CD6_MOUSE
ID CD6_MOUSE Reviewed; 665 AA.
AC Q61003; Q60679; Q61004; Q8BGK1;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=T-cell differentiation antigen CD6;
DE AltName: CD_antigen=CD6;
DE Flags: Precursor;
GN Name=Cd6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Thymocyte;
RX PubMed=7594475;
RA Robinson W.H., Prohaska S.S., Santoro J.C., Robinson H.L., Parnes J.R.;
RT "Identification of a mouse protein homologous to the human CD6 T cell
RT surface protein and sequence of the corresponding cDNA.";
RL J. Immunol. 155:4739-4748(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=7870060; DOI=10.1016/0161-5890(94)00166-x;
RA Whitney G., Bowen M., Neubauer M., Aruffo A.;
RT "Cloning and characterization of murine CD6.";
RL Mol. Immunol. 32:89-92(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ALCAM.
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 [5]
RP FUNCTION, INTERACTION WITH LCP2 AND VAV1, 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).
CC -!- FUNCTION: Cell adhesion molecule that mediates cell-cell contacts and
CC regulates T-cell responses via its interaction with ALCAM/CD166.
CC Contributes to signaling cascades triggered by activation of the
CC TCR/CD3 complex (PubMed:24584089). Functions as costimulatory molecule;
CC promotes T-cell activation and proliferation. Contributes to the
CC formation and maturation of the immunological synapse. Functions as
CC calcium-dependent pattern receptor that binds and aggregates both Gram-
CC positive and Gram-negative bacteria. Binds both lipopolysaccharide
CC (LPS) from Gram-negative bacteria and lipoteichoic acid from Gram-
CC positive bacteria. LPS binding leads to the activation of signaling
CC cascades and down-stream MAP kinases. Mediates activation of the
CC inflammatory response and the secretion of pro-inflammatory cytokines
CC in response to LPS. {ECO:0000250|UniProtKB:P30203,
CC ECO:0000269|PubMed:24584089}.
CC -!- SUBUNIT: Interacts (via extracellular domain) with ALCAM/CD166 (via
CC extracellular domain) (PubMed:16914752). Interacts with the TCR/CD3
CC complex subunit CD3E. Interacts (via tyrosine phosphorylated C-
CC terminus) with LCP2 (via SH2 domain) (PubMed:24584089). Interacts (via
CC glycosylated extracellular domain) with LGALS1 and LGALS3. Interaction
CC with LGALS1 or LGALS3 inhibits interaction with ALCAM (By similarity).
CC Interacts with VAV1 (PubMed:24584089). {ECO:0000250|UniProtKB:P30203,
CC ECO:0000269|PubMed:16914752, ECO:0000269|PubMed:24584089}.
CC -!- INTERACTION:
CC Q61003; Q60787: Lcp2; NbExp=9; IntAct=EBI-12601992, EBI-5324248;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16914752};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P30203}.
CC Note=Detected at the immunological synapse, i.e, at the contact zone
CC between antigen-presenting dendritic cells and T-cells. Colocalizes
CC with the TCR/CD3 complex at the immunological synapse.
CC {ECO:0000250|UniProtKB:P30203}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q61003-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q61003-2; Sequence=VSP_006225, VSP_006226;
CC Name=3;
CC IsoId=Q61003-3; Sequence=VSP_006224;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in thymus, lymph node and
CC spleen.
CC -!- PTM: After T-cell activation, becomes hyperphosphorylated on Ser and
CC Thr residues (By similarity). Phosphorylated on tyrosine residues in
CC response to stimulation of the TCR complex (PubMed:24584089).
CC {ECO:0000250|UniProtKB:P30203, ECO:0000269|PubMed:24584089}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P30203}.
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DR EMBL; U37543; AAA81383.1; -; mRNA.
DR EMBL; U37544; AAA81384.1; -; mRNA.
DR EMBL; U12434; AAA64867.1; -; mRNA.
DR EMBL; AK030822; BAC27147.1; -; mRNA.
DR EMBL; AK030823; BAC27148.1; -; mRNA.
DR CCDS; CCDS37917.1; -. [Q61003-1]
DR CCDS; CCDS50391.1; -. [Q61003-3]
DR PIR; I49100; I49100.
DR RefSeq; NP_001032890.1; NM_001037801.2. [Q61003-3]
DR RefSeq; NP_033982.3; NM_009852.3. [Q61003-1]
DR AlphaFoldDB; Q61003; -.
DR SMR; Q61003; -.
DR BioGRID; 198605; 1.
DR CORUM; Q61003; -.
DR IntAct; Q61003; 3.
DR STRING; 10090.ENSMUSP00000079172; -.
DR GlyGen; Q61003; 8 sites.
DR iPTMnet; Q61003; -.
DR PhosphoSitePlus; Q61003; -.
DR EPD; Q61003; -.
DR PaxDb; Q61003; -.
DR PeptideAtlas; Q61003; -.
DR PRIDE; Q61003; -.
DR ProteomicsDB; 279988; -. [Q61003-1]
DR ProteomicsDB; 279989; -. [Q61003-2]
DR ProteomicsDB; 279990; -. [Q61003-3]
DR Antibodypedia; 3732; 1311 antibodies from 45 providers.
DR DNASU; 12511; -.
DR Ensembl; ENSMUST00000039043; ENSMUSP00000046861; ENSMUSG00000024670. [Q61003-3]
DR Ensembl; ENSMUST00000080292; ENSMUSP00000079172; ENSMUSG00000024670. [Q61003-1]
DR GeneID; 12511; -.
DR KEGG; mmu:12511; -.
DR UCSC; uc008gqy.1; mouse. [Q61003-1]
DR UCSC; uc008gqz.1; mouse. [Q61003-3]
DR CTD; 923; -.
DR MGI; MGI:103566; Cd6.
DR VEuPathDB; HostDB:ENSMUSG00000024670; -.
DR eggNOG; ENOG502QUHF; Eukaryota.
DR GeneTree; ENSGT00940000161029; -.
DR HOGENOM; CLU_026713_1_0_1; -.
DR InParanoid; Q61003; -.
DR OMA; SEQICQD; -.
DR OrthoDB; 1095487at2759; -.
DR PhylomeDB; Q61003; -.
DR TreeFam; TF329295; -.
DR BioGRID-ORCS; 12511; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Cd6; mouse.
DR PRO; PR:Q61003; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q61003; protein.
DR Bgee; ENSMUSG00000024670; Expressed in thymus and 35 other tissues.
DR ExpressionAtlas; Q61003; baseline and differential.
DR Genevisible; Q61003; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0044214; C:spanning component of plasma membrane; ISO:MGI.
DR GO; GO:0042101; C:T cell receptor complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISS:UniProtKB.
DR GO; GO:0070891; F:lipoteichoic acid binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; ISS:UniProtKB.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; ISS:UniProtKB.
DR GO; GO:0001771; P:immunological synapse formation; ISS:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS: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; PS50287; SRCR_2; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..665
FT /note="T-cell differentiation antigen CD6"
FT /id="PRO_0000033228"
FT TOPO_DOM 17..398
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..665
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 45..155
FT /note="SRCR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 160..259
FT /note="SRCR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 264..360
FT /note="SRCR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT REGION 536..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..593
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..642
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..665
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 659
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P30203"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..87
FT /evidence="ECO:0000250|UniProtKB:P30203"
FT DISULFID 69..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 82..154
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 128..136
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 169..203
FT /evidence="ECO:0000250|UniProtKB:P30203"
FT DISULFID 185..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 198..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 229..239
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 289..349
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 302..359
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DISULFID 329..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT VAR_SEQ 461..500
FT /note="APMLFIQPRVPADSDSSSDSDYEHYDFSSQPPVALTTFYN -> D (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:7870060"
FT /id="VSP_006224"
FT VAR_SEQ 557..586
FT /note="NSDSSTSSEEGYCNDPSSKPPPWNSQAFYS -> KDKASGVRAESWVEQTGS
FT GHFLGVVKGHAG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006225"
FT VAR_SEQ 587..665
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006226"
FT CONFLICT 5
FT /note="L -> F (in Ref. 2; AAA64867)"
FT /evidence="ECO:0000305"
FT CONFLICT 8
FT /note="A -> T (in Ref. 2; AAA64867)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="A -> D (in Ref. 1; AAA81383/AAA81384)"
FT /evidence="ECO:0000305"
FT CONFLICT 316..317
FT /note="GL -> AV (in Ref. 1; AAA81383/AAA81384)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 665 AA; 72255 MW; 8FF16DB37494D54F CRC64;
MWLFLGIAGL LTAVLSGLPS PAPSGQHKNG TIPNMTLDLE ERLGIRLVNG SSRCSGSVKV
LLESWEPVCA AHWNRAATEA VCKALNCGDS GKVTYLMPPT SELPPGATSG NTSSAGNTTW
ARAPTERCRG ANWQFCKVQD QECSSDRRLV WVTCAENQAV RLVDGSSRCA GRVEMLEHGE
WGTVCDDTWD LQDAHVVCKQ LKCGWAVKAL AGLHFTPGQG PIHRDQVNCS GTEAYLWDCP
GRPGDQYCGH KEDAGVVCSE HQSWRLTGGI DSCEGQVEVY FRGVWSTVCD SEWYPSEAKV
LCRSLGCGSA VARPRGLPHS LDGRMYYSCK GQEPALSTCS WRFNNSNLCS QSRAARVVCS
GSQRHLNLST SEVPSRVPVT IESSVPVSVK DKDSQGLTLL ILCIVLGILL LVSTIFIVIL
LLRAKGQYAL PASVNHQQLS TANQAGINNY HPVPITIAKE APMLFIQPRV PADSDSSSDS
DYEHYDFSSQ PPVALTTFYN SQRHRVTEEE AQQNRFQMPP LEEGLEELHV SHIPAADPRP
CVADVPSRGS QYHVRNNSDS STSSEEGYCN DPSSKPPPWN SQAFYSEKSP LTEQPPNLEL
AGSPAVFSGP SADDSSSTSS GEWYQNFQPP PQHPPAEQFE CPGPPGPQTD SIDDDEEDYD
DIGAA
