ID PPAP_HUMAN Reviewed; 386 AA. AC P15309; D3DNC6; Q5FBY0; Q96KY0; Q96QK9; Q96QM0; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-1992, sequence version 3. DT 27-MAR-2024, entry version 209. DE RecName: Full=Prostatic acid phosphatase {ECO:0000305}; DE Short=PAP; DE EC=3.1.3.2 {ECO:0000269|PubMed:10506173, ECO:0000269|PubMed:15280042, ECO:0000269|PubMed:9584846}; DE AltName: Full=5'-nucleotidase; DE Short=5'-NT; DE EC=3.1.3.5 {ECO:0000250|UniProtKB:Q8CE08}; DE AltName: Full=Acid phosphatase 3 {ECO:0000312|HGNC:HGNC:125}; DE AltName: Full=Ecto-5'-nucleotidase; DE AltName: Full=Protein tyrosine phosphatase ACP3 {ECO:0000305|PubMed:20498373}; DE EC=3.1.3.48 {ECO:0000269|PubMed:20498373}; DE AltName: Full=Thiamine monophosphatase; DE Short=TMPase; DE Contains: DE RecName: Full=PAPf39; DE Flags: Precursor; GN Name=ACP3 {ECO:0000312|HGNC:HGNC:125}; Synonyms=ACPP; 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] (ISOFORM 1). RX PubMed=1375464; DOI=10.1016/s0006-291x(05)80048-8; RA Sharief F.S., Li S.S.-L.; RT "Structure of human prostatic acid phosphatase gene."; RL Biochem. Biophys. Res. Commun. 184:1468-1476(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, DISULFIDE RP BONDS, AND ACTIVE SITE. RX PubMed=1989985; DOI=10.1016/s0021-9258(18)52245-6; RA van Etten R.L., Davidson R., Stevis P.E., Macarthur H., Moore D.L.; RT "Covalent structure, disulfide bonding, and identification of reactive RT surface and active site residues of human prostatic acid phosphatase."; RL J. Biol. Chem. 266:2313-2319(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2712834; DOI=10.1016/0006-291x(89)91623-9; RA Sharief F.S., Lee H., Leuderman M.M., Lundwall A., Deaven L.L., Lee C.-L., RA Li S.S.-L.; RT "Human prostatic acid phosphatase: cDNA cloning, gene mapping and protein RT sequence homology with lysosomal acid phosphatase."; RL Biochem. Biophys. Res. Commun. 160:79-86(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Prostate; RX PubMed=2842184; DOI=10.1016/0014-5793(88)80037-1; RA Vihko P., Virkkunen P., Henttu P., Roiko K., Solin T., Huhtala M.L.; RT "Molecular cloning and sequence analysis of cDNA encoding human prostatic RT acid phosphatase."; RL FEBS Lett. 236:275-281(1988). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Prostate; RX PubMed=2395659; DOI=10.1093/nar/18.16.4928; RA Tailor P.G., Govindan M.V., Patel P.C.; RT "Nucleotide sequence of human prostatic acid phosphatase determined from a RT full-length cDNA clone."; RL Nucleic Acids Res. 18:4928-4928(1990). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=7951074; RA Sharief F.S., Li S.S.-L.; RT "Nucleotide sequence of human prostatic acid phosphatase ACPP gene, RT including seven Alu repeats."; RL Biochem. Mol. Biol. Int. 33:561-565(1994). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Sameshima E., Tabata Y., Hayashi A., Iida K., Mitsuyama M., Kanai S., RA Furuya T., Saito T.; RT "Acid phosphatase prostate mRNA,nirs splice variant1."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Prostate; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP ASN-15; VAL-124; ARG-226; HIS-330 AND ALA-360. RC TISSUE=Prostate; 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 [12] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=3674882; DOI=10.1016/0003-9861(87)90361-4; RA Risley J.M., Van Etten R.L.; RT "Structures of the carbohydrate moieties of human prostatic acid RT phosphatase elucidated by H1 nuclear magnetic resonance spectroscopy."; RL Arch. Biochem. Biophys. 258:404-412(1987). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, AND MUTAGENESIS OF TRP-206. RX PubMed=9584846; RA Zhang Z., Ostanin K., Van Etten R.L.; RT "Covalent modification and site-directed mutagenesis of an active site RT tryptophan of human prostatic acid phosphatase."; RL Acta Biochim. Pol. 44:659-672(1997). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY. RC TISSUE=Brain; RX PubMed=10506173; DOI=10.1074/jbc.274.41.29172; RA Hiroyama M., Takenawa T.; RT "Isolation of a cDNA encoding human lysophosphatidic acid phosphatase that RT is involved in the regulation of mitochondrial lipid biosynthesis."; RL J. Biol. Chem. 274:29172-29180(1999). RN [15] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15280042; DOI=10.1016/j.febslet.2004.06.083; RA Tanaka M., Kishi Y., Takanezawa Y., Kakehi Y., Aoki J., Arai H.; RT "Prostatic acid phosphatase degrades lysophosphatidic acid in seminal RT plasma."; RL FEBS Lett. 571:197-204(2004). RN [16] RP ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17638863; DOI=10.1158/0008-5472.can-07-1651; RA Quintero I.B., Araujo C.L., Pulkka A.E., Wirkkala R.S., Herrala A.M., RA Eskelinen E.-L., Jokitalo E., Hellstroem P.A., Tuominen H.J., RA Hirvikoski P.P., Vihko P.T.; RT "Prostatic acid phosphatase is not a prostate specific target."; RL Cancer Res. 67:6549-6554(2007). RN [17] RP PROTEOLYTIC PROCESSING, IDENTIFICATION BY MASS SPECTROMETRY OF PAPF39, AND RP FUNCTION IN HIV INFECTION (MICROBIAL INFECTION). RX PubMed=18083097; DOI=10.1016/j.cell.2007.10.014; RA Munch J., Rucker E., Standker L., Adermann K., Goffinet C., Schindler M., RA Wildum S., Chinnadurai R., Rajan D., Specht A., Gimenez-Gallego G., RA Sanchez P.C., Fowler D.M., Koulov A., Kelly J.W., Mothes W., Grivel J.C., RA Margolis L., Keppler O.T., Forssmann W.G., Kirchhoff F.; RT "Semen-derived amyloid fibrils drastically enhance HIV infection."; RL Cell 131:1059-1071(2007). RN [18] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Placenta; RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x; RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., RA Elsaesser H.-P., Mann M., Hasilik A.; RT "Integral and associated lysosomal membrane proteins."; RL Traffic 8:1676-1686(2007). RN [19] RP PROTEOLYTIC PROCESSING, AND FUNTION IN XMRV INFECTION (MICROBIAL RP INFECTION). RX PubMed=19403677; DOI=10.1128/jvi.00268-09; RA Hong S., Klein E.A., Das Gupta J., Hanke K., Weight C.J., Nguyen C., RA Gaughan C., Kim K.A., Bannert N., Kirchhoff F., Munch J., Silverman R.H.; RT "Fibrils of prostatic acid phosphatase fragments boost infections with XMRV RT (xenotropic murine leukemia virus-related virus), a human retrovirus RT associated with prostate cancer."; RL J. Virol. 83:6995-7003(2009). RN [20] RP FUNCTION, AND DEGRADATION OF SEVI AMYLOID FIBRILS (MICROBIAL INFECTION). RX PubMed=19451623; DOI=10.1073/pnas.0811827106; RA Hauber I., Hohenberg H., Holstermann B., Hunstein W., Hauber J.; RT "The main green tea polyphenol epigallocatechin-3-gallate counteracts RT semen-mediated enhancement of HIV infection."; RL Proc. Natl. Acad. Sci. U.S.A. 106:9033-9038(2009). RN [21] RP FUNCTION (MICROBIAL INFECTION), AND INHIBITION OF SEVI ACTIVITY. RX PubMed=19897482; DOI=10.1074/jbc.m109.066167; RA Roan N.R., Sowinski S., Munch J., Kirchhoff F., Greene W.C.; RT "Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer RT of viral infection)."; RL J. Biol. Chem. 285:1861-1869(2010). RN [22] RP FUNCTION (ISOFORM 2), CATALYTIC ACTIVITY (ISOFORM 2), AND SUBCELLULAR RP LOCATION (ISOFORM 2). RX PubMed=20498373; DOI=10.1074/jbc.m109.098301; RA Chuang T.D., Chen S.J., Lin F.F., Veeramani S., Kumar S., Batra S.K., RA Tu Y., Lin M.F.; RT "Human prostatic acid phosphatase, an authentic tyrosine phosphatase, RT dephosphorylates ErbB-2 and regulates prostate cancer cell growth."; RL J. Biol. Chem. 285:23598-23606(2010). RN [23] RP TISSUE SPECIFICITY. RX PubMed=21487525; RA Graddis T.J., McMahan C.J., Tamman J., Page K.J., Trager J.B.; RT "Prostatic acid phosphatase expression in human tissues."; RL Int. J. Clin. Exp. Pathol. 4:295-306(2011). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH RP N-PROPYL-L-TARTRAMATE. RX PubMed=9804805; DOI=10.1074/jbc.273.46.30406; RA Lacount M.W., Handy G., Lebioda L.; RT "Structural origins of L(+)-tartrate inhibition of human prostatic acid RT phosphatase."; RL J. Biol. Chem. 273:30406-30409(1998). RN [25] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 33-374, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-94 AND ASN-220. RX PubMed=10639192; RX DOI=10.1002/(sici)1097-0045(20000215)42:3<211::aid-pros7>3.0.co;2-u; RA Jakob C.G., Lewinski K., Kuciel R., Ostrowski W., Lebioda L.; RT "Crystal structure of human prostatic acid phosphatase."; RL Prostate 42:211-218(2000). RN [26] {ECO:0007744|PDB:1ND5, ECO:0007744|PDB:1ND6} RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 33-386 IN COMPLEX WITH A PHOSPHATE RP ION AND INHIBITOR ALPHA-BENZYLAMINOBENZYLPHOSPHONIC ACID, DISULFIDE BONDS, RP AND GLYCOSYLATION AT ASN-220 AND ASN-333. RX PubMed=12525165; DOI=10.1021/bi0265067; RA Ortlund E., LaCount M.W., Lebioda L.; RT "Crystal structures of human prostatic acid phosphatase in complex with a RT phosphate ion and alpha-benzylaminobenzylphosphonic acid update the RT mechanistic picture and offer new insights into inhibitor design."; RL Biochemistry 42:383-389(2003). RN [27] RP STRUCTURE BY NMR OF 248-286. RX PubMed=19995078; DOI=10.1021/ja908170s; RA Nanga R.P., Brender J.R., Vivekanandan S., Popovych N., Ramamoorthy A.; RT "NMR structure in a membrane environment reveals putative amyloidogenic RT regions of the SEVI precursor peptide PAP(248-286)."; RL J. Am. Chem. Soc. 131:17972-17979(2009). CC -!- FUNCTION: A non-specific tyrosine phosphatase that dephosphorylates a CC diverse number of substrates under acidic conditions (pH 4-6) including CC alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated CC proteins (PubMed:10506173, PubMed:15280042, PubMed:20498373, CC PubMed:9584846). Has lipid phosphatase activity and inactivates CC lysophosphatidic acid in seminal plasma (PubMed:10506173, CC PubMed:15280042). {ECO:0000269|PubMed:10506173, CC ECO:0000269|PubMed:15280042, ECO:0000269|PubMed:20498373, CC ECO:0000269|PubMed:9584846}. CC -!- FUNCTION: [Isoform 2]: Tyrosine phosphatase that acts as a tumor CC suppressor of prostate cancer through dephosphorylation of ERBB2 and CC deactivation of MAPK-mediated signaling (PubMed:20498373). In addition CC to its tyrosine phosphatase activity has ecto-5'-nucleotidase activity CC in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP CC which acts as a pain suppressor (By similarity). CC {ECO:0000250|UniProtKB:Q8CE08, ECO:0000269|PubMed:20498373}. CC -!- FUNCTION: [PAPf39]: (Microbial infection) Forms amyloid beta-sheet CC fibrils in semen. These fibrils, termed SEVI (semen-derived enhancer of CC viral infection) capture HIV virions, attach them to target cells and CC enhance infection (PubMed:18083097, PubMed:19451623, PubMed:19897482). CC SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3- CC gallate (EGCG), a constituent of green tea (PubMed:19451623). Target CC cell attachment and enhancement of HIV infection is inhibited by surfen CC (PubMed:19897482). Also similarly boosts XMRV (xenotropic murine CC leukemia virus-related virus) infection (PubMed:19403677). CC {ECO:0000269|PubMed:18083097, ECO:0000269|PubMed:19403677, CC ECO:0000269|PubMed:19451623, ECO:0000269|PubMed:19897482}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a phosphate monoester + H2O = an alcohol + phosphate; CC Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.2; CC Evidence={ECO:0000269|PubMed:10506173, ECO:0000269|PubMed:15280042, CC ECO:0000269|PubMed:9584846}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z- CC octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544, CC ChEBI:CHEBI:75757; Evidence={ECO:0000269|PubMed:10506173}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836; CC Evidence={ECO:0000305|PubMed:10506173}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + CC phosphate; Xref=Rhea:RHEA:12484, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:18254, ChEBI:CHEBI:43474, ChEBI:CHEBI:58043; EC=3.1.3.5; CC Evidence={ECO:0000250|UniProtKB:Q8CE08}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; CC Evidence={ECO:0000269|PubMed:20498373}; CC -!- ACTIVITY REGULATION: Phosphatase activity inhibited by L(+)-tartrate, CC and by its derivative, alpha-benzylaminobenzylphosphonic acid. CC {ECO:0000269|PubMed:9584846}. CC -!- SUBUNIT: Homodimer; dimer formation is required for phosphatase CC activity. {ECO:0000250|UniProtKB:P20646}. CC -!- INTERACTION: CC P15309; P15309: ACP3; NbExp=4; IntAct=EBI-1222012, EBI-1222012; CC P15309; P04626: ERBB2; NbExp=2; IntAct=EBI-1222012, EBI-641062; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted CC {ECO:0000305|PubMed:17638863}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane CC {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:17897319, CC ECO:0000269|PubMed:20498373}; Single-pass type I membrane protein CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:17638863, CC ECO:0000269|PubMed:17897319}; Single-pass type I membrane protein CC {ECO:0000255}. Nucleus {ECO:0000269|PubMed:20498373}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:20498373}. Note=Appears to shuttle between CC the cell membrane and intracellular vesicles. Colocalizes with FLOT1 at CC cell membrane and in intracellular vesicles (PubMed:17638863). CC Colocalizes with LAMP2 on the lysosome membrane (PubMed:17897319). CC {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:17897319}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Secreted PAP, sPAP; CC IsoId=P15309-1; Sequence=Displayed; CC Name=2; Synonyms=TMPase, TM-PAP {ECO:0000303|PubMed:17638863}, cellular CC PAP, cPAP, cPAcP {ECO:0000303|PubMed:20498373}; CC IsoId=P15309-2; Sequence=VSP_036023; CC Name=3; CC IsoId=P15309-3; Sequence=VSP_053360; CC -!- TISSUE SPECIFICITY: Highly expressed in the prostate, restricted to CC glandular and ductal epithelial cells. Also expressed in bladder, CC kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a CC subset of pancreatic islet cells, squamous epithelia, the pilosebaceous CC unit, colonic neuroendocrine cells and skin adnexal structures. Low CC expression in prostate carcinoma cells and tissues. CC {ECO:0000269|PubMed:17638863, ECO:0000269|PubMed:21487525}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Widely expressed. Expressed in the CC sarcolemma of skeletal muscle. {ECO:0000269|PubMed:17638863}. CC -!- PTM: N-glycosylated. High mannose content, partially sialylated and CC fucosylated biantennary complex. Also fucosylated with partially CC sialylated triantennary complex oligosaccharides. CC {ECO:0000269|PubMed:10639192, ECO:0000269|PubMed:12525165}. CC -!- PTM: Proteolytically cleaved in seminal fluid to produce several CC peptides. Peptide PAPf39, the most prominent, forms amyloid beta-sheet CC fibrils, SEVI (semen-derived enhancer of viral infection). CC {ECO:0000269|PubMed:18083097}. CC -!- MISCELLANEOUS: Has been used as a diagnostic tool for staging CC metastatic prostatic cancer. CC -!- SIMILARITY: Belongs to the histidine acid phosphatase family. CC {ECO:0000305}. 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; M97589; AAA60021.1; -; Genomic_DNA. DR EMBL; M97580; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97581; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97582; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97583; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97584; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97585; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97586; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97587; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M97588; AAA60021.1; JOINED; Genomic_DNA. DR EMBL; M34840; AAA69694.1; -; mRNA. DR EMBL; M24902; AAA60022.1; -; mRNA. DR EMBL; X52174; CAA36422.1; -; mRNA. DR EMBL; X53605; CAA37673.1; -; mRNA. DR EMBL; U07097; AAB60640.1; -; Genomic_DNA. DR EMBL; U07083; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07085; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07086; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07088; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07091; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07092; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07093; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; U07095; AAB60640.1; JOINED; Genomic_DNA. DR EMBL; AB102888; BAD89417.1; -; mRNA. DR EMBL; AK300540; BAG62248.1; -; mRNA. DR EMBL; AC020633; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW79203.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79205.1; -; Genomic_DNA. DR EMBL; BC007460; AAH07460.1; -; mRNA. DR EMBL; BC008493; AAH08493.1; -; mRNA. DR EMBL; BC016344; AAH16344.1; -; mRNA. DR CCDS; CCDS3073.1; -. [P15309-1] DR CCDS; CCDS46916.1; -. [P15309-2] DR CCDS; CCDS77818.1; -. [P15309-3] DR PIR; JH0610; JH0610. DR RefSeq; NP_001090.2; NM_001099.4. [P15309-1] DR RefSeq; NP_001127666.1; NM_001134194.1. [P15309-2] DR RefSeq; NP_001278966.1; NM_001292037.1. [P15309-3] DR PDB; 1CVI; X-ray; 3.20 A; A/B/C/D=33-374. DR PDB; 1ND5; X-ray; 2.90 A; A/B/C/D=33-386. DR PDB; 1ND6; X-ray; 2.40 A; A/B/C/D=33-386. DR PDB; 2HPA; X-ray; 2.90 A; A/B/C/D=33-374. DR PDB; 2L3H; NMR; -; A=248-286. DR PDB; 2L77; NMR; -; A=248-286. DR PDB; 2L79; NMR; -; A=248-286. DR PDB; 2MG0; NMR; -; A=262-270. DR PDB; 3PPD; X-ray; 1.50 A; A=260-265. DR PDB; 7ZZV; NMR; -; A=85-120. DR PDBsum; 1CVI; -. DR PDBsum; 1ND5; -. DR PDBsum; 1ND6; -. DR PDBsum; 2HPA; -. DR PDBsum; 2L3H; -. DR PDBsum; 2L77; -. DR PDBsum; 2L79; -. DR PDBsum; 2MG0; -. DR PDBsum; 3PPD; -. DR PDBsum; 7ZZV; -. DR AlphaFoldDB; P15309; -. DR BMRB; P15309; -. DR SMR; P15309; -. DR BioGRID; 106571; 176. DR ComplexPortal; CPX-120; Prostatic acid phosphatase complex. DR IntAct; P15309; 22. DR MINT; P15309; -. DR STRING; 9606.ENSP00000323036; -. DR BindingDB; P15309; -. DR ChEMBL; CHEMBL2633; -. DR DrugBank; DB03390; (2R,3R)-2,3-Dihydroxy-4-oxo-4-(propylamino)butanoic acid. DR DrugBank; DB03577; Alpha-Benzyl-Aminobenzyl-Phosphonic Acid. DR DrugBank; DB06688; Sipuleucel-T. DR DrugCentral; P15309; -. DR SwissLipids; SLP:000001295; -. [P15309-1] DR DEPOD; ACPP; -. DR GlyConnect; 2001; 6 N-Linked glycans (2 sites). DR GlyCosmos; P15309; 3 sites, 20 glycans. DR GlyGen; P15309; 3 sites, 20 N-linked glycans (2 sites). DR iPTMnet; P15309; -. DR PhosphoSitePlus; P15309; -. DR SwissPalm; P15309; -. DR BioMuta; ACPP; -. DR DMDM; 130730; -. DR EPD; P15309; -. DR jPOST; P15309; -. DR MassIVE; P15309; -. DR MaxQB; P15309; -. DR PaxDb; 9606-ENSP00000323036; -. DR PeptideAtlas; P15309; -. DR ProteomicsDB; 53126; -. [P15309-1] DR ProteomicsDB; 53127; -. [P15309-2] DR ProteomicsDB; 62789; -. DR Pumba; P15309; -. DR Antibodypedia; 1343; 1051 antibodies from 43 providers. DR DNASU; 55; -. DR Ensembl; ENST00000336375.10; ENSP00000337471.5; ENSG00000014257.17. [P15309-1] DR Ensembl; ENST00000351273.12; ENSP00000323036.8; ENSG00000014257.17. [P15309-2] DR Ensembl; ENST00000475741.5; ENSP00000417744.1; ENSG00000014257.17. [P15309-3] DR GeneID; 55; -. DR KEGG; hsa:55; -. DR MANE-Select; ENST00000336375.10; ENSP00000337471.5; NM_001099.5; NP_001090.2. DR UCSC; uc003eon.4; human. [P15309-1] DR AGR; HGNC:125; -. DR CTD; 55; -. DR DisGeNET; 55; -. DR GeneCards; ACP3; -. DR HGNC; HGNC:125; ACP3. DR HPA; ENSG00000014257; Tissue enriched (prostate). DR MIM; 171790; gene. DR neXtProt; NX_P15309; -. DR OpenTargets; ENSG00000014257; -. DR VEuPathDB; HostDB:ENSG00000014257; -. DR eggNOG; KOG3720; Eukaryota. DR GeneTree; ENSGT00940000160450; -. DR HOGENOM; CLU_030431_1_1_1; -. DR InParanoid; P15309; -. DR OMA; GMKQHYE; -. DR OrthoDB; 5489935at2759; -. DR PhylomeDB; P15309; -. DR TreeFam; TF312893; -. DR BRENDA; 3.1.3.2; 2681. DR PathwayCommons; P15309; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SABIO-RK; P15309; -. DR SignaLink; P15309; -. DR SIGNOR; P15309; -. DR BioGRID-ORCS; 55; 12 hits in 1154 CRISPR screens. DR ChiTaRS; ACPP; human. DR EvolutionaryTrace; P15309; -. DR GeneWiki; Prostatic_acid_phosphatase; -. DR GenomeRNAi; 55; -. DR Pharos; P15309; Tchem. DR PRO; PR:P15309; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P15309; Protein. DR Bgee; ENSG00000014257; Expressed in prostate gland and 133 other cell types or tissues. DR ExpressionAtlas; P15309; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0030175; C:filopodium; IEA:Ensembl. DR GO; GO:0031985; C:Golgi cisterna; IEA:Ensembl. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IBA:GO_Central. DR GO; GO:0005771; C:multivesicular body; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0012506; C:vesicle membrane; ISS:CAFA. DR GO; GO:0008253; F:5'-nucleotidase activity; IDA:UniProtKB. DR GO; GO:0003993; F:acid phosphatase activity; IDA:UniProtKB. DR GO; GO:0033265; F:choline binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0052642; F:lysophosphatidic acid phosphatase activity; IDA:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0016791; F:phosphatase activity; IMP:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0042131; F:thiamine phosphate phosphatase activity; ISS:CAFA. DR GO; GO:0106411; F:XMP 5'-nucleosidase activity; IEA:UniProtKB-EC. DR GO; GO:0046085; P:adenosine metabolic process; IDA:UniProtKB. DR GO; GO:0016311; P:dephosphorylation; IMP:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW. DR GO; GO:0007040; P:lysosome organization; IBA:GO_Central. DR GO; GO:0009117; P:nucleotide metabolic process; IEA:Ensembl. DR GO; GO:0060168; P:positive regulation of adenosine receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0006144; P:purine nucleobase metabolic process; IEA:Ensembl. DR GO; GO:0051930; P:regulation of sensory perception of pain; IMP:UniProtKB. DR GO; GO:0006772; P:thiamine metabolic process; ISS:CAFA. DR CDD; cd07061; HP_HAP_like; 1. DR DisProt; DP00628; -. DR Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1. DR InterPro; IPR033379; Acid_Pase_AS. DR InterPro; IPR000560; His_Pase_clade-2. DR InterPro; IPR029033; His_PPase_superfam. DR PANTHER; PTHR11567; ACID PHOSPHATASE-RELATED; 1. DR PANTHER; PTHR11567:SF32; PROSTATIC ACID PHOSPHATASE; 1. DR Pfam; PF00328; His_Phos_2; 1. DR SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1. DR PROSITE; PS00616; HIS_ACID_PHOSPHAT_1; 1. DR PROSITE; PS00778; HIS_ACID_PHOSPHAT_2; 1. DR Genevisible; P15309; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amyloid; Cell membrane; Cytoplasm; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; KW Lipid metabolism; Lysosome; Membrane; Nucleus; Reference proteome; KW Secreted; Signal. FT SIGNAL 1..32 FT /evidence="ECO:0000269|PubMed:10639192" FT CHAIN 33..386 FT /note="Prostatic acid phosphatase" FT /id="PRO_0000023963" FT PEPTIDE 248..286 FT /note="PAPf39" FT /evidence="ECO:0000269|PubMed:18083097" FT /id="PRO_0000411250" FT ACT_SITE 44 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:1989985" FT ACT_SITE 290 FT /note="Proton donor" FT /evidence="ECO:0000305|PubMed:1989985" FT BINDING 43 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:9804805" FT BINDING 47 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:9804805" FT BINDING 111 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:9804805" FT BINDING 289 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:9804805" FT SITE 49 FT /note="Important for substrate specificity" FT SITE 138 FT /note="Required for homodimerization" FT /evidence="ECO:0000250|UniProtKB:P20646" FT SITE 144 FT /note="Required for homodimerization" FT /evidence="ECO:0000250|UniProtKB:P20646" FT SITE 206 FT /note="Required for structural stability" FT /evidence="ECO:0000269|PubMed:9584846" FT CARBOHYD 94 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10639192" FT CARBOHYD 220 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10639192, FT ECO:0000269|PubMed:12525165" FT CARBOHYD 333 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12525165" FT DISULFID 161..372 FT /evidence="ECO:0000269|PubMed:12525165, FT ECO:0000269|PubMed:1989985" FT DISULFID 215..313 FT /evidence="ECO:0000269|PubMed:1989985" FT DISULFID 347..351 FT /evidence="ECO:0000269|PubMed:12525165, FT ECO:0000269|PubMed:1989985" FT VAR_SEQ 153..185 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.7" FT /id="VSP_053360" FT VAR_SEQ 380..386 FT /note="GTEDSTD -> VLKVIFAVAFCLISAVLMVLLFIHIRRGLCWQRESYGNI FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_036023" FT VARIANT 15 FT /note="S -> N (in dbSNP:rs17850347)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047960" FT VARIANT 124 FT /note="F -> V (in dbSNP:rs17856254)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047961" FT VARIANT 226 FT /note="W -> R (in dbSNP:rs17856253)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047962" FT VARIANT 330 FT /note="Y -> H (in dbSNP:rs17851392)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047963" FT VARIANT 360 FT /note="V -> A (in dbSNP:rs17850198)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_047964" FT MUTAGEN 206 FT /note="W->F: Greatly reduced enzyme activity, marked FT decrease in structural stability, and increased binding of FT the inhibitor, L(+)-tartrate." FT /evidence="ECO:0000269|PubMed:9584846" FT MUTAGEN 206 FT /note="W->L: Reduced enzyme activity, marked decrease in FT structural stability, and increased binding of the FT inhibitor, L(+)-tartrate." FT /evidence="ECO:0000269|PubMed:9584846" FT CONFLICT 15..24 FT /note="SLGFLFLLFF -> AFASCFCFFC (in Ref. 5; CAA37673)" FT /evidence="ECO:0000305" FT CONFLICT 15..24 FT /note="SLGFLFLLFF -> ALASCFCFFC (in Ref. 3; AAA60022 and 4; FT CAA36422)" FT /evidence="ECO:0000305" FT CONFLICT 46 FT /note="D -> H (in Ref. 5; CAA37673)" FT /evidence="ECO:0000305" FT CONFLICT 66..73 FT /note="GFGQLTQL -> RIWPTHPA (in Ref. 5; CAA37673)" FT /evidence="ECO:0000305" FT CONFLICT 66..73 FT /note="GFGQLTQL -> WIWPTHPA (in Ref. 4; CAA36422)" FT /evidence="ECO:0000305" FT CONFLICT 95 FT /note="E -> D (in Ref. 3; AAA60022)" FT /evidence="ECO:0000305" FT CONFLICT 116 FT /note="A -> R (in Ref. 3; AAA60022)" FT /evidence="ECO:0000305" FT CONFLICT 139 FT /note="Q -> E (in Ref. 5; CAA37673)" FT /evidence="ECO:0000305" FT CONFLICT 157 FT /note="P -> R (in Ref. 5; CAA37673)" FT /evidence="ECO:0000305" FT CONFLICT 212 FT /note="P -> A (in Ref. 4; CAA36422)" FT /evidence="ECO:0000305" FT CONFLICT 215 FT /note="C -> S (in Ref. 3; AAA60022)" FT /evidence="ECO:0000305" FT CONFLICT 294 FT /note="S -> T (in Ref. 3; AAA60022)" FT /evidence="ECO:0000305" FT CONFLICT 372 FT /note="C -> V (in Ref. 3; AAA60022)" FT /evidence="ECO:0000305" FT CONFLICT 383 FT /note="D -> N (in Ref. 5; CAA37673)" FT /evidence="ECO:0000305" FT STRAND 34..43 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 60..62 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 72..88 FT /evidence="ECO:0007829|PDB:1ND6" FT TURN 89..93 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 99..101 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 110..123 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 128..130 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:1CVI" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 148..150 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 152..155 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 162..173 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 175..181 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 182..184 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 185..195 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 202..208 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 210..218 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 229..247 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 248..251 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 252..258 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 261..276 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:1ND5" FT STRAND 282..288 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 290..299 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 313..321 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 324..332 FT /evidence="ECO:0007829|PDB:1ND6" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:1CVI" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:1ND5" FT STRAND 349..352 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 353..360 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 361..363 FT /evidence="ECO:0007829|PDB:1ND6" FT HELIX 368..371 FT /evidence="ECO:0007829|PDB:1ND6" SQ SEQUENCE 386 AA; 44566 MW; EF81E11DFAECADEA CRC64; MRAAPLLLAR AASLSLGFLF LLFFWLDRSV LAKELKFVTL VFRHGDRSPI DTFPTDPIKE SSWPQGFGQL TQLGMEQHYE LGEYIRKRYR KFLNESYKHE QVYIRSTDVD RTLMSAMTNL AALFPPEGVS IWNPILLWQP IPVHTVPLSE DQLLYLPFRN CPRFQELESE TLKSEEFQKR LHPYKDFIAT LGKLSGLHGQ DLFGIWSKVY DPLYCESVHN FTLPSWATED TMTKLRELSE LSLLSLYGIH KQKEKSRLQG GVLVNEILNH MKRATQIPSY KKLIMYSAHD TTVSGLQMAL DVYNGLLPPY ASCHLTELYF EKGEYFVEMY YRNETQHEPY PLMLPGCSPS CPLERFAELV GPVIPQDWST ECMTTNSHQG TEDSTD //