TVBL3_HUMAN
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 03-AUG-2022, entry version 148.
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; 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 octomeric 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};
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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 AlphaFoldDB; P01733; -.
DR SMR; P01733; -.
DR IntAct; P01733; 2.
DR MINT; P01733; -.
DR IMGT_GENE-DB; TRBV12-3; -.
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 PRIDE; 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 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; SAVFWYR; -.
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 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; -; 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; 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