 during co-translational targeting; experimentally supported.
Supporting Evidence:
PMID:28369529
disrupt the SRP68-SRP72 interaction and their co-localization with ER in
GO:0008312 7S RNA binding
IMP
PMID:27899666
Structures of human SRP72 complexes provide insights into SR... 		ACCEPT
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.
Reason: Core molecular function with direct experimental and structural support (PDB 5M73; RNA-binding mutagenesis).
Supporting Evidence:
PMID:27899666
flexible peptide crawling along the 5e- and 5f-loops of SRP RNA
GO:0030911 TPR domain binding
IPI
PMID:27899666
Structures of human SRP72 complexes provide insights into SR... 		KEEP AS NON CORE
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).
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.
Supporting Evidence:
PMID:27899666
The SRP72-PBD is a tetratricopeptide repeat, which binds an
GO:0043022 ribosome binding
IMP
PMID:27899666
Structures of human SRP72 complexes provide insights into SR... 		ACCEPT
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.
Reason: Supported by structural/functional evidence; contributes_to is the appropriate qualifier for a subunit contributing to a complex-level binding activity.
Supporting Evidence:
PMID:27899666
SRP72-RBD remodels the 5f-loop involved in ribosome binding
GO:0048500 signal recognition particle
IDA
PMID:27899666
Structures of human SRP72 complexes provide insights into SR... 		ACCEPT
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.
Reason: Core cellular component; SRP72 is a defining SRP subunit, directly demonstrated structurally.
Supporting Evidence:
PMID:27899666
SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68)
GO:0005515 protein binding
IPI
PMID:24965446
Host factors that interact with the pestivirus N-terminal pr... 		KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:24965446
components of the ribonucleoprotein complex
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi... 		ACCEPT
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.
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.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Binds the signal recognition particle RNA (7SL RNA) in presence of
GO:0003723 RNA binding
HDA
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on ... 		ACCEPT
Summary: Second high-throughput mRNA-bound proteome study identifying SRP72 as RNA-binding. Consistent with its RNA-binding scaffold role in SRP.
Reason: Correct general molecular function; the specific 7S RNA binding term better captures the core function.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
Binds the signal recognition particle RNA (7SL RNA) in presence of
GO:0005829 cytosol
TAS
Reactome:R-HSA-1799332 		ACCEPT
Summary: Reactome curation of SRP72 cytosolic localization within the SRP-targeting reaction. Core compartment.
Reason: Correct and core compartment; SRP scans translating ribosomes in the cytosol.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005783 endoplasmic reticulum
IDA
PMID:22541560
Exome sequencing identifies autosomal-dominant SRP72 mutatio... 		ACCEPT
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.
Reason: Correct compartment; experimentally supported and mechanistically relevant (variant disrupts ER localization).
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
affects protein localization to
GO:0005047 signal recognition particle binding
IPI
PMID:17254600
Protein-induced conformational changes of RNA during the ass... 		ACCEPT
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.
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.
Supporting Evidence:
PMID:17254600
SRP68/72, together with SRP19, rearranges the 7SL RNA in an SRP54 binding
GO:0005786 signal recognition particle, endoplasmic reticulum targeting
IDA
PMID:18089836
A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydro... 		ACCEPT
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.
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.
Supporting Evidence:
file:human/SRP72/SRP72-uniprot.txt
six protein subunits: SRP72, SRP68, SRP54,

Core Functions

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:
7S RNA binding
In Complex:
signal recognition particle
Supporting Evidence:
  • PMID:27899666
    flexible peptide crawling along the 5e- and 5f-loops of SRP RNA
  • file:human/SRP72/SRP72-uniprot.txt
    Binds the signal recognition particle RNA (7SL RNA) in presence of

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:
signal recognition particle binding
In Complex:
signal recognition particle
Supporting Evidence:
  • file:human/SRP72/SRP72-uniprot.txt
    Heterodimer with SRP68
  • PMID:17254600
    SRP68/72, together with SRP19, rearranges the 7SL RNA in an SRP54 binding

As an integral SRP subunit, participates in SRP-dependent co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum membrane.

Molecular Function:
7S RNA binding
Directly Involved In:
SRP-dependent cotranslational protein targeting to membrane
In Complex:
signal recognition particle, endoplasmic reticulum targeting
Supporting Evidence:
  • file:human/SRP72/SRP72-uniprot.txt
    mediates the cotranslational targeting

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
PMID:16672232
Protein SRP68 of human signal recognition particle: identification of the RNA and SRP72 binding domains.
  • 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.
PMID:17254600
Protein-induced conformational changes of RNA during the assembly of human signal recognition particle.
  • SRP68/72, together with SRP19, rearranges the 7SL RNA into an SRP54-binding-competent state, demonstrating SRP72's role in SRP assembly.
PMID:18089836
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.
  • Identifies the signal recognition particle (SRP) as the cellular target of TAS-103; primarily characterizes SRP54 but assays the intact SRP complex.
PMID:22541560
Exome sequencing identifies autosomal-dominant SRP72 mutations associated with familial aplasia and myelodysplasia.
  • Heterozygous SRP72 mutations cause autosomal-dominant aplastic anemia/myelodysplasia (BMFS1); variants mislocalize the protein and the R207H variant affects ER localization.
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  • Interactome-capture identifies SRP72 among HeLa mRNA-binding proteins, supporting general RNA-binding activity.
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
  • Genome-wide mRNA-interactome study identifying SRP72 as an RNA-binding protein.
PMID:24965446
Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.
  • SRP72 co-purifies with the pestivirus Npro protease among ribosomal/ribonucleoprotein components.
PMID:27899666
Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction.
  • 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.
  • Docking into cryo-EM density reveals multiple contact sites between SRP68/72 and the ribosome, explaining SRP72's role in the SRP pathway.
PMID:28369529
Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation.
  • 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.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:34208095
SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection.
  • Review of SRP function in co-translational protein targeting and signal-sequence recognition; basis for the ComplexPortal NAS annotations.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Reactome:R-HSA-1799332
Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)
file:human/SRP72/SRP72-uniprot.txt
UniProt entry O76094 (SRP72_HUMAN), Signal recognition particle subunit SRP72
  • 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.
PMID:38858088
The nucleolar phase of signal recognition particle assembly.
  • 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.
PMID:30670445
Genetic predisposition to MDS: clinical features and clonal evolution.
  • Review summarizing germline predisposition syndromes to MDS/bone marrow failure, including heterozygous SRP72 mutations described in two autosomal-dominant families with aplastic anemia/myelodysplasia.
PMID:39621795
Flaviviruses induce ER-specific remodelling of protein synthesis.
  • 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.
PMID:39952919
7SL RNA and signal recognition particle orchestrate a global cellular response to acute thermal stress.
  • 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.

Suggested Questions for Experts

Q: 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)?

Q: 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

Experiment: 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.

Experiment: 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.

Deep Research

Falcon

(SRP72-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 31 citations 2 artifacts 2026-06-12T02:41:54.919831
Edison artifact artifact-00 (text/markdown)
## Context ID: pqac-00000018 As requested, Figure 1 (a schematic of mammalian SRP assembly) and relevant panels showing GFP-SRP72 localization to the nucleolus (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Human SRP72 (UniProt O76094) — Functional Annotation

0) Gene/protein verification (mandatory)

The target is human SRP72 (gene symbol SRP72), the signal recognition particle subunit SRP72 (≈72 kDa) that is a canonical SRP protein subunit in mammals (issa2024thenucleolarphase pages 1-2). In mammalian cells, SRP comprises 7SL RNA plus six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72), and SRP68 and SRP72 form a heterodimer (issa2024thenucleolarphase pages 1-2). This matches the provided UniProt context (SRP72 family; RNA-binding and TPR-like features) and the organism is explicitly mammalian/human in the core sources used (issa2024thenucleolarphase pages 1-2, kirwan2012exomesequencingidentifies pages 3-5).

1) Key concepts and definitions (current understanding)

1.1 Signal recognition particle (SRP) pathway (co-translational ER targeting)

The SRP pathway is the principal and best-characterized route for co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (issa2024thenucleolarphase pages 1-2). SRP binds ribosomes translating nascent chains bearing ER-targeting sequences (signal peptides or transmembrane segments), transiently arrests elongation, targets the ribosome–nascent chain complex to the SRP receptor (SR) at the ER membrane, and transfers the nascent chain to the Sec61 translocon, after which translation resumes (issa2024thenucleolarphase pages 1-2, karamysheva2023aberrantproteintargeting pages 1-2).

A widely cited 2023 synthesis emphasizes that SRP-dependent targeting failures can trigger quality control (notably RAPP, Regulation of Aberrant Protein Production) that selectively degrades mRNAs encoding proteins whose signal peptide–SRP interactions are disrupted (karamysheva2023aberrantproteintargeting pages 1-2, guarnizo2023pathogenicsignalpeptide pages 1-2).

1.2 Where SRP72 fits in SRP architecture

SRP is organized around 7SL RNA with two functional regions:
- Alu domain (bound by SRP9/14; linked to elongation arrest)
- S-domain (bound by SRP19, SRP54, and the SRP68/72 heterodimer, which is described as helping “control translocation”) (kellogg2023unravelingsrpbiogenesis pages 147-153, gussakovsky2024theroleof pages 1-2).

SRP72’s role is therefore best understood as structural/organizational and targeting-supportive within the SRP ribonucleoprotein rather than as an enzyme with a catalytic reaction. Recent mechanistic summaries attribute SRP68/72 positioning to the 7SL S-domain and assign SRP68/72 contributions to translocation control and SRP architecture (kellogg2023unravelingsrpbiogenesis pages 26-29, gussakovsky2024theroleof pages 1-2).

2) SRP72 molecular function, interactions, and localization

2.1 Core molecular function: enabling SRP-mediated ER targeting

In mammalian SRP, SRP72 functions as part of the SRP machinery that mediates co-translational targeting to the ER and subsequent handoff to the SR receptor and Sec61 translocon (issa2024thenucleolarphase pages 1-2, kellogg2023unravelingsrpbiogenesis pages 23-26). A 2023 mechanistic overview reiterates that SRP recognizes emerging signal peptides/transmembrane segments (via SRP54), arrests elongation, docks at the ER SR, and transfers to the translocon (karamysheva2023aberrantproteintargeting pages 1-2). In these models, SRP72’s primary function is through its membership in the SRP S-domain and heterodimerization with SRP68, supporting SRP assembly and productive targeting (kellogg2023unravelingsrpbiogenesis pages 23-26, kellogg2023unravelingsrpbiogenesis pages 26-29).

2.2 Key interactions (SRP68, 7SL RNA, and SRP complex integrity)

Experimental evidence for SRP72 as a bona fide SRP component comes from inducible GFP-tagging and immunoprecipitation:
- GFP-SRP72 efficiently co-immunoprecipitates other SRP subunits, consistent with incorporation into mature SRP particles (issa2024thenucleolarphase pages 2-3).
- RNase treatment disrupts many inter-subunit associations between Alu-domain proteins and S-domain proteins (including SRP72), consistent with 7SL RNA-mediated complex architecture (issa2024thenucleolarphase pages 2-3).

A disease-genetics/mechanism study further supports direct SRP72–7SL functional coupling:
- A truncating SRP72 frameshift variant (p.Thr355Lysfs19) was reported to show ~15% of wild-type 7SL RNA co-precipitation*, indicating substantially impaired association with 7SL RNA (kirwan2012exomesequencingidentifies pages 3-5).

2.3 Subcellular localization and SRP72 biogenesis: cytoplasm, nucleolus, and Cajal bodies

Although SRP executes its targeting function in the cytoplasm at translating ribosomes (issa2024thenucleolarphase pages 1-2), SRP biogenesis includes a nuclear/nucleolar phase:
- An SRP assembly model indicates that five of the six SRP proteins (including SRP72) assemble with 7SL RNA in the nucleolus, while SRP54 joins after export to the cytoplasm (issa2024thenucleolarphase pages 2-3, issa2024thenucleolarphase pages 1-2).
- GFP-SRP72 localizes to nucleoli, especially the periphery of the dense fibrillar component (PDFC), and it also localizes to Cajal bodies (CBs) (issa2024thenucleolarphase pages 3-5, issa2024thenucleolarphase media d31564f7).
- Quantitatively, analysis of 45 U2OS cells expressing GFP-SRP72 found SRP72 present in ~50% of analyzed Cajal bodies (issa2024thenucleolarphase pages 2-3).

Proteomic evidence from 2024 further indicates SRP72’s nucleolar connectivity:
- SRP interactome mapping identified ~239 new associations overall and 95 new nucleolar/ribosome-biogenesis proteins interacting with SRP components, bringing nucleolar/ribosome biogenesis SRP interactors to 173 (issa2024thenucleolarphase pages 9-10). These findings support the view that SRP72 (as part of SRP) participates in a biogenesis environment intertwined with nucleolar structure and ribosome assembly (issa2024thenucleolarphase pages 9-10).

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2024: Nucleolar phase of SRP assembly and SRP72 localization (primary data)

A 2024 Life Science Alliance study systematically tested SRP component localization and interactomes and concluded that an intact nucleolus is required for proper SRP protein localization and that SRP72 has a nucleolar/CB phase (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 3-5). This represents a recent consolidation and expansion of SRP biogenesis concepts, providing experimental support for a nucleolar step in SRP72-containing SRP assembly (issa2024thenucleolarphase pages 2-3, issa2024thenucleolarphase media d31564f7).

Two 2023 sources emphasize that ER targeting is tightly coupled to mRNA/protein quality control: when SRP recognition fails (e.g., due to signal peptide defects), RAPP can degrade the corresponding mRNAs (karamysheva2023aberrantproteintargeting pages 1-2, guarnizo2023pathogenicsignalpeptide pages 1-2). While these papers focus heavily on signal peptides and SRP54 function, they contribute to a current “systems” understanding of SRP as both a targeting factor and a gatekeeper for proteostasis (karamysheva2023aberrantproteintargeting pages 1-2, guarnizo2023pathogenicsignalpeptide pages 1-2).

3.3 2024: Viral co-option of SRP factors including SRP72

A 2024 PLOS Pathogens study reports that Zika virus proteins can engage SRP machinery: viral NS3 binding to SRP54 and SRP72 is noted, and infection alters normal SRP receptor engagement, supporting a model where viruses remodel ER-associated translation and translocation via SRP interactions (wong2024flavivirusesinduceerspecific pages 8-10). This is an emerging real-world mechanistic context in which SRP72 may be functionally relevant.

4) Disease relevance and expert synthesis

4.1 Germline SRP72 and autosomal-dominant bone marrow failure (AA/MDS)

A landmark genetics study identified heterozygous SRP72 mutations segregating in two autosomal-dominant families with familial aplastic anemia (AA) and/or myelodysplasia (MDS) (May 2012; https://doi.org/10.1016/j.ajhg.2012.03.020) (kirwan2012exomesequencingidentifies pages 2-3, kirwan2012exomesequencingidentifies pages 1-2). Reported variants included:
- c.1064_1065del; p.Thr355Lysfs*19, predicted truncation deleting a 7SL RNA-binding region (kirwan2012exomesequencingidentifies pages 2-3, kirwan2012exomesequencingidentifies pages 3-5)
- c.620G>A; p.Arg207His, a missense affecting a TPR region (kirwan2012exomesequencingidentifies pages 2-3, kirwan2012exomesequencingidentifies pages 3-5)

Mechanistically, the frameshift variant showed substantially reduced 7SL RNA association (~15% of wild-type co-precipitation), connecting the bone-marrow-failure phenotype to disrupted SRP72–7SL coupling and SRP function (kirwan2012exomesequencingidentifies pages 3-5).

A 2019 Blood review (expert synthesis) explicitly summarizes that two families with heterozygous SRP72 mutations have been described with autosomal-dominant MDS/bone marrow failure, reinforcing SRP72 as a germline predisposition gene in myeloid disease evaluation (kennedy2019geneticpredispositionto pages 10-15).

4.2 Disease-target association summaries (database evidence)

OpenTargets disease–gene associations include “autosomal dominant aplasia and myelodysplasia” linked to SRP72 and cite the same foundational literature evidence (OpenTargets Search: -SRP72). This supports that SRP72 is recognized across curated resources as a disease gene in hereditary bone marrow failure/MDS predisposition.

5) Current applications and real-world implementations

5.1 Clinical genetics: inclusion in hereditary myeloid malignancy screening frameworks

SRP72 appears in gene lists used to triage variants for potential germline evaluation in hereditary myeloid malignancy screening workflows (teranishi2025affirmingtheutility pages 26-30). This indicates real-world implementation in contemporary NGS-based diagnostic pipelines, even when SRP72 pathogenic variants are rare.

5.2 Research implementations

  • Interactome mapping / SRP biogenesis studies: inducible GFP-SRP72 cell lines combined with SILAC IP–MS and nucleolar perturbation were used to define SRP72-containing SRP interactomes and nucleolar dependencies (issa2024thenucleolarphase pages 14-15, issa2024thenucleolarphase pages 9-10).
  • Pathogen–host interface: SRP72 has been implicated as part of SRP machinery engaged by viral non-structural proteins during ER translation remodeling (wong2024flavivirusesinduceerspecific pages 8-10).

6) Relevant statistics and quantitative data highlights

Key quantitative findings relevant to SRP72 functional annotation include:
- Cajal body localization: SRP72 detected in ~50% of analyzed Cajal bodies, based on 45 GFP-SRP72-expressing U2OS cells (2024) (issa2024thenucleolarphase pages 2-3).
- Proteomic network expansion: SRP interactome analysis found ~239 new associations; 95 new nucleolar/ribosome-biogenesis interactors; total nucleolar/ribosome-biogenesis SRP interactors increased to 173 (2024) (issa2024thenucleolarphase pages 9-10).
- Disease-variant biochemical effect: SRP72 frameshift p.Thr355Lysfs*19 showed ~15% of wild-type 7SL RNA co-precipitation (2012) (kirwan2012exomesequencingidentifies pages 3-5).

7) Evidence-linked figures (visual)

The following extracted figure panels provide visual support for SRP72 biogenesis and localization:
- SRP assembly schematic showing nucleolar steps (SRP72 among nucleolar-assembling subunits) (issa2024thenucleolarphase media d31564f7).
- GFP-SRP72 nucleolar marker co-localization panels (issa2024thenucleolarphase media 18da7877).
- GFP-SRP72 co-localization with coilin-marked Cajal bodies (issa2024thenucleolarphase media 082653e8).

8) Summary and interpretation (authoritative analysis)

Taken together, the evidence supports annotating human SRP72 (O76094) as a core structural/functional subunit of the mammalian SRP S-domain, operating primarily in co-translational ER targeting by maintaining proper SRP architecture and assembly (issa2024thenucleolarphase pages 1-2, kellogg2023unravelingsrpbiogenesis pages 26-29). Recent primary data strongly support a nucleolar and Cajal-body phase of SRP72-containing SRP biogenesis, aligning SRP production with ribosome biogenesis environments (issa2024thenucleolarphase pages 2-3, issa2024thenucleolarphase pages 9-10, issa2024thenucleolarphase media d31564f7). Clinically, SRP72 is a validated autosomal-dominant germline predisposition gene for familial aplastic anemia/myelodysplasia, with mechanistic evidence that pathogenic truncation can disrupt SRP72–7SL RNA association (kirwan2012exomesequencingidentifies pages 2-3, kirwan2012exomesequencingidentifies pages 3-5, kennedy2019geneticpredispositionto pages 10-15). Finally, 2024 work suggests SRP72 may be engaged in pathogen-driven ER translation remodeling, adding translationally relevant context beyond canonical secretion (wong2024flavivirusesinduceerspecific pages 8-10).

Category Summary
Identity/domains • Verified target: human SRP72 / signal recognition particle 72 kDa subunit, a canonical component of mammalian SRP containing six proteins plus 7SL RNA (issa2024thenucleolarphase pages 1-2, kellogg2023unravelingsrpbiogenesis pages 111-116) • Forms the SRP68/72 heterodimer within the S-domain of SRP; UniProt O76094 assignment is consistent with literature on human SRP72 (issa2024thenucleolarphase pages 1-2, gussakovsky2024theroleof pages 1-2)
Molecular function • Functions in co-translational targeting of secretory and membrane proteins to the ER as part of SRP, which pauses elongation, targets the ribosome–nascent chain complex to the SRP receptor, and hands substrates to the Sec61 translocon (issa2024thenucleolarphase pages 1-2, kellogg2023unravelingsrpbiogenesis pages 23-26, karamysheva2023aberrantproteintargeting pages 1-2) • SRP68/72 is positioned on the 7SL S-domain and is described as helping control translocation (kellogg2023unravelingsrpbiogenesis pages 26-29, gussakovsky2024theroleof pages 1-2)
Key interactions • SRP72 + SRP68 form a stable heterodimer; GFP-SRP72 co-immunoprecipitates other SRP subunits, confirming assembly into mature SRP (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 2-3) • Interactions between Alu-domain proteins and S-domain proteins including SRP72 are strongly RNase-sensitive, supporting dependence on 7SL RNA (issa2024thenucleolarphase pages 2-3) • Disease-associated frameshift SRP72 shows markedly reduced 7SL RNA co-precipitation (kirwan2012exomesequencingidentifies pages 3-5)
Subcellular localization/biogenesis • Mature SRP72 is found in the cytoplasm, where SRP functions, but SRP72 also has a clear nuclear/nucleolar biogenesis phase (issa2024thenucleolarphase pages 3-5) • Five SRP proteins, including SRP72, assemble with 7SL in the nucleolus before SRP54 joins in the cytoplasm (issa2024thenucleolarphase pages 2-3, issa2024thenucleolarphase pages 1-2) • SRP72 localizes to the PDFC region of the nucleolus and to Cajal bodies, implying additional assembly steps there (issa2024thenucleolarphase pages 2-3, issa2024thenucleolarphase pages 3-5, issa2024thenucleolarphase media d31564f7)
Disease genetics • Heterozygous germline SRP72 mutations are linked to autosomal-dominant familial aplasia / myelodysplasia and bone-marrow failure phenotypes including AA/MDS, pancytopenia, macrocytic anemia, thrombocytopenia (kirwan2012exomesequencingidentifies pages 2-3, kirwan2012exomesequencingidentifies pages 1-2, kennedy2019geneticpredispositionto pages 10-15) • Reported pathogenic variants include p.Thr355Lysfs*19 and p.Arg207His; the frameshift removes the 7SL RNA-binding region and impairs association with 7SL (kirwan2012exomesequencingidentifies pages 2-3, kirwan2012exomesequencingidentifies pages 3-5)
Recent non-canonical roles • 2024 proteomics places SRP72 in a broader nucleolar/ribosome-biogenesis network, suggesting coordinated assembly of SRP and ribosomes (issa2024thenucleolarphase pages 9-10) • Zika virus NS3 was reported to bind SRP72 and other SRP machinery during ER-translation remodeling (wong2024flavivirusesinduceerspecific pages 8-10) • In 2025 heat-shock work, SRP72 depletion altered stress-linked translation programs, implicating SRP72/SRP in acute thermal-stress responses beyond secretion (bujisic20257slrnaand pages 9-10)
Applications/implementations • Clinical genetics: SRP72 is included in hereditary myeloid malignancy / inherited bone-marrow-failure evaluation frameworks and targeted-gene screening lists (kennedy2019geneticpredispositionto pages 10-15, teranishi2025affirmingtheutility pages 26-30) • Cell biology/proteomics tool use: inducible GFP-SRP72 lines and SILAC IP–MS are being used to map SRP assembly and interactomes (issa2024thenucleolarphase pages 14-15, issa2024thenucleolarphase pages 3-5)
Quantitative highlights • In U2OS cells, ~50% of analyzed Cajal bodies were positive for SRP72; based on 45 GFP-SRP72-expressing cells examined (issa2024thenucleolarphase pages 2-3) • SRP proteomics identified ~239 new SRP associations, including 95 new nucleolar/ribosome-biogenesis proteins, bringing the total such SRP interactors to 173 (issa2024thenucleolarphase pages 9-10) • SRP72 frameshift p.Thr355Lysfs*19 retained only ~15% of wild-type 7SL RNA co-precipitation (kirwan2012exomesequencingidentifies pages 3-5) • Heat-shock study reported 33 DEGs and 4 SRP72-dependency clusters upon SRP72 depletion (bujisic20257slrnaand pages 9-10)
Key references/URLs • Issa et al., 2024, Life Science Alliance — nucleolar phase of SRP assembly — https://doi.org/10.26508/lsa.202402614 (issa2024thenucleolarphase pages 1-2) • Kirwan et al., 2012, AJHG — familial aplasia/myelodysplasia genetics — https://doi.org/10.1016/j.ajhg.2012.03.020 (kirwan2012exomesequencingidentifies pages 2-3) • Karamysheva & Karamyshev, 2023, Front Cell Dev Biol — SRP/RAPP overview — https://doi.org/10.3389/fcell.2023.1198184 (karamysheva2023aberrantproteintargeting pages 1-2) • Guarnizo et al., 2023, NAR Genom Bioinform — pathogenic signal peptide variants/SRP pathway — https://doi.org/10.1093/nargab/lqad093 (guarnizo2023pathogenicsignalpeptide pages 1-2) • Wong et al., 2024, PLOS Pathogens — viral remodeling with SRP72 interaction — https://doi.org/10.1371/journal.ppat.1012766 (wong2024flavivirusesinduceerspecific pages 8-10)

Table: This table condenses the most relevant verified findings on human SRP72 (UniProt O76094), covering identity, mechanism, localization, disease links, recent research, and practical clinical/research uses. It is useful as a citation-ready scaffold for the final research report.

References

  1. (issa2024thenucleolarphase pages 1-2): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  2. (kirwan2012exomesequencingidentifies pages 3-5): Michael Kirwan, Amanda J. Walne, Vincent Plagnol, Mark Velangi, Aloysius Ho, Upal Hossain, Tom Vulliamy, and Inderjeet Dokal. Exome sequencing identifies autosomal-dominant srp72 mutations associated with familial aplasia and myelodysplasia. American journal of human genetics, 90 5:888-92, May 2012. URL: https://doi.org/10.1016/j.ajhg.2012.03.020, doi:10.1016/j.ajhg.2012.03.020. This article has 151 citations and is from a highest quality peer-reviewed journal.

  3. (karamysheva2023aberrantproteintargeting pages 1-2): Zemfira N. Karamysheva and Andrey L. Karamyshev. Aberrant protein targeting activates quality control on the ribosome. Frontiers in Cell and Developmental Biology, Jun 2023. URL: https://doi.org/10.3389/fcell.2023.1198184, doi:10.3389/fcell.2023.1198184. This article has 8 citations.

  4. (guarnizo2023pathogenicsignalpeptide pages 1-2): Sneider Alexander Gutierrez Guarnizo, Morgana K Kellogg, Sarah C Miller, Elena B Tikhonova, Zemfira N Karamysheva, and Andrey L Karamyshev. Pathogenic signal peptide variants in the human genome. NAR Genomics and Bioinformatics, Oct 2023. URL: https://doi.org/10.1093/nargab/lqad093, doi:10.1093/nargab/lqad093. This article has 32 citations and is from a peer-reviewed journal.

  5. (kellogg2023unravelingsrpbiogenesis pages 147-153): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.

  6. (gussakovsky2024theroleof pages 1-2): Daniel Gussakovsky, Nicole A. Black, Evan P. Booy, and Sean A. McKenna. The role of srp9/srp14 in regulating alu rna. Nov 2024. URL: https://doi.org/10.1080/15476286.2024.2430817, doi:10.1080/15476286.2024.2430817. This article has 7 citations and is from a peer-reviewed journal.

  7. (kellogg2023unravelingsrpbiogenesis pages 26-29): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.

  8. (kellogg2023unravelingsrpbiogenesis pages 23-26): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.

  9. (issa2024thenucleolarphase pages 2-3): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  10. (issa2024thenucleolarphase pages 3-5): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  11. (issa2024thenucleolarphase media d31564f7): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  12. (issa2024thenucleolarphase pages 9-10): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  13. (wong2024flavivirusesinduceerspecific pages 8-10): Ho Him Wong, Dorian Richard Kenneth Crudgington, Lewis Siu, and Sumana Sanyal. Flaviviruses induce er-specific remodelling of protein synthesis. Dec 2024. URL: https://doi.org/10.1371/journal.ppat.1012766, doi:10.1371/journal.ppat.1012766. This article has 10 citations and is from a highest quality peer-reviewed journal.

  14. (kirwan2012exomesequencingidentifies pages 2-3): Michael Kirwan, Amanda J. Walne, Vincent Plagnol, Mark Velangi, Aloysius Ho, Upal Hossain, Tom Vulliamy, and Inderjeet Dokal. Exome sequencing identifies autosomal-dominant srp72 mutations associated with familial aplasia and myelodysplasia. American journal of human genetics, 90 5:888-92, May 2012. URL: https://doi.org/10.1016/j.ajhg.2012.03.020, doi:10.1016/j.ajhg.2012.03.020. This article has 151 citations and is from a highest quality peer-reviewed journal.

  15. (kirwan2012exomesequencingidentifies pages 1-2): Michael Kirwan, Amanda J. Walne, Vincent Plagnol, Mark Velangi, Aloysius Ho, Upal Hossain, Tom Vulliamy, and Inderjeet Dokal. Exome sequencing identifies autosomal-dominant srp72 mutations associated with familial aplasia and myelodysplasia. American journal of human genetics, 90 5:888-92, May 2012. URL: https://doi.org/10.1016/j.ajhg.2012.03.020, doi:10.1016/j.ajhg.2012.03.020. This article has 151 citations and is from a highest quality peer-reviewed journal.

  16. (kennedy2019geneticpredispositionto pages 10-15): Alyssa L. Kennedy and Akiko Shimamura. Genetic predisposition to mds: clinical features and clonal evolution. Blood, 133 10:1071-1085, Mar 2019. URL: https://doi.org/10.1182/blood-2018-10-844662, doi:10.1182/blood-2018-10-844662. This article has 176 citations and is from a highest quality peer-reviewed journal.

  17. (OpenTargets Search: -SRP72): Open Targets Query (-SRP72, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  18. (teranishi2025affirmingtheutility pages 26-30): E Teranishi. Affirming the utility of somatic genetic testing as a screening tool to identify patients with a possible hereditary myeloid malignancy. Unknown journal, 2025.

  19. (issa2024thenucleolarphase pages 14-15): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  20. (issa2024thenucleolarphase media 18da7877): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  21. (issa2024thenucleolarphase media 082653e8): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.

  22. (kellogg2023unravelingsrpbiogenesis pages 111-116): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.

  23. (bujisic20257slrnaand pages 9-10): Bojan Bujisic, Hun-Goo Lee, Lilei Xu, Uri Weissbein, Carlos Rivera, Ivan Topisirovic, and Jeannie T. Lee. 7sl rna and signal recognition particle orchestrate a global cellular response to acute thermal stress. Nature Communications, Feb 2025. URL: https://doi.org/10.1038/s41467-025-56351-6, doi:10.1038/s41467-025-56351-6. This article has 7 citations and is from a highest quality peer-reviewed journal.

Artifacts

Citations

  1. issa2024thenucleolarphase pages 1-2
  2. karamysheva2023aberrantproteintargeting pages 1-2
  3. issa2024thenucleolarphase pages 2-3
  4. kirwan2012exomesequencingidentifies pages 3-5
  5. issa2024thenucleolarphase pages 9-10
  6. wong2024flavivirusesinduceerspecific pages 8-10
  7. kennedy2019geneticpredispositionto pages 10-15
  8. teranishi2025affirmingtheutility pages 26-30
  9. issa2024thenucleolarphase pages 3-5
  10. kirwan2012exomesequencingidentifies pages 2-3
  11. guarnizo2023pathogenicsignalpeptide pages 1-2
  12. kellogg2023unravelingsrpbiogenesis pages 147-153
  13. gussakovsky2024theroleof pages 1-2
  14. kellogg2023unravelingsrpbiogenesis pages 26-29
  15. kellogg2023unravelingsrpbiogenesis pages 23-26
  16. kirwan2012exomesequencingidentifies pages 1-2
  17. issa2024thenucleolarphase pages 14-15
  18. kellogg2023unravelingsrpbiogenesis pages 111-116
  19. https://doi.org/10.1016/j.ajhg.2012.03.020
  20. https://doi.org/10.26508/lsa.202402614
  21. https://doi.org/10.3389/fcell.2023.1198184
  22. https://doi.org/10.1093/nargab/lqad093
  23. https://doi.org/10.1371/journal.ppat.1012766
  24. https://doi.org/10.26508/lsa.202402614,
  25. https://doi.org/10.1016/j.ajhg.2012.03.020,
  26. https://doi.org/10.3389/fcell.2023.1198184,
  27. https://doi.org/10.1093/nargab/lqad093,
  28. https://doi.org/10.1080/15476286.2024.2430817,
  29. https://doi.org/10.1371/journal.ppat.1012766,
  30. https://doi.org/10.1182/blood-2018-10-844662,
  31. https://doi.org/10.1038/s41467-025-56351-6,

📚 Additional Documentation

Notes

(SRP72-notes.md)

SRP72 (O76094) review notes

Identity and overview

SRP72 is the largest subunit of the mammalian signal recognition particle (SRP), a ribonucleoprotein composed of a 300-nt 7SL RNA and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). SRP72 and SRP68 form a heterodimer that binds a regulatory site on the 7SL RNA and constitutes part of the S-domain.

[file:human/SRP72/SRP72-uniprot.txt "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,"]

[file:human/SRP72/SRP72-uniprot.txt "Heterodimer with SRP68"]

Molecular function

  • SRP72 is an RNA-binding scaffold subunit, NOT a GTPase (the GTPase activity of SRP resides in SRP54 and the SRP receptor).
  • The N-terminal region (~9-163) contains TPR-like repeats and mediates the interaction with SRP68; the C-terminal region (RNA-binding, residues 545-617) binds the 7SL RNA 5e/5f loops.

[file:human/SRP72/SRP72-uniprot.txt "Within the SRP complex,\nCC interacts (via N-terminus) with SRP68 (via C-terminus)"]

[file:human/SRP72/SRP72-uniprot.txt "Binds the signal recognition particle RNA (7SL RNA) in presence of"]

  • The SRP72 RNA-binding domain is "a flexible peptide crawling along the 5e- and 5f-loops of SRP RNA. A conserved tryptophan inserts into the 5e-loop forming a novel type of RNA kink-turn" PMID:27899666.
  • RNA-binding residues mapped by mutagenesis (source PMID:21073748): e.g. 553-558 (KKKKKK->AAAAAA) "Loss of RNA binding"; W577-L578 "Loss of RNA binding" [file:human/SRP72/SRP72-uniprot.txt "KKKKKK->AAAAAA: Loss of RNA binding."].
  • SRP72-PBD is a tetratricopeptide repeat that binds an extended linear motif of SRP68 PMID:27899666. This TPR-mediated SRP68 binding is the experimental basis for the GO:0030911 "TPR domain binding" IPI annotation.

Cellular component / localization

  • SRP72 acts within the cytosolic SRP and at the ER membrane during co-translational targeting.

[file:human/SRP72/SRP72-uniprot.txt "SUBCELLULAR LOCATION: Cytoplasm"]
[file:human/SRP72/SRP72-uniprot.txt "Endoplasmic reticulum {ECO:0000269|PubMed:22541560,"]

  • ComplexPortal SRP complex: CPX-2652. Nucleolus / stress granule associations (CD-CODE) reflect SRP RNA assembly/trafficking; not core function.

Biological process

  • Core process: SRP-dependent cotranslational protein targeting to the ER membrane.

[file:human/SRP72/SRP72-uniprot.txt "mediates the cotranslational targeting\nCC of secretory and membrane proteins to the endoplasmic reticulum (ER)"]

[file:human/SRP72/SRP72-uniprot.txt "The SRP complex targets the\nCC ribosome-nascent chain complex to the SRP receptor (SR), which is\nCC anchored in the ER, where SR compaction and GTPase rearrangement drive\nCC cotranslational protein translocation into the ER"]

  • SRP72/68 binding remodels 7SL RNA into an SRP54 binding competent state PMID:17254600.

Disease

  • Heterozygous SRP72 mutations cause autosomal-dominant bone marrow failure syndrome 1 (BMFS1; aplastic anemia / myelodysplasia). The BMFS1 variant R207H affects localization to the ER. This is a disease association, not a clean GO biological process.

PMID:22541560

[file:human/SRP72/SRP72-uniprot.txt "Bone marrow failure syndrome 1 (BMFS1)"]

Notes on specific references

  • PMID:18089836 (TAS-103): abstract foregrounds SRP54 as the drug target, but the paper assays the intact SRP complex; the SRP72 IDA "signal recognition particle, ER targeting" CC annotation is valid for SRP72 as an SRP subunit. Do not REMOVE on subunit-naming grounds.
  • PMID:24965446: pestivirus Npro interactome — SRP72 co-purified in an RNP/ribosome-associated complex (WITH/FROM is the Npro protease P19712-PRO). Bare protein binding, non-core.
  • PMID:32296183 (HuRI; WITH/FROM SULT2B1 O00204), PMID:33961781 (BioPlex; SRP68 Q9UHB9), PMID:35271311 (OpenCell; SRP68 Q9UHB9): high-throughput interactome captures. Bare protein binding, non-core.
  • PMID:16672232 IPI partner is SRP68 (Q9UHB9) — the physiological heterodimer partner; bare protein binding, kept non-core because GO:0005047 SRP binding captures the informative version.
  • PMID:22658674, PMID:22681889: HeLa mRNA-interactome capture (HDA RNA binding); supports general RNA binding.

Core function summary

  1. 7S/7SL RNA binding scaffold subunit of SRP (heterodimer with SRP68), enabling SRP assembly and ribosome interaction.
  2. Structural/RNA-binding S-domain component participating in SRP-dependent cotranslational protein targeting to the ER membrane.

Falcon deep-research findings (incorporated 2026-06)

  • GFP-SRP72 co-immunoprecipitates other SRP subunits and localizes to the nucleolus (periphery of the dense fibrillar component, PDFC) and to Cajal bodies; five SRP proteins including SRP72 assemble with 7SL RNA in the nucleolus before SRP54 joins in the cytoplasm [PMID:38858088 "an intact organelle is required for their proper localization"; "two SRP proteins in Cajal bodies"]. New localization/biogenesis evidence (nucleolar/CB phase) for SRP72; reference added (relevance HIGH).
  • Alu-domain/S-domain inter-subunit contacts involving SRP72 are RNase-sensitive, confirming 7SL-RNA-mediated complex architecture PMID:38858088.
  • SRP72 reinforced as a germline autosomal-dominant predisposition gene for MDS/aplastic anemia/bone-marrow failure (two families) PMID:30670445. Corroborates existing BMFS1/PMID:22541560 disease annotation; review reference added.
  • Host-pathogen: Zika virus bypasses the SRP receptor via NS3-SRP54/translocon interactions and engages SRP machinery (incl. SRP72) during ER-translation remodeling PMID:39621795. Peripheral (relevance LOW).
  • Non-canonical SRP role: under acute heat shock, 7SL RNA/SRP arrest transcription and translation independent of signal peptides; SRP binds ribosomes and inhibits new protein synthesis PMID:39952919. SRP72-specific contribution not isolated (relevance LOW).
  • Quality-control framing: SRP-targeting failures couple to RAPP mRNA degradation, situating SRP as a proteostasis gatekeeper [PMID:37346176; PMID:37859801] — context noted, not added as SRP72-specific annotations.

Pn Notes

(SRP72-pn-notes.md)

SRP72 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O76094
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-11
  • Batch change status: added

Source Files Checked

Deep Research Files

AIGR Review Snapshot

  • 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).
  • Existing/core annotation action counts: ACCEPT: 22; KEEP_AS_NON_CORE: 7

PN Consistency Summary

  • Consistency: Strong and mutually consistent. Deep research, review YAML, and PN annotation all describe SRP72 as the largest SRP subunit, an RNA-binding scaffold that heterodimerizes with SRP68 (N-terminal TPR), threads along the 7SL 5e/5f loops, and contributes to ribosome contacts. The PN "SRP component" label and GO:0006614 mapping match the review's core BP (GO:0006614 IBA/IEA, ACCEPT). No contradictions.
  • PN story / NEW pressure: PN asserts only the canonical SRP cotranslational-targeting role, already captured (GO:0006614, GO:0008312 7S RNA binding, GO:0005047 SRP binding, GO:0043022 ribosome binding, GO:0005786 SRP membership). The BMFS1 disease link (PMID:22541560) and nucleolar/Cajal-body assembly pool (PMID:38858088) are in the review but outside the PN story. Conclusion: already captured (no NEW pressure).
  • Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:27899666 definitive SRP72 structures; PMID:28369529 apo/SRP68-72 structures; PMID:17254600 RNA-remodeling assembly; PMID:16672232 SRP68-binding TPR; PMID:34208095 SRP review) all encode the SRP cotranslational-targeting biology the PN maps to. No divergence.
  • Verdict: Fully consistent; PN already captured, review more granular (adds 7S RNA binding, SRP binding, ribosome binding, TPR domain binding). No edits warranted.

Full Consistency Review

  • UniProt: O76094 · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE
  • PN placement: ER proteostasis|Protein transport|Signal recognition particle component ; PN-node mapping: group=mapped scope=ok_for_propagation_to_go→GO:0006614 (SRP-dependent cotranslational protein targeting to membrane); class Protein transport=mapped→GO:0015031; branch=no_mapping.
  • Consistency: Strong and mutually consistent. Deep research, review YAML, and PN annotation all describe SRP72 as the largest SRP subunit, an RNA-binding scaffold that heterodimerizes with SRP68 (N-terminal TPR), threads along the 7SL 5e/5f loops, and contributes to ribosome contacts. The PN "SRP component" label and GO:0006614 mapping match the review's core BP (GO:0006614 IBA/IEA, ACCEPT). No contradictions.
  • PN story / NEW pressure: PN asserts only the canonical SRP cotranslational-targeting role, already captured (GO:0006614, GO:0008312 7S RNA binding, GO:0005047 SRP binding, GO:0043022 ribosome binding, GO:0005786 SRP membership). The BMFS1 disease link (PMID:22541560) and nucleolar/Cajal-body assembly pool (PMID:38858088) are in the review but outside the PN story. Conclusion: already captured (no NEW pressure).
  • Mapping strategy: No change needed. GO:0006614 (goa_status already_in_goa_exact) is present and ACCEPTed — exact projection, not broader than the review. The class-level GO:0015031 is a broad class target, not asserted of SRP72.
  • Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:27899666 definitive SRP72 structures; PMID:28369529 apo/SRP68-72 structures; PMID:17254600 RNA-remodeling assembly; PMID:16672232 SRP68-binding TPR; PMID:34208095 SRP review) all encode the SRP cotranslational-targeting biology the PN maps to. No divergence.
  • Verdict: Fully consistent; PN already captured, review more granular (adds 7S RNA binding, SRP binding, ribosome binding, TPR domain binding). No edits warranted.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-11
  • review_yaml: genes/human/SRP72/SRP72-ai-review.yaml
  • PN workbook rows: 1

PN row 1: ER proteostasis | Protein transport | Signal recognition particle component

  • UniProt: O76094
  • In branches: ER
  • PN-node mapping records (path + ancestors):
    • [group] ER proteostasis|Protein transport|Signal recognition particle component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006614 SRP-dependent cotranslational protein targeting to membrane]
      rationale: This PN group captures core signal-recognition-particle machinery used to direct translating ribosome-nascent chain complexes to the ER membrane. The group is machinery-centric rather than process-equivalent, so it propagates to the GO targeting process.
    • [class] ER proteostasis|Protein transport
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0015031 protein transport]
      rationale: The PN ER Protein transport class groups ER-targeting and ER-insertion pathways. GO protein transport is the appropriate propagation target, while the source class remains ER-specific and broader than any single GO transport subtype.
    • [branch] ER proteostasis
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (2)

  • GO:0015031 protein transport | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport
  • GO:0006614 SRP-dependent cotranslational protein targeting to membrane | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Protein transport|Signal recognition particle component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: 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.