ID TVBL3_HUMAN Reviewed; 115 AA. AC P01733; A0A0A6YYD5; A0A5A7; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 18-JUL-2018, sequence version 2. DT 27-MAR-2024, entry version 155. DE RecName: Full=T cell receptor beta variable 12-3 {ECO:0000303|Ref.5}; DE AltName: Full=T-cell receptor beta chain V region YT35 {ECO:0000305|PubMed:6336315}; DE Flags: Precursor; GN Name=TRBV12-3 {ECO:0000303|Ref.5}; GN Synonyms=TCRBV12S3 {ECO:0000303|PubMed:8650574}, TCRBV8S1 GN {ECO:0000303|PubMed:8650574}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6336315; DOI=10.1038/308145a0; RA Yanagi Y., Yoshikai Y., Leggett K., Clark S.P., Aleksander I., Mak T.W.; RT "A human T cell-specific cDNA clone encodes a protein having extensive RT homology to immunoglobulin chains."; RL Nature 308:145-149(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3866244; DOI=10.1073/pnas.82.24.8624; RA Toyonaga B., Yoshikai Y., Vadasz V., Chin B., Mak T.W.; RT "Organization and sequences of the diversity, joining, and constant region RT genes of the human T-cell receptor beta chain."; RL Proc. Natl. Acad. Sci. U.S.A. 82:8624-8628(1985). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (IMGT ALLELE TRBV12-3*01). RX PubMed=8650574; DOI=10.1126/science.272.5269.1755; RA Rowen L., Koop B.F., Hood L.; RT "The complete 685-kilobase DNA sequence of the human beta T cell receptor RT locus."; RL Science 272:1755-1762(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE TRBV12-3*01). RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NOMENCLATURE. RA Lefranc M.P., Lefranc G.; RT "The T Cell Receptor FactsBook."; RL (In) Lefranc M.P., Lefranc G. (eds.); RL The T Cell Receptor FactsBook., pp.1-397, Academic Press, London. (2001). RN [6] RP REVIEW ON T CELL REPERTOIRE DIVERSITY. RX PubMed=15040585; DOI=10.1038/nri1292; RA Nikolich-Zugich J., Slifka M.K., Messaoudi I.; RT "The many important facets of T-cell repertoire diversity."; RL Nat. Rev. Immunol. 4:123-132(2004). RN [7] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-90. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [8] RP REVIEW ON T CELL RECEPTOR-CD3 COMPLEX ASSEMBLY, AND SUBCELLULAR LOCATION. RX PubMed=20452950; DOI=10.1101/cshperspect.a005140; RA Wucherpfennig K.W., Gagnon E., Call M.J., Huseby E.S., Call M.E.; RT "Structural biology of the T-cell receptor: insights into receptor RT assembly, ligand recognition, and initiation of signaling."; RL Cold Spring Harb. Perspect. Biol. 2:A005140-A005140(2010). RN [9] RP REVIEW ON T CELL RECEPTOR SIGNALING. RX PubMed=23524462; DOI=10.1038/nri3403; RA Brownlie R.J., Zamoyska R.; RT "T cell receptor signalling networks: branched, diversified and bounded."; RL Nat. Rev. Immunol. 13:257-269(2013). RN [10] RP NOMENCLATURE. RX PubMed=24600447; DOI=10.3389/fimmu.2014.00022; RA Lefranc M.P.; RT "Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise RT of Immunoinformatics."; RL Front. Immunol. 5:22-22(2014). RN [11] RP REVIEW ON FUNCTION. RX PubMed=25493333; DOI=10.1146/annurev-immunol-032414-112334; RA Rossjohn J., Gras S., Miles J.J., Turner S.J., Godfrey D.I., McCluskey J.; RT "T cell antigen receptor recognition of antigen-presenting molecules."; RL Annu. Rev. Immunol. 33:169-200(2015). CC -!- FUNCTION: V region of the variable domain of T cell receptor (TR) beta CC chain that participates in the antigen recognition (PubMed:24600447). CC Alpha-beta T cell receptors are antigen specific receptors which are CC essential to the immune response and are present on the cell surface of CC T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) CC complexes that are displayed by antigen presenting cells (APC), a CC prerequisite for efficient T cell adaptive immunity against pathogens CC (PubMed:25493333). Binding of alpha-beta TR to pMH complex initiates CC TR-CD3 clustering on the cell surface and intracellular activation of CC LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 CC enabling the recruitment of ZAP70. In turn ZAP70 phosphorylates LAT, CC which recruits numerous signaling molecules to form the LAT CC signalosome. The LAT signalosome propagates signal branching to three CC major signaling pathways, the calcium, the mitogen-activated protein CC kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) CC pathways, leading to the mobilization of transcription factors that are CC critical for gene expression and essential for T cell growth and CC differentiation (PubMed:23524462). The T cell repertoire is generated CC in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped CC by intrathymic selection events to generate a peripheral T cell pool of CC self-MH restricted, non-autoaggressive T cells. Post-thymic interaction CC of alpha-beta TR with the pMH complexes shapes TR structural and CC functional avidity (PubMed:15040585). {ECO:0000303|PubMed:15040585, CC ECO:0000303|PubMed:23524462, ECO:0000303|PubMed:24600447, CC ECO:0000303|PubMed:25493333}. CC -!- SUBUNIT: Alpha-beta TR is a heterodimer composed of an alpha and beta CC chain; disulfide-linked. The alpha-beta TR is associated with the CC transmembrane signaling CD3 coreceptor proteins to form the TR-CD3 (TcR CC or TCR). The assembly of alpha-beta TR heterodimers with CD3 occurs in CC the endoplasmic reticulum where a single alpha-beta TR heterodimer CC associates with one CD3D-CD3E heterodimer, one CD3G-CD3E heterodimer CC and one CD247 homodimer forming a stable octameric structure. CD3D-CD3E CC and CD3G-CD3E heterodimers preferentially associate with TR alpha and CC TR beta chains, respectively. The association of the CD247 homodimer is CC the last step of TcR assembly in the endoplasmic reticulum and is CC required for transport to the cell surface. CC {ECO:0000303|PubMed:20452950}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000303|PubMed:20452950}. CC -!- POLYMORPHISM: There are several alleles. The sequence shown is that of CC IMGT allele TRBV12-3*01. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA60669.1; Type=Miscellaneous discrepancy; Note=Sequence from TRBJ1-2 gene product.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14158; AAA60669.1; ALT_SEQ; Genomic_DNA. DR EMBL; L36092; AAC13336.1; -; Genomic_DNA. DR EMBL; AC244196; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A02000; RWHUVY. DR PIR; S03488; S03488. DR PIR; S03510; S03510. DR AlphaFoldDB; P01733; -. DR SMR; P01733; -. DR IntAct; P01733; 2. DR MINT; P01733; -. DR IMGT_GENE-DB; TRBV12-3; -. DR GlyCosmos; P01733; 1 site, No reported glycans. DR GlyGen; P01733; 1 site. DR iPTMnet; P01733; -. DR MetOSite; P01733; -. DR PhosphoSitePlus; P01733; -. DR BioMuta; ENSG00000274752; -. DR BioMuta; HGNC:12185; -. DR DMDM; 136492; -. DR MassIVE; P01733; -. DR PeptideAtlas; P01733; -. DR ProteomicsDB; 51454; -. DR ABCD; P01733; 1 sequenced antibody. DR Ensembl; ENST00000620569.1; ENSP00000477916.1; ENSG00000274752.1. DR Ensembl; ENST00000633292.1; ENSP00000487964.1; ENSG00000282208.1. DR AGR; HGNC:12185; -. DR GeneCards; TRBV12-3; -. DR HGNC; HGNC:12185; TRBV12-3. DR HPA; ENSG00000274752; Tissue enriched (lymphoid). DR neXtProt; NX_P01733; -. DR OpenTargets; ENSG00000274752; -. DR VEuPathDB; HostDB:ENSG00000274752; -. DR GeneTree; ENSGT00940000162707; -. DR HOGENOM; CLU_077975_9_4_1; -. DR InParanoid; P01733; -. DR OMA; WFSAEMT; -. DR PhylomeDB; P01733; -. DR PathwayCommons; P01733; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains. DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse. DR Reactome; R-HSA-202433; Generation of second messenger molecules. DR Reactome; R-HSA-389948; PD-1 signaling. DR ChiTaRS; TRBV12-3; human. DR Pharos; P01733; Tdark. DR PRO; PR:P01733; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P01733; Protein. DR Bgee; ENSG00000274752; Expressed in lymph node and 82 other cell types or tissues. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0042101; C:T cell receptor complex; IEA:UniProtKB-KW. DR GO; GO:0042287; F:MHC protein binding; NAS:UniProtKB. DR GO; GO:0042605; F:peptide antigen binding; NAS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013106; Ig_V-set. DR PANTHER; PTHR23268:SF122; T CELL RECEPTOR BETA VARIABLE 12-3-RELATED; 1. DR PANTHER; PTHR23268; T-CELL RECEPTOR BETA CHAIN; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00406; IGv; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS50835; IG_LIKE; 1. PE 1: Evidence at protein level; KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity; KW Immunoglobulin domain; Membrane; Receptor; Reference proteome; Signal; KW T cell receptor. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..115 FT /note="T cell receptor beta variable 12-3" FT /evidence="ECO:0000255" FT /id="PRO_5014017119" FT DOMAIN 22..>115 FT /note="Ig-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT CARBOHYD 90 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 42..111 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT CONFLICT 115 FT /note="L -> F (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 115 FT /note="L -> LA (in Ref. 3; AAC13336)" FT /evidence="ECO:0000305" FT NON_TER 115 SQ SEQUENCE 115 AA; 12997 MW; D9BF12E944882F14 CRC64; MDSWTFCCVS LCILVAKHTD AGVIQSPRHE VTEMGQEVTL RCKPISGHNS LFWYRQTMMR GLELLIYFNN NVPIDDSGMP EDRFSAKMPN ASFSTLKIQP SEPRDSAVYF CASSL //