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   27-MAR-2024, entry version 172.
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 a costimulatory
CC       molecule; promotes T-cell activation and proliferation. Contributes to
CC       the formation and maturation of the immunological synapse. Functions as
CC       a calcium-dependent pattern receptor that binds and aggregates both
CC       Gram-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   GlyCosmos; Q61003; 8 sites, No reported glycans.
DR   GlyGen; Q61003; 8 sites.
DR   iPTMnet; Q61003; -.
DR   PhosphoSitePlus; Q61003; -.
DR   EPD; Q61003; -.
DR   PaxDb; 10090-ENSMUSP00000079172; -.
DR   PeptideAtlas; Q61003; -.
DR   ProteomicsDB; 279988; -. [Q61003-1]
DR   ProteomicsDB; 279989; -. [Q61003-2]
DR   ProteomicsDB; 279990; -. [Q61003-3]
DR   Antibodypedia; 3732; 1398 antibodies from 45 providers.
DR   DNASU; 12511; -.
DR   Ensembl; ENSMUST00000039043.15; ENSMUSP00000046861.9; ENSMUSG00000024670.18. [Q61003-3]
DR   Ensembl; ENSMUST00000080292.12; ENSMUSP00000079172.6; ENSMUSG00000024670.18. [Q61003-1]
DR   GeneID; 12511; -.
DR   KEGG; mmu:12511; -.
DR   UCSC; uc008gqy.1; mouse. [Q61003-1]
DR   UCSC; uc008gqz.1; mouse. [Q61003-3]
DR   AGR; MGI:103566; -.
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; 5322637at2759; -.
DR   PhylomeDB; Q61003; -.
DR   TreeFam; TF329295; -.
DR   BioGRID-ORCS; 12511; 2 hits in 78 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 38 other cell types or tissues.
DR   ExpressionAtlas; Q61003; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0042101; C:T cell receptor complex; IEA:Ensembl.
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: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; SRCR-like domain; 3.
DR   InterPro; IPR001190; SRCR.
DR   InterPro; IPR017448; SRCR-like_dom.
DR   InterPro; IPR036772; SRCR-like_dom_sf.
DR   PANTHER; PTHR48071; SRCR DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR48071:SF22; SRCR DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF00530; SRCR; 3.
DR   PRINTS; PR00258; SPERACTRCPTR.
DR   SMART; SM00202; SR; 3.
DR   SUPFAM; SSF56487; SRCR-like; 3.
DR   PROSITE; PS50287; SRCR_2; 3.
DR   Genevisible; Q61003; MM.
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
//