CD6_HUMAN
ID CD6_HUMAN Reviewed; 668 AA.
AC P30203; A4KAD4; A4KAD5; Q8WWJ3; Q8WWJ4; Q8WWJ5; Q8WWJ6; Q8WWJ7; Q9UMF2;
AC Q9Y4K7; Q9Y4K8; Q9Y4K9; Q9Y4L0;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=T-cell differentiation antigen CD6 {ECO:0000305};
DE AltName: Full=T12;
DE AltName: Full=TP120;
DE AltName: CD_antigen=CD6;
DE Contains:
DE RecName: Full=Soluble CD6;
DE Flags: Precursor;
GN Name=CD6 {ECO:0000312|HGNC:HGNC:1691};
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 [GENOMIC DNA / MRNA] (ISOFORMS CD6A; CD6B; CD6C; CD6D
RP AND CD6E), ALTERNATIVE SPLICING, VARIANTS VAL-257 AND SER-606, AND
RP SUBCELLULAR LOCATION.
RX PubMed=9013954;
RA Bowen M.A., Whitney G.S., Neubauer M., Starling G.C., Palmer D., Zhang J.,
RA Nowak N.J., Shows T.B., Aruffo A.;
RT "Structure and chromosomal location of the human CD6 gene: detection of
RT five human CD6 isoforms.";
RL J. Immunol. 158:1149-1156(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-468, AND VARIANT VAL-257.
RX PubMed=1919444; DOI=10.1084/jem.174.4.949;
RA Aruffo A., Melnick M.B., Linsley P.S., Seed B.;
RT "The lymphocyte glycoprotein CD6 contains a repeated domain structure
RT characteristic of a new family of cell surface and secreted proteins.";
RL J. Exp. Med. 174:949-952(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-278 (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 1-300 (ISOFORM 7), SUBCELLULAR LOCATION, VARIANTS MET-217 AND VAL-257,
RP AND ALTERNATIVE SPLICING.
RX PubMed=17371992; DOI=10.4049/jimmunol.178.7.4351;
RA Castro M.A., Oliveira M.I., Nunes R.J., Fabre S., Barbosa R., Peixoto A.,
RA Brown M.H., Parnes J.R., Bismuth G., Moreira A., Rocha B., Carmo A.M.;
RT "Extracellular isoforms of CD6 generated by alternative splicing regulate
RT targeting of CD6 to the immunological synapse.";
RL J. Immunol. 178:4351-4361(2007).
RN [5]
RP PHOSPHORYLATION AT SERINE RESIDUES, DISULFIDE BONDS, AND GLYCOSYLATION.
RX PubMed=2016320; DOI=10.1016/s0021-9258(20)89621-5;
RA Swack J.A., Mier J.W., Romain P.L., Hull S.R., Rudd C.E.;
RT "Biosynthesis and post-translational modification of CD6, a T cell signal-
RT transducing molecule.";
RL J. Biol. Chem. 266:7137-7143(1991).
RN [6]
RP PHOSPHORYLATION AT TYROSINE RESIDUES.
RX PubMed=7678115; DOI=10.1084/jem.177.1.219;
RA Wee S., Schieven G.L., Kirihara J.M., Tsu T.T., Ledbetter J.A., Aruffo A.;
RT "Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the
RT CD4 and CD2 coreceptors.";
RL J. Exp. Med. 177:219-223(1993).
RN [7]
RP FUNCTION, INTERACTION WITH ALCAM, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15048703; DOI=10.1002/eji.200424856;
RA Hassan N.J., Barclay A.N., Brown M.H.;
RT "Frontline: Optimal T cell activation requires the engagement of CD6 and
RT CD166.";
RL Eur. J. Immunol. 34:930-940(2004).
RN [8]
RP FUNCTION, INTERACTION WITH CD3E AND THE TCR/CD3 COMPLEX, SUBUNIT,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15294938; DOI=10.4049/jimmunol.173.4.2262;
RA Gimferrer I., Calvo M., Mittelbrunn M., Farnos M., Sarrias M.R., Enrich C.,
RA Vives J., Sanchez-Madrid F., Lozano F.;
RT "Relevance of CD6-mediated interactions in T cell activation and
RT proliferation.";
RL J. Immunol. 173:2262-2270(2004).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ALCAM, AND TISSUE
RP SPECIFICITY.
RX PubMed=16352806; DOI=10.1182/blood-2005-09-3881;
RA Zimmerman A.W., Joosten B., Torensma R., Parnes J.R., van Leeuwen F.N.,
RA Figdor C.G.;
RT "Long-term engagement of CD6 and ALCAM is essential for T-cell
RT proliferation induced by dendritic cells.";
RL Blood 107:3212-3220(2006).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ALCAM AND LCP2,
RP PHOSPHORYLATION AT TYR-662, AND MUTAGENESIS OF TYR-662.
RX PubMed=16914752; DOI=10.1128/mcb.00688-06;
RA Hassan N.J., Simmonds S.J., Clarkson N.G., Hanrahan S., Puklavec M.J.,
RA Bomb M., Barclay A.N., Brown M.H.;
RT "CD6 regulates T-cell responses through activation-dependent recruitment of
RT the positive regulator SLP-76.";
RL Mol. Cell. Biol. 26:6727-6738(2006).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17601777; DOI=10.1073/pnas.0702815104;
RA Sarrias M.R., Farnos M., Mota R., Sanchez-Barbero F., Ibanez A.,
RA Gimferrer I., Vera J., Fenutria R., Casals C., Yelamos J., Lozano F.;
RT "CD6 binds to pathogen-associated molecular patterns and protects from LPS-
RT induced septic shock.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11724-11729(2007).
RN [12]
RP INTERACTION WITH ALCAM; LGALS1 AND LGALS3, GLYCOSYLATION, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=24945728; DOI=10.1016/j.febslet.2014.05.064;
RA Escoda-Ferran C., Carrasco E., Caballero-Banos M., Miro-Julia C.,
RA Martinez-Florensa M., Consuegra-Fernandez M., Martinez V.G., Liu F.T.,
RA Lozano F.;
RT "Modulation of CD6 function through interaction with galectin-1 and -3.";
RL FEBS Lett. 588:2805-2813(2014).
RN [13]
RP FUNCTION, INTERACTION WITH LCP2, AND PHOSPHORYLATION.
RX PubMed=24584089; DOI=10.1038/ni.2843;
RA Roncagalli R., Hauri S., Fiore F., Liang Y., Chen Z., Sansoni A.,
RA Kanduri K., Joly R., Malzac A., Laehdesmaeki H., Lahesmaa R., Yamasaki S.,
RA Saito T., Malissen M., Aebersold R., Gstaiger M., Malissen B.;
RT "Quantitative proteomics analysis of signalosome dynamics in primary T
RT cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR
RT signaling hub.";
RL Nat. Immunol. 15:384-392(2014).
RN [14] {ECO:0007744|PDB:5A2E}
RP X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) OF 1-364, DISULFIDE BONDS,
RP GLYCOSYLATION AT ASN-28 ASN-49 AND ASN-229, IDENTIFICATION BY MASS
RP SPECTROMETRY, INTERACTION WITH ALCAM, CHARACTERIZATION OF VARIANT ASN-351,
RP AND MUTAGENESIS OF ASP-291; GLU-293; TYR-295; GLU-298; ARG-314; TYR-327;
RP SER-329; ASN-346; LEU-349; GLN-352 AND SER-353.
RX PubMed=26146185; DOI=10.1016/j.str.2015.05.019;
RA Chappell P.E., Garner L.I., Yan J., Metcalfe C., Hatherley D., Johnson S.,
RA Robinson C.V., Lea S.M., Brown M.H.;
RT "Structures of CD6 and its ligand CD166 give insight into their
RT interaction.";
RL Structure 23:1426-1436(2015).
CC -!- FUNCTION: Cell adhesion molecule that mediates cell-cell contacts and
CC regulates T-cell responses via its interaction with ALCAM/CD166
CC (PubMed:15048703, PubMed:15294938, PubMed:16352806, PubMed:16914752,
CC PubMed:24945728, PubMed:24584089). Contributes to signaling cascades
CC triggered by activation of the TCR/CD3 complex (PubMed:24584089).
CC Functions as costimulatory molecule; promotes T-cell activation and
CC proliferation (PubMed:15294938, PubMed:16352806, PubMed:16914752).
CC Contributes to the formation and maturation of the immunological
CC synapse (PubMed:15294938, PubMed:16352806). Functions as calcium-
CC dependent pattern receptor that binds and aggregates both Gram-positive
CC and Gram-negative bacteria. Binds both lipopolysaccharide (LPS) from
CC Gram-negative bacteria and lipoteichoic acid from Gram-positive
CC bacteria (PubMed:17601777). LPS binding leads to the activation of
CC signaling cascades and down-stream MAP kinases (PubMed:17601777).
CC Mediates activation of the inflammatory response and the secretion of
CC pro-inflammatory cytokines in response to LPS (PubMed:17601777).
CC {ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:15294938,
CC ECO:0000269|PubMed:16352806, ECO:0000269|PubMed:16914752,
CC ECO:0000269|PubMed:17601777, ECO:0000269|PubMed:24584089,
CC ECO:0000269|PubMed:24945728}.
CC -!- SUBUNIT: Interacts (via extracellular domain) with ALCAM/CD166 (via
CC extracellular domain) (PubMed:15048703, PubMed:16352806,
CC PubMed:16914752, PubMed:24945728, PubMed:26146185). Interacts with the
CC TCR/CD3 complex subunit CD3E (PubMed:15294938). Interacts (via tyrosine
CC phosphorylated C-terminus) with LCP2 (via SH2 domain)
CC (PubMed:16914752). Interacts with VAV1 (By similarity). Interacts (via
CC glycosylated extracellular domain) with LGALS1 and LGALS3
CC (PubMed:24945728). Interaction with LGALS1 or LGALS3 inhibits
CC interaction with ALCAM (PubMed:24945728).
CC {ECO:0000250|UniProtKB:Q61003, ECO:0000269|PubMed:15048703,
CC ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:16352806,
CC ECO:0000269|PubMed:16914752, ECO:0000269|PubMed:24945728,
CC ECO:0000269|PubMed:26146185}.
CC -!- INTERACTION:
CC P30203; Q13740: ALCAM; NbExp=5; IntAct=EBI-2873748, EBI-1188108;
CC P30203; P30203: CD6; NbExp=3; IntAct=EBI-2873748, EBI-2873748;
CC P30203; Q13094: LCP2; NbExp=3; IntAct=EBI-2873748, EBI-346946;
CC P30203; P09382: LGALS1; NbExp=2; IntAct=EBI-2873748, EBI-1048875;
CC P30203; P17931: LGALS3; NbExp=2; IntAct=EBI-2873748, EBI-1170392;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15048703,
CC ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:16352806,
CC ECO:0000269|PubMed:16914752, ECO:0000269|PubMed:17371992,
CC ECO:0000269|PubMed:17601777, ECO:0000269|PubMed:24945728,
CC ECO:0000269|PubMed:9013954}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:17371992}. Note=Detected at the immunological
CC synapse, i.e, at the contact zone between antigen-presenting dendritic
CC cells and T-cells (PubMed:15294938, PubMed:16352806). Colocalizes with
CC the TCR/CD3 complex at the immunological synapse (PubMed:15294938).
CC {ECO:0000269|PubMed:15294938}.
CC -!- SUBCELLULAR LOCATION: [Soluble CD6]: Secreted
CC {ECO:0000269|PubMed:17601777}. Note=The origins of the secreted form
CC are not clear, but it might be created by proteolytic shedding of the
CC ectodomain. {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=CD6A;
CC IsoId=P30203-1; Sequence=Displayed;
CC Name=CD6B;
CC IsoId=P30203-2; Sequence=VSP_006221, VSP_061447;
CC Name=CD6C;
CC IsoId=P30203-3; Sequence=VSP_006221, VSP_006222;
CC Name=CD6D;
CC IsoId=P30203-4; Sequence=VSP_006221, VSP_006223;
CC Name=CD6E;
CC IsoId=P30203-5; Sequence=VSP_006222, VSP_006223;
CC Name=6; Synonyms=CD6deltaD3Ex6;
CC IsoId=P30203-6; Sequence=VSP_054246;
CC Name=7; Synonyms=CD6deltaD3;
CC IsoId=P30203-7; Sequence=VSP_054245;
CC -!- TISSUE SPECIFICITY: Detected on thymocytes (PubMed:15294938). Detected
CC on peripheral blood T-cells (PubMed:15048703, PubMed:16352806).
CC Detected on natural killer (NK) cells (PubMed:16352806). Soluble CD6 is
CC detected in blood serum (at protein level) (PubMed:17601777). Detected
CC in spleen, thymus, appendix, lymph node and peripheral blood leukocytes
CC (PubMed:9013954). Expressed by thymocytes, mature T-cells, a subset of
CC B-cells known as B-1 cells, and by some cells in the brain.
CC {ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:15294938,
CC ECO:0000269|PubMed:16352806, ECO:0000269|PubMed:17601777,
CC ECO:0000269|PubMed:9013954}.
CC -!- PTM: After T-cell activation, becomes hyperphosphorylated on Ser and
CC Thr residues and phosphorylated on Tyr residues.
CC {ECO:0000269|PubMed:16914752, ECO:0000269|PubMed:2016320,
CC ECO:0000269|PubMed:24584089, ECO:0000269|PubMed:7678115}.
CC -!- PTM: Glycosylated. {ECO:0000305|PubMed:24945728}.
CC -!- MISCELLANEOUS: [Isoform 6]: Lacks the third SRCR domain and doesn't
CC bind ALCAM/CD166. Doesn't localize to the immunological synapse.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 7]: Lacks the third SRCR domain and doesn't
CC bind ALCAM/CD166. Doesn't localize to the immunological synapse.
CC Constitutes the only expressed species in a small percentage of T-
CC cells. {ECO:0000269|PubMed:17371992}.
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DR EMBL; AH011243; AAL40085.1; -; Genomic_DNA.
DR EMBL; L78837; AAL40085.1; JOINED; Genomic_DNA.
DR EMBL; AH011243; AAL40086.1; -; Genomic_DNA.
DR EMBL; AH011243; AAL40087.1; -; Genomic_DNA.
DR EMBL; AH011243; AAL40088.1; -; Genomic_DNA.
DR EMBL; L78837; AAL40088.1; JOINED; Genomic_DNA.
DR EMBL; AH011243; AAL40089.1; -; Genomic_DNA.
DR EMBL; U66142; AAC51161.1; -; mRNA.
DR EMBL; U66143; AAC51162.1; -; Genomic_DNA.
DR EMBL; U66144; AAC51163.1; -; Genomic_DNA.
DR EMBL; U66145; AAC51164.1; -; mRNA.
DR EMBL; U66146; AAC51165.1; -; mRNA.
DR EMBL; AP003721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X60992; CAA43306.1; -; mRNA.
DR EMBL; DQ786329; ABH04237.1; -; mRNA.
DR EMBL; DQ786330; ABH04238.1; -; mRNA.
DR CCDS; CCDS58137.1; -. [P30203-5]
DR CCDS; CCDS58138.1; -. [P30203-4]
DR CCDS; CCDS7999.1; -. [P30203-1]
DR PIR; S26741; S26741.
DR RefSeq; NP_001241679.1; NM_001254750.1. [P30203-4]
DR RefSeq; NP_001241680.1; NM_001254751.1. [P30203-5]
DR RefSeq; NP_006716.3; NM_006725.4. [P30203-1]
DR RefSeq; XP_006718801.1; XM_006718738.1. [P30203-2]
DR RefSeq; XP_006718804.1; XM_006718741.1. [P30203-3]
DR RefSeq; XP_011543664.1; XM_011545362.1. [P30203-7]
DR PDB; 5A2E; X-ray; 3.15 A; A=1-364.
DR PDBsum; 5A2E; -.
DR AlphaFoldDB; P30203; -.
DR SMR; P30203; -.
DR BioGRID; 107361; 170.
DR DIP; DIP-43704N; -.
DR IntAct; P30203; 9.
DR MINT; P30203; -.
DR STRING; 9606.ENSP00000323280; -.
DR ChEMBL; CHEMBL3712853; -.
DR GuidetoPHARMACOLOGY; 2917; -.
DR GlyGen; P30203; 8 sites.
DR iPTMnet; P30203; -.
DR PhosphoSitePlus; P30203; -.
DR BioMuta; CD6; -.
DR DMDM; 281185506; -.
DR CPTAC; CPTAC-1316; -.
DR CPTAC; CPTAC-1317; -.
DR CPTAC; CPTAC-1318; -.
DR jPOST; P30203; -.
DR MassIVE; P30203; -.
DR PaxDb; P30203; -.
DR PeptideAtlas; P30203; -.
DR PRIDE; P30203; -.
DR ProteomicsDB; 54640; -. [P30203-1]
DR ProteomicsDB; 54641; -. [P30203-2]
DR ProteomicsDB; 54642; -. [P30203-3]
DR ProteomicsDB; 54643; -. [P30203-4]
DR ProteomicsDB; 54644; -. [P30203-5]
DR ABCD; P30203; 3 sequenced antibodies.
DR Antibodypedia; 3732; 1311 antibodies from 45 providers.
DR DNASU; 923; -.
DR Ensembl; ENST00000313421.11; ENSP00000323280.7; ENSG00000013725.14. [P30203-1]
DR Ensembl; ENST00000352009.9; ENSP00000340628.5; ENSG00000013725.14. [P30203-4]
DR Ensembl; ENST00000452451.6; ENSP00000390676.2; ENSG00000013725.14. [P30203-5]
DR GeneID; 923; -.
DR KEGG; hsa:923; -.
DR MANE-Select; ENST00000313421.11; ENSP00000323280.7; NM_006725.5; NP_006716.3.
DR UCSC; uc001nqq.4; human. [P30203-1]
DR CTD; 923; -.
DR DisGeNET; 923; -.
DR GeneCards; CD6; -.
DR HGNC; HGNC:1691; CD6.
DR HPA; ENSG00000013725; Tissue enhanced (intestine, lymphoid tissue).
DR MIM; 186720; gene.
DR neXtProt; NX_P30203; -.
DR OpenTargets; ENSG00000013725; -.
DR PharmGKB; PA26230; -.
DR VEuPathDB; HostDB:ENSG00000013725; -.
DR eggNOG; ENOG502QUHF; Eukaryota.
DR GeneTree; ENSGT00940000161029; -.
DR HOGENOM; CLU_026713_1_0_1; -.
DR InParanoid; P30203; -.
DR OMA; SEQICQD; -.
DR PhylomeDB; P30203; -.
DR TreeFam; TF329295; -.
DR PathwayCommons; P30203; -.
DR SignaLink; P30203; -.
DR BioGRID-ORCS; 923; 12 hits in 1065 CRISPR screens.
DR ChiTaRS; CD6; human.
DR GeneWiki; CD6; -.
DR GenomeRNAi; 923; -.
DR Pharos; P30203; Tbio.
DR PRO; PR:P30203; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P30203; protein.
DR Bgee; ENSG00000013725; Expressed in granulocyte and 173 other tissues.
DR ExpressionAtlas; P30203; baseline and differential.
DR Genevisible; P30203; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0044214; C:spanning component of plasma membrane; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0070891; F:lipoteichoic acid binding; IMP:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IMP:UniProtKB.
DR GO; GO:0001771; P:immunological synapse formation; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB.
DR Gene3D; 3.10.250.10; -; 3.
DR InterPro; IPR001190; SRCR.
DR InterPro; IPR017448; SRCR-like_dom.
DR InterPro; IPR036772; SRCR-like_dom_sf.
DR Pfam; PF00530; SRCR; 3.
DR PRINTS; PR00258; SPERACTRCPTR.
DR SMART; SM00202; SR; 3.
DR SUPFAM; SSF56487; SSF56487; 3.
DR PROSITE; PS00420; SRCR_1; 1.
DR PROSITE; PS50287; SRCR_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell adhesion;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunity; Innate immunity;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..668
FT /note="T-cell differentiation antigen CD6"
FT /id="PRO_0000033227"
FT CHAIN 18..?
FT /note="Soluble CD6"
FT /id="PRO_0000435133"
FT TOPO_DOM 18..402
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..668
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 45..156
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 161..260
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 265..361
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 18..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..668
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..601
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..631
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 662
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16914752"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26146185"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26146185"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:26146185"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..88
FT /evidence="ECO:0000269|PubMed:26146185,
FT ECO:0007744|PDB:5A2E"
FT DISULFID 70..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 83..155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 129..137
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 170..204
FT /evidence="ECO:0000269|PubMed:26146185,
FT ECO:0007744|PDB:5A2E"
FT DISULFID 186..249
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 199..259
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 230..240
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 290..350
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 303..360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT DISULFID 330..340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196,
FT ECO:0000269|PubMed:26146185, ECO:0007744|PDB:5A2E"
FT VAR_SEQ 259..359
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:17371992"
FT /id="VSP_054245"
FT VAR_SEQ 261..383
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:17371992"
FT /id="VSP_054246"
FT VAR_SEQ 431..462
FT /note="Missing (in isoform CD6B, isoform CD6C and isoform
FT CD6D)"
FT /evidence="ECO:0000305"
FT /id="VSP_006221"
FT VAR_SEQ 463..504
FT /note="VFMLPIQVQAPPPEDSDSGSDSDYEHYDFSAQPPVALTTFYN -> D (in
FT isoform CD6C and isoform CD6E)"
FT /evidence="ECO:0000305"
FT /id="VSP_006222"
FT VAR_SEQ 613..647
FT /note="Missing (in isoform CD6D and isoform CD6E)"
FT /evidence="ECO:0000305"
FT /id="VSP_006223"
FT VAR_SEQ 613
FT /note="Missing (in isoform CD6B)"
FT /id="VSP_061447"
FT VARIANT 217
FT /note="T -> M (in dbSNP:rs11230562)"
FT /evidence="ECO:0000269|PubMed:17371992"
FT /id="VAR_059809"
FT VARIANT 225
FT /note="R -> W (in dbSNP:rs11230563)"
FT /id="VAR_057202"
FT VARIANT 257
FT /note="A -> V (in dbSNP:rs2074225)"
FT /evidence="ECO:0000269|PubMed:17371992,
FT ECO:0000269|PubMed:1919444, ECO:0000269|PubMed:9013954"
FT /id="VAR_060790"
FT VARIANT 271
FT /note="A -> T (in dbSNP:rs12360861)"
FT /id="VAR_057203"
FT VARIANT 351
FT /note="S -> N (adds an additional glycosylation site and
FT impairs interaction with ALCAM; dbSNP:rs34974368)"
FT /evidence="ECO:0000269|PubMed:26146185"
FT /id="VAR_057204"
FT VARIANT 606
FT /note="G -> S (in dbSNP:rs2074233)"
FT /evidence="ECO:0000269|PubMed:9013954"
FT /id="VAR_057205"
FT MUTAGEN 291
FT /note="D->A: Strongly reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 293
FT /note="E->A: Reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 295
FT /note="Y->A: Abolishes interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 298
FT /note="E->A: Nearly abolishes interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 314
FT /note="R->A: Reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 327
FT /note="Y->A: Nearly abolishes interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 329
FT /note="S->A: Reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 346
FT /note="N->A: Strongly reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 349
FT /note="L->A: Reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 352
FT /note="Q->A: Reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 353
FT /note="S->A: Reduces interaction with ALCAM."
FT /evidence="ECO:0000269|PubMed:26146185"
FT MUTAGEN 662
FT /note="Y->F: Reduces tyrosine phosphorylation. Reduces
FT affinity for LCP2. Impairs activation of T-cells."
FT /evidence="ECO:0000269|PubMed:16914752"
FT CONFLICT 47
FT /note="L -> R (in Ref. 4; ABH04237)"
FT /evidence="ECO:0000305"
FT CONFLICT 463..468
FT /note="VFMLPI -> GPGPAP (in Ref. 3; CAA43306)"
FT /evidence="ECO:0000305"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:5A2E"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 126..134
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 171..180
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:5A2E"
FT HELIX 192..202
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:5A2E"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 264..272
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 275..282
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 285..291
FT /evidence="ECO:0007829|PDB:5A2E"
FT HELIX 296..306
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:5A2E"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 340..345
FT /evidence="ECO:0007829|PDB:5A2E"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5A2E"
FT STRAND 357..363
FT /evidence="ECO:0007829|PDB:5A2E"
SQ SEQUENCE 668 AA; 71801 MW; 59E6790E77FFBC42 CRC64;
MWLFFGITGL LTAALSGHPS PAPPDQLNTS SAESELWEPG ERLPVRLTNG SSSCSGTVEV
RLEASWEPAC GALWDSRAAE AVCRALGCGG AEAASQLAPP TPELPPPPAA GNTSVAANAT
LAGAPALLCS GAEWRLCEVV EHACRSDGRR ARVTCAENRA LRLVDGGGAC AGRVEMLEHG
EWGSVCDDTW DLEDAHVVCR QLGCGWAVQA LPGLHFTPGR GPIHRDQVNC SGAEAYLWDC
PGLPGQHYCG HKEDAGAVCS EHQSWRLTGG ADRCEGQVEV HFRGVWNTVC DSEWYPSEAK
VLCQSLGCGT AVERPKGLPH SLSGRMYYSC NGEELTLSNC SWRFNNSNLC SQSLAARVLC
SASRSLHNLS TPEVPASVQT VTIESSVTVK IENKESRELM LLIPSIVLGI LLLGSLIFIA
FILLRIKGKY ALPVMVNHQH LPTTIPAGSN SYQPVPITIP KEVFMLPIQV QAPPPEDSDS
GSDSDYEHYD FSAQPPVALT TFYNSQRHRV TDEEVQQSRF QMPPLEEGLE ELHASHIPTA
NPGHCITDPP SLGPQYHPRS NSESSTSSGE DYCNSPKSKL PPWNPQVFSS ERSSFLEQPP
NLELAGTQPA FSAGPPADDS SSTSSGEWYQ NFQPPPQPPS EEQFGCPGSP SPQPDSTDND
DYDDISAA
