TRAT1

Summary

TRAT1 (T cell receptor associated transmembrane adaptor 1, HGNC:30698) is a protein-coding gene on chromosome 3q13.13, encoding T-cell receptor-associated transmembrane adapter 1 (Q6PIZ9). Stabilizes the TCR (T-cell antigen receptor)/CD3 complex at the surface of T-cells.

Predicted to enable transmembrane receptor protein tyrosine kinase adaptor activity. Acts upstream of or within negative regulation of receptor recycling; negative regulation of transport; and positive regulation of signal transduction. Located in centriolar satellite; mitotic spindle; and plasma membrane. Part of T cell receptor complex.

Source: NCBI Gene 50852 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_016388

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30698
Approved symbol	TRAT1
Name	T cell receptor associated transmembrane adaptor 1
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Aliases	HSPC062, TRIM
Ensembl gene	ENSG00000163519
Ensembl biotype	protein_coding
OMIM	604962
Entrez	50852

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000295756, ENST00000426646, ENST00000478830, ENST00000484927, ENST00000493604

RefSeq mRNA: 2 — MANE Select: NM_016388 NM_001317747, NM_016388

CCDS: CCDS33813, CCDS82814

Canonical transcript exons

ENST00000295756 — 6 exons

Exon	Start	End
ENSE00001075594	108849166	108849254
ENSE00001075606	108847068	108847129
ENSE00001841994	108822786	108822934
ENSE00001928820	108853620	108855005
ENSE00003536733	108838934	108838967
ENSE00003541508	108830670	108830780

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 88.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.4186 / max 629.3168, expressed in 166 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37832	5.4774	146
37831	1.0236	93
37833	0.4644	64
37830	0.4532	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.99	gold quality
lymph node	UBERON:0000029	86.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.70	gold quality
blood	UBERON:0000178	83.11	gold quality
granulocyte	CL:0000094	82.72	gold quality
vermiform appendix	UBERON:0001154	81.25	gold quality
epithelium of nasopharynx	UBERON:0001951	78.97	gold quality
nasopharynx	UBERON:0001728	78.95	gold quality
thymus	UBERON:0002370	77.87	gold quality
caecum	UBERON:0001153	74.15	gold quality
spleen	UBERON:0002106	72.67	gold quality
colonic epithelium	UBERON:0000397	72.66	gold quality
gall bladder	UBERON:0002110	72.41	gold quality
bone marrow	UBERON:0002371	71.07	gold quality
tonsil	UBERON:0002372	68.88	gold quality
bone marrow cell	CL:0002092	68.43	gold quality
rectum	UBERON:0001052	68.04	gold quality
amniotic fluid	UBERON:0000173	65.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.20	gold quality
endometrium epithelium	UBERON:0004811	63.29	gold quality
jejunal mucosa	UBERON:0000399	62.83	gold quality
small intestine	UBERON:0002108	62.36	gold quality
omental fat pad	UBERON:0010414	61.50	gold quality
peritoneum	UBERON:0002358	61.44	gold quality
leukocyte	CL:0000738	61.12	gold quality
mucosa of transverse colon	UBERON:0004991	60.80	gold quality
adipose tissue of abdominal region	UBERON:0007808	60.54	gold quality
upper lobe of left lung	UBERON:0008952	60.51	gold quality
upper lobe of lung	UBERON:0008948	60.28	gold quality
right lung	UBERON:0002167	59.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-122	yes	51.66
E-CURD-46	yes	34.49
E-ANND-3	yes	14.78
E-CURD-112	yes	8.85
E-CURD-89	no	699.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting TRAT1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4502	99.65	66.99	1021

Literature-anchored findings (GeneRIF, showing 2)

• TRIM acts to chaperone CTLA-4 transport to the cell surface; this function would be required to account for the phenotypic and functional properties of CD8(+) Tregs. (PMID:18817831)
• The Roles and Mechanisms of TRAT1 in the Progression of Non-Small Cell Lung Cancer. (PMID:36184729)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trat1	ENSMUSG00000030775
rattus_norvegicus	Trat1	ENSRNOG00000029564

Protein

Protein identifiers

T-cell receptor-associated transmembrane adapter 1 — Q6PIZ9 (reviewed: Q6PIZ9)

Alternative names: T-cell receptor-interacting molecule, pp29/30

All UniProt accessions (2): C9JF66, Q6PIZ9

UniProt curated annotations — full annotation on UniProt →

Function. Stabilizes the TCR (T-cell antigen receptor)/CD3 complex at the surface of T-cells.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with CD3Z. When phosphorylated, interacts with PIK3R1.

Subcellular location. Cell membrane.

Tissue specificity. Strongly expressed in thymus, and to a lesser extent in spleen, lymph node and peripheral blood lymphocytes. Present in T-cells and NK cells, but not B-cells (at protein level).

Post-translational modifications. Phosphorylated on tyrosines by LCK or FYN upon TCR activation.

RefSeq proteins (2): NP_001304676, NP_057472* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020399	T-cell_rcpt-assoc_TM_adapter-1	Family

Pfam: PF15330

UniProt features (14 total): topological domain 2, sequence variant 2, region of interest 2, compositionally biased region 2, modified residue 2, chain 1, disulfide bond 1, mutagenesis site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PIZ9-F1	64.24	0.13

Functional residue map

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

Post-translational modifications (2): 46, 79

Disulfide bonds (1): 7

Mutagenesis-validated functional residues (1):

Position	Phenotype
79	abolishes interaction with pik3r1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-202424	Downstream TCR signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 227 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, REACTOME_DOWNSTREAM_TCR_SIGNALING, GOCC_CENTROSOME, GOBP_POSITIVE_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RECEPTOR_METABOLIC_PROCESS

GO Biological Process (9): negative regulation of receptor recycling (GO:0001920), adaptive immune response (GO:0002250), cellular defense response (GO:0006968), signal transduction (GO:0007165), positive regulation of calcium-mediated signaling (GO:0050850), positive regulation of T cell receptor signaling pathway (GO:0050862), negative regulation of transport (GO:0051051), immune system process (GO:0002376), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169)

GO Molecular Function (2): transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), centriolar satellite (GO:0034451), T cell receptor complex (GO:0042101), mitotic spindle (GO:0072686), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Intracellular signaling by second messengers	1
TCR signaling	1
PI3K/AKT Signaling in Cancer	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
receptor recycling	1
regulation of receptor recycling	1
negative regulation of macromolecule metabolic process	1
negative regulation of signaling	1
immune response	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
transport	1
negative regulation of biological process	1
regulation of transport	1
biological_process	1
enzyme-linked receptor protein signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
signaling receptor complex adaptor activity	1
receptor tyrosine kinase binding	1
binding	1
membrane	1
cell periphery	1
centrosome	1
plasma membrane signaling receptor complex	1
spindle	1

Protein interactions and networks

STRING

1834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAT1	BBOX1	O75936	980
TRAT1	TRIM22	Q8IYM9	964
TRAT1	TRIM5	Q9C035	947
TRAT1	LAX1	Q8IWV1	932
TRAT1	TMLHE	Q9NVH6	930
TRAT1	TRIM17	Q9Y577	924
TRAT1	TRIM34	Q9BYJ4	923
TRAT1	TRIM14	Q14142	918
TRAT1	TRIM6	Q9C030	912
TRAT1	TRIM21	P19474	899
TRAT1	TRIM29	Q14134	875
TRAT1	TRIM9	Q9C026	862
TRAT1	RAB8A	P24407	858
TRAT1	TRIM41	Q8WV44	851
TRAT1	TRIM11	Q96F44	845

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TRAT1	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
TRAT1	ACADVL	psi-mi:“MI:0914”(association)	0.530
TRAT1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
SSR3	HMGCS2	psi-mi:“MI:0914”(association)	0.350
SPMIP9	PCBP4	psi-mi:“MI:0914”(association)	0.350
DACT3	PKD2	psi-mi:“MI:0914”(association)	0.350
TRAT1	CAMK2B	psi-mi:“MI:0914”(association)	0.350
TRAT1	PML	psi-mi:“MI:0914”(association)	0.350
SEC22A	TRAT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): TRAT1 (Proximity Label-MS), TRAT1 (Synthetic Lethality), TRAT1 (Two-hybrid), TRAT1 (Two-hybrid), TRAT1 (Affinity Capture-Western), TRAT1 (Reconstituted Complex), TRAT1 (Reconstituted Complex), TRAT1 (Reconstituted Complex), TRAT1 (Reconstituted Complex), TRAT1 (Reconstituted Complex), ACADVL (Affinity Capture-MS), TRAT1 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), GOPC (Affinity Capture-MS), IFT22 (Affinity Capture-MS)

ESM2 similar proteins: A4F4L0, B4DS77, O08843, O43914, O54885, P04234, P04235, P07766, P09693, P11942, P18438, P19377, P20963, P24161, P27597, P29328, P29329, Q28072, Q28073, Q2KIP5, Q3SYX1, Q3U1F9, Q3UU41, Q3UU67, Q5DTU0, Q64159, Q6ITQ4, Q6PIZ9, Q6UWF3, Q6X9T7, Q764N2, Q8CB93, Q8N292, Q8N8Z6, Q8R4V1, Q8WNQ8, Q91ZV2, Q95J79, Q95LI5, Q95LI7

Diamond homologs: Q3SYX1, Q3UU67, Q6PIZ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

607 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108849139:T:TA	acceptor_gain	1.0000
3:108849156:A:AG	acceptor_gain	1.0000
3:108849157:A:G	acceptor_gain	1.0000
3:108849160:CCCAA:C	acceptor_loss	1.0000
3:108849161:CCAA:C	acceptor_loss	1.0000
3:108849162:CAAGA:C	acceptor_loss	1.0000
3:108849163:A:AG	acceptor_gain	1.0000
3:108849163:AAG:A	acceptor_loss	1.0000
3:108849164:A:AG	acceptor_gain	1.0000
3:108849164:AGAAC:A	acceptor_loss	1.0000
3:108849165:G:GA	acceptor_gain	1.0000
3:108849165:GA:G	acceptor_gain	1.0000
3:108849165:GAA:G	acceptor_gain	1.0000
3:108849251:ACAGG:A	donor_loss	1.0000
3:108849252:CAGGT:C	donor_loss	1.0000
3:108849253:AGG:A	donor_loss	1.0000
3:108849254:GGT:G	donor_loss	1.0000
3:108849255:G:A	donor_loss	1.0000
3:108849256:T:G	donor_loss	1.0000
3:108847062:TTATA:T	acceptor_loss	0.9900
3:108847063:TATAG:T	acceptor_loss	0.9900
3:108847064:ATAGG:A	acceptor_loss	0.9900
3:108847065:TAGG:T	acceptor_loss	0.9900
3:108847066:A:G	acceptor_loss	0.9900
3:108847066:AG:A	acceptor_gain	0.9900
3:108847067:G:T	acceptor_loss	0.9900
3:108847067:GG:G	acceptor_gain	0.9900
3:108847125:TTCAG:T	donor_loss	0.9900
3:108847126:TCAGG:T	donor_loss	0.9900
3:108847127:CAGG:C	donor_loss	0.9900

AlphaMissense

1239 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:108849196:T:C	M82T	0.968
3:108849197:G:A	M82I	0.967
3:108849197:G:C	M82I	0.967
3:108849197:G:T	M82I	0.967
3:108853837:T:C	L174P	0.966
3:108830696:T:A	W12R	0.964
3:108830696:T:C	W12R	0.964
3:108830717:G:C	G19R	0.963
3:108830749:T:A	N29K	0.963
3:108830749:T:G	N29K	0.963
3:108853825:A:G	D170G	0.950
3:108853839:T:C	F175L	0.948
3:108853841:T:A	F175L	0.948
3:108853841:T:G	F175L	0.948
3:108830699:G:A	G13R	0.945
3:108830699:G:C	G13R	0.945
3:108830739:T:C	L26P	0.940
3:108853837:T:A	L174Q	0.929
3:108830724:C:A	A21D	0.928
3:108853849:T:C	I178T	0.927
3:108830733:T:A	I24K	0.924
3:108853827:C:T	P171S	0.923
3:108830718:G:A	G19D	0.922
3:108853828:C:A	P171H	0.922
3:108853835:A:C	R173S	0.918
3:108853835:A:T	R173S	0.918
3:108849191:A:C	E80D	0.917
3:108849191:A:T	E80D	0.917
3:108853828:C:G	P171R	0.912
3:108853825:A:T	D170V	0.910

dbSNP variants (sampled 300 via entrez): RS1000028582 (3:108843343 AAC>A), RS1000046156 (3:108840399 A>G), RS1000293930 (3:108825882 T>A,C), RS1000414408 (3:108852786 A>C,G), RS1000465363 (3:108852507 G>A), RS1000521296 (3:108832133 G>A,C,T), RS1000580341 (3:108823449 G>A), RS1000664672 (3:108829563 G>A), RS1000741538 (3:108832399 T>C), RS1000775354 (3:108823088 T>C), RS1000945043 (3:108835198 C>T), RS1000974007 (3:108841600 C>T), RS1001029364 (3:108844704 T>C), RS1001037995 (3:108838357 G>A,T), RS1001145087 (3:108844423 G>A)

Disease associations

OMIM: gene MIM:604962 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010571_20	Autoimmune thyroid disease	4.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Asbestos	affects expression	1
Nickel	increases expression	1
Dronabinol	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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