SSR2

Summary

SSR2 (signal sequence receptor subunit 2, HGNC:11324) is a protein-coding gene on chromosome 1q22, encoding Translocon-associated protein subunit beta (P43308). TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.

The signal sequence receptor (SSR) is a glycosylated endoplasmic reticulum (ER) membrane receptor associated with protein translocation across the ER membrane. The SSR consists of 2 subunits, a 34-kD glycoprotein (alpha-SSR or SSR1) and a 22-kD glycoprotein (beta-SSR or SSR2). The human beta-signal sequence receptor gene (SSR2) maps to chromosome bands 1q21-q23.

Source: NCBI Gene 6746 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_003145

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11324
Approved symbol	SSR2
Name	signal sequence receptor subunit 2
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	TLAP, TRAPB
Ensembl gene	ENSG00000163479
Ensembl biotype	protein_coding
OMIM	600867
Entrez	6746

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 19 protein_coding, 8 retained_intron, 4 nonsense_mediated_decay

ENST00000295702, ENST00000368311, ENST00000466905, ENST00000467041, ENST00000472467, ENST00000472898, ENST00000473699, ENST00000474377, ENST00000480176, ENST00000480567, ENST00000484320, ENST00000488179, ENST00000496742, ENST00000526212, ENST00000529008, ENST00000531790, ENST00000531917, ENST00000532074, ENST00000905734, ENST00000905735, ENST00000905736, ENST00000905737, ENST00000905738, ENST00000923682, ENST00000923683, ENST00000923684, ENST00000923685, ENST00000923686, ENST00000952326, ENST00000952327, ENST00000952328

RefSeq mRNA: 1 — MANE Select: NM_003145 NM_003145

CCDS: CCDS1126

Canonical transcript exons

ENST00000295702 — 6 exons

Exon	Start	End
ENSE00001952855	156009048	156009650
ENSE00002206749	156020888	156020951
ENSE00003676903	156014961	156015069
ENSE00003760277	156020013	156020167
ENSE00003786666	156011810	156011887
ENSE00003786893	156018270	156018368

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 215.9247 / max 1125.1196, expressed in 1826 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15060	210.1550	1826
201752	3.5618	1518
15056	0.8817	536
15057	0.5765	324
15059	0.4931	283
15058	0.2565	99

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.42	gold quality
islet of Langerhans	UBERON:0000006	99.39	gold quality
stromal cell of endometrium	CL:0002255	99.33	gold quality
ganglionic eminence	UBERON:0004023	99.31	gold quality
pancreas	UBERON:0001264	99.22	gold quality
endocervix	UBERON:0000458	99.20	gold quality
left adrenal gland	UBERON:0001234	99.17	gold quality
left ovary	UBERON:0002119	99.16	gold quality
cortical plate	UBERON:0005343	99.16	gold quality
granulocyte	CL:0000094	99.15	gold quality
left adrenal gland cortex	UBERON:0035825	99.15	gold quality
right adrenal gland	UBERON:0001233	99.11	gold quality
right ovary	UBERON:0002118	99.10	gold quality
adrenal cortex	UBERON:0001235	99.06	gold quality
right adrenal gland cortex	UBERON:0035827	99.04	gold quality
gall bladder	UBERON:0002110	99.02	gold quality
adrenal gland	UBERON:0002369	98.99	gold quality
rectum	UBERON:0001052	98.98	gold quality
smooth muscle tissue	UBERON:0001135	98.98	gold quality
body of stomach	UBERON:0001161	98.93	gold quality
ovary	UBERON:0000992	98.92	gold quality
lymph node	UBERON:0000029	98.90	gold quality
ventricular zone	UBERON:0003053	98.90	gold quality
left uterine tube	UBERON:0001303	98.86	gold quality
upper lobe of left lung	UBERON:0008952	98.86	gold quality
body of uterus	UBERON:0009853	98.86	gold quality
stomach	UBERON:0000945	98.81	gold quality
leukocyte	CL:0000738	98.79	gold quality
upper lobe of lung	UBERON:0008948	98.78	gold quality
monocyte	CL:0000576	98.77	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	42.69
E-HCAD-1	yes	31.92
E-HCAD-9	yes	18.59
E-MTAB-10042	yes	10.50
E-CURD-114	yes	8.11
E-CURD-112	yes	6.02
E-MTAB-7606	no	817.63
E-MTAB-6379	no	739.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting SSR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-2467-5P	97.36	67.71	991

Literature-anchored findings (GeneRIF, showing 2)

• The Unfolded Protein Response (UPR) to ER stress was shown as an inducer of SSR2 via transcriptional regulation through X-Box Binding Protein 1s (XBP1s). (PMID:27180333)
• Translocon-Associated Protein Complex (TRAP) is Crucial for Co-Translational Translocation of Pre-Proinsulin. (PMID:33137310)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ssr2	ENSDARG00000005230
mus_musculus	Ssr2	ENSMUSG00000041355
rattus_norvegicus	Ssr2	ENSRNOG00000019940
drosophila_melanogaster	SsRbeta	FBGN0011016
caenorhabditis_elegans		WBGENE00010678
caenorhabditis_elegans		WBGENE00020216

Protein

Protein identifiers

Translocon-associated protein subunit beta — P43308 (reviewed: P43308)

Alternative names: Signal sequence receptor subunit beta

All UniProt accessions (8): P43308, E9PJ35, E9PLP2, E9PN13, E9PNP2, E9PQ05, E9PQI4, E9PQJ7

UniProt curated annotations — full annotation on UniProt →

Function. TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.

Subunit / interactions. Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma. Interacts with STING1.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the TRAP-beta family.

RefSeq proteins (1): NP_003136* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008856	TRAP_beta	Family

Pfam: PF05753

UniProt features (8 total): topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9N9J	ELECTRON MICROSCOPY	3.2
9YGY	ELECTRON MICROSCOPY	4.1
8B6L	ELECTRON MICROSCOPY	7.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43308-F1	91.67	0.78

Functional residue map

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

Glycosylation sites (2): 88, 104

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 169 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MORF_UBE2I, AAGCCAT_MIR135A_MIR135B, GOBP_PROTEIN_TARGETING, HSIAO_HOUSEKEEPING_GENES, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, MORF_SKP1A, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_CTBP1, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, chr1q22

GO Biological Process (2): in utero embryonic development (GO:0001701), cotranslational protein targeting to membrane (GO:0006613)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	1
protein targeting to membrane	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1141 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSR2	SSR1	P43307	999
SSR2	SSR3	Q9UNL2	996
SSR2	SSR4	P51571	960
SSR2	RHBDF2	Q6PJF5	950
SSR2	TRAM1	Q15629	889
SSR2	SEC61A1	P38378	829
SSR2	EXOC2	Q96KP1	827
SSR2	SEC61B	P38390	753
SSR2	STING1	Q86WV6	675
SSR2	RNF5	Q99942	614
SSR2	SEC63	Q9UGP8	575
SSR2	MAVS	Q7Z434	569
SSR2	TBK1	Q9UHD2	569
SSR2	RPL31	P12947	528
SSR2	SST	P01166	527

IntAct

11 interactions, top by confidence:

A	B	Type	Score
STING1	SSR2	psi-mi:“MI:0915”(physical association)	0.480
STING1	SSR2	psi-mi:“MI:0914”(association)	0.480
BTAF1	SSR2	psi-mi:“MI:0915”(physical association)	0.400
SSR2	SSR3	psi-mi:“MI:0915”(physical association)	0.400
SSR2	iglC2	psi-mi:“MI:0915”(physical association)	0.370
SSR2	SEC61B	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SSR2	PEX1	psi-mi:“MI:0914”(association)	0.350
	SSR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (70): SSR2 (Affinity Capture-RNA), RPN1 (Co-fractionation), SSR2 (Co-fractionation), UQCRC2 (Co-fractionation), SSR2 (Affinity Capture-RNA), SSR2 (Proximity Label-MS), SSR3 (Proximity Label-MS), SSR4 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), HEMK1 (Affinity Capture-MS), AP3M1 (Affinity Capture-MS), INTS12 (Affinity Capture-MS), SRPR (Co-purification), SRPR (Co-fractionation)

ESM2 similar proteins: A0JN27, A5PJI5, A5PKD9, B5DFK7, D3Z7P3, D3ZTX0, G3MWR8, G3V9T7, O43681, O54984, O94925, P13264, P16298, P23438, P43308, Q15303, Q15363, Q1LZ53, Q28D01, Q2HJ19, Q4V899, Q4W5Z4, Q5E9E4, Q5JUK3, Q5NVE6, Q5RIC0, Q5TA45, Q5XIJ5, Q5ZIH0, Q5ZJX1, Q61527, Q62956, Q63524, Q6AY25, Q6NVL5, Q6PCB6, Q6ZPR4, Q78IS1, Q7RTP6, Q8CJ19

Diamond homologs: P23438, P43308, Q22169, Q5E9E4, Q9CPW5, Q54VI6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SSR2	“form complex”	“TRAP complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

973 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156009647:CCAG:C	acceptor_gain	1.0000
1:156009648:CAG:C	acceptor_gain	1.0000
1:156009648:CAGC:C	acceptor_gain	1.0000
1:156009650:GC:G	acceptor_loss	1.0000
1:156009651:C:CC	acceptor_gain	1.0000
1:156011807:TACAA:T	donor_loss	1.0000
1:156011808:A:AC	donor_gain	1.0000
1:156011809:C:CC	donor_gain	1.0000
1:156011809:C:CT	donor_loss	1.0000
1:156011809:CA:C	donor_gain	1.0000
1:156011809:CAAA:C	donor_gain	1.0000
1:156011839:C:CA	donor_gain	1.0000
1:156011884:CAAT:C	acceptor_gain	1.0000
1:156011888:C:CC	acceptor_gain	1.0000
1:156011889:T:C	acceptor_loss	1.0000
1:156018364:CAGCA:C	acceptor_gain	1.0000
1:156018367:CA:C	acceptor_gain	1.0000
1:156018369:C:CC	acceptor_gain	1.0000
1:156020008:GTTAC:G	donor_loss	1.0000
1:156020009:TTACC:T	donor_loss	1.0000
1:156020010:TACC:T	donor_loss	1.0000
1:156020011:A:AT	donor_loss	1.0000
1:156020012:C:CT	donor_loss	1.0000
1:156020163:CTCAT:C	acceptor_gain	1.0000
1:156020165:CAT:C	acceptor_gain	1.0000
1:156020167:TCTT:T	acceptor_loss	1.0000
1:156020168:C:A	acceptor_loss	1.0000
1:156020168:C:CC	acceptor_gain	1.0000
1:156020170:T:C	acceptor_gain	1.0000
1:156020170:T:TC	acceptor_gain	1.0000

AlphaMissense

1166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156009601:G:C	P164R	1.000
1:156009601:G:T	P164H	1.000
1:156009607:C:T	G162D	1.000
1:156009608:C:G	G162R	1.000
1:156009616:G:C	P159R	1.000
1:156009616:G:T	P159H	1.000
1:156009625:A:C	M156R	1.000
1:156009625:A:T	M156K	1.000
1:156009628:A:T	V155D	1.000
1:156009631:C:T	G154E	1.000
1:156009632:C:G	G154R	1.000
1:156009632:C:T	G154R	1.000
1:156009633:A:C	F153L	1.000
1:156009633:A:T	F153L	1.000
1:156009635:A:G	F153L	1.000
1:156009637:G:T	A152D	1.000
1:156009642:C:A	W150C	1.000
1:156009642:C:G	W150C	1.000
1:156009644:A:G	W150R	1.000
1:156009644:A:T	W150R	1.000
1:156011815:G:C	H146D	1.000
1:156011822:G:C	F143L	1.000
1:156011822:G:T	F143L	1.000
1:156011824:A:G	F143L	1.000
1:156011834:A:C	F139L	1.000
1:156011834:A:T	F139L	1.000
1:156011835:A:C	F139C	1.000
1:156011836:A:G	F139L	1.000
1:156011853:A:G	I133T	1.000
1:156011853:A:T	I133N	1.000

dbSNP variants (sampled 300 via entrez): RS1000022759 (1:156020859 G>A,T), RS1000461854 (1:156012857 C>A,T), RS1000816775 (1:156017896 C>T), RS1001115883 (1:156011035 G>A), RS1001527171 (1:156011467 A>G,T), RS1001586811 (1:156018474 G>A), RS1002236438 (1:156016649 CTAAACG>C), RS1002473316 (1:156009784 T>A), RS1002818383 (1:156015233 T>C), RS1003129731 (1:156015521 AAAAAAAAAAAAAAAATATATATATAT>A), RS1003824695 (1:156008793 A>C,G), RS1004173405 (1:156008921 T>A), RS1004618385 (1:156014058 A>C,G), RS1004805660 (1:156019739 C>T), RS1005142589 (1:156012420 G>C)

Disease associations

OMIM: gene MIM:600867 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases methylation	4
Cyclosporine	increases expression	4
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Air Pollutants	affects expression, affects cotreatment, increases abundance, increases oxidation	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CD 437	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Diazinon	increases methylation	1
Diuron	decreases expression	1
Mercury	decreases expression	1
Methapyrilene	increases methylation	1
Dihydrotestosterone	increases expression	1
Asbestos, Serpentine	increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression	1
Sertraline	increases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	increases oxidation, affects cotreatment	1

Clinical trials (associated diseases)

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