SRPRB

Summary

SRPRB (SRP receptor subunit beta, HGNC:24085) is a protein-coding gene on chromosome 3q22.1, encoding Signal recognition particle receptor subunit beta (Q9Y5M8). Component of the signal recognition particle (SRP) complex receptor (SR). It is a selective cancer dependency (DepMap: 71.4% of cell lines).

The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane.

Source: NCBI Gene 58477 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 43 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 71.4% of screened cell lines
• MANE Select transcript: NM_001379313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24085
Approved symbol	SRPRB
Name	SRP receptor subunit beta
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Aliases	APMCF1, SR-beta
Ensembl gene	ENSG00000144867
Ensembl biotype	protein_coding
OMIM	616883
Entrez	58477

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000466490, ENST00000466636, ENST00000481356, ENST00000484684, ENST00000494297, ENST00000678299, ENST00000961954

RefSeq mRNA: 2 — MANE Select: NM_001379313 NM_001379313, NM_021203

CCDS: CCDS3081

Canonical transcript exons

ENST00000678299 — 7 exons

Exon	Start	End
ENSE00001018374	133806609	133806703
ENSE00001872786	133819553	133821492
ENSE00003494572	133815590	133815726
ENSE00003523838	133807746	133807823
ENSE00003567072	133811117	133811199
ENSE00003614007	133816878	133816932
ENSE00003906272	133805815	133806002

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.7115 / max 330.1643, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38696	49.6994	1822
38694	0.0120	4

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.05	gold quality
parotid gland	UBERON:0001831	97.36	gold quality
islet of Langerhans	UBERON:0000006	97.07	gold quality
pancreas	UBERON:0001264	97.03	gold quality
tongue squamous epithelium	UBERON:0006919	96.17	gold quality
cartilage tissue	UBERON:0002418	96.04	gold quality
tibia	UBERON:0000979	95.86	gold quality
adrenal tissue	UBERON:0018303	95.40	gold quality
esophagus squamous epithelium	UBERON:0006920	95.28	gold quality
epithelium of nasopharynx	UBERON:0001951	95.26	gold quality
stromal cell of endometrium	CL:0002255	95.25	gold quality
epithelium of esophagus	UBERON:0001976	95.03	gold quality
periodontal ligament	UBERON:0008266	94.58	gold quality
pericardium	UBERON:0002407	94.55	gold quality
corpus epididymis	UBERON:0004359	94.41	gold quality
choroid plexus epithelium	UBERON:0003911	94.33	gold quality
squamous epithelium	UBERON:0006914	93.89	gold quality
nephron tubule	UBERON:0001231	93.82	gold quality
trachea	UBERON:0003126	93.63	gold quality
palpebral conjunctiva	UBERON:0001812	93.51	gold quality
tonsil	UBERON:0002372	93.41	gold quality
liver	UBERON:0002107	93.32	gold quality
type B pancreatic cell	CL:0000169	93.29	gold quality
middle temporal gyrus	UBERON:0002771	93.26	gold quality
adult organism	UBERON:0007023	93.13	gold quality
right testis	UBERON:0004534	93.12	gold quality
esophagus mucosa	UBERON:0002469	93.06	gold quality
left testis	UBERON:0004533	92.95	gold quality
pharyngeal mucosa	UBERON:0000355	92.84	gold quality
caput epididymis	UBERON:0004358	92.72	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	90.78
E-CURD-122	yes	36.88
E-HCAD-11	yes	17.52
E-ENAD-27	no	786.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 71.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• APMCF1 may be the gene coding human signal recognition particle receptor beta and belongs to the small-G protein superfamily. Its strong expression pattern in colon cancer suggests it may play a role in colon cancer development. (PMID:12918107)
• APMCF1 participates at least partially in cell cycle regulation through regulating genes such as p21 and TIMP3. (PMID:17080297)
• Results show that SRPRB promotes cell apoptosis through NF-kappaB activation. Its expression is regulated by SERP1 in pancreatic ductal adenocarcinoma. (PMID:28902358)
• Variation in SRPRB was associated with lower blood alcohol content in Korean subjects, suggesting likely involvement in alcohol metabolism and possible association with the development of alcohol-related diseases in Korea. (PMID:31002879)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sxph	ENSDARG00000013240
mus_musculus	Srprb	ENSMUSG00000032553
rattus_norvegicus	Tf	ENSRNOG00000030625

Paralogs (3): LTF (ENSG00000012223), TF (ENSG00000091513), MELTF (ENSG00000163975)

Protein

Protein identifiers

Signal recognition particle receptor subunit beta — Q9Y5M8 (reviewed: Q9Y5M8)

Alternative names: Protein APMCF1

All UniProt accessions (4): Q9Y5M8, C9J5Z8, H7C4H2, Q549N5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the signal recognition particle (SRP) complex receptor (SR). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system. May mediate the membrane association of SR.

Subunit / interactions. Heterodimer with SRPRA.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the SRP receptor beta subunit family.

RefSeq proteins (2): NP_001366242, NP_067026 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019009	SRP_receptor_beta_su	Family
IPR024156	Small_GTPase_ARF	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF09439

Enzyme classification (BRENDA):

• EC 3.6.5.4 — signal-recognition-particle GTPase (BRENDA: 41 organisms, 49 substrates, 10 inhibitors, 41 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0005–0.1764	36
ATP	0.0249	1

UniProt features (11 total): binding site 4, sequence conflict 2, modified residue 2, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7NFX	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5M8-F1	87.30	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 71–79; 92–95; 120; 248

Post-translational modifications (2): 112, 214

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 161 (showing top): HORIUCHI_WTAP_TARGETS_DN, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WEI_MYCN_TARGETS_WITH_E_BOX, MODULE_331, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, MODULE_480, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE

GO Biological Process (2): SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition (GO:0006617), protein targeting to ER (GO:0045047)

GO Molecular Function (3): GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), signal recognition particle receptor complex (GO:0005785), endoplasmic reticulum membrane (GO:0005789), cytoplasmic microtubule (GO:0005881), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Translation	1
IRE1alpha activates chaperones	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
SRP-dependent cotranslational protein targeting to membrane	1
protein-containing complex assembly	1
protein targeting	1
establishment of protein localization to endoplasmic reticulum	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
rough endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
microtubule	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRPRB	SRPRA	P08240	997
SRPRB	SRP54	P13624	867
SRPRB	SRP68	Q9UHB9	853
SRPRB	SRP72	O76094	821
SRPRB	SEC61A1	P38378	702
SRPRB	SRP19	P09132	690
SRPRB	SRP14	P37108	678
SRPRB	SRP9	P49458	644
SRPRB	SEC62	Q99442	582
SRPRB	RPN1	P04843	578
SRPRB	SEC63	Q9UGP8	576
SRPRB	SPCS2	Q15005	560
SRPRB	SYVN1	Q86TM6	551
SRPRB	FDFT1	P37268	548
SRPRB	UBL4A	P11441	526

IntAct

216 interactions, top by confidence:

A	B	Type	Score
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STX5	GOSR2	psi-mi:“MI:0914”(association)	0.670
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
RHEB	UBB	psi-mi:“MI:0914”(association)	0.530
USP14	PSMD11	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
ARF5	ARF4	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SRPRB	SRPRB	psi-mi:“MI:0407”(direct interaction)	0.440
ALPK3	SRPRB	psi-mi:“MI:0915”(physical association)	0.400
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Baz2b	CACNA2D1	psi-mi:“MI:0914”(association)	0.350
Batf3	SF3B2	psi-mi:“MI:0914”(association)	0.350
Tnpo1	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Tube1		psi-mi:“MI:0914”(association)	0.350
Atp7a	RTL8C	psi-mi:“MI:0914”(association)	0.350
NCSTN	ESYT2	psi-mi:“MI:0914”(association)	0.350
Get4	BAG6	psi-mi:“MI:0914”(association)	0.350
TENT5A	GOLGA8R	psi-mi:“MI:0914”(association)	0.350

BioGRID (504): SRPRB (Affinity Capture-MS), SRPRB (Affinity Capture-MS), SRPRB (Affinity Capture-MS), SRPR (Affinity Capture-MS), DCAKD (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), VRK2 (Affinity Capture-MS), ARL5B (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), TMX2 (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS), TTC1 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS)

ESM2 similar proteins: A2YPT7, A3KPF2, A3KPP3, A7SKJ3, A7TTC4, O01757, O75002, O95163, P40123, P47123, P47758, P52481, P53738, Q09454, Q14AI0, Q2TAQ1, Q32PE2, Q3SYG4, Q4FZX7, Q501D5, Q54ML6, Q5JS54, Q5R5X8, Q5YLB4, Q66I84, Q6AX60, Q6C619, Q6GL75, Q6GMB0, Q6PD82, Q74ZJ1, Q7TT37, Q7XI75, Q811G0, Q84W92, Q8LPK4, Q8LPL6, Q8VHU4, Q8WND5, Q8X0S4

Diamond homologs: O13950, P47758, Q4FZX7, Q9Y5M8, P36057, Q06849, Q6P068

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SRP54	“up-regulates activity”	SRPRB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 234 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	5	15.9×	9e-04
Downstream signal transduction	5	12.7×	2e-03
SRP-dependent cotranslational protein targeting to membrane	13	8.7×	2e-06
Maturation of DENV proteins	6	8.5×	2e-03
Regulation of RAS by GAPs	6	7.7×	3e-03
ER to Golgi Anterograde Transport	8	7.1×	1e-03
COPI-mediated anterograde transport	9	6.6×	9e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	9	6.3×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	6	18.6×	3e-04
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	7	12.2×	3e-04
cell surface receptor protein tyrosine kinase signaling pathway	12	10.8×	2e-06
ERAD pathway	8	7.5×	2e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	10	7.0×	3e-04
protein autophosphorylation	9	6.7×	1e-03
positive regulation of MAPK cascade	13	5.4×	3e-04
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	13	5.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

43 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1094 predictions. Top by Δscore:

Variant	Effect	Δscore
3:133805999:C:G	donor_gain	1.0000
3:133807744:A:AC	acceptor_loss	1.0000
3:133807744:A:AG	acceptor_gain	1.0000
3:133807745:G:GG	acceptor_gain	1.0000
3:133807745:G:GT	acceptor_loss	1.0000
3:133807745:GTT:G	acceptor_gain	1.0000
3:133807820:CAGGG:C	donor_loss	1.0000
3:133807821:AGGGT:A	donor_loss	1.0000
3:133807822:GG:G	donor_gain	1.0000
3:133807822:GGGTA:G	donor_loss	1.0000
3:133807823:GG:G	donor_gain	1.0000
3:133807824:GT:G	donor_loss	1.0000
3:133815589:GGGCT:G	acceptor_gain	1.0000
3:133815676:G:GG	donor_gain	1.0000
3:133815718:A:AG	donor_gain	1.0000
3:133815723:CAAG:C	donor_loss	1.0000
3:133815727:GTGCC:G	donor_loss	1.0000
3:133816872:TTACA:T	acceptor_loss	1.0000
3:133816873:TACA:T	acceptor_loss	1.0000
3:133816874:ACAGA:A	acceptor_loss	1.0000
3:133816875:CAGAT:C	acceptor_loss	1.0000
3:133816876:A:AG	acceptor_gain	1.0000
3:133816876:AGA:A	acceptor_loss	1.0000
3:133816877:G:GA	acceptor_gain	1.0000
3:133816877:GA:G	acceptor_gain	1.0000
3:133816877:GAT:G	acceptor_gain	1.0000
3:133816877:GATA:G	acceptor_gain	1.0000
3:133816877:GATAT:G	acceptor_gain	1.0000
3:133816928:GAACT:G	donor_gain	1.0000
3:133816929:AACT:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000175485 (3:133818420 A>G), RS1000227919 (3:133784916 T>A), RS1000247711 (3:133818104 T>G), RS1000277957 (3:133798337 C>T), RS1000349254 (3:133823605 G>C), RS1000402282 (3:133792996 G>A,T), RS1000470716 (3:133811748 A>G,T), RS1000481391 (3:133824186 T>C), RS1000522725 (3:133812061 A>G), RS1000524974 (3:133811443 C>T), RS1000656903 (3:133793207 G>A), RS1000828412 (3:133798166 T>C,G), RS1000930993 (3:133806125 C>A), RS1000988983 (3:133818324 C>G), RS1001150586 (3:133814431 G>A)

Disease associations

OMIM: gene MIM:616883 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001103_3	Alcohol consumption (transferrin glycosylation)	2.000000e-17
GCST005993_69	Mean corpuscular hemoglobin	3.000000e-16
GCST006011_100	Mean corpuscular volume	4.000000e-14
GCST010105_63	Nicotine dependence symptom count	2.000000e-06
GCST90002390_163	Mean corpuscular hemoglobin	1.000000e-17
GCST90002392_310	Mean corpuscular volume	4.000000e-13
GCST90002403_551	Red blood cell count	3.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0004527	mean corpuscular hemoglobin
EFO:0009262	nicotine dependence symptom count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295993 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17376019	Metabolism/PK	3	ethanol

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17376019	SRPRB	3	2.00	1	ethanol

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
bisphenol A	affects expression, increases expression	2
Estradiol	affects binding, increases reaction, increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Particulate Matter	increases abundance, increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
dicrotophos	decreases expression	1
tremortin	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
perfluorooctanoic acid	affects methylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
calfactant	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118952	Binding	Binding affinity to SRPRB in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.