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   16-OCT-2019, entry version 137.
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},
GN   TCRBV8S1 {ECO:0000303|PubMed:8650574};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   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
RT   region 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
RT   receptor locus.";
RL   Science 272:1755-1762(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE
RP   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.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   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.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., 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.
RL   (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-
RT   linked cell surface glycoproteins.";
RL   Nat. Biotechnol. 27:378-386(2009).
RN   [8]
RP   REVIEW ON T CELL RECEPTOR-CD3 COMPLEX ASSEMBLY, AND SUBCELLULAR
RP   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
RT   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
RT   Rise 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.,
RA   McCluskey J.;
RT   "T cell antigen receptor recognition of antigen-presenting
RT   molecules.";
RL   Annu. Rev. Immunol. 33:169-200(2015).
CC   -!- FUNCTION: V region of the variable domain of T cell receptor (TR)
CC       beta chain that participates in the antigen recognition
CC       (PubMed:24600447). Alpha-beta T cell receptors are antigen
CC       specific receptors which are essential to the immune response and
CC       are present on the cell surface of T lymphocytes. Recognize
CC       peptide-major histocompatibility (MH) (pMH) complexes that are
CC       displayed by antigen presenting cells (APC), a prerequisite for
CC       efficient T cell adaptive immunity against pathogens
CC       (PubMed:25493333). Binding of alpha-beta TR to pMH complex
CC       initiates TR-CD3 clustering on the cell surface and intracellular
CC       activation of LCK that phosphorylates the ITAM motifs of CD3G,
CC       CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn
CC       ZAP70 phosphorylates LAT, which recruits numerous signaling
CC       molecules to form the LAT signalosome. The LAT signalosome
CC       propagates signal branching to three major signaling pathways, the
CC       calcium, the mitogen-activated protein kinase (MAPK) kinase and
CC       the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the
CC       mobilization of transcription factors that are critical for gene
CC       expression and essential for T cell growth and differentiation
CC       (PubMed:23524462). The T cell repertoire is generated in the
CC       thymus, by V-(D)-J rearrangement. This repertoire is then shaped
CC       by intrathymic selection events to generate a peripheral T cell
CC       pool of self-MH restricted, non-autoaggressive T cells. Post-
CC       thymic interaction of alpha-beta TR with the pMH complexes shapes
CC       TR structural and functional avidity (PubMed:15040585).
CC       {ECO:0000303|PubMed:15040585, ECO:0000303|PubMed:23524462,
CC       ECO:0000303|PubMed:24600447, ECO:0000303|PubMed:25493333}.
CC   -!- SUBUNIT: Alpha-beta TR is a heterodimer composed of an alpha and
CC       beta chain; disulfide-linked. The alpha-beta TR is associated with
CC       the transmembrane signaling CD3 coreceptor proteins to form the
CC       TR-CD3 (TcR or TCR). The assembly of alpha-beta TR heterodimers
CC       with CD3 occurs in the endoplasmic reticulum where a single alpha-
CC       beta TR heterodimer associates with one CD3D-CD3E heterodimer, one
CC       CD3G-CD3E heterodimer and one CD247 homodimer forming a stable
CC       octomeric structure. CD3D-CD3E and CD3G-CD3E heterodimers
CC       preferentially associate with TR alpha and TR beta chains,
CC       respectively. The association of the CD247 homodimer is the last
CC       step of TcR assembly in the endoplasmic reticulum and is required
CC       for transport to the cell surface. {ECO:0000303|PubMed:20452950}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000303|PubMed:20452950}.
CC   -!- POLYMORPHISM: There are several alleles. The sequence shown is
CC       that of 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};
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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   SMR; P01733; -.
DR   IntAct; P01733; 2.
DR   MINT; P01733; -.
DR   IMGT_GENE-DB; TRBV12-3; -.
DR   iPTMnet; P01733; -.
DR   PhosphoSitePlus; P01733; -.
DR   BioMuta; ENSG00000274752; -.
DR   BioMuta; HGNC:12185; -.
DR   DMDM; 136492; -.
DR   PeptideAtlas; P01733; -.
DR   PRIDE; P01733; -.
DR   ProteomicsDB; 51454; -.
DR   ABCD; P01733; -.
DR   Ensembl; ENST00000620569; ENSP00000477916; ENSG00000274752.
DR   Ensembl; ENST00000633292; ENSP00000487964; ENSG00000282208.
DR   GeneCards; TRBV12-3; -.
DR   HGNC; HGNC:12185; TRBV12-3.
DR   OpenTargets; ENSG00000274752; -.
DR   GeneTree; ENSGT00940000162707; -.
DR   InParanoid; P01733; -.
DR   OMA; SAVFWYR; -.
DR   PhylomeDB; 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; -.
DR   PRO; PR:P01733; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000274752; Expressed in 72 organ(s), highest expression level in adrenal gland.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0006955; P:immune response; NAS:UniProtKB.
DR   GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR   Gene3D; 2.60.40.10; -; 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   Pfam; PF07686; V-set; 1.
DR   SMART; SM00406; IGv; 1.
DR   SUPFAM; SSF48726; SSF48726; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
PE   1: Evidence at protein level;
KW   Adaptive immunity; Cell membrane; Complete proteome; Disulfide bond;
KW   Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Polymorphism;
KW   Receptor; Reference proteome; Signal; T cell receptor.
FT   SIGNAL        1     21       {ECO:0000255}.
FT   CHAIN        22    115       T cell receptor beta variable 12-3.
FT                                {ECO:0000255}.
FT                                /FTId=PRO_5014017119.
FT   DOMAIN       22   >115       Ig-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00114}.
FT   CARBOHYD     90     90       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     42    111       {ECO:0000255|PROSITE-ProRule:PRU00114}.
FT   CONFLICT    115    115       L -> F (in Ref. 1). {ECO:0000305}.
FT   CONFLICT    115    115       L -> LA (in Ref. 3; AAC13336).
FT                                {ECO:0000305}.
FT   NON_TER     115    115
SQ   SEQUENCE   115 AA;  12997 MW;  D9BF12E944882F14 CRC64;
     MDSWTFCCVS LCILVAKHTD AGVIQSPRHE VTEMGQEVTL RCKPISGHNS LFWYRQTMMR
     GLELLIYFNN NVPIDDSGMP EDRFSAKMPN ASFSTLKIQP SEPRDSAVYF CASSL
//