ID   PSCA_HUMAN              Reviewed;         114 AA.
AC   O43653; Q6UW92;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 2.
DT   13-FEB-2019, entry version 155.
DE   RecName: Full=Prostate stem cell antigen;
DE   Flags: Precursor;
GN   Name=PSCA; ORFNames=UNQ206/PRO232;
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], SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RC   TISSUE=Prostatic carcinoma;
RX   PubMed=9465086; DOI=10.1073/pnas.95.4.1735;
RA   Reiter R.E., Gu Z., Watabe T., Thomas G., Szigeti K., Davis E.,
RA   Wahl M., Nisitani S., Yamashiro J., le Beau M.M., Losa M., Witte O.N.;
RT   "Prostate stem cell antigen: a cell surface marker overexpressed in
RT   prostate cancer.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:1735-1740(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Urothelium;
RX   PubMed=10973799; DOI=10.1006/bbrc.2000.3393;
RA   Bahrenberg G., Brauers A., Joost H.G., Jakse G.;
RT   "Reduced expression of PSCA, a member of the LY-6 family of cell
RT   surface antigens, in bladder, esophagus, and stomach tumors.";
RL   Biochem. Biophys. Res. Commun. 275:783-788(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16421571; DOI=10.1038/nature04406;
RA   Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA   Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA   Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA   Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA   DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA   Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA   Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA   Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA   Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA   O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA   Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA   Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA   Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA   Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA   Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 8.";
RL   Nature 439:331-335(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Melanoma;
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   [6]
RP   PROTEIN SEQUENCE OF 12-26.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally
RT   verified cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=10713670; DOI=10.1038/sj.onc.1203426;
RA   Gu Z., Thomas G., Yamashiro J., Shintaku I.P., Dorey F., Raitano A.,
RA   Witte O.N., Said J.W., Loda M., Reiter R.E.;
RT   "Prostate stem cell antigen (PSCA) expression increases with high
RT   gleason score, advanced stage and bone metastasis in prostate
RT   cancer.";
RL   Oncogene 19:1288-1296(2000).
RN   [8]
RP   FUNCTION, TISSUE SPECIFICITY, INDUCTION, ASSOCIATION WITH
RP   SUSCEPTIBILITY TO DIFFUSE-TYPE GASTRIC CANCER, AND VARIANT LYS-30.
RX   PubMed=18488030; DOI=10.1038/ng.152;
RG   The study group of millennium genome project for cancer;
RA   Sakamoto H., Yoshimura K., Saeki N., Katai H., Shimoda T., Matsuno Y.,
RA   Saito D., Sugimura H., Tanioka F., Kato S., Matsukura N., Matsuda N.,
RA   Nakamura T., Hyodo I., Nishina T., Yasui W., Hirose H., Hayashi M.,
RA   Toshiro E., Ohnami S., Sekine A., Sato Y., Totsuka H., Ando M.,
RA   Takemura R., Takahashi Y., Ohdaira M., Aoki K., Honmyo I., Chiku S.,
RA   Aoyagi K., Sasaki H., Ohnami S., Yanagihara K., Yoon K.-A.,
RA   Kook M.-C., Lee Y.-S., Park S.R., Kim C.G., Choi I.J., Yoshida T.,
RA   Nakamura Y., Hirohashi S.;
RT   "Genetic variation in PSCA is associated with susceptibility to
RT   diffuse-type gastric cancer.";
RL   Nat. Genet. 40:730-740(2008).
RN   [9]
RP   ASSOCIATION WITH SUSCEPTIBILITY TO URINARY BLADDER CANCER.
RX   PubMed=19648920; DOI=10.1038/ng.421;
RA   Wu X., Ye Y., Kiemeney L.A., Sulem P., Rafnar T., Matullo G.,
RA   Seminara D., Yoshida T., Saeki N., Andrew A.S., Dinney C.P.,
RA   Czerniak B., Zhang Z.F., Kiltie A.E., Bishop D.T., Vineis P.,
RA   Porru S., Buntinx F., Kellen E., Zeegers M.P., Kumar R., Rudnai P.,
RA   Gurzau E., Koppova K., Mayordomo J.I., Sanchez M., Saez B.,
RA   Lindblom A., de Verdier P., Steineck G., Mills G.B., Schned A.,
RA   Guarrera S., Polidoro S., Chang S.C., Lin J., Chang D.W., Hale K.S.,
RA   Majewski T., Grossman H.B., Thorlacius S., Thorsteinsdottir U.,
RA   Aben K.K., Witjes J.A., Stefansson K., Amos C.I., Karagas M.R., Gu J.;
RT   "Genetic variation in the prostate stem cell antigen gene PSCA confers
RT   susceptibility to urinary bladder cancer.";
RL   Nat. Genet. 41:991-995(2009).
RN   [10]
RP   FUNCTION, INTERACTION WITH CHRNA4, AND TISSUE SPECIFICITY.
RX   PubMed=25680266; DOI=10.1016/j.neurobiolaging.2015.01.001;
RA   Jensen M.M., Arvaniti M., Mikkelsen J.D., Michalski D., Pinborg L.H.,
RA   Haertig W., Thomsen M.S.;
RT   "Prostate stem cell antigen interacts with nicotinic acetylcholine
RT   receptors and is affected in Alzheimer's disease.";
RL   Neurobiol. Aging 36:1629-1638(2015).
CC   -!- FUNCTION: May be involved in the regulation of cell proliferation.
CC       Has a cell-proliferation inhibition activity in vitro.
CC       {ECO:0000269|PubMed:18488030}.
CC   -!- FUNCTION: May act as a modulator of nicotinic acetylcholine
CC       receptors (nAChRs) activity. In vitro inhibits nicotine-induced
CC       signaling probably implicating alpha-3:beta-2- or alpha-7-
CC       containing nAChRs. {ECO:0000305|PubMed:25680266}.
CC   -!- SUBUNIT: Interacts with CHRNA4. {ECO:0000269|PubMed:25680266}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9465086};
CC       Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:9465086}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in prostate (basal, secretory
CC       and neuroendocrine epithelium cells). Also found in bladder
CC       (transitional epithelium), placenta (trophoblasts), stomach
CC       (neuroendocrine cells), colon (neuroendocrine cells) and kidney
CC       (collecting ducts). Overexpressed in prostate cancers and
CC       expression is correlated with tumor stage, grade and androgen-
CC       independence. Highly expressed in prostate cancer bone metastases.
CC       Expressed in gastric epithelial cells, mainly in the isthmus (at
CC       protein level). Not detected in normal intestinal epithelium (at
CC       protein level). Expressed in brain cortex; expression is
CC       significantly increased in the front cortex of Alzheimer disease
CC       patients. {ECO:0000269|PubMed:10713670,
CC       ECO:0000269|PubMed:18488030, ECO:0000269|PubMed:25680266}.
CC   -!- INDUCTION: Down-regulated in gastric cancer cells.
CC       {ECO:0000269|PubMed:18488030}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9465086}.
CC   -!- POLYMORPHISM: Genetic variations in PSCA may influence
CC       susceptibility to some cancers. A polymorphism gives rise to an
CC       upstream methionine which produces a longer protein of 123
CC       residues associated with various cancers including diffuse-type
CC       gastric cancer and urinary bladder cancer.
CC       {ECO:0000269|PubMed:18488030, ECO:0000269|PubMed:19648920}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC39607.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=AAH23582.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=AAH65183.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=AAQ89271.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=CAB97347.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/PSCAID41881ch8q24.html";
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DR   EMBL; AF043498; AAC39607.1; ALT_INIT; mRNA.
DR   EMBL; AJ297436; CAB97347.1; ALT_INIT; mRNA.
DR   EMBL; AC108002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AY358912; AAQ89271.1; ALT_INIT; mRNA.
DR   EMBL; BC023582; AAH23582.1; ALT_INIT; mRNA.
DR   EMBL; BC065183; AAH65183.1; ALT_INIT; mRNA.
DR   CCDS; CCDS47925.2; -.
DR   RefSeq; NP_005663.2; NM_005672.4.
DR   UniGene; Hs.652235; -.
DR   ProteinModelPortal; O43653; -.
DR   IntAct; O43653; 6.
DR   STRING; 9606.ENSP00000301258; -.
DR   ChEMBL; CHEMBL3712961; -.
DR   iPTMnet; O43653; -.
DR   PhosphoSitePlus; O43653; -.
DR   BioMuta; PSCA; -.
DR   EPD; O43653; -.
DR   jPOST; O43653; -.
DR   PaxDb; O43653; -.
DR   PeptideAtlas; O43653; -.
DR   PRIDE; O43653; -.
DR   ProteomicsDB; 49089; -.
DR   Ensembl; ENST00000301258; ENSP00000301258; ENSG00000167653.
DR   GeneID; 8000; -.
DR   KEGG; hsa:8000; -.
DR   UCSC; uc003ywu.4; human.
DR   CTD; 8000; -.
DR   DisGeNET; 8000; -.
DR   EuPathDB; HostDB:ENSG00000167653.4; -.
DR   GeneCards; PSCA; -.
DR   H-InvDB; HIX0007826; -.
DR   H-InvDB; HIX0034247; -.
DR   HGNC; HGNC:9500; PSCA.
DR   HPA; HPA030783; -.
DR   HPA; HPA056418; -.
DR   MIM; 602470; gene.
DR   neXtProt; NX_O43653; -.
DR   OpenTargets; ENSG00000167653; -.
DR   eggNOG; ENOG410JCNA; Eukaryota.
DR   eggNOG; ENOG4111DN6; LUCA.
DR   GeneTree; ENSGT00940000153378; -.
DR   HOGENOM; HOG000035114; -.
DR   HOVERGEN; HBG008309; -.
DR   InParanoid; O43653; -.
DR   PhylomeDB; O43653; -.
DR   TreeFam; TF336080; -.
DR   Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR   ChiTaRS; PSCA; human.
DR   PRO; PR:O43653; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; ENSG00000167653; Expressed in 85 organ(s), highest expression level in fundus of stomach.
DR   ExpressionAtlas; O43653; baseline and differential.
DR   GO; GO:0031225; C:anchored component of membrane; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0033130; F:acetylcholine receptor binding; IDA:UniProtKB.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:0099601; P:regulation of neurotransmitter receptor activity; IDA:UniProtKB.
DR   InterPro; IPR016054; LY6_UPA_recep-like.
DR   Pfam; PF00021; UPAR_LY6; 1.
DR   SMART; SM00134; LU; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Complete proteome; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW   Polymorphism; Reference proteome; Signal.
FT   SIGNAL        1     11       {ECO:0000269|PubMed:15340161}.
FT   CHAIN        12     86       Prostate stem cell antigen.
FT                                /FTId=PRO_0000036162.
FT   PROPEP       86    114       Removed in mature form. {ECO:0000255}.
FT                                /FTId=PRO_0000036163.
FT   DOMAIN       12     86       UPAR/Ly6.
FT   LIPID        86     86       GPI-anchor amidated serine.
FT                                {ECO:0000255}.
FT   CARBOHYD     31     31       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     14     39       {ECO:0000250|UniProtKB:P0DP57}.
FT   DISULFID     17     26       {ECO:0000250|UniProtKB:P0DP57}.
FT   DISULFID     32     57       {ECO:0000250|UniProtKB:P0DP57}.
FT   DISULFID     61     77       {ECO:0000250|UniProtKB:P0DP57}.
FT   DISULFID     78     83       {ECO:0000250|UniProtKB:P0DP57}.
FT   VARIANT       1      1       M -> MKAVLLALLM (in dbSNP:rs2294008).
FT                                {ECO:0000269|PubMed:18488030,
FT                                ECO:0000269|PubMed:19648920}.
FT                                /FTId=VAR_080777.
FT   VARIANT      30     30       E -> K (in dbSNP:rs3736001).
FT                                {ECO:0000269|PubMed:18488030}.
FT                                /FTId=VAR_020173.
FT   CONFLICT      1      1       M -> T (in Ref. 3; AC108002).
FT                                {ECO:0000305}.
SQ   SEQUENCE   114 AA;  11959 MW;  65B3683767990740 CRC64;
     MAGLALQPGT ALLCYSCKAQ VSNEDCLQVE NCTQLGEQCW TARIRAVGLL TVISKGCSLN
     CVDDSQDYYV GKKNITCCDT DLCNASGAHA LQPAAAILAL LPALGLLLWG PGQL
//