CTLA4_HUMAN
ID CTLA4_HUMAN Reviewed; 223 AA.
AC P16410; A0N1S0; E9PDH0; O95653; Q0PP65; Q52MC1; Q53TD5; Q5S005; Q8WXJ1;
AC Q96P43; Q9UKN9;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2003, sequence version 3.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Cytotoxic T-lymphocyte protein 4;
DE AltName: Full=Cytotoxic T-lymphocyte-associated antigen 4;
DE Short=CTLA-4;
DE AltName: CD_antigen=CD152;
DE Flags: Precursor;
GN Name=CTLA4; Synonyms=CD152;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP ALTERNATIVE SPLICING, AND VARIANT ALA-17.
RX PubMed=1713603;
RA Harper K., Balzano C., Rouvier E., Mattei M.-G., Luciani M.-F.,
RA Golstein P.;
RT "CTLA-4 and CD28 activated lymphocyte molecules are closely related in both
RT mouse and human as to sequence, message expression, gene structure, and
RT chromosomal location.";
RL J. Immunol. 147:1037-1044(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11735222; DOI=10.1006/geno.2001.6655;
RA Ling V., Wu P.W., Finnerty H.F., Agostino M.J., Graham J.R., Chen S.,
RA Jussiff J.M., Fisk G.J., Miller C.P., Collins M.;
RT "Assembly and annotation of human chromosome 2q33 sequence containing the
RT CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative,
RT and microarray approaches.";
RL Genomics 78:155-168(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), VARIANT ALA-17,
RP ALTERNATIVE SPLICING, AND POLYMORPHISM.
RX PubMed=18595775; DOI=10.1016/j.clim.2008.05.006;
RA Gu M., Kakoulidou M., Giscombe R., Pirskanen R., Lefvert A.K.,
RA Klareskog L., Wang X.;
RT "Identification of CTLA-4 isoforms produced by alternative splicing and
RT their association with myasthenia gravis.";
RL Clin. Immunol. 128:374-381(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Wu P.W., Ling V.;
RT "Full length sequence of hCTLA4 cDNA.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-223.
RC TISSUE=Lymphocyte;
RX PubMed=3220103; DOI=10.1002/eji.1830181206;
RA Dariavach P., Mattei M.-G., Golstein P., Lefranc M.-P.;
RT "Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of
RT protein sequence between murine and human CTLA-4 cytoplasmic domains.";
RL Eur. J. Immunol. 18:1901-1905(1988).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-223 (ISOFORM 5).
RC TISSUE=Lymph node;
RA Oaks M.K.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 140-223, AND TISSUE SPECIFICITY.
RX PubMed=10493833; DOI=10.1006/geno.1999.5930;
RA Ling V., Wu P.W., Finnerty H.F., Sharpe A.H., Gray G.S., Collins M.;
RT "Complete sequence determination of the mouse and human CTLA4 gene loci:
RT cross-species DNA sequence similarity beyond exon borders.";
RL Genomics 60:341-355(1999).
RN [11]
RP FUNCTION.
RX PubMed=1714933; DOI=10.1084/jem.174.3.561;
RA Linsley P.S., Brady W., Urnes M., Griosmaire L.S., Damle N.K.,
RA Ledbetter J.A.;
RT "CTLA-4 is a second receptor for the B cell activation antigen B7.";
RL J. Exp. Med. 174:561-569(1991).
RN [12]
RP PHOSPHORYLATION AT TYR-201.
RX PubMed=9175836; DOI=10.1016/s1074-7613(00)80346-5;
RA Shiratori T., Miyatake S., Ohno H., Nakaseko C., Isono K., Bonifacino J.S.,
RA Saito T.;
RT "Tyrosine phosphorylation controls internalization of CTLA-4 by regulating
RT its interaction with clathrin-associated adaptor complex AP-2.";
RL Immunity 6:583-589(1997).
RN [13]
RP PHOSPHORYLATION AT TYR-201.
RX PubMed=9813138; DOI=10.1006/bbrc.1998.9559;
RA Schneider H., Schwartzberg P.L., Rudd C.E.;
RT "Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and
RT regulates PI 3-kinase binding to T-cell antigen CTLA-4.";
RL Biochem. Biophys. Res. Commun. 252:14-19(1998).
RN [14]
RP PHOSPHORYLATION AT TYR-201 BY JAK2.
RX PubMed=10842319;
RX DOI=10.1002/(sici)1097-4644(20000801)78:2<241::aid-jcb7>3.0.co;2-k;
RA Chikuma S., Murakami M., Tanaka K., Uede T.;
RT "Janus kinase 2 is associated with a box 1-like motif and phosphorylates a
RT critical tyrosine residue in the cytoplasmic region of cytotoxic T
RT lymphocyte associated molecule-4.";
RL J. Cell. Biochem. 78:241-250(2000).
RN [15]
RP POLYMORPHISM.
RX PubMed=12724780; DOI=10.1038/nature01621;
RA Ueda H., Howson J.M., Esposito L., Heward J., Snook H., Chamberlain G.,
RA Rainbow D.B., Hunter K.M., Smith A.N., Di Genova G., Herr M.H., Dahlman I.,
RA Payne F., Smyth D., Lowe C., Twells R.C., Howlett S., Healy B., Nutland S.,
RA Rance H.E., Everett V., Smink L.J., Lam A.C., Cordell H.J., Walker N.M.,
RA Bordin C., Hulme J., Motzo C., Cucca F., Hess J.F., Metzker M.L.,
RA Rogers J., Gregory S., Allahabadia A., Nithiyananthan R.,
RA Tuomilehto-Wolf E., Tuomilehto J., Bingley P., Gillespie K.M.,
RA Undlien D.E., Ronningen K.S., Guja C., Ionescu-Tirgoviste C., Savage D.A.,
RA Maxwell A.P., Carson D.J., Patterson C.C., Franklyn J.A., Clayton D.G.,
RA Peterson L.B., Wicker L.S., Todd J.A., Gough S.C.;
RT "Association of the T-cell regulatory gene CTLA4 with susceptibility to
RT autoimmune disease.";
RL Nature 423:506-511(2003).
RN [16]
RP GLYCOSYLATION AT ASN-113 AND ASN-145.
RX PubMed=16002699; DOI=10.4049/jimmunol.175.2.996;
RA Darlington P.J., Kirchhof M.G., Criado G., Sondhi J., Madrenas J.;
RT "Hierarchical regulation of CTLA-4 dimer-based lattice formation and its
RT biological relevance for T cell inactivation.";
RL J. Immunol. 175:996-1004(2005).
RN [17]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16551244; DOI=10.1146/annurev.immunol.24.021605.090535;
RA Teft W.A., Kirchhof M.G., Madrenas J.;
RT "A molecular perspective of CTLA-4 function.";
RL Annu. Rev. Immunol. 24:65-97(2006).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=18468488; DOI=10.1016/j.it.2008.02.011;
RA Valk E., Rudd C.E., Schneider H.;
RT "CTLA-4 trafficking and surface expression.";
RL Trends Immunol. 29:272-279(2008).
RN [19]
RP PHARMACEUTICAL.
RX PubMed=19426230; DOI=10.1111/j.1600-065x.2009.00780.x;
RA Linsley P.S., Nadler S.G.;
RT "The clinical utility of inhibiting CD28-mediated costimulation.";
RL Immunol. Rev. 229:307-321(2009).
RN [20]
RP STRUCTURE BY NMR OF 37-161, AND DISULFIDE BONDS.
RX PubMed=9228944; DOI=10.1038/nsb0797-527;
RA Metzler W.J., Bajorath J., Fenderson W., Shaw S.Y., Constantine K.L.,
RA Naemura J., Leytze G., Peach R.J., Lavoie T.B., Mueller L., Linsley P.S.;
RT "Solution structure of human CTLA-4 and delineation of a CD80/CD86 binding
RT site conserved in CD28.";
RL Nat. Struct. Biol. 4:527-531(1997).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 36-161 IN COMPLEX WITH CD86,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=11279501; DOI=10.1038/35069112;
RA Schwartz J.C., Zhang X., Fedorov A.A., Nathenson S.G., Almo S.C.;
RT "Structural basis for co-stimulation by the human CTLA-4/B7-2 complex.";
RL Nature 410:604-608(2001).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 36-161 IN COMPLEX WITH CD80,
RP SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-113 AND ASN-145.
RX PubMed=11279502; DOI=10.1038/35069118;
RA Stamper C.C., Zhang Y., Tobin J.F., Erbe D.V., Ikemizu S., Davis S.J.,
RA Stahl M.L., Seehra J., Somers W.S., Mosyak L.;
RT "Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune
RT responses.";
RL Nature 410:608-611(2001).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 38-161, DISULFIDE BONDS, AND
RP SUBUNIT.
RA Schonfeld D.L., Matschiner G., Chatwell L., Trentmann S., Schlehuber S.,
RA Hohlbaum A., Skerra A.;
RT "High affinity molecular recognition and functional blockade of CTLA-4 by
RT an engineered human lipocalin.";
RL Submitted (JAN-2008) to the PDB data bank.
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 36-161, GLYCOSYLATION AT ASN-113,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=21156796; DOI=10.1074/jbc.m110.182394;
RA Yu C., Sonnen A.F., George R., Dessailly B.H., Stagg L.J., Evans E.J.,
RA Orengo C.A., Stuart D.I., Ladbury J.E., Ikemizu S., Gilbert R.J.,
RA Davis S.J.;
RT "Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4
RT (CTLA-4) receptor triggering.";
RL J. Biol. Chem. 286:6685-6696(2011).
RN [25] {ECO:0007744|PDB:5TRU}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 37-154 IN COMPLEX WITH
RP THERAPEUTIC ANTIBODY IPILIMUMAB, SUBUNIT, INTERACTION WITH CD80; CD86 AND
RP ICOSLG, SUBCELLULAR LOCATION, TOPOLOGY, DISULFIDE BONDS, AND MUTAGENESIS OF
RP VAL-45; LEU-47; SER-49; ARG-70; LYS-130; GLU-132; TYR-139 AND ILE-143.
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., Deshpande S.,
RA Korman A.J., Almo S.C.;
RT "Structural basis for cancer immunotherapy by the first-in-class checkpoint
RT inhibitor ipilimumab.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E4223-E4232(2017).
RN [26]
RP VARIANT ALA-17, AND INVOLVEMENT IN IDDM12.
RX PubMed=9259273; DOI=10.1093/hmg/6.8.1275;
RA Marron M.P., Raffel L.J., Garchon H.-J., Jacob C.O., Serrano-Rios M.,
RA Martinez Larrad M.T., Teng W.-P., Park Y., Zhang Z.-X., Goldstein D.R.,
RA Tao Y.-W., Beaurain G., Bach J.-F., Huang H.-S., Luo D.-F., Zeidler A.,
RA Rotter J.I., Yang M.C.K., Modilevsky T., Maclaren N.K., She J.-X.;
RT "Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4
RT polymorphisms in multiple ethnic groups.";
RL Hum. Mol. Genet. 6:1275-1282(1997).
RN [27]
RP POLYMORPHISM, AND INVOLVEMENT IN CELIAC3.
RX PubMed=10189842; DOI=10.1136/gut.43.2.187;
RA Djilali-Saiah I., Schmitz J., Harfouch-Hammoud E., Mougenot J.-F.,
RA Bach J.-F., Caillat-Zucman S.;
RT "CTLA-4 gene polymorphism is associated with predisposition to coeliac
RT disease.";
RL Gut 43:187-189(1998).
RN [28]
RP VARIANT ALA-17, AND INVOLVEMENT IN THYROID ASSOCIATED ORBITOPATHY.
RX PubMed=10475192; DOI=10.1016/s0140-6736(99)01465-8;
RA Vaidya B., Imrie H., Perros P., Dickinson J., McCarthy M.I.,
RA Kendall-Taylor P., Pearce S.H.S.;
RT "Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers
RT susceptibility to thyroid associated orbitopathy.";
RL Lancet 354:743-744(1999).
RN [29]
RP POLYMORPHISM, VARIANT ALA-17, AND INVOLVEMENT IN GRAVES DISEASE.
RX PubMed=10924276; DOI=10.1006/mgme.2000.3007;
RA Chistyakov D.A., Savost'anov K.V., Turakulov R.I., Petunina N.A.,
RA Trukhina L.V., Kudinova A.V., Balabolkin M.I., Nosikov V.V.;
RT "Complex association analysis of Graves disease using a set of polymorphic
RT markers.";
RL Mol. Genet. Metab. 70:214-218(2000).
RN [30]
RP VARIANT ALA-17.
RX PubMed=10903931; DOI=10.1086/303059;
RA Deng Z., Morse J.H., Slager S.L., Cuervo N., Moore K.J., Venetos G.,
RA Kalachikov S., Cayanis E., Fischer S.G., Barst R.J., Hodge S.E.,
RA Knowles J.A.;
RT "Familial primary pulmonary hypertension (gene PPH1) is caused by mutations
RT in the bone morphogenetic protein receptor-II gene.";
RL Am. J. Hum. Genet. 67:737-744(2000).
RN [31]
RP POLYMORPHISM, AND INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
RX PubMed=15138458; DOI=10.1038/sj.ejhg.5201214;
RA Barreto M., Santos E., Ferreira R., Fesel C., Fontes M.F., Pereira C.,
RA Martins B., Andreia R., Viana J.F., Crespo F., Vasconcelos C., Ferreira C.,
RA Vicente A.M.;
RT "Evidence for CTLA4 as a susceptibility gene for systemic lupus
RT erythematosus.";
RL Eur. J. Hum. Genet. 12:620-626(2004).
RN [32]
RP POLYMORPHISM, INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION, AND VARIANT
RP ALA-17.
RX PubMed=15452244; DOI=10.1128/jvi.78.20.11258-11262.2004;
RA Thio C.L., Mosbruger T.L., Kaslow R.A., Karp C.L., Strathdee S.A.,
RA Vlahov D., O'Brien S.J., Astemborski J., Thomas D.L.;
RT "Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus
RT infection.";
RL J. Virol. 78:11258-11262(2004).
RN [33]
RP POLYMORPHISM, AND INVOLVEMENT IN CELIAC3.
RX PubMed=15657618; DOI=10.1038/sj.ejhg.5201357;
RA Hunt K.A., McGovern D.P.B., Kumar P.J., Ghosh S., Travis S.P.L.,
RA Walters J.R.F., Jewell D.P., Playford R.J., van Heel D.A.;
RT "A common CTLA4 haplotype associated with coeliac disease.";
RL Eur. J. Hum. Genet. 13:440-444(2005).
RN [34]
RP POLYMORPHISM, AND INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
RX PubMed=15688186; DOI=10.1007/s00439-004-1244-1;
RA Lee Y.H., Harley J.B., Nath S.K.;
RT "CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-
RT analysis.";
RL Hum. Genet. 116:361-367(2005).
RN [35]
RP POLYMORPHISM, INVOLVEMENT IN ALPS5, AND VARIANT ALPS5 TRP-70.
RX PubMed=25329329; DOI=10.1038/nm.3746;
RA Schubert D., Bode C., Kenefeck R., Hou T.Z., Wing J.B., Kennedy A.,
RA Bulashevska A., Petersen B.S., Schaeffer A.A., Gruening B.A., Unger S.,
RA Frede N., Baumann U., Witte T., Schmidt R.E., Dueckers G., Niehues T.,
RA Seneviratne S., Kanariou M., Speckmann C., Ehl S., Rensing-Ehl A.,
RA Warnatz K., Rakhmanov M., Thimme R., Hasselblatt P., Emmerich F.,
RA Cathomen T., Backofen R., Fisch P., Seidl M., May A., Schmitt-Graeff A.,
RA Ikemizu S., Salzer U., Franke A., Sakaguchi S., Walker L.S., Sansom D.M.,
RA Grimbacher B.;
RT "Autosomal dominant immune dysregulation syndrome in humans with CTLA4
RT mutations.";
RL Nat. Med. 20:1410-1416(2014).
RN [36]
RP POLYMORPHISM, AND INVOLVEMENT IN ALPS5.
RX PubMed=25213377; DOI=10.1126/science.1255904;
RA Kuehn H.S., Ouyang W., Lo B., Deenick E.K., Niemela J.E., Avery D.T.,
RA Schickel J.N., Tran D.Q., Stoddard J., Zhang Y., Frucht D.M., Dumitriu B.,
RA Scheinberg P., Folio L.R., Frein C.A., Price S., Koh C., Heller T.,
RA Seroogy C.M., Huttenlocher A., Rao V.K., Su H.C., Kleiner D.,
RA Notarangelo L.D., Rampertaap Y., Olivier K.N., McElwee J., Hughes J.,
RA Pittaluga S., Oliveira J.B., Meffre E., Fleisher T.A., Holland S.M.,
RA Lenardo M.J., Tangye S.G., Uzel G.;
RT "Immune dysregulation in human subjects with heterozygous germline
RT mutations in CTLA4.";
RL Science 345:1623-1627(2014).
CC -!- FUNCTION: Inhibitory receptor acting as a major negative regulator of
CC T-cell responses. The affinity of CTLA4 for its natural B7 family
CC ligands, CD80 and CD86, is considerably stronger than the affinity of
CC their cognate stimulatory coreceptor CD28.
CC {ECO:0000269|PubMed:16551244, ECO:0000269|PubMed:1714933}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:11279501, PubMed:11279502,
CC Ref.23, PubMed:21156796, PubMed:28484017). Binds to CD80/B7-1 and
CC CD86/B7.2 (PubMed:11279501, PubMed:11279502, PubMed:28484017).
CC Interacts with ICOSLG (PubMed:28484017). {ECO:0000269|PubMed:11279501,
CC ECO:0000269|PubMed:11279502, ECO:0000269|PubMed:21156796,
CC ECO:0000269|PubMed:28484017, ECO:0000269|Ref.23}.
CC -!- INTERACTION:
CC P16410; P33681: CD80; NbExp=7; IntAct=EBI-1030991, EBI-1031024;
CC P16410; P42081: CD86; NbExp=3; IntAct=EBI-1030991, EBI-1030956;
CC P16410; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-1030991, EBI-12019274;
CC P16410; Q13021: MALL; NbExp=3; IntAct=EBI-1030991, EBI-750078;
CC P16410; P27986: PIK3R1; NbExp=3; IntAct=EBI-1030991, EBI-79464;
CC P16410; A2RU14: TMEM218; NbExp=3; IntAct=EBI-1030991, EBI-10173151;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18468488,
CC ECO:0000269|PubMed:28484017}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18468488, ECO:0000269|PubMed:28484017}. Note=Exists
CC primarily an intracellular antigen whose surface expression is tightly
CC regulated by restricted trafficking to the cell surface and rapid
CC internalization.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P16410-1; Sequence=Displayed;
CC Name=2; Synonyms=ss-CTLA-4;
CC IsoId=P16410-2; Sequence=VSP_041284;
CC Name=3;
CC IsoId=P16410-3; Sequence=VSP_041284, VSP_041287;
CC Name=4;
CC IsoId=P16410-4; Sequence=VSP_041285, VSP_041286, VSP_041287;
CC Name=5;
CC IsoId=P16410-5; Sequence=VSP_047238, VSP_047239;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in lymphoid
CC tissues. Detected in activated T-cells where expression levels are
CC 30- to 50-fold less than CD28, the stimulatory coreceptor, on the cell
CC surface following activation. {ECO:0000269|PubMed:10493833,
CC ECO:0000269|PubMed:16551244, ECO:0000269|PubMed:1713603}.
CC -!- PTM: N-glycosylation is important for dimerization.
CC {ECO:0000269|PubMed:11279502, ECO:0000269|PubMed:16002699,
CC ECO:0000269|PubMed:21156796}.
CC -!- PTM: Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter
CC complex, blocks endocytosis, and leads to retention of CTLA4 on the
CC cell surface. {ECO:0000269|PubMed:10842319, ECO:0000269|PubMed:9175836,
CC ECO:0000269|PubMed:9813138}.
CC -!- POLYMORPHISM: Genetic variations in CTLA4 are associated with
CC susceptibility to several autoimmune disorders (PubMed:18595775,
CC PubMed:12724780, PubMed:10189842, PubMed:10924276, PubMed:15138458,
CC PubMed:15657618, PubMed:15688186, PubMed:25329329, PubMed:25213377).
CC They influence responsiveness to hepatitis B virus (HBV) infection
CC [MIM:610424] (PubMed:15452244). {ECO:0000269|PubMed:10189842,
CC ECO:0000269|PubMed:10924276, ECO:0000269|PubMed:12724780,
CC ECO:0000269|PubMed:15138458, ECO:0000269|PubMed:15452244,
CC ECO:0000269|PubMed:15657618, ECO:0000269|PubMed:15688186,
CC ECO:0000269|PubMed:18595775, ECO:0000269|PubMed:25213377,
CC ECO:0000269|PubMed:25329329}.
CC -!- DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic,
CC relapsing, inflammatory, and often febrile multisystemic disorder of
CC connective tissue, characterized principally by involvement of the
CC skin, joints, kidneys and serosal membranes. It is of unknown etiology,
CC but is thought to represent a failure of the regulatory mechanisms of
CC the autoimmune system. The disease is marked by a wide range of system
CC dysfunctions, an elevated erythrocyte sedimentation rate, and the
CC formation of LE cells in the blood or bone marrow.
CC {ECO:0000269|PubMed:15138458, ECO:0000269|PubMed:15688186}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Note=Genetic variations in CTLA4 may influence susceptibility
CC to Graves disease, an autoimmune disorder associated with overactivity
CC of the thyroid gland and hyperthyroidism.
CC {ECO:0000269|PubMed:10924276}.
CC -!- DISEASE: Diabetes mellitus, insulin-dependent, 12 (IDDM12)
CC [MIM:601388]: A multifactorial disorder of glucose homeostasis that is
CC characterized by susceptibility to ketoacidosis in the absence of
CC insulin therapy. Clinical features are polydipsia, polyphagia and
CC polyuria which result from hyperglycemia-induced osmotic diuresis and
CC secondary thirst. These derangements result in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:9259273}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Celiac disease 3 (CELIAC3) [MIM:609755]: A multifactorial,
CC chronic disorder of the small intestine caused by intolerance to
CC gluten. It is characterized by immune-mediated enteropathy associated
CC with failed intestinal absorption, and malnutrition. In predisposed
CC individuals, the ingestion of gluten-containing food such as wheat and
CC rye induces a flat jejunal mucosa with infiltration of lymphocytes.
CC {ECO:0000269|PubMed:10189842, ECO:0000269|PubMed:15657618}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Autoimmune lymphoproliferative syndrome 5 (ALPS5)
CC [MIM:616100]: An autosomal dominant primary immunodeficiency
CC characterized by severe autoimmunity, infiltration of non-lymphoid
CC organs, such as the intestine, lungs and brain, by hyperactive T cells
CC and B cells, autoimmune cytopenias, and hypogammaglobulinemia in early
CC childhood. {ECO:0000269|PubMed:25213377, ECO:0000269|PubMed:25329329}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- PHARMACEUTICAL: Engineered fusion proteins consisting of the
CC extracellular domain of CTLA4 and the IgG Fc region (Ctla4-Ig), inhibit
CC T-cell-dependent antibody responses, and are used as immunosuppressive
CC agents. They are soluble, have an enhanced affinity for B7 ligands and
CC act as a competitive inhibitor of CD28.
CC -!- MISCELLANEOUS: The therapeutic antibody Ipilimumab competes for the
CC binding site of the endogenous ligands CD80/B7-1, CD86/B7-2 and ICOSLG.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CLTA-4 entry;
CC URL="https://en.wikipedia.org/wiki/CTLA-4";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L15006; AAB59385.1; -; mRNA.
DR EMBL; M74363; AAA52127.1; -; Genomic_DNA.
DR EMBL; AF411058; AAL40932.1; -; Genomic_DNA.
DR EMBL; AY792514; AAV66331.1; -; mRNA.
DR EMBL; AY999702; AAY00166.1; -; mRNA.
DR EMBL; DQ785106; ABG85285.1; -; mRNA.
DR EMBL; AF414120; AAL07473.1; -; mRNA.
DR EMBL; DQ357942; ABC67470.1; -; Genomic_DNA.
DR EMBL; AC010138; AAX93176.1; -; Genomic_DNA.
DR EMBL; BC074842; AAH74842.1; -; mRNA.
DR EMBL; BC074893; AAH74893.1; -; mRNA.
DR EMBL; AH002733; AAA52773.1; -; Genomic_DNA.
DR EMBL; U90273; AAD00698.1; -; mRNA.
DR EMBL; AF142144; AAF02499.1; -; Genomic_DNA.
DR CCDS; CCDS2362.1; -. [P16410-1]
DR CCDS; CCDS42803.1; -. [P16410-5]
DR PIR; S08614; S08614.
DR RefSeq; NP_001032720.1; NM_001037631.2. [P16410-5]
DR RefSeq; NP_005205.2; NM_005214.4. [P16410-1]
DR PDB; 1AH1; NMR; -; A=37-161.
DR PDB; 1H6E; X-ray; 3.60 A; P=197-207.
DR PDB; 1I85; X-ray; 3.20 A; C/D=36-161.
DR PDB; 1I8L; X-ray; 3.00 A; C/D=36-161.
DR PDB; 2X44; X-ray; 2.60 A; D=36-161.
DR PDB; 3BX7; X-ray; 2.10 A; C=38-161.
DR PDB; 3OSK; X-ray; 1.80 A; A/B=36-161.
DR PDB; 5GGV; X-ray; 2.00 A; Y=36-161.
DR PDB; 5TRU; X-ray; 3.00 A; C/c=37-154.
DR PDB; 5XJ3; X-ray; 3.20 A; C/F/I/L=36-161.
DR PDB; 6RP8; X-ray; 2.60 A; C/c=37-154.
DR PDB; 6RPJ; X-ray; 3.25 A; A/C/E/G=37-156.
DR PDB; 6RQM; X-ray; 3.00 A; A=37-161.
DR PDB; 6XY2; X-ray; 3.05 A; A=38-160.
DR PDB; 7CIO; X-ray; 1.10 A; B=199-206.
DR PDB; 7DV4; X-ray; 2.38 A; A/C/E/G=36-153.
DR PDB; 7ELX; X-ray; 2.14 A; C/c=36-161.
DR PDB; 7SU0; X-ray; 2.41 A; C/D=36-153.
DR PDB; 7SU1; X-ray; 2.53 A; C=36-153.
DR PDBsum; 1AH1; -.
DR PDBsum; 1H6E; -.
DR PDBsum; 1I85; -.
DR PDBsum; 1I8L; -.
DR PDBsum; 2X44; -.
DR PDBsum; 3BX7; -.
DR PDBsum; 3OSK; -.
DR PDBsum; 5GGV; -.
DR PDBsum; 5TRU; -.
DR PDBsum; 5XJ3; -.
DR PDBsum; 6RP8; -.
DR PDBsum; 6RPJ; -.
DR PDBsum; 6RQM; -.
DR PDBsum; 6XY2; -.
DR PDBsum; 7CIO; -.
DR PDBsum; 7DV4; -.
DR PDBsum; 7ELX; -.
DR PDBsum; 7SU0; -.
DR PDBsum; 7SU1; -.
DR AlphaFoldDB; P16410; -.
DR SMR; P16410; -.
DR BioGRID; 107875; 134.
DR DIP; DIP-35607N; -.
DR ELM; P16410; -.
DR IntAct; P16410; 15.
DR MINT; P16410; -.
DR STRING; 9606.ENSP00000303939; -.
DR ChEMBL; CHEMBL2364164; -.
DR DrugBank; DB06186; Ipilimumab.
DR DrugBank; DB11771; Tremelimumab.
DR DrugCentral; P16410; -.
DR GuidetoPHARMACOLOGY; 2743; -.
DR GlyGen; P16410; 2 sites.
DR iPTMnet; P16410; -.
DR PhosphoSitePlus; P16410; -.
DR BioMuta; CTLA4; -.
DR DMDM; 27735177; -.
DR MassIVE; P16410; -.
DR PaxDb; P16410; -.
DR PeptideAtlas; P16410; -.
DR PRIDE; P16410; -.
DR ABCD; P16410; 165 sequenced antibodies.
DR Antibodypedia; 19961; 1745 antibodies from 48 providers.
DR CPTC; P16410; 1 antibody.
DR DNASU; 1493; -.
DR Ensembl; ENST00000295854.10; ENSP00000295854.6; ENSG00000163599.17. [P16410-5]
DR Ensembl; ENST00000472206.1; ENSP00000417779.1; ENSG00000163599.17. [P16410-4]
DR Ensembl; ENST00000487393.1; ENSP00000497319.1; ENSG00000163599.17. [P16410-3]
DR Ensembl; ENST00000648405.2; ENSP00000497102.1; ENSG00000163599.17. [P16410-1]
DR GeneID; 1493; -.
DR KEGG; hsa:1493; -.
DR MANE-Select; ENST00000648405.2; ENSP00000497102.1; NM_005214.5; NP_005205.2.
DR UCSC; uc002vak.3; human. [P16410-1]
DR CTD; 1493; -.
DR DisGeNET; 1493; -.
DR GeneCards; CTLA4; -.
DR HGNC; HGNC:2505; CTLA4.
DR HPA; ENSG00000163599; Tissue enriched (lymphoid).
DR MalaCards; CTLA4; -.
DR MIM; 109100; phenotype.
DR MIM; 123890; gene.
DR MIM; 152700; phenotype.
DR MIM; 601388; phenotype.
DR MIM; 609755; phenotype.
DR MIM; 610424; phenotype.
DR MIM; 616100; phenotype.
DR neXtProt; NX_P16410; -.
DR OpenTargets; ENSG00000163599; -.
DR Orphanet; 391490; Adult-onset myasthenia gravis.
DR Orphanet; 436159; Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency.
DR Orphanet; 2584; Classic mycosis fungoides.
DR Orphanet; 900; Granulomatosis with polyangiitis.
DR Orphanet; 3162; Sezary syndrome.
DR Orphanet; 536; Systemic lupus erythematosus.
DR PharmGKB; PA27006; -.
DR VEuPathDB; HostDB:ENSG00000163599; -.
DR eggNOG; ENOG502RZVK; Eukaryota.
DR GeneTree; ENSGT00530000063873; -.
DR HOGENOM; CLU_085095_0_0_1; -.
DR InParanoid; P16410; -.
DR OMA; WPCSALF; -.
DR OrthoDB; 1222373at2759; -.
DR PhylomeDB; P16410; -.
DR TreeFam; TF335679; -.
DR PathwayCommons; P16410; -.
DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling.
DR Reactome; R-HSA-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs).
DR SignaLink; P16410; -.
DR SIGNOR; P16410; -.
DR BioGRID-ORCS; 1493; 6 hits in 1071 CRISPR screens.
DR EvolutionaryTrace; P16410; -.
DR GeneWiki; CTLA-4; -.
DR GenomeRNAi; 1493; -.
DR Pharos; P16410; Tclin.
DR PRO; PR:P16410; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P16410; protein.
DR Bgee; ENSG00000163599; Expressed in lymph node and 123 other tissues.
DR Genevisible; P16410; HS.
DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; IDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098636; C:protein complex involved in cell adhesion; IDA:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; IEA:Ensembl.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; IDA:BHF-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR008096; CTLA4.
DR InterPro; IPR040216; CTLA4/CD28.
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 PANTHER; PTHR11494; PTHR11494; 1.
DR PANTHER; PTHR11494:SF8; PTHR11494:SF8; 1.
DR Pfam; PF07686; V-set; 1.
DR PRINTS; PR01720; CTLANTIGEN4.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Diabetes mellitus; Disease variant; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Membrane; Pharmaceutical; Phosphoprotein;
KW Reference proteome; Signal; Systemic lupus erythematosus; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..223
FT /note="Cytotoxic T-lymphocyte protein 4"
FT /id="PRO_0000014734"
FT TOPO_DOM 36..161
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28484017"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 39..140
FT /note="Ig-like V-type"
FT REGION 46..50
FT /note="Homodimerization"
FT /evidence="ECO:0000269|PubMed:21156796"
FT REGION 134..139
FT /note="Important for interaction with CD80 and CD86"
FT /evidence="ECO:0000269|PubMed:28484017"
FT REGION 150..155
FT /note="Homodimerization"
FT /evidence="ECO:0000269|PubMed:21156796,
FT ECO:0000269|PubMed:28484017"
FT MOD_RES 201
FT /note="Phosphotyrosine; by TXK and JAK2"
FT /evidence="ECO:0000269|PubMed:10842319,
FT ECO:0000269|PubMed:9175836, ECO:0000269|PubMed:9813138"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11279502,
FT ECO:0000269|PubMed:16002699, ECO:0000269|PubMed:21156796"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11279502,
FT ECO:0000269|PubMed:16002699"
FT DISULFID 58..129
FT /evidence="ECO:0000269|PubMed:11279501,
FT ECO:0000269|PubMed:11279502, ECO:0000269|PubMed:21156796,
FT ECO:0000269|PubMed:28484017, ECO:0000269|PubMed:9228944,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:3BX7,
FT ECO:0007744|PDB:5TRU"
FT DISULFID 85..103
FT /evidence="ECO:0000269|PubMed:11279501,
FT ECO:0000269|PubMed:11279502, ECO:0000269|PubMed:21156796,
FT ECO:0000269|PubMed:28484017, ECO:0000269|PubMed:9228944,
FT ECO:0000269|Ref.23, ECO:0007744|PDB:3BX7,
FT ECO:0007744|PDB:5TRU"
FT DISULFID 157
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:28484017, ECO:0000269|Ref.23,
FT ECO:0007744|PDB:3BX7"
FT VAR_SEQ 38..204
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:18595775"
FT /id="VSP_041284"
FT VAR_SEQ 58
FT /note="C -> S (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:18595775"
FT /id="VSP_041285"
FT VAR_SEQ 59..204
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:18595775"
FT /id="VSP_041286"
FT VAR_SEQ 153..174
FT /note="DPEPCPDSDFLLWILAAVSSGL -> AKEKKPSYNRGLCENAPNRARM (in
FT isoform 5)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_047238"
FT VAR_SEQ 175..223
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_047239"
FT VAR_SEQ 205..223
FT /note="PPTEPECEKQFQPYFIPIN -> KEKKPSYNRGLCENAPNRARM (in
FT isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:18595775"
FT /id="VSP_041287"
FT VARIANT 17
FT /note="T -> A (increased risk for Graves disease, insulin-
FT dependent diabetes mellitus, thyroid-associated
FT orbitopathy, systemic lupus erythematosus and
FT susceptibility to HBV infection; dbSNP:rs231775)"
FT /evidence="ECO:0000269|PubMed:10475192,
FT ECO:0000269|PubMed:10903931, ECO:0000269|PubMed:10924276,
FT ECO:0000269|PubMed:15452244, ECO:0000269|PubMed:1713603,
FT ECO:0000269|PubMed:18595775, ECO:0000269|PubMed:9259273"
FT /id="VAR_013577"
FT VARIANT 70
FT /note="R -> W (in ALPS5; dbSNP:rs606231422)"
FT /evidence="ECO:0000269|PubMed:25329329"
FT /id="VAR_072681"
FT MUTAGEN 45
FT /note="V->D: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 47
FT /note="L->D: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 49
FT /note="S->A: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 70
FT /note="R->A,D: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 130
FT /note="K->A,D: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 132
FT /note="E->A,R: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 139
FT /note="Y->A,D: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT MUTAGEN 143
FT /note="I->A,D: Strongly reduced interaction with CD80, CD86
FT and ICOSLG."
FT /evidence="ECO:0000269|PubMed:28484017"
FT CONFLICT 37
FT /note="A -> V (in Ref. 3; ABG85285)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="T -> A (in Ref. 8; AAA52773)"
FT /evidence="ECO:0000305"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:5GGV"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:1I8L"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1I85"
FT STRAND 68..77
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 80..90
FT /evidence="ECO:0007829|PDB:3OSK"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:6RP8"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:6RP8"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:3OSK"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 125..138
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:3OSK"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1AH1"
SQ SEQUENCE 223 AA; 24656 MW; 6F9466FB2E139A5A CRC64;
MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS RGIASFVCEY
ASPGKATEVR VTVLRQADSQ VTEVCAATYM MGNELTFLDD SICTGTSSGN QVNLTIQGLR
AMDTGLYICK VELMYPPPYY LGIGNGTQIY VIDPEPCPDS DFLLWILAAV SSGLFFYSFL
LTAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN
