ID   ICOS_MOUSE              Reviewed;         200 AA.
AC   Q9WVS0; Q9JL17;
DT   19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 2.
DT   24-JAN-2024, entry version 142.
DE   RecName: Full=Inducible T-cell costimulator;
DE   AltName: Full=Activation-inducible lymphocyte immunomediatory molecule;
DE   AltName: Full=CD28 and CTLA-4-like protein;
DE            Short=CCLP;
DE   AltName: Full=CD28-related protein 1;
DE            Short=CRP-1;
DE   AltName: CD_antigen=CD278;
DE   Flags: Precursor;
GN   Name=Icos; Synonyms=Ailim;
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, FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Intestinal epithelium;
RX   PubMed=10617205; DOI=10.1038/45582;
RA   Yoshinaga S.K., Whoriskey J.S., Khare S.D., Sarmiento U., Guo J., Horan T.,
RA   Shih G., Zhang M., Coccia M.A., Kohno T., Tafuri-Bladt A., Brankow D.,
RA   Campbell P., Chang D., Chiu L., Dai T., Duncan G., Elliott G.S., Hui A.,
RA   McCabe S.M., Scully S., Shahinian A., Shaklee C.L., Van G., Mak T.W.,
RA   Senaldi G.;
RT   "T-cell co-stimulation through B7RP-1 and ICOS.";
RL   Nature 402:827-832(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE, AND TISSUE SPECIFICITY.
RC   TISSUE=Spleen;
RX   PubMed=11006126; DOI=10.1006/bbrc.2000.3466;
RA   Tezuka K., Tsuji T., Hirano D., Tamatani T., Sakamaki K., Kobayashi Y.,
RA   Kamada M.;
RT   "Identification and characterization of rat AILIM/ICOS, a novel T-cell
RT   costimulatory molecule, related to the CD28/CTLA4 family.";
RL   Biochem. Biophys. Res. Commun. 276:335-345(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, SUBUNIT, AND TISSUE SPECIFICITY.
RC   STRAIN=BALB/cJ; TISSUE=Spleen;
RX   PubMed=10760791;
RX   DOI=10.1002/(sici)1521-4141(200004)30:4<1040::aid-immu1040>3.0.co;2-6;
RA   Mages H.W., Hutloff A., Heuck C., Buechner K., Himmelbauer H., Oliveri F.,
RA   Kroczek R.A.;
RT   "Molecular cloning and characterization of murine ICOS and identification
RT   of B7h as ICOS ligand.";
RL   Eur. J. Immunol. 30:1040-1047(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE, AND FUNCTION.
RC   STRAIN=129/Ola;
RX   PubMed=11343122; DOI=10.1038/35051107;
RA   McAdam A.J., Greenwald R.J., Levin M.A., Chernova T., Malenkovich N.,
RA   Ling V., Freeman G.J., Sharpe A.H.;
RT   "The inducible costimulatory (ICOS) molecule is critical for CD40-mediated
RT   antibody class switching.";
RL   Nature 409:102-105(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=BALB/cJ; TISSUE=Spleen;
RA   Wu D., Giannoni M.A., Kiesecker C.L., Faas S.J., Mickle A.P., Matis L.A.,
RA   Rother R.P.;
RT   "CCLP, A novel molecule that regulates T cell activation.";
RL   Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=11343123; DOI=10.1038/35051113;
RA   Tafuri A., Shahinian A., Bladt F., Yoshinaga S.K., Jordana M., Wakeham A.,
RA   Boucher L.-M., Bouchard D., Chan V.S., Duncan G., Odermatt B., Ho A.,
RA   Itie A., Horan T., Whoriskey J.S., Pawson T., Penninger J.M., Ohashi P.S.,
RA   Mak T.W.;
RT   "ICOS is essential for effective T-helper-cell responses.";
RL   Nature 409:105-109(2001).
CC   -!- FUNCTION: Enhances all basic T-cell responses to a foreign antigen,
CC       namely proliferation, secretion of lymphokines, up-regulation of
CC       molecules that mediate cell-cell interaction, and effective help for
CC       antibody secretion by B-cells. Essential both for efficient interaction
CC       between T and B-cells and for normal antibody responses to T-cell
CC       dependent antigens. Does not up-regulate the production of interleukin-
CC       2, but superinduces the synthesis of interleukin-10. Prevents the
CC       apoptosis of pre-activated T-cells. Plays a critical role in CD40-
CC       mediated class switching of immunoglobin isotypes (By similarity).
CC       {ECO:0000250, ECO:0000269|PubMed:10617205, ECO:0000269|PubMed:11343122,
CC       ECO:0000269|PubMed:11343123}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:10760791}.
CC   -!- INTERACTION:
CC       Q9WVS0; P26450: Pik3r1; NbExp=2; IntAct=EBI-16721736, EBI-641764;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed on activated T-cells and resting memory
CC       T-cells. High expression seen in the thymic medulla and in the germinal
CC       centers and T-cell zones of lymph nodes and Peyer patches. Expressed at
CC       low levels in the spleen. {ECO:0000269|PubMed:10617205,
CC       ECO:0000269|PubMed:10760791, ECO:0000269|PubMed:11006126}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10760791}.
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DR   EMBL; AF216748; AAF45150.1; -; mRNA.
DR   EMBL; AB023132; BAA82126.1; -; mRNA.
DR   EMBL; AJ250559; CAB71153.1; -; mRNA.
DR   EMBL; AF327185; AAG48732.1; -; Genomic_DNA.
DR   EMBL; AF327184; AAG48732.1; JOINED; Genomic_DNA.
DR   EMBL; AF257230; AAF70099.1; -; mRNA.
DR   EMBL; BC034852; AAH34852.1; -; mRNA.
DR   CCDS; CCDS14994.1; -.
DR   RefSeq; NP_059508.2; NM_017480.2.
DR   RefSeq; XP_006496201.1; XM_006496138.1.
DR   RefSeq; XP_006496202.1; XM_006496139.1.
DR   AlphaFoldDB; Q9WVS0; -.
DR   SMR; Q9WVS0; -.
DR   IntAct; Q9WVS0; 2.
DR   STRING; 10090.ENSMUSP00000099891; -.
DR   GlyCosmos; Q9WVS0; 3 sites, No reported glycans.
DR   GlyGen; Q9WVS0; 3 sites.
DR   iPTMnet; Q9WVS0; -.
DR   PhosphoSitePlus; Q9WVS0; -.
DR   EPD; Q9WVS0; -.
DR   PaxDb; 10090-ENSMUSP00000099891; -.
DR   ProteomicsDB; 273088; -.
DR   Antibodypedia; 34168; 1181 antibodies from 42 providers.
DR   DNASU; 54167; -.
DR   Ensembl; ENSMUST00000102827.4; ENSMUSP00000099891.4; ENSMUSG00000026009.15.
DR   GeneID; 54167; -.
DR   KEGG; mmu:54167; -.
DR   UCSC; uc011wlz.2; mouse.
DR   AGR; MGI:1858745; -.
DR   CTD; 29851; -.
DR   MGI; MGI:1858745; Icos.
DR   VEuPathDB; HostDB:ENSMUSG00000026009; -.
DR   eggNOG; ENOG502S59F; Eukaryota.
DR   GeneTree; ENSGT00390000000801; -.
DR   HOGENOM; CLU_1315009_0_0_1; -.
DR   InParanoid; Q9WVS0; -.
DR   OMA; QDKEDCF; -.
DR   OrthoDB; 4570780at2759; -.
DR   TreeFam; TF335679; -.
DR   Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   BioGRID-ORCS; 54167; 0 hits in 79 CRISPR screens.
DR   PRO; PR:Q9WVS0; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q9WVS0; Protein.
DR   Bgee; ENSMUSG00000026009; Expressed in peripheral lymph node and 44 other cell types or tissues.
DR   ExpressionAtlas; Q9WVS0; baseline and differential.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0098609; P:cell-cell adhesion; ISO:MGI.
DR   GO; GO:0031295; P:T cell costimulation; ISO:MGI.
DR   GO; GO:0002517; P:T cell tolerance induction; ISO:MGI.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   InterPro; IPR039943; ICOS.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR013106; Ig_V-set.
DR   PANTHER; PTHR20904:SF0; INDUCIBLE T-CELL COSTIMULATOR; 1.
DR   PANTHER; PTHR20904; INDUCIBLE T-CELL COSTIMULATOR ICOS; 1.
DR   Pfam; PF15910; V-set_2; 1.
DR   Genevisible; Q9WVS0; MM.
PE   1: Evidence at protein level;
KW   Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..200
FT                   /note="Inducible T-cell costimulator"
FT                   /id="PRO_0000014807"
FT   TOPO_DOM        21..144
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        145..165
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        166..200
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          30..133
FT                   /note="Ig-like V-type"
FT   CARBOHYD        23
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        89
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        123
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        42..109
FT                   /evidence="ECO:0000250"
FT   DISULFID        63..83
FT                   /evidence="ECO:0000250"
FT   CONFLICT        7
FT                   /note="R -> H (in Ref. 2, 3 and 5)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   200 AA;  22709 MW;  87D97F0DC44ADCA7 CRC64;
     MKPYFCRVFV FCFLIRLLTG EINGSADHRM FSFHNGGVQI SCKYPETVQQ LKMRLFRERE
     VLCELTKTKG SGNAVSIKNP MLCLYHLSNN SVSFFLNNPD SSQGSYYFCS LSIFDPPPFQ
     ERNLSGGYLH IYESQLCCQL KLWLPVGCAA FVVVLLFGCI LIIWFSKKKY GSSVHDPNSE
     YMFMAAVNTN KKSRLAGVTS
//