TRBR2_HUMAN
ID TRBR2_HUMAN Reviewed; 315 AA.
AC P0DTU4;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-JUN-2020, sequence version 1.
DT 25-MAY-2022, entry version 8.
DE RecName: Full=T cell receptor beta chain MC.7.G5;
DE AltName: Full=TR beta chain TRBV25-1*01J2S3*01C2*01;
DE Short=MC.7.G5 TRB;
DE Flags: Precursor;
GN Name=TRB {ECO:0000312|HGNC:HGNC:12155};
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], REGION, CDR3 DOMAIN, FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CAUTION.
RX PubMed=31959982; DOI=10.1038/s41590-019-0578-8;
RA Crowther M.D., Dolton G., Legut M., Caillaud M.E., Lloyd A., Attaf M.,
RA Galloway S.A.E., Rius C., Farrell C.P., Szomolay B., Ager A., Parker A.L.,
RA Fuller A., Donia M., McCluskey J., Rossjohn J., Svane I.M., Phillips J.D.,
RA Sewell A.K.;
RT "Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer
RT targeting via the monomorphic MHC class I-related protein MR1.";
RL Nat. Immunol. 21:178-185(2020).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (IMGT ALLELE TRBC2*01).
RX PubMed=3860845; DOI=10.1073/pnas.82.15.5068;
RA Tunnacliffe A., Kefford R., Milstein C., Forster A., Rabbitts T.H.;
RT "Sequence and evolution of the human T-cell antigen receptor beta-chain
RT genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:5068-5072(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE TRBJ2-3*01).
RX PubMed=11181995; DOI=10.1126/science.1058040;
RA Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G.,
RA Smith H.O., Yandell M., Evans C.A., Holt R.A., Gocayne J.D., Amanatides P.,
RA Ballew R.M., Huson D.H., Wortman J.R., Zhang Q., Kodira C.D., Zheng X.H.,
RA Chen L., Skupski M., Subramanian G., Thomas P.D., Zhang J.,
RA Gabor Miklos G.L., Nelson C., Broder S., Clark A.G., Nadeau J.,
RA McKusick V.A., Zinder N., Levine A.J., Roberts R.J., Simon M., Slayman C.,
RA Hunkapiller M., Bolanos R., Delcher A., Dew I., Fasulo D., Flanigan M.,
RA Florea L., Halpern A., Hannenhalli S., Kravitz S., Levy S., Mobarry C.,
RA Reinert K., Remington K., Abu-Threideh J., Beasley E., Biddick K.,
RA Bonazzi V., Brandon R., Cargill M., Chandramouliswaran I., Charlab R.,
RA Chaturvedi K., Deng Z., Di Francesco V., Dunn P., Eilbeck K.,
RA Evangelista C., Gabrielian A.E., Gan W., Ge W., Gong F., Gu Z., Guan P.,
RA Heiman T.J., Higgins M.E., Ji R.R., Ke Z., Ketchum K.A., Lai Z., Lei Y.,
RA Li Z., Li J., Liang Y., Lin X., Lu F., Merkulov G.V., Milshina N.,
RA Moore H.M., Naik A.K., Narayan V.A., Neelam B., Nusskern D., Rusch D.B.,
RA Salzberg S., Shao W., Shue B., Sun J., Wang Z., Wang A., Wang X., Wang J.,
RA Wei M., Wides R., Xiao C., Yan C., Yao A., Ye J., Zhan M., Zhang W.,
RA Zhang H., Zhao Q., Zheng L., Zhong F., Zhong W., Zhu S., Zhao S.,
RA Gilbert D., Baumhueter S., Spier G., Carter C., Cravchik A., Woodage T.,
RA Ali F., An H., Awe A., Baldwin D., Baden H., Barnstead M., Barrow I.,
RA Beeson K., Busam D., Carver A., Center A., Cheng M.L., Curry L.,
RA Danaher S., Davenport L., Desilets R., Dietz S., Dodson K., Doup L.,
RA Ferriera S., Garg N., Gluecksmann A., Hart B., Haynes J., Haynes C.,
RA Heiner C., Hladun S., Hostin D., Houck J., Howland T., Ibegwam C.,
RA Johnson J., Kalush F., Kline L., Koduru S., Love A., Mann F., May D.,
RA McCawley S., McIntosh T., McMullen I., Moy M., Moy L., Murphy B.,
RA Nelson K., Pfannkoch C., Pratts E., Puri V., Qureshi H., Reardon M.,
RA Rodriguez R., Rogers Y.H., Romblad D., Ruhfel B., Scott R., Sitter C.,
RA Smallwood M., Stewart E., Strong R., Suh E., Thomas R., Tint N.N., Tse S.,
RA Vech C., Wang G., Wetter J., Williams S., Williams M., Windsor S.,
RA Winn-Deen E., Wolfe K., Zaveri J., Zaveri K., Abril J.F., Guigo R.,
RA Campbell M.J., Sjolander K.V., Karlak B., Kejariwal A., Mi H., Lazareva B.,
RA Hatton T., Narechania A., Diemer K., Muruganujan A., Guo N., Sato S.,
RA Bafna V., Istrail S., Lippert R., Schwartz R., Walenz B., Yooseph S.,
RA Allen D., Basu A., Baxendale J., Blick L., Caminha M., Carnes-Stine J.,
RA Caulk P., Chiang Y.H., Coyne M., Dahlke C., Mays A., Dombroski M.,
RA Donnelly M., Ely D., Esparham S., Fosler C., Gire H., Glanowski S.,
RA Glasser K., Glodek A., Gorokhov M., Graham K., Gropman B., Harris M.,
RA Heil J., Henderson S., Hoover J., Jennings D., Jordan C., Jordan J.,
RA Kasha J., Kagan L., Kraft C., Levitsky A., Lewis M., Liu X., Lopez J.,
RA Ma D., Majoros W., McDaniel J., Murphy S., Newman M., Nguyen T., Nguyen N.,
RA Nodell M., Pan S., Peck J., Peterson M., Rowe W., Sanders R., Scott J.,
RA Simpson M., Smith T., Sprague A., Stockwell T., Turner R., Venter E.,
RA Wang M., Wen M., Wu D., Wu M., Xia A., Zandieh A., Zhu X.;
RT "The sequence of the human genome.";
RL Science 291:1304-1351(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE TRBV25-1*01;
RP ALLELE TRBJ2-3*01 AND ALLELE TRBC2*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 CDR1 AND CDR2 DOMAINS.
RX PubMed=11096259; DOI=10.1159/000019140;
RA Folch G., Scaviner D., Contet V., Lefranc M.P.;
RT "Protein displays of the human T cell receptor alpha, beta, gamma and delta
RT variable and joining regions.";
RL Exp. Clin. Immunogenet. 17:205-215(2000).
RN [6]
RP NOMENCLATURE.
RX PubMed=19568742; DOI=10.1007/s00251-009-0383-x;
RA Yassai M.B., Naumov Y.N., Naumova E.N., Gorski J.;
RT "A clonotype nomenclature for T cell receptors.";
RL Immunogenetics 61:493-502(2009).
CC -!- FUNCTION: The beta chain of TRAV38-2DV8*01J31*01C*01/TRBV25-
CC 1*01J2S3*01C2*01 alpha-beta T cell receptor (TR) clonotype that
CC displays pan-cancer cell recognition via the invariant MR1 molecule. On
CC CD8-positive T cell clone MC.7.G5, likely recognizes tumor-specific or
CC -associated metabolite(s) essential for cancer cell survival,
CC triggering killing of many cancer cell types including lung, melanoma,
CC leukemia, colon, breast, prostate, bone and ovarian cancer cells.
CC Mediates cancer cell cytotoxicity in an HLA-independent manner. Has no
CC reactivity to healthy cells even stressed or infected by bacteria
CC (PubMed:31959982). Antigen recognition initiates TR-CD3 clustering on
CC the cell surface and intracellular activation of LCK that
CC phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling
CC the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which
CC recruits numerous signaling molecules to form the LAT signalosome. The
CC LAT signalosome propagates signal branching to three major signaling
CC pathways, the calcium, the mitogen-activated protein kinase (MAPK)
CC kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to
CC the mobilization of transcription factors that are critical for gene
CC expression and essential for T cell differentiation into
CC effector/memory T cells (By similarity). {ECO:0000250|UniProtKB:P01848,
CC ECO:0000269|PubMed:31959982}.
CC -!- SUBUNIT: Disulfide-linked heterodimer with TRAV38-2DV8*01J31*01C*01
CC alpha chain (PubMed:31959982). The alpha-beta TR associates with the
CC transmembrane signaling CD3 coreceptor proteins to form the TR-CD3
CC (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 (via TM domain), respectively. The association of the
CC CD247 homodimer is the last step of TCR assembly in the endoplasmic
CC reticulum and is required for transport to the cell surface (By
CC similarity). {ECO:0000250|UniProtKB:P01848,
CC ECO:0000269|PubMed:31959982}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31959982}.
CC -!- TISSUE SPECIFICITY: Expressed in MR1-restricted CD8-positive T cells.
CC {ECO:0000269|PubMed:31959982}.
CC -!- DOMAIN: The complementarity-determining region CDR1 confers specificity
CC to the metabolite antigen. {ECO:0000250|UniProtKB:P0DSE1}.
CC -!- DOMAIN: The complementarity-determining region CDR2 confers specificity
CC to the metabolite antigen. {ECO:0000250|UniProtKB:P0DSE1}.
CC -!- DOMAIN: The complementarity-determining region CDR3 confers specificity
CC to the metabolite antigen. {ECO:0000250|UniProtKB:P0DSE1}.
CC -!- DOMAIN: The connecting peptide (CP) domain is essential for signal
CC transmission in response to antigenic stimulation, likely downstream
CC from ZAP70 recruitment. {ECO:0000250|UniProtKB:P01848}.
CC -!- DOMAIN: The TM domain mediates the interaction with the CD3 subunits.
CC {ECO:0000250|UniProtKB:P01848}.
CC -!- CAUTION: This sequence is an example of a full-length TR beta chain.
CC Pan-cancer TRBV25-1*01J2S3*01C2*01 TCR beta chain is generated by
CC somatic recombination of variable TRBV25-1 (AC A0A075B6N4) and joining
CC TRBJ2-3 (AC A0A0B4J200) gene segments spliced to constant TRBC2*01 (AC
CC A0A5B9) gene segment. {ECO:0000269|PubMed:31959982}.
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DR EMBL; MN782534; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M12888; AAA60662.1; -; Genomic_DNA.
DR EMBL; CH471198; EAW51910.1; -; Genomic_DNA.
DR EMBL; AC244472; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC239618; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC245427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DTU4; -.
DR SMR; P0DTU4; -.
DR GlyGen; P0DTU4; 2 sites.
DR MassIVE; P0DTU4; -.
DR PeptideAtlas; P0DTU4; -.
DR GeneCards; TRB; -.
DR HGNC; HGNC:12155; TRB.
DR MalaCards; TRB; -.
DR neXtProt; NX_P0DTU4; -.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR Proteomes; UP000005640; Unplaced.
DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0038023; F:signaling receptor activity; IDA:UniProtKB.
DR GO; GO:0002355; P:detection of tumor cell; IDA:UniProtKB.
DR GO; GO:0002419; P:T cell mediated cytotoxicity directed against tumor cell target; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunity; Membrane;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..315
FT /note="T cell receptor beta chain MC.7.G5"
FT /id="PRO_0000450078"
FT TRANSMEM 282..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..315
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..114
FT /note="Ig-like V-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 145..254
FT /note="Ig-like C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 22..114
FT /note="T cell receptor beta variable 25-1"
FT /evidence="ECO:0000269|PubMed:31959982"
FT REGION 46..50
FT /note="CDR1"
FT /evidence="ECO:0000305|PubMed:11096259"
FT REGION 68..73
FT /note="CDR2"
FT /evidence="ECO:0000305|PubMed:11096259"
FT REGION 110..127
FT /note="CDR3"
FT /evidence="ECO:0000269|PubMed:31959982,
FT ECO:0000305|PubMed:11096259"
FT REGION 122..136
FT /note="T cell receptor beta joining 2-3"
FT /evidence="ECO:0000269|PubMed:31959982"
FT REGION 138..315
FT /note="T cell receptor beta constant 2"
FT /evidence="ECO:0000269|PubMed:31959982"
FT REGION 267..281
FT /note="Connecting peptide"
FT /evidence="ECO:0000250|UniProtKB:P01850"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 42..110
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 167..232
FT /evidence="ECO:0000250|UniProtKB:A0A5B9,
FT ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 267
FT /note="Interchain (with C-94 in TRAC)"
FT /evidence="ECO:0000250|UniProtKB:P01850"
SQ SEQUENCE 315 AA; 35490 MW; 39C3AF5D0035A10A CRC64;
MTIRLLCYMG FYFLGAGLME ADIYQTPRYL VIGTGKKITL ECSQTMGHDK MYWYQQDPGM
ELHLIHYSYG VNSTEKGDLS SESTVSRIRT EHFPLTLESA RPSHTSQYLC ASSEARGLAE
FTDTQYFGPG TRLTVLEDLK NVFPPEVAVF EPSEAEISHT QKATLVCLAT GFYPDHVELS
WWVNGKEVHS GVSTDPQPLK EQPALNDSRY CLSSRLRVSA TFWQNPRNHF RCQVQFYGLS
ENDEWTQDRA KPVTQIVSAE AWGRADCGFT SESYQQGVLS ATILYEILLG KATLYAVLVS
ALVLMAMVKR KDSRG
