ID PPB1_HUMAN Reviewed; 535 AA. AC P05187; P05188; P06861; Q53S78; Q96DB7; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 2. DT 27-MAR-2024, entry version 236. DE RecName: Full=Alkaline phosphatase, placental type; DE EC=3.1.3.1; DE AltName: Full=Alkaline phosphatase Regan isozyme; DE AltName: Full=Placental alkaline phosphatase 1 {ECO:0000303|PubMed:1939159}; DE Short=PLAP-1; DE Flags: Precursor; GN Name=ALPP {ECO:0000312|HGNC:HGNC:439}; GN Synonyms=PLAP {ECO:0000303|PubMed:1939159}; 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]. RX PubMed=3042787; DOI=10.1016/s0021-9258(18)37887-6; RA Knoll B.J., Rothblum K.N., Longley M.A.; RT "Nucleotide sequence of the human placental alkaline phosphatase gene. RT Evolution of the 5' flanking region by deletion/substitution."; RL J. Biol. Chem. 263:12020-12027(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PRO-231. RX PubMed=3512548; DOI=10.1016/s0021-9258(17)35755-1; RA Millan J.L.; RT "Molecular cloning and sequence analysis of human placental alkaline RT phosphatase."; RL J. Biol. Chem. 261:3112-3115(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANTS LEU-25 AND RP HIS-263, AND POLYMORPHISM. RX PubMed=3461452; DOI=10.1073/pnas.83.15.5597; RA Henthorn P.S., Knoll B.J., Raducha M., Rothblum K.N., Slaughter C., RA Weiss M., Lafferty M.A., Fischer T., Harris H.; RT "Products of two common alleles at the locus for human placental alkaline RT phosphatase differ by seven amino acids."; RL Proc. Natl. Acad. Sci. U.S.A. 83:5597-5601(1986). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-89. RC TISSUE=Cervix, and Placenta; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 6-535, AND VARIANT LEU-25. RX PubMed=3001717; DOI=10.1073/pnas.82.24.8715; RA Kam W., Clauser E., Kim Y.S., Kan Y.W., Rutter W.J.; RT "Cloning, sequencing, and chromosomal localization of human term placental RT alkaline phosphatase cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 82:8715-8719(1985). RN [7] RP PROTEIN SEQUENCE OF 23-64. RX PubMed=6651840; DOI=10.1016/s0006-291x(83)80252-6; RA Ezra E., Blacher R., Udenfriend S.; RT "Purification and partial sequencing of human placental alkaline RT phosphatase."; RL Biochem. Biophys. Res. Commun. 116:1076-1083(1983). RN [8] RP NUCLEOTIDE SEQUENCE OF 382-535. RX PubMed=3459156; DOI=10.1073/pnas.83.11.3781; RA Ovitt C.E., Strauss A.W., Alpers D.H., Chou J.Y., Boime I.; RT "Expression of different-sized placental alkaline phosphatase mRNAs in RT placenta and choriocarcinoma cells."; RL Proc. Natl. Acad. Sci. U.S.A. 83:3781-3785(1986). RN [9] RP PROTEIN SEQUENCE OF 485-535. RX PubMed=3422741; DOI=10.1073/pnas.85.5.1398; RA Micanovic R., Bailey C.A., Brink L., Gerber L., Pan Y.C.E., Hulmes J.D., RA Udenfriend S.; RT "Aspartic acid-484 of nascent placental alkaline phosphatase condenses with RT a phosphatidylinositol glycan to become the carboxyl terminus of the mature RT enzyme."; RL Proc. Natl. Acad. Sci. U.S.A. 85:1398-1402(1988). RN [10] RP GPI-ANCHOR AT ASP-506. RX PubMed=2153284; DOI=10.1073/pnas.87.1.157; RA Micanovic R., Gerber L.D., Berger J., Kodukula K., Udenfriend S.; RT "Selectivity of the cleavage/attachment site of phosphatidylinositol- RT glycan-anchored membrane proteins determined by site-specific mutagenesis RT at Asp-484 of placental alkaline phosphatase."; RL Proc. Natl. Acad. Sci. U.S.A. 87:157-161(1990). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=1939159; DOI=10.1016/s0021-9258(18)54836-5; RA Watanabe T., Wada N., Kim E.E., Wyckoff H.W., Chou J.Y.; RT "Mutation of a single amino acid converts germ cell alkaline phosphatase to RT placental alkaline phosphatase."; RL J. Biol. Chem. 266:21174-21178(1991). RN [12] RP GPI-ANCHOR. RX PubMed=1730777; DOI=10.1083/jcb.116.3.799; RA Lowe M.E.; RT "Site-specific mutations in the COOH-terminus of placental alkaline RT phosphatase: a single amino acid change converts a phosphatidylinositol- RT glycan-anchored protein to a secreted protein."; RL J. Cell Biol. 116:799-807(1992). RN [13] RP DISULFIDE BONDS. RX PubMed=11937510; DOI=10.1074/jbc.m202298200; RA Kozlenkov A., Manes T., Hoylaerts M.F., Millan J.L.; RT "Function assignment to conserved residues in mammalian alkaline RT phosphatases."; RL J. Biol. Chem. 277:22992-22999(2002). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=25775211; DOI=10.1371/journal.pone.0119874; RA Hoylaerts M.F., Van Kerckhoven S., Kiffer-Moreira T., Sheen C., RA Narisawa S., Millan J.L.; RT "Functional significance of calcium binding to tissue-nonspecific alkaline RT phosphatase."; RL PLoS ONE 10:e0119874-e0119874(2015). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 23-535 IN COMPLEX WITH MAGNESIUM RP AND ZINC, COFACTOR, DISULFIDE BOND, AND SUBUNIT. RX PubMed=11124260; DOI=10.1074/jbc.m009250200; RA Le Du M.H., Stigbrand T., Taussig M.J., Menez A., Stura E.A.; RT "Crystal structure of alkaline phosphatase from human placenta at 1.8 A RT resolution. Implication for a substrate specificity."; RL J. Biol. Chem. 276:9158-9165(2001). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 23-506 IN COMPLEX WITH MAGNESIUM RP AND ZINC, GLYCOSYLATION AT ASN-144 AND ASN-271, COFACTOR, DISULFIDE BOND, RP AND SUBUNIT. RX PubMed=15946677; DOI=10.1016/j.jmb.2005.04.068; RA Llinas P., Stura E.A., Menez A., Kiss Z., Stigbrand T., Millan J.L., RA Le Du M.H.; RT "Structural studies of human placental alkaline phosphatase in complex with RT functional ligands."; RL J. Mol. Biol. 350:441-451(2005). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 23-506 IN COMPLEX WITH MAGNESIUM RP AND ZINC, GLYCOSYLATION AT ASN-144 AND ASN-271, COFACTOR, DISULFIDE BOND, RP AND SUBUNIT. RX PubMed=16815919; DOI=10.1110/ps.062123806; RA Llinas P., Masella M., Stigbrand T., Menez A., Stura E.A., Le Du M.H.; RT "Structural studies of human alkaline phosphatase in complex with RT strontium: implication for its secondary effect in bones."; RL Protein Sci. 15:1691-1700(2006). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 23-506 IN COMPLEX WITH MAGNESIUM RP AND ZINC, GLYCOSYLATION AT ASN-144 AND ASN-271, COFACTOR, DISULFIDE BOND, RP SUBUNIT, AND TISSUE SPECIFICITY. RX PubMed=20693656; DOI=10.1107/s1744309110019767; RA Stec B., Cheltsov A., Millan J.L.; RT "Refined structures of placental alkaline phosphatase show a consistent RT pattern of interactions at the peripheral site."; RL Acta Crystallogr. F 66:866-870(2010). CC -!- FUNCTION: Alkaline phosphatase that can hydrolyze various phosphate CC compounds. {ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}. 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=3.1.3.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10042, CC ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15018; CC Evidence={ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11124260, ECO:0000269|PubMed:15946677, CC ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656}; CC Note=Binds 1 Mg(2+) ion. {ECO:0000269|PubMed:11124260, CC ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, CC ECO:0000269|PubMed:20693656}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:11124260, ECO:0000269|PubMed:15946677, CC ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656}; CC Note=Binds 2 Zn(2+) ions. {ECO:0000269|PubMed:11124260, CC ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, CC ECO:0000269|PubMed:20693656}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000305|PubMed:25775211}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11124260, CC ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, CC ECO:0000269|PubMed:20693656}. CC -!- INTERACTION: CC P05187; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-1211484, EBI-10173507; CC P05187; Q9UGL9: CRCT1; NbExp=3; IntAct=EBI-1211484, EBI-713677; CC P05187; Q02930-3: CREB5; NbExp=3; IntAct=EBI-1211484, EBI-10192698; CC P05187; P42830: CXCL5; NbExp=3; IntAct=EBI-1211484, EBI-12175919; CC P05187; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1211484, EBI-3867333; CC P05187; Q9NWN3: FBXO34; NbExp=3; IntAct=EBI-1211484, EBI-719816; CC P05187; P57678: GEMIN4; NbExp=3; IntAct=EBI-1211484, EBI-356700; CC P05187; O15499: GSC2; NbExp=3; IntAct=EBI-1211484, EBI-19954058; CC P05187; P49639: HOXA1; NbExp=7; IntAct=EBI-1211484, EBI-740785; CC P05187; P24592: IGFBP6; NbExp=3; IntAct=EBI-1211484, EBI-947015; CC P05187; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-1211484, EBI-11959885; CC P05187; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-1211484, EBI-11749135; CC P05187; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1211484, EBI-10171774; CC P05187; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-1211484, EBI-739863; CC P05187; P26371: KRTAP5-9; NbExp=6; IntAct=EBI-1211484, EBI-3958099; CC P05187; Q5T752: LCE1D; NbExp=3; IntAct=EBI-1211484, EBI-11741311; CC P05187; Q5T753: LCE1E; NbExp=3; IntAct=EBI-1211484, EBI-11955335; CC P05187; Q5T754: LCE1F; NbExp=3; IntAct=EBI-1211484, EBI-11958008; CC P05187; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-1211484, EBI-11973993; CC P05187; Q5TA76: LCE3A; NbExp=5; IntAct=EBI-1211484, EBI-9394625; CC P05187; Q5TA77: LCE3B; NbExp=3; IntAct=EBI-1211484, EBI-11974495; CC P05187; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-1211484, EBI-10245291; CC P05187; Q9BYE3: LCE3D; NbExp=5; IntAct=EBI-1211484, EBI-6658837; CC P05187; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-1211484, EBI-10245456; CC P05187; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-1211484, EBI-11955689; CC P05187; Q5T871: LELP1; NbExp=3; IntAct=EBI-1211484, EBI-18115868; CC P05187; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1211484, EBI-16439278; CC P05187; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-1211484, EBI-22310682; CC P05187; Q92570: NR4A3; NbExp=3; IntAct=EBI-1211484, EBI-13644623; CC P05187; P32242: OTX1; NbExp=3; IntAct=EBI-1211484, EBI-740446; CC P05187; Q12837: POU4F2; NbExp=3; IntAct=EBI-1211484, EBI-17236143; CC P05187; P49795: RGS19; NbExp=3; IntAct=EBI-1211484, EBI-874907; CC P05187; O76081-6: RGS20; NbExp=3; IntAct=EBI-1211484, EBI-10178530; CC P05187; P49901: SMCP; NbExp=3; IntAct=EBI-1211484, EBI-750494; CC P05187; P22735: TGM1; NbExp=3; IntAct=EBI-1211484, EBI-2562368; CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor CC {ECO:0000269|PubMed:1730777, ECO:0000269|PubMed:2153284}. CC -!- TISSUE SPECIFICITY: Detected in placenta (at protein level). CC {ECO:0000269|PubMed:20693656}. CC -!- POLYMORPHISM: Placental ALP is highly polymorphic, there are at least CC three common alleles. {ECO:0000269|PubMed:3461452}. CC -!- MISCELLANEOUS: In most mammals there are four different isozymes: CC placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non- CC specific (liver/bone/kidney) (ALPL/TNAP). CC -!- SIMILARITY: Belongs to the alkaline phosphatase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA51708.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alkaline phosphatase entry; CC URL="https://en.wikipedia.org/wiki/Alkaline_phosphatase"; 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; M19159; AAA51710.1; -; Genomic_DNA. DR EMBL; M13077; AAC97139.1; -; mRNA. DR EMBL; M14169; AAA51708.1; ALT_INIT; mRNA. DR EMBL; M14170; AAA51709.1; -; mRNA. DR EMBL; AC068134; AAY24087.1; -; Genomic_DNA. DR EMBL; BC009647; AAH09647.1; -; mRNA. DR EMBL; BC068501; AAH68501.1; -; mRNA. DR EMBL; BC094743; AAH94743.1; -; mRNA. DR EMBL; M12551; AAA51706.1; -; mRNA. DR CCDS; CCDS2490.1; -. DR PIR; A31074; PAHUA. DR RefSeq; NP_001623.3; NM_001632.4. DR PDB; 1EW2; X-ray; 1.82 A; A=23-535. DR PDB; 1ZEB; X-ray; 1.90 A; A=23-506. DR PDB; 1ZED; X-ray; 1.57 A; A=23-506. DR PDB; 1ZEF; X-ray; 1.90 A; A=23-506. DR PDB; 2GLQ; X-ray; 1.60 A; A=23-506. DR PDB; 3MK0; X-ray; 1.90 A; A=23-506. DR PDB; 3MK1; X-ray; 1.57 A; A=23-506. DR PDB; 3MK2; X-ray; 1.89 A; A=23-503. DR PDBsum; 1EW2; -. DR PDBsum; 1ZEB; -. DR PDBsum; 1ZED; -. DR PDBsum; 1ZEF; -. DR PDBsum; 2GLQ; -. DR PDBsum; 3MK0; -. DR PDBsum; 3MK1; -. DR PDBsum; 3MK2; -. DR AlphaFoldDB; P05187; -. DR SMR; P05187; -. DR BioGRID; 106751; 131. DR IntAct; P05187; 51. DR MINT; P05187; -. DR STRING; 9606.ENSP00000375881; -. DR BindingDB; P05187; -. DR ChEMBL; CHEMBL4458; -. DR DrugBank; DB01373; Calcium. DR DrugBank; DB08413; METHYL-PHOSPHONIC ACID MONO-(4-NITRO-PHENYL) ESTER. DR DEPOD; ALPP; -. DR GlyCosmos; P05187; 2 sites, No reported glycans. DR GlyGen; P05187; 2 sites. DR iPTMnet; P05187; -. DR MetOSite; P05187; -. DR PhosphoSitePlus; P05187; -. DR BioMuta; ALPP; -. DR DMDM; 130737; -. DR EPD; P05187; -. DR jPOST; P05187; -. DR MassIVE; P05187; -. DR MaxQB; P05187; -. DR PaxDb; 9606-ENSP00000375881; -. DR PeptideAtlas; P05187; -. DR ProteomicsDB; 51823; -. DR Pumba; P05187; -. DR ABCD; P05187; 14 sequenced antibodies. DR Antibodypedia; 3515; 1944 antibodies from 45 providers. DR DNASU; 250; -. DR Ensembl; ENST00000392027.3; ENSP00000375881.2; ENSG00000163283.7. DR GeneID; 250; -. DR KEGG; hsa:250; -. DR MANE-Select; ENST00000392027.3; ENSP00000375881.2; NM_001632.5; NP_001623.3. DR UCSC; uc002vsq.4; human. DR AGR; HGNC:439; -. DR CTD; 250; -. DR DisGeNET; 250; -. DR GeneCards; ALPP; -. DR HGNC; HGNC:439; ALPP. DR HPA; ENSG00000163283; Group enriched (cervix, placenta). DR MIM; 171800; gene. DR neXtProt; NX_P05187; -. DR OpenTargets; ENSG00000163283; -. DR PharmGKB; PA24730; -. DR VEuPathDB; HostDB:ENSG00000163283; -. DR eggNOG; KOG4126; Eukaryota. DR GeneTree; ENSGT00950000183063; -. DR HOGENOM; CLU_008539_4_0_1; -. DR InParanoid; P05187; -. DR OMA; NMPCSAR; -. DR OrthoDB; 35876at2759; -. DR PhylomeDB; P05187; -. DR TreeFam; TF323513; -. DR BRENDA; 3.1.3.1; 2681. DR PathwayCommons; P05187; -. DR Reactome; R-HSA-6811438; Intra-Golgi traffic. DR SABIO-RK; P05187; -. DR SignaLink; P05187; -. DR BioGRID-ORCS; 250; 13 hits in 1095 CRISPR screens. DR ChiTaRS; ALPP; human. DR EvolutionaryTrace; P05187; -. DR GeneWiki; Placental_alkaline_phosphatase; -. DR GenomeRNAi; 250; -. DR Pharos; P05187; Tbio. DR PRO; PR:P05187; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P05187; Protein. DR Bgee; ENSG00000163283; Expressed in placenta and 52 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW. DR GO; GO:0004035; F:alkaline phosphatase activity; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0016311; P:dephosphorylation; IBA:GO_Central. DR CDD; cd16012; ALP; 1. DR Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1. DR InterPro; IPR001952; Alkaline_phosphatase. DR InterPro; IPR018299; Alkaline_phosphatase_AS. DR InterPro; IPR017850; Alkaline_phosphatase_core_sf. DR PANTHER; PTHR11596; ALKALINE PHOSPHATASE; 1. DR PANTHER; PTHR11596:SF90; ALKALINE PHOSPHATASE, PLACENTAL TYPE; 1. DR Pfam; PF00245; Alk_phosphatase; 1. DR PRINTS; PR00113; ALKPHPHTASE. DR SMART; SM00098; alkPPc; 1. DR SUPFAM; SSF53649; Alkaline phosphatase-like; 1. DR PROSITE; PS00123; ALKALINE_PHOSPHATASE; 1. DR Genevisible; P05187; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cell membrane; Direct protein sequencing; KW Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; KW Magnesium; Membrane; Metal-binding; Reference proteome; Signal; KW Transmembrane; Transmembrane helix; Zinc. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:6651840" FT CHAIN 23..506 FT /note="Alkaline phosphatase, placental type" FT /id="PRO_0000024031" FT PROPEP 507..535 FT /note="Removed in mature form" FT /id="PRO_0000024032" FT TRANSMEM 513..529 FT /note="Helical" FT REGION 425..449 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 114 FT /note="Phosphoserine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10042" FT BINDING 64 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 64 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 114 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 177 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 238 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P05186" FT BINDING 291 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P05186" FT BINDING 292 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P05186" FT BINDING 307 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P05186" FT BINDING 333 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 338 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 342 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 379 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 380 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT BINDING 454 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, FT ECO:0000269|PubMed:20693656" FT LIPID 506 FT /note="GPI-anchor amidated aspartate" FT /evidence="ECO:0000269|PubMed:2153284" FT CARBOHYD 144 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15946677, FT ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656" FT CARBOHYD 271 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15946677, FT ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656" FT DISULFID 143..205 FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:11937510, ECO:0000269|PubMed:15946677, FT ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656" FT DISULFID 489..496 FT /evidence="ECO:0000269|PubMed:11124260, FT ECO:0000269|PubMed:11937510, ECO:0000269|PubMed:15946677, FT ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656" FT VARIANT 25 FT /note="P -> L (in dbSNP:rs1130335)" FT /evidence="ECO:0000269|PubMed:3001717, FT ECO:0000269|PubMed:3461452" FT /id="VAR_017419" FT VARIANT 89 FT /note="I -> L (in dbSNP:rs13026692)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_050520" FT VARIANT 231 FT /note="R -> P (in dbSNP:rs1048988)" FT /evidence="ECO:0000269|PubMed:3512548" FT /id="VAR_050521" FT VARIANT 263 FT /note="R -> H (in dbSNP:rs2853378)" FT /evidence="ECO:0000269|PubMed:3461452" FT /id="VAR_050522" FT VARIANT 451 FT /note="E -> G (in dbSNP:rs1048994)" FT /id="VAR_050523" FT CONFLICT 66 FT /note="M -> V (in Ref. 3; AAA51709)" FT /evidence="ECO:0000305" FT CONFLICT 261..262 FT /note="AK -> GE (in Ref. 6; AAA51706)" FT /evidence="ECO:0000305" FT CONFLICT 277 FT /note="Q -> R (in Ref. 3; AAA51709)" FT /evidence="ECO:0000305" FT CONFLICT 285 FT /note="T -> A (in Ref. 3; AAA51709)" FT /evidence="ECO:0000305" FT CONFLICT 324 FT /note="N -> H (in Ref. 6; AAA51706)" FT /evidence="ECO:0000305" FT CONFLICT 389 FT /note="Y -> C (in Ref. 3; AAA51709)" FT /evidence="ECO:0000305" FT CONFLICT 394 FT /note="S -> G (in Ref. 3; AAA51709)" FT /evidence="ECO:0000305" FT CONFLICT 396..397 FT /note="IF -> FI (in Ref. 6; AAA51706)" FT /evidence="ECO:0000305" FT CONFLICT 401 FT /note="P -> A (in Ref. 6; AAA51706)" FT /evidence="ECO:0000305" FT HELIX 26..29 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 31..47 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 56..63 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 68..81 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 93..95 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 97..103 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 114..123 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 143..145 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 154..160 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 164..172 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 176..179 FT /evidence="ECO:0007829|PDB:1ZED" FT TURN 180..182 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 198..202 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 208..214 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 219..224 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 226..229 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 243..245 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 255..261 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 266..269 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 272..279 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 285..290 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:1ZED" FT TURN 304..306 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 310..321 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 328..334 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 337..342 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 346..366 FT /evidence="ECO:0007829|PDB:1ZED" FT TURN 369..371 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 372..379 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 381..386 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 411..418 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 433..436 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 445..447 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 459..465 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 468..470 FT /evidence="ECO:0007829|PDB:1ZED" FT STRAND 473..476 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 479..487 FT /evidence="ECO:0007829|PDB:1ZED" FT HELIX 491..493 FT /evidence="ECO:0007829|PDB:1ZED" SQ SEQUENCE 535 AA; 57954 MW; 13C136679A70C76B CRC64; MLGPCMLLLL LLLGLRLQLS LGIIPVEEEN PDFWNREAAE ALGAAKKLQP AQTAAKNLII FLGDGMGVST VTAARILKGQ KKDKLGPEIP LAMDRFPYVA LSKTYNVDKH VPDSGATATA YLCGVKGNFQ TIGLSAAARF NQCNTTRGNE VISVMNRAKK AGKSVGVVTT TRVQHASPAG TYAHTVNRNW YSDADVPASA RQEGCQDIAT QLISNMDIDV ILGGGRKYMF RMGTPDPEYP DDYSQGGTRL DGKNLVQEWL AKRQGARYVW NRTELMQASL DPSVTHLMGL FEPGDMKYEI HRDSTLDPSL MEMTEAALRL LSRNPRGFFL FVEGGRIDHG HHESRAYRAL TETIMFDDAI ERAGQLTSEE DTLSLVTADH SHVFSFGGYP LRGSSIFGLA PGKARDRKAY TVLLYGNGPG YVLKDGARPD VTESESGSPE YRQQSAVPLD EETHAGEDVA VFARGPQAHL VHGVQEQTFI AHVMAFAACL EPYTACDLAP PAGTTDAAHP GRSVVPALLP LLAGTLLLLE TATAP //