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P30203

- CD6_HUMAN

UniProt

P30203 - CD6_HUMAN

Protein

T-cell differentiation antigen CD6

Gene

CD6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 3 (15 Dec 2009)
      Previous versions | rss
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    Functioni

    Involved in cell adhesion. Binds to CD166.

    GO - Molecular functioni

    1. scavenger receptor activity Source: InterPro

    GO - Biological processi

    1. cell adhesion Source: UniProtKB-KW

    Keywords - Biological processi

    Cell adhesion

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    T-cell differentiation antigen CD6
    Alternative name(s):
    T12
    TP120
    CD_antigen: CD6
    Gene namesi
    Name:CD6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:1691. CD6.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA26230.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Sequence AnalysisAdd
    BLAST
    Chaini18 – 668651T-cell differentiation antigen CD6PRO_0000033227Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi28 – 281N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi70 ↔ 144PROSITE-ProRule annotation
    Disulfide bondi83 ↔ 155PROSITE-ProRule annotation
    Glycosylationi112 – 1121N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi118 – 1181N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi129 ↔ 137PROSITE-ProRule annotation
    Disulfide bondi186 ↔ 249PROSITE-ProRule annotation
    Disulfide bondi199 ↔ 259PROSITE-ProRule annotation
    Glycosylationi229 – 2291N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi230 ↔ 240PROSITE-ProRule annotation
    Disulfide bondi290 ↔ 350PROSITE-ProRule annotation
    Disulfide bondi303 ↔ 360PROSITE-ProRule annotation
    Disulfide bondi330 ↔ 340PROSITE-ProRule annotation
    Glycosylationi339 – 3391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi368 – 3681N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    After T-cell activation, becomes hyperphosphorylated on Ser and Thr residues and phosphorylated on Tyr residues.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP30203.
    PRIDEiP30203.

    PTM databases

    PhosphoSiteiP30203.

    Expressioni

    Tissue specificityi

    Expressed by thymocytes, mature T-cells, a subset of B-cells known as B-1 cells, and by some cells in the brain.

    Gene expression databases

    ArrayExpressiP30203.
    BgeeiP30203.
    CleanExiHS_CD6.
    GenevestigatoriP30203.

    Organism-specific databases

    HPAiCAB002489.
    CAB016252.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ALCAMQ137402EBI-2873748,EBI-1188108
    LGALS1P093822EBI-2873748,EBI-1048875
    LGALS3P179312EBI-2873748,EBI-1170392

    Protein-protein interaction databases

    BioGridi107361. 6 interactions.
    IntActiP30203. 7 interactions.
    MINTiMINT-1351620.
    STRINGi9606.ENSP00000323280.

    Structurei

    3D structure databases

    ProteinModelPortaliP30203.
    SMRiP30203. Positions 161-361.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini18 – 402385ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini424 – 668245CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei403 – 42321HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini45 – 156112SRCR 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini161 – 260100SRCR 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini265 – 36197SRCR 3PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 3 SRCR domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG76003.
    HOGENOMiHOG000137917.
    HOVERGENiHBG005289.
    InParanoidiP30203.
    KOiK06456.
    OMAiGEDYCNS.
    OrthoDBiEOG7DRJ2P.
    PhylomeDBiP30203.
    TreeFamiTF329295.

    Family and domain databases

    Gene3Di3.10.250.10. 3 hits.
    InterProiIPR001190. SRCR.
    IPR017448. SRCR-like_dom.
    [Graphical view]
    PfamiPF00530. SRCR. 3 hits.
    [Graphical view]
    PRINTSiPR00258. SPERACTRCPTR.
    SMARTiSM00202. SR. 3 hits.
    [Graphical view]
    SUPFAMiSSF56487. SSF56487. 3 hits.
    PROSITEiPS00420. SRCR_1. 1 hit.
    PS50287. SRCR_2. 3 hits.
    [Graphical view]

    Sequences (7)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 7 isoformsi produced by alternative splicing. Align

    Isoform CD6A (identifier: P30203-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MWLFFGITGL LTAALSGHPS PAPPDQLNTS SAESELWEPG ERLPVRLTNG    50
    SSSCSGTVEV RLEASWEPAC GALWDSRAAE AVCRALGCGG AEAASQLAPP 100
    TPELPPPPAA GNTSVAANAT LAGAPALLCS GAEWRLCEVV EHACRSDGRR 150
    ARVTCAENRA LRLVDGGGAC AGRVEMLEHG EWGSVCDDTW DLEDAHVVCR 200
    QLGCGWAVQA LPGLHFTPGR GPIHRDQVNC SGAEAYLWDC PGLPGQHYCG 250
    HKEDAGAVCS EHQSWRLTGG ADRCEGQVEV HFRGVWNTVC DSEWYPSEAK 300
    VLCQSLGCGT AVERPKGLPH SLSGRMYYSC NGEELTLSNC SWRFNNSNLC 350
    SQSLAARVLC SASRSLHNLS TPEVPASVQT VTIESSVTVK IENKESRELM 400
    LLIPSIVLGI LLLGSLIFIA FILLRIKGKY ALPVMVNHQH LPTTIPAGSN 450
    SYQPVPITIP KEVFMLPIQV QAPPPEDSDS GSDSDYEHYD FSAQPPVALT 500
    TFYNSQRHRV TDEEVQQSRF QMPPLEEGLE ELHASHIPTA NPGHCITDPP 550
    SLGPQYHPRS NSESSTSSGE DYCNSPKSKL PPWNPQVFSS ERSSFLEQPP 600
    NLELAGTQPA FSAGPPADDS SSTSSGEWYQ NFQPPPQPPS EEQFGCPGSP 650
    SPQPDSTDND DYDDISAA 668
    Length:668
    Mass (Da):71,801
    Last modified:December 15, 2009 - v3
    Checksum:i59E6790E77FFBC42
    GO
    Isoform CD6B (identifier: P30203-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         431-462: Missing.

    Show »
    Length:636
    Mass (Da):68,368
    Checksum:i8EC9117BF4AAD154
    GO
    Isoform CD6C (identifier: P30203-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         431-462: Missing.
         463-504: VFMLPIQVQAPPPEDSDSGSDSDYEHYDFSAQPPVALTTFYN → D

    Show »
    Length:595
    Mass (Da):63,824
    Checksum:i04D85EE0DBB4A885
    GO
    Isoform CD6D (identifier: P30203-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         431-462: Missing.
         613-647: Missing.

    Show »
    Length:601
    Mass (Da):64,663
    Checksum:i0D8DCC42B53BDA2E
    GO
    Isoform CD6E (identifier: P30203-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         463-504: VFMLPIQVQAPPPEDSDSGSDSDYEHYDFSAQPPVALTTFYN → D
         613-647: Missing.

    Show »
    Length:592
    Mass (Da):63,552
    Checksum:i504C102257DA7B3C
    GO
    Isoform 6 (identifier: P30203-6) [UniParc]FASTAAdd to Basket

    Also known as: CD6deltaD3Ex6

    The sequence of this isoform differs from the canonical sequence as follows:
         261-383: Missing.

    Note: Lacks the third SRCR domain and doesn't bind CD166. Doesn't localize to the immunological synapse.

    Show »
    Length:545
    Mass (Da):58,283
    Checksum:i54FA60E898D7DF82
    GO
    Isoform 7 (identifier: P30203-7) [UniParc]FASTAAdd to Basket

    Also known as: CD6deltaD3

    The sequence of this isoform differs from the canonical sequence as follows:
         259-359: Missing.

    Note: Lacks the third SRCR domain and doesn't bind CD166. Doesn't localize to the immunological synapse. Constitutes the only expressed species in a small percentage of T-cells.

    Show »
    Length:567
    Mass (Da):60,572
    Checksum:iC99852C6756B3154
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti47 – 471L → R in ABH04237. (PubMed:17371992)Curated
    Sequence conflicti463 – 4686VFMLPI → GPGPAP in CAA43306. (PubMed:1919444)Curated
    Sequence conflicti613 – 6131Missing in AAC51162. (PubMed:9013954)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti217 – 2171T → M.1 Publication
    Corresponds to variant rs11230562 [ dbSNP | Ensembl ].
    VAR_059809
    Natural varianti225 – 2251R → W.
    Corresponds to variant rs11230563 [ dbSNP | Ensembl ].
    VAR_057202
    Natural varianti257 – 2571A → V.3 Publications
    Corresponds to variant rs2074225 [ dbSNP | Ensembl ].
    VAR_060790
    Natural varianti271 – 2711A → T.
    Corresponds to variant rs12360861 [ dbSNP | Ensembl ].
    VAR_057203
    Natural varianti351 – 3511S → N.
    Corresponds to variant rs34974368 [ dbSNP | Ensembl ].
    VAR_057204
    Natural varianti606 – 6061G → S.
    Corresponds to variant rs2074233 [ dbSNP | Ensembl ].
    VAR_057205

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei259 – 359101Missing in isoform 7. 1 PublicationVSP_054245Add
    BLAST
    Alternative sequencei261 – 383123Missing in isoform 6. 1 PublicationVSP_054246Add
    BLAST
    Alternative sequencei431 – 46232Missing in isoform CD6B, isoform CD6C and isoform CD6D. CuratedVSP_006221Add
    BLAST
    Alternative sequencei463 – 50442VFMLP…TTFYN → D in isoform CD6C and isoform CD6E. CuratedVSP_006222Add
    BLAST
    Alternative sequencei613 – 64735Missing in isoform CD6D and isoform CD6E. CuratedVSP_006223Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U66142 mRNA. Translation: AAC51161.1.
    U66143 Genomic DNA. Translation: AAC51162.1.
    U66144 Genomic DNA. Translation: AAC51163.1.
    U66145 mRNA. Translation: AAC51164.1.
    U66146 mRNA. Translation: AAC51165.1.
    AP003721 Genomic DNA. No translation available.
    X60992 mRNA. Translation: CAA43306.1.
    DQ786329 mRNA. Translation: ABH04237.1.
    DQ786330 mRNA. Translation: ABH04238.1.
    CCDSiCCDS58137.1. [P30203-5]
    CCDS58138.1. [P30203-4]
    CCDS7999.1. [P30203-1]
    PIRiS26741.
    RefSeqiNP_001241679.1. NM_001254750.1. [P30203-4]
    NP_001241680.1. NM_001254751.1. [P30203-5]
    NP_006716.3. NM_006725.4. [P30203-1]
    XP_006718801.1. XM_006718738.1. [P30203-2]
    XP_006718804.1. XM_006718741.1. [P30203-3]
    UniGeneiHs.744366.

    Genome annotation databases

    EnsembliENST00000313421; ENSP00000323280; ENSG00000013725. [P30203-1]
    ENST00000352009; ENSP00000340628; ENSG00000013725. [P30203-4]
    ENST00000452451; ENSP00000390676; ENSG00000013725. [P30203-5]
    GeneIDi923.
    KEGGihsa:923.
    UCSCiuc001nqq.3. human. [P30203-1]
    uc001nqr.3. human. [P30203-4]
    uc001nqt.3. human. [P30203-5]

    Polymorphism databases

    DMDMi281185506.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U66142 mRNA. Translation: AAC51161.1 .
    U66143 Genomic DNA. Translation: AAC51162.1 .
    U66144 Genomic DNA. Translation: AAC51163.1 .
    U66145 mRNA. Translation: AAC51164.1 .
    U66146 mRNA. Translation: AAC51165.1 .
    AP003721 Genomic DNA. No translation available.
    X60992 mRNA. Translation: CAA43306.1 .
    DQ786329 mRNA. Translation: ABH04237.1 .
    DQ786330 mRNA. Translation: ABH04238.1 .
    CCDSi CCDS58137.1. [P30203-5 ]
    CCDS58138.1. [P30203-4 ]
    CCDS7999.1. [P30203-1 ]
    PIRi S26741.
    RefSeqi NP_001241679.1. NM_001254750.1. [P30203-4 ]
    NP_001241680.1. NM_001254751.1. [P30203-5 ]
    NP_006716.3. NM_006725.4. [P30203-1 ]
    XP_006718801.1. XM_006718738.1. [P30203-2 ]
    XP_006718804.1. XM_006718741.1. [P30203-3 ]
    UniGenei Hs.744366.

    3D structure databases

    ProteinModelPortali P30203.
    SMRi P30203. Positions 161-361.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107361. 6 interactions.
    IntActi P30203. 7 interactions.
    MINTi MINT-1351620.
    STRINGi 9606.ENSP00000323280.

    PTM databases

    PhosphoSitei P30203.

    Polymorphism databases

    DMDMi 281185506.

    Proteomic databases

    PaxDbi P30203.
    PRIDEi P30203.

    Protocols and materials databases

    DNASUi 923.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000313421 ; ENSP00000323280 ; ENSG00000013725 . [P30203-1 ]
    ENST00000352009 ; ENSP00000340628 ; ENSG00000013725 . [P30203-4 ]
    ENST00000452451 ; ENSP00000390676 ; ENSG00000013725 . [P30203-5 ]
    GeneIDi 923.
    KEGGi hsa:923.
    UCSCi uc001nqq.3. human. [P30203-1 ]
    uc001nqr.3. human. [P30203-4 ]
    uc001nqt.3. human. [P30203-5 ]

    Organism-specific databases

    CTDi 923.
    GeneCardsi GC11P060743.
    H-InvDB HIX0009678.
    HGNCi HGNC:1691. CD6.
    HPAi CAB002489.
    CAB016252.
    MIMi 186720. gene.
    neXtProti NX_P30203.
    PharmGKBi PA26230.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG76003.
    HOGENOMi HOG000137917.
    HOVERGENi HBG005289.
    InParanoidi P30203.
    KOi K06456.
    OMAi GEDYCNS.
    OrthoDBi EOG7DRJ2P.
    PhylomeDBi P30203.
    TreeFami TF329295.

    Miscellaneous databases

    GeneWikii CD6.
    GenomeRNAii 923.
    NextBioi 35461816.
    PROi P30203.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P30203.
    Bgeei P30203.
    CleanExi HS_CD6.
    Genevestigatori P30203.

    Family and domain databases

    Gene3Di 3.10.250.10. 3 hits.
    InterProi IPR001190. SRCR.
    IPR017448. SRCR-like_dom.
    [Graphical view ]
    Pfami PF00530. SRCR. 3 hits.
    [Graphical view ]
    PRINTSi PR00258. SPERACTRCPTR.
    SMARTi SM00202. SR. 3 hits.
    [Graphical view ]
    SUPFAMi SSF56487. SSF56487. 3 hits.
    PROSITEi PS00420. SRCR_1. 1 hit.
    PS50287. SRCR_2. 3 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Structure and chromosomal location of the human CD6 gene: detection of five human CD6 isoforms."
      Bowen M.A., Whitney G.S., Neubauer M., Starling G.C., Palmer D., Zhang J., Nowak N.J., Shows T.B., Aruffo A.
      J. Immunol. 158:1149-1156(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, VARIANT VAL-257.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins."
      Aruffo A., Melnick M.B., Linsley P.S., Seed B.
      J. Exp. Med. 174:949-952(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-468, VARIANT VAL-257.
    4. "Extracellular isoforms of CD6 generated by alternative splicing regulate targeting of CD6 to the immunological synapse."
      Castro M.A., Oliveira M.I., Nunes R.J., Fabre S., Barbosa R., Peixoto A., Brown M.H., Parnes J.R., Bismuth G., Moreira A., Rocha B., Carmo A.M.
      J. Immunol. 178:4351-4361(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-278 (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA] OF 1-300 (ISOFORM 7), SUBCELLULAR LOCATION, VARIANTS MET-217 AND VAL-257, ALTERNATIVE SPLICING.
    5. "Biosynthesis and post-translational modification of CD6, a T cell signal-transducing molecule."
      Swack J.A., Mier J.W., Romain P.L., Hull S.R., Rudd C.E.
      J. Biol. Chem. 266:7137-7143(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SERINE RESIDUES, DISULFIDE BONDS, GLYCOSYLATION.
    6. "Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors."
      Wee S., Schieven G.L., Kirihara J.M., Tsu T.T., Ledbetter J.A., Aruffo A.
      J. Exp. Med. 177:219-223(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES.

    Entry informationi

    Entry nameiCD6_HUMAN
    AccessioniPrimary (citable) accession number: P30203
    Secondary accession number(s): A4KAD4
    , A4KAD5, Q9UMF2, Q9Y4K7, Q9Y4K8, Q9Y4K9, Q9Y4L0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: December 15, 2009
    Last modified: October 1, 2014
    This is version 126 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3