Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006614 SRP-dependent cotranslational protein targeting to membrane	IBA GO_REF:0000033	ACCEPT	Summary: SRP68 is a core SRP subunit and participates directly in SRP-dependent cotranslational targeting of secretory and membrane proteins to the ER. This is the defining biological process of the gene and is conserved across the SRP68 family. Reason: Phylogenetically (IBA) and experimentally supported core biological process; SRP68 is an essential S-domain subunit of the targeting SRP complex. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER)
GO:0005047 signal recognition particle binding	IBA GO_REF:0000033	ACCEPT	Summary: SRP68 binds within the SRP complex, contacting the 7SL RNA and the SRP72/SRP19 components; signal recognition particle binding captures its integral association with the particle. Reason: Core molecular function corroborated by structural and biochemical evidence of SRP68 binding SRP RNA and SRP72 within the particle. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently
GO:0005786 signal recognition particle, endoplasmic reticulum targeting	IBA GO_REF:0000033	ACCEPT	Summary: SRP68 is a constitutive subunit of the ER-targeting signal recognition particle. Conserved across the family. Reason: Core cellular component; SRP68 is one of the six defining SRP protein subunits. Supporting Evidence: file:human/SRP68/SRP68-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, SRP19, SRP14 and SRP9
GO:0003723 RNA binding	IEA GO_REF:0000002	ACCEPT	Summary: SRP68 binds the SRP (7SL) RNA via its N-terminal RNA-binding domain; the general RNA binding term is a correct parent of the more specific 7S RNA binding. Reason: Correct general molecular function; the more precise GO:0008312 (7S RNA binding) better captures the specific activity. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt The N-terminus is required for RNA-binding.
GO:0005047 signal recognition particle binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic assignment of signal recognition particle binding, consistent with the experimental/IBA evidence. Reason: Correct core molecular function; redundant with IBA and IPI evidence. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently
GO:0005730 nucleolus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: A pool of SRP68 traffics through the nucleolus, consistent with partial SRP assembly there; this is not its core site of action. Reason: Real localization (UniProt subcellular location; PMID:10618370) reflecting SRP assembly trafficking, not the core cytosolic/ER targeting function. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Nucleus, nucleolus PMID:10618370 green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: SRP68 is predominantly cytoplasmic, consistent with the cytosolic SRP targeting cycle. Reason: Correct compartment; SRP acts in the cytoplasm to capture nascent chains on translating ribosomes. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000044	ACCEPT	Summary: SRP68 accumulates at the ER, consistent with delivery of the SRP-ribosome-nascent chain complex to the ER-bound SRP receptor. Reason: Correct; ER association reflects the targeting endpoint where SRP docks the nascent-chain complex. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Endoplasmic reticulum {ECO:0000269\|PubMed:28369529}
GO:0005786 signal recognition particle, endoplasmic reticulum targeting	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based electronic assignment to the ER-targeting SRP, consistent with experimental evidence. Reason: Correct core cellular component; redundant with IBA/IDA. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Component of a signal recognition particle (SRP) complex
GO:0005829 cytosol	IEA GO_REF:0000117	ACCEPT	Summary: Cytosolic localization consistent with the cytoplasmic SRP targeting cycle. Reason: Correct compartment; redundant with the IDA cytosol annotation and the UniProt cytoplasm location. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0006614 SRP-dependent cotranslational protein targeting to membrane	IEA GO_REF:0000002	ACCEPT	Summary: Electronic (InterPro) assignment of the defining SRP cotranslational targeting process, consistent with IBA/NAS evidence. Reason: Correct core biological process; redundant with experimentally supported annotations. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum
GO:0008312 7S RNA binding	IEA GO_REF:0000002	ACCEPT	Summary: SRP68 directly binds the 7SL (7S) SRP RNA through its N-terminal RNA-binding domain and remodels it; 7S RNA binding is the core molecular function. Reason: Core molecular function with structural support (crystal structures of SRP68-RBD with SRP RNA); also supported by IMP. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Binds the signal recognition particle RNA (7SL RNA) PMID:24700861 We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19.
GO:0030942 endoplasmic reticulum signal sequence receptor activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: This activity describes the ER signal-sequence receptor (the SRP receptor / TRAP-type signal sequence receptor), not the 7SL-RNA-binding SRP68 scaffold subunit. The InterPro mapping over-extends a receptor function onto an SRP S-domain protein. Reason: SRP68 is an RNA-binding scaffold subunit of the cytosolic SRP, not a membrane signal-sequence receptor; signal-sequence receptor activity belongs to the SRP receptor (SRPR/SRPRB) and the SSR/TRAP complex, not to SRP68. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt The N-terminus is required for RNA-binding.
GO:0005515 protein binding	IPI PMID:16672232 Protein SRP68 of human signal recognition particle: identifi...	KEEP AS NON CORE	Summary: SRP68 binds SRP72 (and SRP RNA); this captures the SRP68-SRP72 heterodimer interaction. The informative aspect (SRP/SRP72 binding) is better represented by signal recognition particle binding; bare protein binding is uninformative. Reason: Records the real SRP68-SRP72 interaction but the bare protein binding term is uninformative; the SRP-binding function is captured by GO:0005047. Supporting Evidence: PMID:16672232 Human SRP68 was purified from overexpressing Escherichia coli cells and was found to bind to recombinant SRP72
GO:0005515 protein binding	IPI PMID:24700861 SRP RNA remodeling by SRP68 explains its role in protein tra...	KEEP AS NON CORE	Summary: Structural study of SRP68-RBD in complex with SRP19 and SRP RNA; the interaction captured is with SRP partners. Bare protein binding is uninformative. Reason: Real interaction within SRP (SRP19/RNA) but bare protein binding is uninformative; SRP function is captured by other terms. Supporting Evidence: PMID:24700861 in complex with SRP RNA and SRP19
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: High-throughput interactome (BioPlex) capture; bare protein binding is uninformative for core function. Reason: High-throughput interactome interaction; bare protein binding is uninformative and not elevated to core per guidelines. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Q9UHB9; O76094: SRP72
GO:0005515 protein binding	IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy...	KEEP AS NON CORE	Summary: CFTR-interactome mammalian membrane two-hybrid screen captured SRP68; the CFTR interaction is consistent with SRP engaging nascent membrane proteins but bare protein binding is uninformative. Reason: Screen-derived interaction; bare protein binding is uninformative and the CFTR partner reflects SRP substrate capture rather than a distinct core function. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Q9UHB9; P13569: CFTR
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 capture; bare protein binding is uninformative. Reason: High-throughput interactome interaction; uninformative bare term not elevated to core. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Q9UHB9; O76094: SRP72
GO:0005515 protein binding	IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ...	KEEP AS NON CORE	Summary: CFTR-interactome proximity-labeling capture; bare protein binding is uninformative. Reason: Screen-derived interaction; uninformative bare term not elevated to core. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Q9UHB9; P13569: CFTR
GO:0005786 signal recognition particle, endoplasmic reticulum targeting	NAS PMID:34208095 SRPassing Co-translational Targeting: The Role of the Signal...	ACCEPT	Summary: Review-based assertion that SRP68 is part of the ER-targeting SRP. Reason: Consistent with the experimentally supported SRP membership; the cited review summarizes mammalian SRP composition and function. Supporting Evidence: PMID:34208095 It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals.
GO:0006617 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition	NAS PMID:34208095 SRPassing Co-translational Targeting: The Role of the Signal...	ACCEPT	Summary: SRP, of which SRP68 is a core subunit, recognizes the signal sequence of nascent chains during cotranslational targeting; SRP68 participates in this signal-sequence-recognition step as part of the particle. Reason: Consistent with SRP's signal-sequence recognition role; SRP68 is an integral S-domain subunit of the recognizing particle. Supporting Evidence: PMID:34208095 SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with the cytoplasmic SRP targeting cycle. Reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005737 cytoplasm	EXP PMID:10618370 Signal recognition particle components in the nucleolus.	ACCEPT	Summary: Experimental (GFP-fusion) evidence that SRP68 localizes to the cytoplasm. Reason: Correct compartment; SRP acts in the cytoplasm. Supporting Evidence: PMID:10618370 green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm
GO:0005783 endoplasmic reticulum	EXP PMID:28369529 Human apo-SRP72 and SRP68/72 complex structures reveal the m...	ACCEPT	Summary: Experimental evidence for SRP68 ER localization, consistent with SRP docking at the ER-bound receptor. Reason: Correct; ER association reflects the targeting endpoint. The F590L mutant (disrupting SRP72 interaction) diminishes ER localization, linking ER targeting to heterodimer formation. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt F->L: Loss of interaction with SRP72. Diminished
GO:0008312 7S RNA binding	IMP PMID:27899666 Structures of human SRP72 complexes provide insights into SR...	ACCEPT	Summary: SRP68 binds and remodels the SRP (7S/7SL) RNA; structures of SRP68/72-RNA complexes establish the direct RNA-binding/remodeling activity. Reason: Core molecular function with direct structural support; SRP68-RBD binds the SRP RNA three-way junction and remodels the 5f loop. Supporting Evidence: PMID:27899666 the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68)
GO:0019904 protein domain specific binding	IPI PMID:27899666 Structures of human SRP72 complexes provide insights into SR...	KEEP AS NON CORE	Summary: SRP68 binds the SRP72 protein-binding domain (a TPR module) via an extended linear motif in its C-terminus; this domain-specific interaction mediates heterodimer formation. Reason: Captures the structurally defined SRP68-SRP72 PBD interaction; a genuine and informative interaction, but subsidiary to the core RNA-binding and SRP-targeting functions. Supporting Evidence: PMID:27899666 The SRP72-PBD is a tetratricopeptide repeat, which binds an extended linear motif of SRP68 with high affinity.
GO:0043022 ribosome binding	IMP PMID:27899666 Structures of human SRP72 complexes provide insights into SR...	ACCEPT	Summary: SRP68/72 contribute to SRP-ribosome contacts; SRP72-RBD remodels the 5f loop involved in ribosome binding, and the SRP68/72 module makes multiple ribosome contacts. Reason: Supported; the SRP68/72 heterodimer contributes to the particle's interaction with the translating ribosome during targeting. Supporting Evidence: PMID:27899666 SRP72-RBD remodels the 5f-loop involved in ribosome binding PMID:30649417
GO:0048500 signal recognition particle	IDA PMID:27899666 Structures of human SRP72 complexes provide insights into SR...	ACCEPT	Summary: SRP68 is a structurally demonstrated component of the signal recognition particle S domain. Reason: Core cellular component; directly demonstrated by structures of SRP68 within the SRP S domain. Supporting Evidence: PMID:27899666 the 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: SRP68 was identified as a component of a pestivirus Npro-associated ribonucleoprotein complex; bare protein binding is uninformative for core SRP function. Reason: Captures a virus-host interactome observation; bare protein binding is uninformative and peripheral to core SRP function. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Q9UHB9; O76094: SRP72
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	ACCEPT	Summary: SRP68 was captured in a high-throughput mRNA-interactome (RNA-binding proteome) study; consistent with its 7SL-RNA-binding function. Reason: Correct general molecular function; SRP68 is an RNA-binding protein (the more specific 7S RNA binding captures its physiological target). Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt The N-terminus is required for RNA-binding.
GO:0005829 cytosol	TAS Reactome:R-HSA-1799332	ACCEPT	Summary: Reactome curation of SRP68 cytosolic localization within the SRP targeting reaction. Reason: Correct compartment; redundant with experimental cytosol/cytoplasm annotations. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005047 signal recognition particle binding	IPI PMID:17254600 Protein-induced conformational changes of RNA during the ass...	ACCEPT	Summary: SRP68 interacts with the SRP RNA/particle during assembly, driving protein-induced conformational changes of the SRP RNA. Reason: Core molecular function; SRP68 binding within the particle is supported by assembly/conformational-change studies. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently
GO:0005786 signal recognition particle, endoplasmic reticulum targeting	IDA PMID:18089836 A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydro...	ACCEPT	Summary: SRP68 was identified as part of the SRP via affinity capture; consistent with its established SRP membership. Reason: Correct core cellular component; redundant with stronger structural evidence. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Component of a signal recognition particle (SRP) complex
GO:0009410 response to xenobiotic stimulus	IDA PMID:18089836 A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydro...	KEEP AS NON CORE	Summary: SRP68/SRP72 were pulled out as binding targets of the anticancer drug TAS-103 using drug-immobilized affinity beads; this is an affinity-capture observation, peripheral to SRP68's core SRP function. Reason: Drug target-screening (affinity capture) observation; does not represent a core biological process of SRP68. Supporting Evidence: file:human/SRP68/SRP68-uniprot.txt Component of a signal recognition particle (SRP) complex
GO:0005730 nucleolus	TAS PMID:10618370 Signal recognition particle components in the nucleolus.	KEEP AS NON CORE	Summary: SRP68 localizes to the nucleolus (in addition to cytoplasm and ER), consistent with partial SRP assembly there; not the core site of action. Reason: Genuine localization reflecting SRP assembly trafficking, not the core cytosolic/ER targeting function. Supporting Evidence: PMID:10618370 green fluorescent protein fusions of SRP19, SRP68, and SRP72 localized to the nucleolus, as well as to the cytoplasm PMID:38858088
GO:0005783 endoplasmic reticulum	TAS PMID:10618370 Signal recognition particle components in the nucleolus.	ACCEPT	Summary: SRP68 accumulates at the ER, consistent with its affinity for the ER-bound SRP receptor. Reason: Correct; ER association reflects the targeting endpoint where SRP docks the nascent-chain complex. Supporting Evidence: PMID:10618370 SRP68 also accumulated in the ER, consistent with its affinity for the ER-bound SRP receptor.
GO:0005786 signal recognition particle, endoplasmic reticulum targeting	TAS PMID:10618370 Signal recognition particle components in the nucleolus.	ACCEPT	Summary: SRP68 is a component of the S domain of the ER-targeting SRP. Reason: Correct core cellular component. Supporting Evidence: PMID:10618370 The S domain contains unique sequence SRP RNA and four SRP proteins: SRP19, SRP54, SRP68, and SRP72.
GO:0005840 ribosome	TAS PMID:10618370 Signal recognition particle components in the nucleolus.	KEEP AS NON CORE	Summary: SRP, via the SRP68/72 module, contacts the translating ribosome; the ribosome localization reflects SRP engagement with ribosome-nascent chain complexes rather than SRP68 being a ribosomal protein. Reason: SRP68 is not a ribosomal subunit; it transiently associates with ribosomes during targeting. The functional ribosome-contact role is better captured by GO:0043022 ribosome binding. Supporting Evidence: PMID:10618370 SRP interacts with ribosomes to bring translating membrane and secreted proteins to the endoplasmic reticulum

Core Functions

RNA-binding scaffold subunit of the signal recognition particle that binds and remodels the SRP (7SL) RNA, opening the conserved 5f loop required for cotranslational targeting.

Molecular Function:

7S RNA binding

In Complex:

signal recognition particle

Supporting Evidence:

PMID:24700861
We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19.
file:human/SRP68/SRP68-uniprot.txt
Binds the signal recognition particle RNA (7SL RNA)

Component of the SRP S-domain that, in heterodimer with SRP72, mediates SRP-dependent cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum.

Molecular Function:

signal recognition particle binding

Directly Involved In:

SRP-dependent cotranslational protein targeting to membrane

In Complex:

signal recognition particle, endoplasmic reticulum targeting

Supporting Evidence:

file:human/SRP68/SRP68-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, SRP19, SRP14 and SRP9

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:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:10618370

Signal recognition particle components in the nucleolus.

GFP fusions of SRP19, SRP68 and SRP72 localize to the nucleolus and cytoplasm; SRP68 also accumulates in the ER, consistent with partial SRP assembly in the nucleolus.

PMID:16672232

Protein SRP68 of human signal recognition particle: identification of the RNA and SRP72 binding domains.

Human SRP68 binds recombinant SRP72 and in vitro-transcribed SRP RNA; the RNA-binding domain spans residues 52-252 and ~94 C-terminal residues mediate SRP72 binding.

PMID:17254600

Protein-induced conformational changes of RNA during the assembly of human signal recognition particle.

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.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:24700861

SRP RNA remodeling by SRP68 explains its role in protein translocation.

Crystal structures of SRP68-RBD alone and with SRP RNA and SRP19; SRP68-RBD is a TPR-like module that binds the RNA three-way junction, bends the RNA, and opens the conserved 5f loop required for translocation.

PMID:24965446

Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.

PMID:27899666

Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction.

Crystal structures of SRP68-PBD/SRP72-PBD and SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19, SRP68); SRP72-RBD remodels the 5f loop involved in ribosome binding and SRP68/72 make multiple ribosome contacts.

PMID:28369529

Human apo-SRP72 and SRP68/72 complex structures reveal the molecular basis of protein translocation.

Crystal structures of apo-SRP72 and the SRP68/72 complex; the SRP68-binding domain of SRP72 contains four TPR motifs; SRP68/72 heterodimer is essential for protein translocation.

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.

Mammalian SRP consists of six proteins and one noncoding RNA; SRP co-translationally targets secretory proteins to the ER and additionally protects their mRNAs.

PMID:35156780

CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:36012204

Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.

Reactome:R-HSA-1799332

Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)

file:human/SRP68/SRP68-uniprot.txt

UniProt entry Q9UHB9 (SRP68_HUMAN), Signal recognition particle subunit SRP68

SRP68 is an S-domain SRP subunit that binds the 7SL RNA via its N-terminal RNA-binding domain (52-252) and forms a heterodimer with SRP72; SRP mediates cotranslational targeting of secretory/membrane proteins to the ER. Cytoplasm, nucleolus and ER localizations. Biallelic variants cause SCN10.

PMID:30649417

Reconstitution of the human SRP system and quantitative and systematic analysis of its ribosome interactions.

Reconstitution of recombinant human SRP shows the SRP68/72 heterodimer binds the 80S ribosome with ultrasensitive (avidity-driven, multi-site) nanomolar affinity dominated by the SRP72 C-terminus, quantifying the SRP68/72 contribution to SRP-ribosome engagement.

PMID:38858088

The nucleolar phase of signal recognition particle assembly.

Quantitative proteomics shows SRP proteins (including SRP68) associate with scores of nucleolar/ribosome-biogenesis factors; an intact nucleolus is required for proper SRP protein localization, and some SRP proteins are detected in Cajal bodies, defining a nucleolar phase of SRP assembly.

PMID:32273475

Identification of biallelic germline variants of SRP68 in a sporadic case with severe congenital neutropenia.

Biallelic germline SRP68 loss-of-function variants cause severe congenital neutropenia; patient granulocytic cells show reduced SRP68 protein, impaired granulopoiesis, ER-stress (spliced XBP1) and p53-pathway activation.

Suggested Experiments

Experiment: Reconstitute SRP with wild-type versus RNA-binding-deficient SRP68 and measure SRP RNA 5f-loop remodeling and cotranslational targeting efficiency to a model secretory substrate in vitro.

Experiment: Introduce patient SCN10 SRP68 variants into a human myeloid differentiation model and quantify SRP assembly, ER targeting, and granulopoiesis to define the disease mechanism.

Deep Research

Falcon

(SRP68-deep-research-falcon.md)

Research report: Human SRP68 (UniProt Q9UHB9) functional annotation Falcon Edison Scientific Literature 22 citations 2 artifacts 2026-06-12T02:49:37.403644

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000018 The requested information can be found in several figures throughout the document. - Figure 1A illustrates the architecture of the (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
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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.

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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.

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Research report: Human SRP68 (UniProt Q9UHB9) functional annotation

Executive summary

Signal recognition particle subunit SRP68 (gene SRP68, UniProt Q9UHB9) is a core protein component of the mammalian signal recognition particle (SRP), a ribonucleoprotein that mediates co-translational targeting of nascent secretory and membrane proteins to the endoplasmic reticulum (ER). SRP68 is not an enzyme or transporter; rather, it is a structural/coordinating SRP subunit that forms a stable heterodimer with SRP72, binds/remodels 7SL (SRP) RNA, and contributes substantially to ribosome binding during targeting. Multiple recent studies (2023–2024) emphasize SRP68’s participation in a nucleolar/nuclear phase of SRP biogenesis and highlight open mechanistic questions about SRP68/72’s precise role in later targeting steps. A strong, direct clinical association exists with severe congenital neutropenia caused by biallelic SRP68 loss-of-function variants, supported by patient-derived functional assays showing reduced SRP68 protein, impaired granulopoiesis, ER stress signaling, and p53-pathway activation. (wild2019reconstitutionofthe pages 1-2, kellogg2022signalrecognitionparticle pages 1-2, kellogg2023unravelingsrpbiogenesis pages 26-29, issa2024thenucleolarphase pages 1-2, schmaltzpanneau2021identificationofbiallelic pages 6-10)

0) Mandatory verification of gene/protein identity

Target confirmed: The literature evidence explicitly connects human SRP68 to UniProt accession Q9UHB9 as a subunit of mammalian SRP. In particular, a reconstitution/biophysics study of the human SRP system lists SRP68 (UniProt Q9UHB9) as one of the six SRP proteins assembled on 7SL RNA. (wild2019reconstitutionofthe pages 1-2)

Organism confirmed: The cited SRP68 evidence is for human/mammalian SRP (e.g., “human SRP system,” “mammalian SRP,” human cell lines). (wild2019reconstitutionofthe pages 1-2, issa2024thenucleolarphase pages 1-2)

Family/domain consistency: SRP68 is consistently described as an SRP68/SRP72 heterodimeric subunit of the SRP S-domain, with SRP68 featuring a TPR-like RNA-binding/remodeling role in 7SL RNA positioning, consistent with SRP68-family annotations. (kellogg2023unravelingsrpbiogenesisa pages 26-29, kellogg2023unravelingsrpbiogenesis pages 26-29)

1) Key concepts and definitions (current understanding)

1.1 Signal recognition particle (SRP)

The signal recognition particle is a conserved ribonucleoprotein complex that recognizes hydrophobic signal sequences on nascent polypeptides as they emerge from the ribosome and delivers translating ribosomes to the ER membrane, enabling co-translational translocation or membrane insertion. In mammals, SRP is composed of 7SL RNA and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). (kellogg2022signalrecognitionparticle pages 1-2, issa2024thenucleolarphase pages 1-2)

SRP is organized into:
- an Alu domain (SRP9/SRP14) that contacts the ribosomal factor-binding site and contributes to elongation arrest, and
- an S domain (SRP19, SRP54, SRP68, SRP72) that contains the major signal-sequence recognition and receptor-docking machinery. (kellogg2022signalrecognitionparticle pages 1-2, wild2019reconstitutionofthe pages 1-2)

1.2 SRP68 definition in the context of the SRP cycle

SRP68 is an S-domain SRP subunit that forms a heterodimer with SRP72 and contributes to SRP assembly and ribosome binding. The primary signal-sequence recognition and GTPase-based docking with the SRP receptor are attributed to SRP54 (signal-binding M-domain; NG-domain for receptor interaction), while SRP68/72 are best supported as structural/coordinating factors that shape SRP RNA and stabilize SRP–ribosome interactions. (kellogg2022signalrecognitionparticle pages 1-2, kellogg2023unravelingsrpbiogenesisa pages 26-29, kellogg2023unravelingsrpbiogenesis pages 26-29, wild2019reconstitutionofthe pages 1-2)

2) SRP68 molecular function, biological processes, and localization

2.1 Molecular function (what SRP68 “does”)

Evidence supports SRP68 as an SRP subunit that:
1. Heterodimerizes with SRP72 and helps incorporate SRP72 into the SRP complex. (kellogg2023unravelingsrpbiogenesis pages 26-29, kellogg2023unravelingsrpbiogenesis pages 23-26)
2. Binds and remodels 7SL RNA, bending it to enable specific RNA loop positioning that supports ribosome contacts (e.g., facilitating the 7SL RNA “5f loop” contacting the ribosome). (kellogg2023unravelingsrpbiogenesisa pages 26-29, kellogg2023unravelingsrpbiogenesis pages 26-29)
3. Promotes ribosome binding of SRP via multivalent/avidity interactions together with SRP72. Quantitatively, the full-length SRP68/72 heterodimer binds the human 80S ribosome with ~160 ± 20 nM affinity and apparent ultrasensitivity (Hill coefficient ~2.3), consistent with multiple interaction sites rather than a single-point contact. (wild2019reconstitutionofthe pages 5-5)

Collectively, SRP68 can be annotated as an RNA-binding SRP structural subunit that helps organize the SRP ribonucleoprotein for efficient ribosome engagement and targeting.

2.2 Biological process: co-translational targeting to the ER

A widely cited model of the mammalian SRP cycle is:
- SRP recognizes N-terminal signal sequences on nascent chains and can induce a transient elongation pause.
- SRP–ribosome complexes engage the SRP receptor on the ER membrane.
- The ribosome is transferred to the SEC61 translocon, and translation resumes with co-translational translocation/insertion.
- GTP hydrolysis resets the SRP/SR receptor cycle.
SRP68 contributes to this process as part of the SRP S-domain that engages the ribosome and positions SRP RNA/protein components, even though SRP54 is the key signal-sequence and receptor-docking subunit. (kellogg2022signalrecognitionparticle pages 1-2, wild2019reconstitutionofthe pages 1-2, kellogg2023unravelingsrpbiogenesis pages 26-29)

2.3 Subcellular localization and biogenesis of SRP68-containing complexes

SRP68 is implicated in a nuclear/nucleolar phase of SRP assembly and in export of SRP assembly intermediates:
- A 2024 study reports that SRP biogenesis occurs “in part in the nucleolus,” with SRP proteins associating with nucleolar proteins involved in ribosome biogenesis and nucleolar structure; and that an intact nucleolus is required for proper SRP protein localization. (issa2024thenucleolarphase pages 1-2)
- A 2023 synthesis describes an ordered SRP assembly pathway on 7SL RNA in which SRP19 binds first, followed by SRP68/72 and then SRP9/14, creating a “pre-SRP” complex. SRP68/72 are described as required for pre-SRP export in yeast, with a similar role assumed in mammals via Exportin-5; SRP54 joins later in the cytoplasm to yield mature SRP. (kellogg2023unravelingsrpbiogenesis pages 23-26)
- The 2024 nucleolar biogenesis study also observed SRP proteins (including SRP72 and SRP19 in the reported excerpt) in Cajal bodies, suggesting additional (previously underappreciated) assembly/trafficking steps. (issa2024thenucleolarphase pages 10-13)

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

3.1 2024: nucleolar phase of SRP assembly and proteomics-defined interactomes

Issa et al. (Life Science Alliance; June 2024; https://doi.org/10.26508/lsa.202402614) used quantitative proteomics and localization perturbations to argue that SRP assembly is coordinated with nucleolar organization and ribosome biogenesis. The work reports extensive associations of SRP proteins with nucleolar factors and shows that controlled nucleolar disruption alters SRP protein localization, concluding that an intact nucleolus is required for proper SRP protein localization. This strengthens the “SRP biogenesis is nucleolar” view and provides a modern framework for annotating SRP68 as participating not only in cytosolic targeting but also in upstream assembly and localization control. (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 10-13)

3.2 2023: SRP biogenesis/quality control synthesis emphasizes SRP68/72 as RNA-remodeling and export-linked subunits

A 2023 synthesis on SRP biogenesis and quality control summarizes mechanistic ideas and open questions. It reiterates that SRP68/72 bind 7SL RNA helices 5/6/8 during pre-SRP formation, that SRP68 promotes SRP72 binding, and that Exportin-5 is implicated in mammalian pre-SRP export. It also emphasizes that SRP68’s role includes remodeling/bending 7SL RNA to support ribosome interactions while noting that “little is currently known” about SRP68/72’s exact roles in later steps like SRβ binding and translocon transfer. This is an important expert-level caution: SRP68 is essential and structurally influential, but many mechanistic details remain unresolved. (kellogg2023unravelingsrpbiogenesis pages 26-29, kellogg2023unravelingsrpbiogenesis pages 23-26)

4) Current applications and real-world implementations

4.1 Mechanistic cell biology and ribonucleoprotein biogenesis research

SRP68 is actively used as a handle for studying SRP assembly and localization through:
- GFP-tagged SRP component cell lines and nucleolar perturbations to dissect SRP assembly pathways (e.g., nucleolar disruption by low-dose actinomycin D or ribosomal protein depletion, which re-distributes SRP proteins). (issa2024thenucleolarphase pages 10-13)
- Quantitative proteomics interactome mapping of SRP components to identify nucleolar and quality-control associated proteins linked to SRP biogenesis. (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 10-13)

4.2 Clinical genetics/diagnostics in severe congenital neutropenia

A direct real-world implementation is in rare disease diagnosis: identification of pathogenic biallelic SRP68 variants as a cause of severe congenital neutropenia with marrow maturation arrest, placing SRP68 among SRP-pathway genes relevant to hematologic diagnostic pipelines. (schmaltzpanneau2021identificationofbiallelic pages 1-6)

5) Expert opinions and analysis (authoritative interpretations)

5.1 SRP68 is essential but not the “core catalytic” SRP subunit

Across reviews and mechanistic studies, SRP54 is framed as the central signal-sequence recognition and SR receptor GTPase docking subunit, while SRP68/72 are described as contributing to SRP architecture, RNA remodeling, and ribosome binding. This division of labor is relevant for functional annotation: SRP68 is best categorized as a non-enzymatic RNP structural organizer whose disruption compromises SRP function and triggers downstream stress/quality control. (kellogg2022signalrecognitionparticle pages 1-2, kellogg2023unravelingsrpbiogenesisa pages 26-29, wild2019reconstitutionofthe pages 1-2)

5.2 SRP biogenesis is increasingly viewed as coordinated with nucleolar/ribosome biogenesis

The 2024 nucleolar assembly study explicitly argues that SRP and ribosomes, which collaborate in the cytoplasm, are assembled in the same condensate (nucleolus), and that nucleolar integrity is required for proper SRP localization. This supports an expert-level interpretation that SRP68 function should be annotated in two coupled processes: (i) SRP biogenesis/assembly (nuclear/nucleolar) and (ii) SRP-mediated co-translational targeting (cytosol/ER interface). (issa2024thenucleolarphase pages 1-2)

6) Disease relevance: severe congenital neutropenia due to SRP68 defects

6.1 Patient-level clinical data (statistics)

A 2021 Haematologica report (April 2021; https://doi.org/10.3324/haematol.2020.247825) describes a single sporadic pediatric case with biallelic SRP68 variants ([c.184+2T>C];[exon 1 deletion]) presenting at 6 weeks with:
- WBC 6.1×10^9/L, neutrophils 0.2×10^9/L, monocytes 1.7×10^9/L,
- hemoglobin 7.5 g/dL, platelets 149×10^9/L,
- serial monitoring (n=41) showing persistent profound neutropenia (0.200×10^9/L, range 0–1.800). (schmaltzpanneau2021identificationofbiallelic pages 1-6)

6.2 Functional consequences (granulopoiesis, ER stress, apoptosis)

In patient-derived granulocytic differentiation cultures, SRP68 protein was decreased to 68% of control in immature granulocytic cells and 39% of control in more mature granulocytic cells, with ~6-fold lower granulocytic proliferation. The study also reports increased spliced XBP1 (indicative of IRE1 arm activation of the unfolded protein response) and increased expression of p53-pathway target genes (e.g., BAX, NOXA1, P21, MDM2), consistent with increased p53-dependent apoptosis. (schmaltzpanneau2021identificationofbiallelic pages 6-10)

These findings provide a mechanistic link between SRP68 loss-of-function and ER proteostasis stress in granulopoiesis, consistent with an SRP-mediated translocation defect model. (schmaltzpanneau2021identificationofbiallelic pages 6-10, kellogg2023unravelingsrpbiogenesis pages 46-51)

7) Quantitative mechanistic data: SRP68/72 ribosome binding

Biochemical reconstitution of the human SRP system provides quantitative evidence that SRP68/72 is a major determinant of SRP–ribosome interaction:
- SRP68/72 heterodimer binds the 80S ribosome with KD ~160 ± 20 nM and apparent Hill coefficient ~2.3, supporting multivalent/avidity binding. (wild2019reconstitutionofthe pages 5-5)
- Visual schematics and tables in the same work summarize SRP architecture (Alu vs S-domain) and the SRP68/72 ribosome contact with KD on the order of ~200 nM. (wild2019reconstitutionofthe media 8320e838)

Supporting visual evidence (figures/tables)

The following cropped figures/tables from Wild et al. visually summarize SRP architecture and SRP68/72 binding contributions. (wild2019reconstitutionofthe media 8320e838, wild2019reconstitutionofthe media b811f4ad, wild2019reconstitutionofthe media eee3cd7f)

8) Evidence map summary

The table below links major annotation claims to their strongest supporting sources.

Topic	Key points	Best supporting citations (pqac IDs)
Identity/domains	Human SRP68 corresponds to UniProt Q9UHB9; it is an S-domain SRP subunit that forms a heterodimer with SRP72 on 7SL RNA. Reviews describe an SRP68 TPR-containing RNA-binding/remodeling region that bends 7SL RNA to help position the 5f loop for ribosome contact.	(wild2019reconstitutionofthe pages 1-2, kellogg2023unravelingsrpbiogenesis pages 26-29, kellogg2023unravelingsrpbiogenesisa pages 26-29)
Complex membership	Mammalian SRP contains 6 proteins + 7SL RNA; SRP68 and SRP72 are the larger S-domain proteins, distinct from the Alu-domain pair SRP9/14. SRP68 is therefore a structural/core SRP component rather than a standalone enzyme or transporter.	(kellogg2022signalrecognitionparticle pages 1-2, wild2019reconstitutionofthe pages 1-2, issa2024thenucleolarphase pages 1-2)
Localization/biogenesis	SRP68 participates in a nuclear/nucleolar phase of SRP assembly with 7SL RNA and is implicated in pre-SRP export to the cytoplasm; intact nucleoli are required for proper localization of SRP proteins, and Cajal bodies may host additional assembly steps.	(kellogg2023unravelingsrpbiogenesis pages 23-26, issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 10-13)
Mechanistic role in SRP targeting	SRP68 is best supported as a structural/coordinating subunit: it promotes SRP72 association, remodels 7SL RNA, and contributes to ribosome engagement during co-translational ER targeting. Primary signal-sequence recognition and SRP receptor GTPase docking remain centered on SRP54, so SRP68 is not the primary signal-binding catalyst.	(kellogg2023unravelingsrpbiogenesisa pages 26-29, kellogg2023unravelingsrpbiogenesis pages 26-29, wild2019reconstitutionofthe pages 1-2, kellogg2022signalrecognitionparticle pages 1-2)
Quantitative binding data	Reconstituted human SRP studies showed the full-length SRP68/72 heterodimer binds the 80S ribosome with ~160 ± 20 nM affinity and apparent ultrasensitivity (Hill coefficient ~2.3), consistent with multivalent/avidity-based binding; schematic summaries place SRP68/72 ribosome contact in the ~200 nM range.	(wild2019reconstitutionofthe pages 5-5, wild2019reconstitutionofthe media 8320e838)
Disease association/variant	The clearest direct human disease link is severe congenital neutropenia (SCN) from biallelic SRP68 variants: c.184+2T>C plus exon 1 deletion, causing aberrant splicing and residual but markedly reduced SRP68 protein. Reviews also summarize SRP68 loss as causing ER-stress-related translocation defects.	(schmaltzpanneau2021identificationofbiallelic pages 1-6, schmaltzpanneau2021identificationofbiallelic pages 6-10, kellogg2023unravelingsrpbiogenesis pages 46-51)
Key quantitative clinical/functional data	In the reported SRP68-SCN case: onset at 6 weeks; initial counts WBC 6.1×10^9/L, neutrophils 0.2×10^9/L, monocytes 1.7×10^9/L, Hb 7.5 g/dL, platelets 149×10^9/L; serial counts (n=41) confirmed profound neutropenia. Patient-derived granulocytic cells showed SRP68 protein reduced to 68% in immature and 39% in mature granulocytic cells, with ~6-fold lower granulocytic proliferation and increased spliced XBP1 plus p53-pathway targets.	(schmaltzpanneau2021identificationofbiallelic pages 1-6, schmaltzpanneau2021identificationofbiallelic pages 6-10)
Recent 2023-2024 developments	2024 work strengthened the concept that SRP68 functions within a nucleolar SRP assembly program connected to ribosome biogenesis and possibly Cajal bodies. 2023 synthesis emphasized open mechanistic questions: how SRP68/72 regulate export, ribosome transfer, and quality control, even though their structural role in RNA remodeling and ribosome engagement is increasingly clear.	(issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 10-13, kellogg2023unravelingsrpbiogenesis pages 23-26, kellogg2023unravelingsrpbiogenesisa pages 23-26)

Table: This table summarizes the main functional annotations, mechanistic evidence, quantitative data, and disease relevance for human SRP68 (UniProt Q9UHB9). It is useful as a compact evidence map linking SRP68 biology to the strongest available primary and review sources.

9) Limitations and gaps in the current evidence base

While SRP68/72 structural roles in RNA remodeling and ribosome binding are supported, mechanistic details of how SRP68/72 contributes to later targeting steps (e.g., SRβ engagement and translocon handover) remain explicitly described as incompletely understood in recent synthesis work. (kellogg2023unravelingsrpbiogenesisa pages 26-29, kellogg2023unravelingsrpbiogenesis pages 26-29)
Tool-retrieved 2023–2024 literature did not yield strong, SRP68-specific evidence for mature “biomarker panels” or therapeutic targeting beyond mechanistic proteomics/localization studies and rare-disease genetics; broader proteomics mentions of SRP68 occur but were not supported by extracted evidence snippets.

References (URLs and dates where available)

Wild K, et al. Reconstitution of the human SRP system and quantitative and systematic analysis of its ribosome interactions. Nucleic Acids Research. Jan 2019. https://doi.org/10.1093/nar/gky1324 (wild2019reconstitutionofthe pages 1-2, wild2019reconstitutionofthe pages 5-5, wild2019reconstitutionofthe media 8320e838)
Kellogg MK, Tikhonova EB, Karamyshev AL. Signal Recognition Particle in Human Diseases. Frontiers in Genetics. Jun 2022. https://doi.org/10.3389/fgene.2022.898083 (kellogg2022signalrecognitionparticle pages 1-2)
Issa A, et al. The nucleolar phase of signal recognition particle assembly. Life Science Alliance. Jun 2024. https://doi.org/10.26508/lsa.202402614 (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 10-13)
Schmaltz-Panneau B, et al. Identification of biallelic germline variants of SRP68 in a sporadic case with severe congenital neutropenia. Haematologica. Apr 2021. https://doi.org/10.3324/haematol.2020.247825 (schmaltzpanneau2021identificationofbiallelic pages 1-6, schmaltzpanneau2021identificationofbiallelic pages 6-10)
Kellogg MK. Unraveling SRP biogenesis and quality control: Implications for human disease pathogenesis. 2023 (journal not captured in tool metadata). (kellogg2023unravelingsrpbiogenesis pages 26-29, kellogg2023unravelingsrpbiogenesis pages 23-26, kellogg2023unravelingsrpbiogenesis pages 46-51)

References

(wild2019reconstitutionofthe pages 1-2): Klemens Wild, Keven D Juaire, Komal Soni, Vivekanandan Shanmuganathan, Astrid Hendricks, Bernd Segnitz, Roland Beckmann, and Irmgard Sinning. Reconstitution of the human srp system and quantitative and systematic analysis of its ribosome interactions. Nucleic Acids Research, 47:3184-3196, Jan 2019. URL: https://doi.org/10.1093/nar/gky1324, doi:10.1093/nar/gky1324. This article has 43 citations and is from a highest quality peer-reviewed journal.
(kellogg2022signalrecognitionparticle pages 1-2): Morgana K. Kellogg, Elena B. Tikhonova, and Andrey L. Karamyshev. Signal recognition particle in human diseases. Frontiers in Genetics, Jun 2022. URL: https://doi.org/10.3389/fgene.2022.898083, doi:10.3389/fgene.2022.898083. This article has 30 citations and is from a peer-reviewed journal.
(kellogg2023unravelingsrpbiogenesis pages 26-29): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(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.
(schmaltzpanneau2021identificationofbiallelic pages 6-10): Barbara Schmaltz-Panneau, Anne Pagnier, Séverine Clauin, Julien Buratti, Caroline Marty, Odile Fenneteau, Klaus Dieterich, Blandine Beaupain, Jean Donadieu, Isabelle Plo, and Christine Bellanné-Chantelot. Identification of biallelic germline variants of srp68 in a sporadic case with severe congenital neutropenia. Haematologica, 106:1216-1219, Apr 2021. URL: https://doi.org/10.3324/haematol.2020.247825, doi:10.3324/haematol.2020.247825. This article has 15 citations.
(kellogg2023unravelingsrpbiogenesisa pages 26-29): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(kellogg2023unravelingsrpbiogenesis pages 23-26): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(wild2019reconstitutionofthe pages 5-5): Klemens Wild, Keven D Juaire, Komal Soni, Vivekanandan Shanmuganathan, Astrid Hendricks, Bernd Segnitz, Roland Beckmann, and Irmgard Sinning. Reconstitution of the human srp system and quantitative and systematic analysis of its ribosome interactions. Nucleic Acids Research, 47:3184-3196, Jan 2019. URL: https://doi.org/10.1093/nar/gky1324, doi:10.1093/nar/gky1324. This article has 43 citations and is from a highest quality peer-reviewed journal.
(issa2024thenucleolarphase pages 10-13): 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.
(schmaltzpanneau2021identificationofbiallelic pages 1-6): Barbara Schmaltz-Panneau, Anne Pagnier, Séverine Clauin, Julien Buratti, Caroline Marty, Odile Fenneteau, Klaus Dieterich, Blandine Beaupain, Jean Donadieu, Isabelle Plo, and Christine Bellanné-Chantelot. Identification of biallelic germline variants of srp68 in a sporadic case with severe congenital neutropenia. Haematologica, 106:1216-1219, Apr 2021. URL: https://doi.org/10.3324/haematol.2020.247825, doi:10.3324/haematol.2020.247825. This article has 15 citations.
(kellogg2023unravelingsrpbiogenesis pages 46-51): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(wild2019reconstitutionofthe media 8320e838): Klemens Wild, Keven D Juaire, Komal Soni, Vivekanandan Shanmuganathan, Astrid Hendricks, Bernd Segnitz, Roland Beckmann, and Irmgard Sinning. Reconstitution of the human srp system and quantitative and systematic analysis of its ribosome interactions. Nucleic Acids Research, 47:3184-3196, Jan 2019. URL: https://doi.org/10.1093/nar/gky1324, doi:10.1093/nar/gky1324. This article has 43 citations and is from a highest quality peer-reviewed journal.
(wild2019reconstitutionofthe media b811f4ad): Klemens Wild, Keven D Juaire, Komal Soni, Vivekanandan Shanmuganathan, Astrid Hendricks, Bernd Segnitz, Roland Beckmann, and Irmgard Sinning. Reconstitution of the human srp system and quantitative and systematic analysis of its ribosome interactions. Nucleic Acids Research, 47:3184-3196, Jan 2019. URL: https://doi.org/10.1093/nar/gky1324, doi:10.1093/nar/gky1324. This article has 43 citations and is from a highest quality peer-reviewed journal.
(wild2019reconstitutionofthe media eee3cd7f): Klemens Wild, Keven D Juaire, Komal Soni, Vivekanandan Shanmuganathan, Astrid Hendricks, Bernd Segnitz, Roland Beckmann, and Irmgard Sinning. Reconstitution of the human srp system and quantitative and systematic analysis of its ribosome interactions. Nucleic Acids Research, 47:3184-3196, Jan 2019. URL: https://doi.org/10.1093/nar/gky1324, doi:10.1093/nar/gky1324. This article has 43 citations and is from a highest quality peer-reviewed journal.
(kellogg2023unravelingsrpbiogenesisa pages 23-26): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.

Artifacts

Edison artifact artifact-00

Citations

wild2019reconstitutionofthe pages 1-2
wild2019reconstitutionofthe pages 5-5
issa2024thenucleolarphase pages 1-2
kellogg2023unravelingsrpbiogenesis pages 23-26
issa2024thenucleolarphase pages 10-13
schmaltzpanneau2021identificationofbiallelic pages 1-6
schmaltzpanneau2021identificationofbiallelic pages 6-10
kellogg2022signalrecognitionparticle pages 1-2
kellogg2023unravelingsrpbiogenesis pages 26-29
kellogg2023unravelingsrpbiogenesisa pages 26-29
kellogg2023unravelingsrpbiogenesis pages 46-51
kellogg2023unravelingsrpbiogenesisa pages 23-26
c.184+2T>C
exon 1 deletion
https://doi.org/10.26508/lsa.202402614
https://doi.org/10.3324/haematol.2020.247825
https://doi.org/10.1093/nar/gky1324
https://doi.org/10.3389/fgene.2022.898083
https://doi.org/10.1093/nar/gky1324,
https://doi.org/10.3389/fgene.2022.898083,
https://doi.org/10.26508/lsa.202402614,
https://doi.org/10.3324/haematol.2020.247825,

📚 Additional Documentation

Notes

(SRP68-notes.md)

SRP68 (Q9UHB9) review notes

Identity / overview

SRP68 is the 68 kDa subunit of the signal recognition particle (SRP), a cytosolic ribonucleoprotein
(7SL RNA + 6 proteins: SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). SRP68 and SRP72 form the
heterodimeric "S-domain" component that binds the large/S-domain of 7SL RNA and remodels the RNA
into the conformation required for SRP function and for SRP receptor docking.

UniProt FUNCTION: "Component of the signal recognition particle (SRP) complex, a ribonucleoprotein
complex that mediates the cotranslational targeting of secretory and membrane proteins to the
endoplasmic reticulum (ER)" [file:human/SRP68/SRP68-uniprot.txt].
SUBUNIT: "Heterodimer with SRP72"; "Within the SRP complex, interacts (via C-terminus) with SRP72
(via N-terminus)" [file:human/SRP68/SRP68-uniprot.txt].
DOMAIN: "The N-terminus is required for RNA-binding." Region 52-252 = RNA-binding; region 588-610 =
required for interaction with SRP72 [file:human/SRP68/SRP68-uniprot.txt].

Key functional evidence

RNA remodeling / 7SL (7S) RNA binding: PMID:24700861 "SRP RNA remodeling by SRP68 explains its role
in protein translocation" (crystal structure of SRP68-RBD with SRP19 + 7SL RNA). IMP for 7S RNA
binding from PMID:27899666.
SRP68-SRP72 heterodimer and ribosome interaction: PMID:27899666, PMID:28369529 (X-ray structures).
Cryo-EM of SRP-RNC-SR: PMID:34020957 "Receptor compaction and GTPase rearrangement drive SRP-mediated
cotranslational protein translocation into the ER" (FUNCTION evidence; not in local cache).
Nucleolar pool: PMID:10618370 "Signal recognition particle components in the nucleolus" — SRP proteins
including SRP68 traffic through the nucleolus during SRP assembly. UniProt records nucleolus + cytoplasm.
ER association: PMID:28369529 (SUBCELLULAR LOCATION: Endoplasmic reticulum). MUTAGEN F590L "Diminished
localization to endoplasmic reticulum" reflects SRP72-dependent ER targeting.

Annotation review decisions

Core MF: SRP/7SL (7S) RNA binding (GO:0008312) + signal recognition particle binding (GO:0005047).
Core CC: signal recognition particle, ER targeting (GO:0005786) / SRP (GO:0048500).
Core BP: SRP-dependent cotranslational protein targeting to membrane (GO:0006614) and the
signal-sequence-recognition child (GO:0006617).
GO:0030942 "endoplasmic reticulum signal sequence receptor activity" (IEA/InterPro): the SRP receptor
(signal-sequence-receptor) activity is a property of the SRP receptor (SRPR/SRPRB), not of SRP68 itself,
which is a 7SL-RNA-binding scaffold subunit. The InterPro mapping over-extends. MARK_AS_OVER_ANNOTATED.
(Some sources also use SSR for the TRAP complex; not SRP68.)
GO:0009410 "response to xenobiotic stimulus" (IDA, PMID:18089836): SRP68/SRP72 were pulled out as
binding targets of the anticancer drug TAS-103 on drug-immobilized affinity beads; this is an
affinity-capture observation, peripheral to SRP68's core SRP function. KEEP_AS_NON_CORE.
GO:0005730 nucleolus: real (PMID:10618370) but reflects SRP assembly trafficking, not the core ER
targeting site of action. KEEP_AS_NON_CORE.
protein binding (GO:0005515) IPI rows: many are SRP72 (O76094) or SRP19 (P09132) captures — i.e. the
informative interactions are already captured by GO:0005047/GO:0019904; CFTR (P13569) captures are from
CFTR-interactome screens. Bare protein binding kept as KEEP_AS_NON_CORE per guidelines.
GO:0043022 ribosome binding (contributes_to, IMP PMID:27899666): SRP68/72 contribute to SRP-ribosome
interaction; supported. KEEP as supporting (not the single core MF but valid).

Disease

Biallelic SRP68 variants -> severe congenital neutropenia (SCN10) PMID:32273475. Not a GO BP per se.

Falcon deep-research findings (incorporated 2026-06)

Reconstituted human SRP shows the SRP68/72 heterodimer binds the 80S ribosome with ultrasensitive, avidity-driven nanomolar affinity dominated by the SRP72 C-terminus PMID:30649417. Added to ribosome binding (GO:0043022) supported_by.
SRP54 binds the ribosome via a two-step mechanism while SRP RNA alone does not bind the ribosome PMID:30649417.
A modern nucleolar phase of SRP assembly: SRP proteins (incl. SRP68) associate with scores of nucleolar/ribosome-biogenesis factors and require an intact nucleolus for proper localization; some SRP proteins are in Cajal bodies PMID:38858088. Added to nucleolus (GO:0005730) supported_by.
SRP and ribosomes are assembled in the same condensate (nucleolus), suggesting coordinated biogenesis PMID:38858088.
Disease: biallelic germline SRP68 loss-of-function variants cause severe congenital neutropenia, with patient granulopoiesis defects, ER stress (spliced XBP1) and p53-pathway activation [PMID:32273475 (Haematologica 2021; abstract not in PubMed, verified by title/journal/MeSH "Neutropenia"; Congenital Bone Marrow Failure Syndromes)]. Reference added (already cited in description).
SRP68 remains best classified as a non-enzymatic RNA-binding S-domain scaffold; SRP54 is the signal-sequence/receptor GTPase subunit (consistent with existing review framing).

Pn Notes

(SRP68-pn-notes.md)

SRP68 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9UHB9
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-11
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/SRP68/SRP68-ai-review.yaml
AIGR review HTML: missing - genes/human/SRP68/SRP68-ai-review.html
Gene notes: present - genes/human/SRP68/SRP68-notes.md
GOA TSV: present - genes/human/SRP68/SRP68-goa.tsv
UniProt record: present - genes/human/SRP68/SRP68-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/SRP68.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/SRP68.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/SRP68/SRP68-deep-research-falcon.md

AIGR Review Snapshot

Description: SRP68 is the 68 kDa subunit of the signal recognition particle (SRP), a cytosolic ribonucleoprotein composed of the 7SL (7S) RNA and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). SRP68 and SRP72 form the heterodimeric "S-domain" module of SRP; SRP68 binds the large/S-domain of the 7SL RNA through an N-terminal RNA-binding domain (residues ~52-252) and, via its C-terminus, recruits SRP72. SRP68 is an RNA-binding scaffold subunit, not a GTPase. Its RNA-binding domain is a tetratricopeptide-like module that bends the SRP RNA at a three-way junction and remodels the conserved 5f loop, a rearrangement required for SRP function in cotranslational targeting and for productive engagement of the SRP receptor. Within SRP, the particle binds the signal sequence of nascent secretory and membrane proteins emerging from the translating ribosome and delivers the ribosome-nascent chain complex to the ER-anchored SRP receptor, where translocation through the Sec61 channel proceeds. SRP68 is predominantly cytosolic; pools are also detected in the nucleolus (reflecting SRP assembly trafficking) and at the endoplasmic reticulum. Biallelic germline SRP68 variants cause severe congenital neutropenia (SCN10).
Existing/core annotation action counts: ACCEPT: 25; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 1

PN Consistency Summary

Consistency: Strong and mutually consistent. Deep research, review YAML, and PN annotation all describe SRP68 as the 68 kDa S-domain SRP subunit that binds/remodels 7SL RNA (opening the 5f loop) and heterodimerizes with SRP72. 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:0005786 SRP membership). The disease link (SCN10, PMID:32273475) and nucleolar assembly pool 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:24700861 SRP68-RBD RNA remodeling; PMID:27899666 SRP68/72 S-domain structures; PMID:16672232 RNA/SRP72 binding domains; 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). No edits warranted.

Full Consistency Review

UniProt: Q9UHB9 · 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 SRP68 as the 68 kDa S-domain SRP subunit that binds/remodels 7SL RNA (opening the 5f loop) and heterodimerizes with SRP72. 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:0005786 SRP membership). The disease link (SCN10, PMID:32273475) and nucleolar assembly pool 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 SRP68. Note the review independently flags GO:0030942 (ER signal-sequence receptor activity, IEA) as over-annotated — that activity belongs to SRPR/SRPRB, not the SRP S-domain scaffold; internal QC unrelated to the PN node.
Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:24700861 SRP68-RBD RNA remodeling; PMID:27899666 SRP68/72 S-domain structures; PMID:16672232 RNA/SRP72 binding domains; 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). No edits warranted.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-11
review_yaml: genes/human/SRP68/SRP68-ai-review.yaml
PN workbook rows: 1

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

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

SRP68

Gene Description

Existing Annotations Review

Core Functions

RNA-binding scaffold subunit of the signal recognition particle that binds and remodels the SRP (7SL) RNA, opening the conserved 5f loop required for cotranslational targeting.

Component of the SRP S-domain that, in heterodimer with SRP72, mediates SRP-dependent cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research report: Human SRP68 (UniProt Q9UHB9) functional annotation

Executive summary

0) Mandatory verification of gene/protein identity

1) Key concepts and definitions (current understanding)

1.1 Signal recognition particle (SRP)

1.2 SRP68 definition in the context of the SRP cycle

2) SRP68 molecular function, biological processes, and localization

2.1 Molecular function (what SRP68 “does”)

2.2 Biological process: co-translational targeting to the ER

2.3 Subcellular localization and biogenesis of SRP68-containing complexes

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

3.1 2024: nucleolar phase of SRP assembly and proteomics-defined interactomes

3.2 2023: SRP biogenesis/quality control synthesis emphasizes SRP68/72 as RNA-remodeling and export-linked subunits

4) Current applications and real-world implementations

4.1 Mechanistic cell biology and ribonucleoprotein biogenesis research

4.2 Clinical genetics/diagnostics in severe congenital neutropenia

5) Expert opinions and analysis (authoritative interpretations)

5.1 SRP68 is essential but not the “core catalytic” SRP subunit

5.2 SRP biogenesis is increasingly viewed as coordinated with nucleolar/ribosome biogenesis

6) Disease relevance: severe congenital neutropenia due to SRP68 defects

6.1 Patient-level clinical data (statistics)

6.2 Functional consequences (granulopoiesis, ER stress, apoptosis)

7) Quantitative mechanistic data: SRP68/72 ribosome binding

Supporting visual evidence (figures/tables)

8) Evidence map summary

9) Limitations and gaps in the current evidence base

References (URLs and dates where available)

Artifacts

Citations

📚 Additional Documentation

Notes

SRP68 (Q9UHB9) review notes

Identity / overview

Key functional evidence

Annotation review decisions

Disease

Falcon deep-research findings (incorporated 2026-06)

Pn Notes

SRP68 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

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

Projected GO annotations (2)

Note

📄 View Raw YAML