PPB1_HUMAN
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 03-AUG-2022, entry version 227.
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";
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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; 130.
DR IntAct; P05187; 50.
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 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; P05187; -.
DR PeptideAtlas; P05187; -.
DR PRIDE; P05187; -.
DR ProteomicsDB; 51823; -.
DR ABCD; P05187; 14 sequenced antibodies.
DR Antibodypedia; 3515; 1774 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 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; MFRMGTP; -.
DR OrthoDB; 454880at2759; -.
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; 11 hits in 1002 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 tissues.
DR Genevisible; P05187; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; -; 1.
DR InterPro; IPR001952; Alkaline_phosphatase.
DR InterPro; IPR018299; Alkaline_phosphatase_AS.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR PANTHER; PTHR11596; PTHR11596; 1.
DR Pfam; PF00245; Alk_phosphatase; 1.
DR PRINTS; PR00113; ALKPHPHTASE.
DR SMART; SM00098; alkPPc; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
DR PROSITE; PS00123; ALKALINE_PHOSPHATASE; 1.
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
