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Q9Y6W8

- ICOS_HUMAN

UniProt

Q9Y6W8 - ICOS_HUMAN

Protein

Inducible T-cell costimulator

Gene

ICOS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 113 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes By similarity.By similarity

    GO - Biological processi

    1. immune response Source: UniProtKB
    2. single organismal cell-cell adhesion Source: Ensembl
    3. T cell costimulation Source: Reactome
    4. T cell tolerance induction Source: Ensembl

    Enzyme and pathway databases

    ReactomeiREACT_19344. Costimulation by the CD28 family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inducible T-cell costimulator
    Alternative name(s):
    Activation-inducible lymphocyte immunomediatory molecule
    CD_antigen: CD278
    Gene namesi
    Name:ICOS
    Synonyms:AILIM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:5351. ICOS.

    Subcellular locationi

    GO - Cellular componenti

    1. external side of plasma membrane Source: Ensembl
    2. extracellular region Source: UniProtKB-SubCell
    3. integral component of plasma membrane Source: Ensembl
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Immunodeficiency, common variable, 1 (CVID1) [MIM:607594]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Organism-specific databases

    MIMi607594. phenotype.
    Orphaneti1572. Common variable immunodeficiency.
    PharmGKBiPA29599.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2020Sequence AnalysisAdd
    BLAST
    Chaini21 – 199179Inducible T-cell costimulatorPRO_0000014806Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi23 – 231N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi42 ↔ 109By similarity
    Disulfide bondi63 ↔ 83By similarity
    Glycosylationi89 – 891N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ9Y6W8.
    PRIDEiQ9Y6W8.

    PTM databases

    PhosphoSiteiQ9Y6W8.

    Expressioni

    Tissue specificityi

    Activated T-cells. Highly expressed on tonsillar T-cells, which are closely associated with B-cells in the apical light zone of germinal centers, the site of terminal B-cell maturation. Expressed at lower levels in thymus, lung, lymph node and peripheral blood leukocytes. Expressed in the medulla of fetal and newborn thymus.3 Publications

    Inductioni

    By phorbol myristate acetate (PMA) and ionomycin. Up-regulated early on T-cells and continues to be expressed into the later phases of T-cell activation.1 Publication

    Gene expression databases

    ArrayExpressiQ9Y6W8.
    BgeeiQ9Y6W8.
    CleanExiHS_ICOS.
    GenevestigatoriQ9Y6W8.

    Organism-specific databases

    HPAiCAB032575.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked.2 Publications

    Protein-protein interaction databases

    BioGridi118933. 4 interactions.
    IntActiQ9Y6W8. 1 interaction.
    STRINGi9606.ENSP00000319476.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Y6W8.
    SMRiQ9Y6W8. Positions 25-115.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini21 – 140120ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini162 – 19938CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei141 – 16121HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini30 – 132103Ig-like V-typeAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG69972.
    HOGENOMiHOG000112996.
    HOVERGENiHBG052079.
    InParanoidiQ9Y6W8.
    KOiK06713.
    OMAiHSHANYY.
    OrthoDBiEOG7JMGFN.
    PhylomeDBiQ9Y6W8.
    TreeFamiTF335679.

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9Y6W8-1) [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

    MKSGLWYFFL FCLRIKVLTG EINGSANYEM FIFHNGGVQI LCKYPDIVQQ    50
    FKMQLLKGGQ ILCDLTKTKG SGNTVSIKSL KFCHSQLSNN SVSFFLYNLD 100
    HSHANYYFCN LSIFDPPPFK VTLTGGYLHI YESQLCCQLK FWLPIGCAAF 150
    VVVCILGCIL ICWLTKKKYS SSVHDPNGEY MFMRAVNTAK KSRLTDVTL 199
    Length:199
    Mass (Da):22,625
    Last modified:November 1, 1999 - v1
    Checksum:i214EC741C9BDC9FC
    GO
    Isoform 2 (identifier: Q9Y6W8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         168-199: KYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL → M

    Note: No experimental confirmation available.

    Show »
    Length:168
    Mass (Da):19,127
    Checksum:i499CFB5E6860A365
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei168 – 19932KYSSS…TDVTL → M in isoform 2. 1 PublicationVSP_010788Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ277832 mRNA. Translation: CAC06612.1.
    AB023135 mRNA. Translation: BAA82129.1.
    AF218312 mRNA. Translation: AAF71301.1.
    AF411058 Genomic DNA. Translation: AAL40933.1.
    AF411059 Genomic DNA. Translation: AAL40934.1.
    AF488347, AF488346 Genomic DNA. Translation: AAM00909.1.
    AJ535718 Genomic DNA. Translation: CAD59742.1.
    BC028006 mRNA. Translation: AAH28006.1.
    BC028210 mRNA. Translation: AAH28210.1.
    CCDSiCCDS2363.1. [Q9Y6W8-1]
    PIRiS78540.
    RefSeqiNP_036224.1. NM_012092.3. [Q9Y6W8-1]
    UniGeneiHs.56247.

    Genome annotation databases

    EnsembliENST00000316386; ENSP00000319476; ENSG00000163600. [Q9Y6W8-1]
    ENST00000435193; ENSP00000415951; ENSG00000163600. [Q9Y6W8-2]
    GeneIDi29851.
    KEGGihsa:29851.
    UCSCiuc002vam.3. human. [Q9Y6W8-1]
    uc010fua.3. human. [Q9Y6W8-2]

    Polymorphism databases

    DMDMi50400701.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    ICOSbase

    ICOS mutation db

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ277832 mRNA. Translation: CAC06612.1 .
    AB023135 mRNA. Translation: BAA82129.1 .
    AF218312 mRNA. Translation: AAF71301.1 .
    AF411058 Genomic DNA. Translation: AAL40933.1 .
    AF411059 Genomic DNA. Translation: AAL40934.1 .
    AF488347 , AF488346 Genomic DNA. Translation: AAM00909.1 .
    AJ535718 Genomic DNA. Translation: CAD59742.1 .
    BC028006 mRNA. Translation: AAH28006.1 .
    BC028210 mRNA. Translation: AAH28210.1 .
    CCDSi CCDS2363.1. [Q9Y6W8-1 ]
    PIRi S78540.
    RefSeqi NP_036224.1. NM_012092.3. [Q9Y6W8-1 ]
    UniGenei Hs.56247.

    3D structure databases

    ProteinModelPortali Q9Y6W8.
    SMRi Q9Y6W8. Positions 25-115.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 118933. 4 interactions.
    IntActi Q9Y6W8. 1 interaction.
    STRINGi 9606.ENSP00000319476.

    PTM databases

    PhosphoSitei Q9Y6W8.

    Polymorphism databases

    DMDMi 50400701.

    Proteomic databases

    PaxDbi Q9Y6W8.
    PRIDEi Q9Y6W8.

    Protocols and materials databases

    DNASUi 29851.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000316386 ; ENSP00000319476 ; ENSG00000163600 . [Q9Y6W8-1 ]
    ENST00000435193 ; ENSP00000415951 ; ENSG00000163600 . [Q9Y6W8-2 ]
    GeneIDi 29851.
    KEGGi hsa:29851.
    UCSCi uc002vam.3. human. [Q9Y6W8-1 ]
    uc010fua.3. human. [Q9Y6W8-2 ]

    Organism-specific databases

    CTDi 29851.
    GeneCardsi GC02P204765.
    GeneReviewsi ICOS.
    HGNCi HGNC:5351. ICOS.
    HPAi CAB032575.
    MIMi 604558. gene.
    607594. phenotype.
    neXtProti NX_Q9Y6W8.
    Orphaneti 1572. Common variable immunodeficiency.
    PharmGKBi PA29599.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG69972.
    HOGENOMi HOG000112996.
    HOVERGENi HBG052079.
    InParanoidi Q9Y6W8.
    KOi K06713.
    OMAi HSHANYY.
    OrthoDBi EOG7JMGFN.
    PhylomeDBi Q9Y6W8.
    TreeFami TF335679.

    Enzyme and pathway databases

    Reactomei REACT_19344. Costimulation by the CD28 family.

    Miscellaneous databases

    GeneWikii CD278.
    GenomeRNAii 29851.
    NextBioi 52391.
    PROi Q9Y6W8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y6W8.
    Bgeei Q9Y6W8.
    CleanExi HS_ICOS.
    Genevestigatori Q9Y6W8.

    Family and domain databases

    ProtoNeti Search...

    Publicationsi

    1. "ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28."
      Hutloff A., Dittrich A.M., Beier K.C., Eljaschewitsch B., Kraft R., Anagnostopoulos I., Kroczek R.A.
      Nature 397:263-266(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), PROTEIN SEQUENCE OF 192-198, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
    2. "Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family."
      Tezuka K., Tsuji T., Hirano D., Tamatani T., Sakamaki K., Kobayashi Y., Kamada M.
      Biochem. Biophys. Res. Commun. 276:335-345(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), TISSUE SPECIFICITY.
      Tissue: Blood.
    3. Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
      Tissue: Thymus.
    4. "Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches."
      Ling V., Wu P.W., Finnerty H.F., Agostino M.J., Graham J.R., Chen S., Jussiff J.M., Fisk G.J., Miller C.P., Collins M.
      Genomics 78:155-168(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    5. "Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation."
      Haaning Andersen A.D., Lange M., Lillevang S.T.
      Tissue Antigens 61:276-285(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
    6. Todd J.A.
      Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Blood.
    8. Cited for: FUNCTION, GLYCOSYLATION, SUBUNIT, INDUCTION, TISSUE SPECIFICITY.
    9. Cited for: INVOLVEMENT IN CVID1.

    Entry informationi

    Entry nameiICOS_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y6W8
    Secondary accession number(s): Q8N6W8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 113 of the entry and version 1 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, Direct protein sequencing, Reference proteome

    Documents

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

    External Data

    Dasty 3