ICOS_MOUSE
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 03-AUG-2022, entry version 135.
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 GlyGen; Q9WVS0; 3 sites.
DR iPTMnet; Q9WVS0; -.
DR PhosphoSitePlus; Q9WVS0; -.
DR EPD; Q9WVS0; -.
DR PaxDb; Q9WVS0; -.
DR PRIDE; Q9WVS0; -.
DR ProteomicsDB; 273088; -.
DR Antibodypedia; 34168; 1030 antibodies from 42 providers.
DR DNASU; 54167; -.
DR Ensembl; ENSMUST00000102827; ENSMUSP00000099891; ENSMUSG00000026009.
DR GeneID; 54167; -.
DR KEGG; mmu:54167; -.
DR UCSC; uc011wlz.2; mouse.
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; 1298290at2759; -.
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 74 CRISPR screens.
DR PRO; PR:Q9WVS0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9WVS0; protein.
DR Bgee; ENSMUSG00000026009; Expressed in peripheral lymph node and 43 other tissues.
DR ExpressionAtlas; Q9WVS0; baseline and differential.
DR Genevisible; Q9WVS0; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of 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; -; 1.
DR InterPro; IPR039943; ICOS.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR PANTHER; PTHR20904; PTHR20904; 1.
DR Pfam; PF15910; V-set_2; 1.
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