PSCA_HUMAN
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 03-AUG-2022, entry version 172.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Wahl M.,
RA 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 surface
RT 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., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., 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., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., 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., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT 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 project:
RT 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 verified
RT 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 gleason
RT score, advanced stage and bone metastasis in prostate cancer.";
RL Oncogene 19:1288-1296(2000).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, ASSOCIATION WITH SUSCEPTIBILITY TO
RP 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., Kook M.-C.,
RA Lee Y.-S., Park S.R., Kim C.G., Choi I.J., Yoshida T., Nakamura Y.,
RA Hirohashi S.;
RT "Genetic variation in PSCA is associated with susceptibility to diffuse-
RT 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., Seminara D.,
RA Yoshida T., Saeki N., Andrew A.S., Dinney C.P., Czerniak B., Zhang Z.F.,
RA Kiltie A.E., Bishop D.T., Vineis P., Porru S., Buntinx F., Kellen E.,
RA Zeegers M.P., Kumar R., Rudnai P., Gurzau E., Koppova K., Mayordomo J.I.,
RA Sanchez M., Saez B., Lindblom A., de Verdier P., Steineck G., Mills G.B.,
RA Schned A., Guarrera S., Polidoro S., Chang S.C., Lin J., Chang D.W.,
RA Hale K.S., 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. Has
CC a cell-proliferation inhibition activity in vitro.
CC {ECO:0000269|PubMed:18488030}.
CC -!- FUNCTION: May act as a modulator of nicotinic acetylcholine receptors
CC (nAChRs) activity. In vitro inhibits nicotine-induced signaling
CC probably implicating alpha-3:beta-2- or alpha-7-containing nAChRs.
CC {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 and
CC neuroendocrine epithelium cells). Also found in bladder (transitional
CC epithelium), placenta (trophoblasts), stomach (neuroendocrine cells),
CC colon (neuroendocrine cells) and kidney (collecting ducts).
CC Overexpressed in prostate cancers and expression is correlated with
CC tumor stage, grade and androgen-independence. Highly expressed in
CC prostate cancer bone metastases. Expressed in gastric epithelial cells,
CC mainly in the isthmus (at protein level). Not detected in normal
CC intestinal epithelium (at protein level). Expressed in brain cortex;
CC expression is significantly increased in the front cortex of Alzheimer
CC disease 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 susceptibility
CC to some cancers. A polymorphism gives rise to an upstream methionine
CC which produces a longer protein of 123 residues associated with various
CC cancers including diffuse-type gastric cancer and urinary bladder
CC cancer. {ECO:0000269|PubMed:18488030, ECO:0000269|PubMed:19648920}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC39607.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH23582.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH65183.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAQ89271.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB97347.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC 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 AlphaFoldDB; O43653; -.
DR SMR; O43653; -.
DR IntAct; O43653; 2.
DR STRING; 9606.ENSP00000301258; -.
DR ChEMBL; CHEMBL3712961; -.
DR GlyGen; O43653; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O43653; -.
DR PhosphoSitePlus; O43653; -.
DR BioMuta; PSCA; -.
DR EPD; O43653; -.
DR jPOST; O43653; -.
DR MassIVE; O43653; -.
DR PaxDb; O43653; -.
DR PeptideAtlas; O43653; -.
DR PRIDE; O43653; -.
DR ProteomicsDB; 49089; -.
DR Antibodypedia; 7385; 361 antibodies from 38 providers.
DR DNASU; 8000; -.
DR Ensembl; ENST00000301258.5; ENSP00000301258.4; ENSG00000167653.5.
DR GeneID; 8000; -.
DR KEGG; hsa:8000; -.
DR MANE-Select; ENST00000301258.5; ENSP00000301258.4; NM_005672.5; NP_005663.2.
DR UCSC; uc003ywu.4; human.
DR CTD; 8000; -.
DR DisGeNET; 8000; -.
DR GeneCards; PSCA; -.
DR HGNC; HGNC:9500; PSCA.
DR HPA; ENSG00000167653; Tissue enriched (stomach).
DR MIM; 602470; gene.
DR neXtProt; NX_O43653; -.
DR OpenTargets; ENSG00000167653; -.
DR VEuPathDB; HostDB:ENSG00000167653; -.
DR eggNOG; ENOG502SCWD; Eukaryota.
DR GeneTree; ENSGT00940000153378; -.
DR HOGENOM; CLU_141358_1_0_1; -.
DR InParanoid; O43653; -.
DR OMA; ISKGCTS; -.
DR PhylomeDB; O43653; -.
DR TreeFam; TF336080; -.
DR PathwayCommons; O43653; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; O43653; -.
DR ChiTaRS; PSCA; human.
DR Pharos; O43653; Tbio.
DR PRO; PR:O43653; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O43653; protein.
DR Bgee; ENSG00000167653; Expressed in lower esophagus mucosa and 94 other tissues.
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: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 CDD; cd00117; LU; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR016054; LY6_UPA_recep-like.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR Pfam; PF00021; UPAR_LY6; 1.
DR SMART; SM00134; LU; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW GPI-anchor; Lipoprotein; Membrane; Reference proteome; Signal.
FT SIGNAL 1..11
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 12..86
FT /note="Prostate stem cell antigen"
FT /id="PRO_0000036162"
FT PROPEP 86..114
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036163"
FT DOMAIN 12..86
FT /note="UPAR/Ly6"
FT LIPID 86
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 14..39
FT /evidence="ECO:0000250|UniProtKB:P0DP57"
FT DISULFID 17..26
FT /evidence="ECO:0000250|UniProtKB:P0DP57"
FT DISULFID 32..57
FT /evidence="ECO:0000250|UniProtKB:P0DP57"
FT DISULFID 61..77
FT /evidence="ECO:0000250|UniProtKB:P0DP57"
FT DISULFID 78..83
FT /evidence="ECO:0000250|UniProtKB:P0DP57"
FT VARIANT 1
FT /note="M -> MKAVLLALLM (in dbSNP:rs2294008)"
FT /evidence="ECO:0000269|PubMed:18488030,
FT ECO:0000269|PubMed:19648920"
FT /id="VAR_080777"
FT VARIANT 30
FT /note="E -> K (in dbSNP:rs3736001)"
FT /evidence="ECO:0000269|PubMed:18488030"
FT /id="VAR_020173"
FT CONFLICT 1
FT /note="M -> T (in Ref. 3; AC108002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 114 AA; 11959 MW; 65B3683767990740 CRC64;
MAGLALQPGT ALLCYSCKAQ VSNEDCLQVE NCTQLGEQCW TARIRAVGLL TVISKGCSLN
CVDDSQDYYV GKKNITCCDT DLCNASGAHA LQPAAAILAL LPALGLLLWG PGQL
