ID   ICOSL_HUMAN             Reviewed;         302 AA.
AC   O75144; A8MUZ1; Q9HD18; Q9NRQ1;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   14-AUG-2001, sequence version 2.
DT   13-FEB-2019, entry version 175.
DE   RecName: Full=ICOS ligand;
DE   AltName: Full=B7 homolog 2;
DE            Short=B7-H2;
DE   AltName: Full=B7-like protein Gl50;
DE   AltName: Full=B7-related protein 1;
DE            Short=B7RP-1;
DE   AltName: CD_antigen=CD275;
DE   Flags: Precursor;
GN   Name=ICOSLG; Synonyms=B7H2, B7RP1, ICOSL, KIAA0653;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Dendritic cell;
RX   PubMed=11023515;
RA   Wang S., Zhu G., Chapoval A.I., Dong H., Tamada K., Ni J., Chen L.;
RT   "Costimulation of T cells by B7-H2, a B7-like molecule that binds
RT   ICOS.";
RL   Blood 96:2808-2813(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Peripheral blood lymphocyte;
RX   PubMed=11007762; DOI=10.1093/intimm/12.10.1439;
RA   Yoshinaga S.K., Zhang M., Pistillo J., Horan T., Khare S.D., Miner K.,
RA   Sonnenberg M., Boone T., Brankow D., Dai T., Delaney J., Han H.,
RA   Hui A., Kohno T., Manoukian R., Whoriskey J.S., Coccia M.A.;
RT   "Characterization of a new human B7-related protein: B7RP-1 is the
RT   ligand to the co-stimulatory protein ICOS.";
RL   Int. Immunol. 12:1439-1447(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Leukocyte;
RX   PubMed=10657606; DOI=10.4049/jimmunol.164.4.1653;
RA   Ling V., Wu P.W., Finnerty H.F., Bean K.M., Spaulding V., Fouser L.A.,
RA   Leonard J.P., Hunter S.E., Zollner R., Thomas J.L., Miyashiro J.S.,
RA   Jacobs K.A., Collins M.;
RT   "Identification of GL50, a novel B7-like protein that functionally
RT   binds to ICOS receptor.";
RL   J. Immunol. 164:1653-1657(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Ling V., Dunussi-Joannopolulos K.;
RT   "GL50 molecules and uses therefor.";
RL   Patent number WO0121796, 29-MAR-2001.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA   Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA   Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. X.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for large proteins in vitro.";
RL   DNA Res. 5:169-176(1998).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T.,
RA   Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA   Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA   Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA   Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA   Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA   Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA   Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA   Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA   Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA   Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA   Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [10]
RP   TISSUE SPECIFICITY.
RX   PubMed=10779774; DOI=10.4049/jimmunol.164.9.4689;
RA   Aicher A., Hayden-Ledbetter M., Brady W.A., Pezzutto A., Richter G.,
RA   Magaletti D., Buckwalter S., Ledbetter J.A., Clark E.A.;
RT   "Characterization of human inducible costimulator ligand expression
RT   and function.";
RL   J. Immunol. 164:4689-4696(2000).
RN   [11]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70 AND ASN-186.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA   Moore R.J., Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [12]
RP   INTERACTION WITH CTLA4.
RX   PubMed=28484017; DOI=10.1073/pnas.1617941114;
RA   Ramagopal U.A., Liu W., Garrett-Thomson S.C., Bonanno J.B., Yan Q.,
RA   Srinivasan M., Wong S.C., Bell A., Mankikar S., Rangan V.S.,
RA   Deshpande S., Korman A.J., Almo S.C.;
RT   "Structural basis for cancer immunotherapy by the first-in-class
RT   checkpoint inhibitor ipilimumab.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:E4223-E4232(2017).
CC   -!- FUNCTION: Ligand for the T-cell-specific cell surface receptor
CC       ICOS. Acts as a costimulatory signal for T-cell proliferation and
CC       cytokine secretion; induces also B-cell proliferation and
CC       differentiation into plasma cells. Could play an important role in
CC       mediating local tissue responses to inflammatory conditions, as
CC       well as in modulating the secondary immune response by co-
CC       stimulating memory T-cell function (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with CTLA4 (in vitro).
CC       {ECO:0000269|PubMed:28484017}.
CC   -!- INTERACTION:
CC       Self; NbExp=7; IntAct=EBI-12923856, EBI-12923856;
CC       Q9Y6W8:ICOS; NbExp=8; IntAct=EBI-12923856, EBI-3922712;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11007762};
CC       Single-pass type I membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=1;
CC         IsoId=O75144-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O75144-2; Sequence=VSP_002520;
CC       Name=3;
CC         IsoId=O75144-3; Sequence=VSP_054718;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is widely expressed (brain, heart,
CC       kidney, liver, lung, pancreas, placenta, skeletal muscle, bone
CC       marrow, colon, ovary, prostate, testis, lymph nodes, leukocytes,
CC       spleen, thymus and tonsil), while isoform 2 is detected only in
CC       lymph nodes, leukocytes and spleen. Expressed on activated
CC       monocytes and dendritic cells. {ECO:0000269|PubMed:10779774}.
CC   -!- INDUCTION: Constitutive expression is further enhanced by
CC       treatment with TNF in peripheral blood B-cells and monocytes,
CC       while it is decreased in dendritic cells.
CC   -!- SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA31628.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=BAA31628.1; Type=Miscellaneous discrepancy; Note=The sequence differs from that shown in position 300 onward for unknown reason.; Evidence={ECO:0000305};
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DR   EMBL; AF199028; AAF34739.1; -; mRNA.
DR   EMBL; AF289028; AAG01176.1; -; mRNA.
DR   EMBL; AF216749; AAK16241.1; -; mRNA.
DR   EMBL; AX100595; CAC36465.1; -; mRNA.
DR   EMBL; AB014553; BAA31628.1; ALT_SEQ; mRNA.
DR   EMBL; AK090492; BAG52170.1; -; mRNA.
DR   EMBL; AP001058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP001059; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471079; EAX09446.1; -; Genomic_DNA.
DR   EMBL; BC064637; AAH64637.1; -; mRNA.
DR   CCDS; CCDS42952.1; -. [O75144-1]
DR   CCDS; CCDS63377.1; -. [O75144-3]
DR   CCDS; CCDS63379.1; -. [O75144-2]
DR   RefSeq; NP_001269979.1; NM_001283050.1. [O75144-2]
DR   RefSeq; NP_001269980.1; NM_001283051.1. [O75144-3]
DR   RefSeq; NP_056074.1; NM_015259.5. [O75144-1]
DR   RefSeq; XP_006723963.1; XM_006723900.2.
DR   UniGene; Hs.14155; -.
DR   ProteinModelPortal; O75144; -.
DR   SMR; O75144; -.
DR   BioGrid; 116900; 8.
DR   IntAct; O75144; 2.
DR   STRING; 9606.ENSP00000384432; -.
DR   ChEMBL; CHEMBL3712949; -.
DR   GlyConnect; 740; -.
DR   iPTMnet; O75144; -.
DR   PhosphoSitePlus; O75144; -.
DR   SwissPalm; O75144; -.
DR   UniCarbKB; O75144; -.
DR   BioMuta; ICOSLG; -.
DR   EPD; O75144; -.
DR   jPOST; O75144; -.
DR   MaxQB; O75144; -.
DR   PaxDb; O75144; -.
DR   PeptideAtlas; O75144; -.
DR   PRIDE; O75144; -.
DR   ProteomicsDB; 49806; -.
DR   ProteomicsDB; 49807; -. [O75144-2]
DR   TopDownProteomics; O75144-2; -. [O75144-2]
DR   DNASU; 23308; -.
DR   Ensembl; ENST00000344330; ENSP00000339477; ENSG00000160223. [O75144-2]
DR   Ensembl; ENST00000400377; ENSP00000383228; ENSG00000160223. [O75144-3]
DR   Ensembl; ENST00000407780; ENSP00000384432; ENSG00000160223. [O75144-1]
DR   GeneID; 102723996; -.
DR   GeneID; 23308; -.
DR   KEGG; hsa:23308; -.
DR   UCSC; uc002zee.5; human. [O75144-1]
DR   CTD; 23308; -.
DR   DisGeNET; 102723996; -.
DR   DisGeNET; 23308; -.
DR   EuPathDB; HostDB:ENSG00000160223.16; -.
DR   EuPathDB; HostDB:ENSG00000277117.4; -.
DR   GeneCards; ICOSLG; -.
DR   H-InvDB; HIX0016164; -.
DR   HGNC; HGNC:17087; ICOSLG.
DR   HPA; CAB026037; -.
DR   HPA; HPA029179; -.
DR   MIM; 605717; gene.
DR   neXtProt; NX_O75144; -.
DR   OpenTargets; ENSG00000160223; -.
DR   OpenTargets; ENSG00000277117; -.
DR   PharmGKB; PA134977297; -.
DR   eggNOG; ENOG410IYI6; Eukaryota.
DR   eggNOG; ENOG410Z67K; LUCA.
DR   GeneTree; ENSGT00940000161590; -.
DR   HOGENOM; HOG000036913; -.
DR   HOVERGEN; HBG106483; -.
DR   InParanoid; O75144; -.
DR   KO; K06710; -.
DR   OMA; YWINRTD; -.
DR   OrthoDB; 1537230at2759; -.
DR   PhylomeDB; O75144; -.
DR   TreeFam; TF331083; -.
DR   Reactome; R-HSA-388841; Costimulation by the CD28 family.
DR   ChiTaRS; ICOSLG; human.
DR   GeneWiki; ICOSLG; -.
DR   PRO; PR:O75144; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   Bgee; ENSG00000160223; Expressed in 106 organ(s), highest expression level in C1 segment of cervical spinal cord.
DR   ExpressionAtlas; O75144; baseline and differential.
DR   Genevisible; O75144; HS.
DR   GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0042113; P:B cell activation; IEA:UniProtKB-KW.
DR   GO; GO:0006952; P:defense response; NAS:UniProtKB.
DR   GO; GO:0006972; P:hyperosmotic response; NAS:UniProtKB.
DR   GO; GO:0042104; P:positive regulation of activated T cell proliferation; TAS:UniProtKB.
DR   GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR   GO; GO:0042110; P:T cell activation; NAS:UniProtKB.
DR   GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR   Gene3D; 2.60.40.10; -; 2.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR013106; Ig_V-set.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 1.
DR   SUPFAM; SSF48726; SSF48726; 2.
DR   PROSITE; PS50835; IG_LIKE; 2.
PE   1: Evidence at protein level;
KW   Adaptive immunity; Alternative splicing; B-cell activation;
KW   Cell membrane; Complete proteome; Disulfide bond; Glycoprotein;
KW   Immunity; Immunoglobulin domain; Membrane; Polymorphism;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     18       {ECO:0000255}.
FT   CHAIN        19    302       ICOS ligand.
FT                                /FTId=PRO_0000014803.
FT   TOPO_DOM     19    256       Extracellular. {ECO:0000255}.
FT   TRANSMEM    257    277       Helical. {ECO:0000255}.
FT   TOPO_DOM    278    302       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       19    129       Ig-like V-type.
FT   DOMAIN      141    227       Ig-like C2-type.
FT   CARBOHYD     70     70       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:16335952}.
FT   CARBOHYD    137    137       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    173    173       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    186    186       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:16335952}.
FT   CARBOHYD    225    225       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     37    113       {ECO:0000255|PROSITE-ProRule:PRU00114}.
FT   DISULFID    158    216       {ECO:0000255|PROSITE-ProRule:PRU00114}.
FT   VAR_SEQ      18    134       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_054718.
FT   VAR_SEQ     300    302       GHV -> ESWNLLLLLS (in isoform 2).
FT                                {ECO:0000303|PubMed:10657606,
FT                                ECO:0000303|Ref.4}.
FT                                /FTId=VSP_002520.
FT   VARIANT     128    128       V -> I (in dbSNP:rs11558819).
FT                                /FTId=VAR_049880.
SQ   SEQUENCE   302 AA;  33349 MW;  647934E21B55E34A CRC64;
     MRLGSPGLLF LLFSSLRADT QEKEVRAMVG SDVELSCACP EGSRFDLNDV YVYWQTSESK
     TVVTYHIPQN SSLENVDSRY RNRALMSPAG MLRGDFSLRL FNVTPQDEQK FHCLVLSQSL
     GFQEVLSVEV TLHVAANFSV PVVSAPHSPS QDELTFTCTS INGYPRPNVY WINKTDNSLL
     DQALQNDTVF LNMRGLYDVV SVLRIARTPS VNIGCCIENV LLQQNLTVGS QTGNDIGERD
     KITENPVSTG EKNAATWSIL AVLCLLVVVA VAIGWVCRDR CLQHSYAGAW AVSPETELTG
     HV
//