PPBT_HUMAN
ID PPBT_HUMAN Reviewed; 524 AA.
AC P05186; A1A4E7; B2RMP8; B7Z387; B7Z4Y6; O75090; Q2TAI7; Q59EJ7; Q5BKZ5;
AC Q5VTG5; Q6NZI8; Q8WU32; Q9UBK0;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 4.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=Alkaline phosphatase, tissue-nonspecific isozyme {ECO:0000303|PubMed:2220817};
DE Short=AP-TNAP;
DE Short=TNS-ALP {ECO:0000303|PubMed:2220817};
DE Short=TNSALP;
DE EC=3.1.3.1 {ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064};
DE AltName: Full=Alkaline phosphatase liver/bone/kidney isozyme {ECO:0000303|PubMed:3532105};
DE AltName: Full=Phosphoamidase {ECO:0000305};
DE AltName: Full=Phosphocreatine phosphatase {ECO:0000250|UniProtKB:P09242};
DE EC=3.9.1.1 {ECO:0000250|UniProtKB:P09242};
DE Flags: Precursor;
GN Name=ALPL {ECO:0000303|PubMed:8406453, ECO:0000312|HGNC:HGNC:438};
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] (ISOFORM 1).
RC TISSUE=Osteosarcoma;
RX PubMed=3532105; DOI=10.1073/pnas.83.19.7182;
RA Weiss M.J., Henthorn P.S., Lafferty M.A., Slaughter C., Raducha M.,
RA Harris H.;
RT "Isolation and characterization of a cDNA encoding a human
RT liver/bone/kidney-type alkaline phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7182-7186(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Osteosarcoma;
RX PubMed=3165380; DOI=10.1016/s0021-9258(18)37885-2;
RA Weiss M.J., Ray K., Henthorn P.S., Lamb B., Kadesch T., Harris H.;
RT "Structure of the human liver/bone/kidney alkaline phosphatase gene.";
RL J. Biol. Chem. 263:12002-12010(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-263.
RC TISSUE=Liver;
RX PubMed=2928120; DOI=10.1093/nar/17.5.2129;
RA Kishi F., Matsuura S., Kajii T.;
RT "Nucleotide sequence of the human liver-type alkaline phosphatase cDNA.";
RL Nucleic Acids Res. 17:2129-2129(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HOPS PHE-289.
RX PubMed=9747027; DOI=10.1007/s100380050061;
RA Sugimoto N., Iwamoto S., Hoshino Y., Kajii E.;
RT "A novel missense mutation of the tissue-nonspecific alkaline phosphatase
RT gene detected in a patient with hypophosphatasia.";
RL J. Hum. Genet. 43:160-164(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Hippocampus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-152.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-263.
RC TISSUE=Brain, Cerebellum, Lymphoma, and Peripheral nerve;
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 [10]
RP PROTEIN SEQUENCE OF 18-49.
RC TISSUE=Liver;
RX PubMed=3954357; DOI=10.1016/0003-9861(86)90223-7;
RA Garattini E., Hua J.-C., Pan Y.C.E., Udenfriend S.;
RT "Human liver alkaline phosphatase, purification and partial sequencing:
RT homology with the placental isozyme.";
RL Arch. Biochem. Biophys. 245:331-337(1986).
RN [11]
RP PROTEIN SEQUENCE OF 18-32, AND GLYCOSYLATION.
RX PubMed=1458595;
RA Nishihara Y., Hayashi Y., Adachi T., Koyama I., Stigbrand T., Hirano K.;
RT "Chemical nature of intestinal-type alkaline phosphatase in human kidney.";
RL Clin. Chem. 38:2539-2542(1992).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=2220817;
RA Fedde K.N., Whyte M.P.;
RT "Alkaline phosphatase (tissue-nonspecific isoenzyme) is a
RT phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and
RT hypophosphatasia fibroblast study.";
RL Am. J. Hum. Genet. 47:767-775(1990).
RN [13]
RP COFACTOR.
RX PubMed=11395499; DOI=10.1074/jbc.m102788200;
RA Mornet E., Stura E., Lia-Baldini A.S., Stigbrand T., Menez A., Le Du M.H.;
RT "Structural evidence for a functional role of human tissue nonspecific
RT alkaline phosphatase in bone mineralization.";
RL J. Biol. Chem. 276:31171-31178(2001).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17566972; DOI=10.1002/pmic.200700068;
RA Omaetxebarria M.J., Elortza F., Rodriguez-Suarez E., Aloria K.,
RA Arizmendi J.M., Jensen O.N., Matthiesen R.;
RT "Computational approach for identification and characterization of GPI-
RT anchored peptides in proteomics experiments.";
RL Proteomics 7:1951-1960(2007).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-430.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, AND MUTAGENESIS OF GLU-235;
RP TRP-270; ARG-272; PHE-290; GLU-291 AND ASP-306.
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 [18]
RP FUNCTION, AND INVOLVEMENT IN HOPS.
RX PubMed=20049532; DOI=10.1007/s10545-009-9012-y;
RA Balasubramaniam S., Bowling F., Carpenter K., Earl J., Chaitow J., Pitt J.,
RA Mornet E., Sillence D., Ellaway C.;
RT "Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy
RT with abnormal neurotransmitter metabolism secondary to reduced co-factor
RT pyridoxal-5'-phosphate availability.";
RL J. Inherit. Metab. Dis. 33:S25-S33(2010).
RN [19]
RP FUNCTION.
RX PubMed=28448526; DOI=10.1371/journal.pone.0175936;
RA Pettengill M., Matute J.D., Tresenriter M., Hibbert J., Burgner D.,
RA Richmond P., Millan J.L., Ozonoff A., Strunk T., Currie A., Levy O.;
RT "Human alkaline phosphatase dephosphorylates microbial products and is
RT elevated in preterm neonates with a history of late-onset sepsis.";
RL PLoS ONE 12:e0175936-e0175936(2017).
RN [20]
RP VARIANT HOPS THR-179.
RX PubMed=3174660; DOI=10.1073/pnas.85.20.7666;
RA Weiss M.J., Cole D.E.C., Ray K., Whyte M.P., Lafferty M.A., Mulivor R.A.,
RA Harris H.;
RT "A missense mutation in the human liver/bone/kidney alkaline phosphatase
RT gene causing a lethal form of hypophosphatasia.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7666-7669(1988).
RN [21]
RP VARIANTS HOPS VAL-33; CYS-71; PRO-71; LYS-191; PRO-207; ALA-294; VAL-378
RP AND HIS-436, AND VARIANT HIS-263.
RX PubMed=1409720; DOI=10.1073/pnas.89.20.9924;
RA Henthorn P.S., Raducha M., Fedde K.N., Lafferty M.A., Whyte M.P.;
RT "Different missense mutations at the tissue-nonspecific alkaline
RT phosphatase gene locus in autosomal recessively inherited forms of mild and
RT severe hypophosphatasia.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9924-9928(1992).
RN [22]
RP VARIANT HOPS ASP-334.
RX PubMed=8406453; DOI=10.1006/geno.1993.1305;
RA Greenberg C.R., Taylor C.L., Haworth J.C., Seargeant L.E., Philipps S.,
RA Triggs-Raine B., Chodirker B.N.;
RT "A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal)
RT form of hypophosphatasia in Canadian mennonites.";
RL Genomics 17:215-217(1993).
RN [23]
RP INVOLVEMENT IN HPPI, AND VARIANT HPPI LYS-298.
RX PubMed=7833929; DOI=10.1093/hmg/3.9.1683;
RA Orimo H., Hayashi Z., Watanabe A., Hirayama T., Hirayama T., Shimada T.;
RT "Novel missense and frameshift mutations in the tissue-nonspecific alkaline
RT phosphatase gene in a Japanese patient with hypophosphatasia.";
RL Hum. Mol. Genet. 3:1683-1684(1994).
RN [24]
RP INVOLVEMENT IN HPPI, AND VARIANTS HPPI LEU-327 AND ARG-456.
RX PubMed=8954059; DOI=10.1210/jcem.81.12.8954059;
RA Ozono K., Yamagata M., Michigami T., Nakajima S., Sakai N., Cai G.,
RA Satomura K., Yasui N., Okada S., Nakayama M.;
RT "Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a
RT neonatal case of hypophosphatasia.";
RL J. Clin. Endocrinol. Metab. 81:4458-4461(1996).
RN [25]
RP VARIANTS HOPS PHE-17; VAL-40; SER-75; ARG-120; ARG-129; ASP-170; TRP-184;
RP LYS-191; TRP-223; LYS-291; ASP-334; PRO-445; CYS-450; SER-473 AND ARG-491,
RP AND VARIANT HIS-263.
RX PubMed=9781036; DOI=10.1038/sj.ejhg.5200190;
RA Mornet E., Taillandier A., Peyramaure S., Kaper F., Muller F., Brenner R.,
RA Bussiere P., Freisinger P., Godard J., Le Merrer M., Oury J.F., Plauchu H.,
RA Puddu R., Rival J.M., Superti-Furga A., Touraine R.L., Serre J.L.,
RA Simon-Bouy B.;
RT "Identification of fifteen novel mutations in the tissue-nonspecific
RT alkaline phosphatase (TNSALP) gene in European patients with severe
RT hypophosphatasia.";
RL Eur. J. Hum. Genet. 6:308-314(1998).
RN [26]
RP VARIANTS HOPS THR-111; THR-177; GLY-191; LEU-327 AND ILE-382.
RX PubMed=9452105; DOI=10.1002/humu.1380110184;
RA Goseki-Sone M., Orimo H., Iimura T., Takagi Y., Watanabe H., Taketa K.,
RA Sato S., Mayanagi H., Shimada T., Oida S.;
RT "Hypophosphatasia: identification of five novel missense mutations (G507A,
RT G705A, A748G, T1155C, G1320A) in the tissue-nonspecific alkaline
RT phosphatase gene among Japanese patients.";
RL Hum. Mutat. Suppl. 1:S263-S267(1998).
RN [27]
RP VARIANTS HOPS VAL-40; LEU-62; SER-75; THR-111; ARG-120; ARG-129; HIS-136;
RP VAL-162; ASP-170; TYR-171; TRP-184; LYS-191; TRP-223; VAL-249; LYS-291;
RP VAL-306; ASP-334; CYS-391; PRO-445; CYS-450; SER-473; LYS-476 AND ARG-491,
RP 3D-STRUCTURE MODELING, AND CHARACTERIZATION OF VARIANTS.
RX PubMed=10332035; DOI=10.1093/hmg/8.6.1039;
RA Zurutuza L., Muller F., Gibrat J.F., Taillandier A., Simon-Bouy B.,
RA Serre J.L., Mornet E.;
RT "Correlations of genotype and phenotype in hypophosphatasia.";
RL Hum. Mol. Genet. 8:1039-1046(1999).
RN [28]
RP VARIANTS HOPS LEU-62; HIS-136; VAL-162; TYR-171; LYS-191; TYR-201; VAL-249;
RP VAL-306 AND LYS-476.
RX PubMed=10094560;
RX DOI=10.1002/(sici)1098-1004(1999)13:2<171::aid-humu16>3.0.co;2-t;
RA Taillandier A., Zurutuza L., Muller F., Simon-Bouy B., Serre J.L., Bird L.,
RA Brenner R., Boute O., Cousin J., Gaillard D., Heidemann P.H., Steinmann B.,
RA Wallot M., Mornet E.;
RT "Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V,
RT H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-
RT nonspecific alkaline phosphatase (TNSALP) gene in patients with severe
RT hypophosphatasia.";
RL Hum. Mutat. 13:171-172(1999).
RN [29]
RP VARIANTS HPPI GLU-224 AND CYS-426.
RX PubMed=10834525; DOI=10.1007/s004310051290;
RA Mochizuki H., Saito M., Michigami T., Ohashi H., Koda N., Yamaguchi S.,
RA Ozono K.;
RT "Severe hypercalcaemia and respiratory insufficiency associated with
RT infantile hypophosphatasia caused by two novel mutations of the tissue-
RT nonspecific alkaline phosphatase gene.";
RL Eur. J. Pediatr. 159:375-379(2000).
RN [30]
RP VARIANTS HOPS VAL-40; THR-111; ASN-134; THR-176; LYS-191; TYR-201; SER-246;
RP THR-348; ARG-381; GLY-406; HIS-450; ILE-478 AND SER-489.
RX PubMed=10679946;
RX DOI=10.1002/(sici)1098-1004(200003)15:3<293::aid-humu11>3.0.co;2-q;
RA Taillandier A., Cozien E., Muller F., Merrien Y., Bonnin E., Fribourg C.,
RA Simon-Bouy B., Serre J.L., Bieth E., Brenner R., Cordier M.P., De Bie S.,
RA Fellmann F., Freisinger P., Hesse V., Hennekam R.C.M., Josifova D.,
RA Kerzin-Storrar L., Leporrier N., Zabot M.-T., Mornet E.;
RT "Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S,
RT 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the
RT tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with
RT hypophosphatasia.";
RL Hum. Mutat. 15:293-293(2000).
RN [31]
RP VARIANT HOPS VAL-378, AND VARIANT ALA-522.
RX PubMed=10690885; DOI=10.1210/jcem.85.2.6373;
RA Mueller H.L., Yamazaki M., Michigami T., Kageyama T., Schoenau E.,
RA Schneider P., Ozono K.;
RT "Asp361Val mutant of alkaline phosphatase found in patients with dominantly
RT inherited hypophosphatasia inhibits the activity of the wild-type enzyme.";
RL J. Clin. Endocrinol. Metab. 85:743-747(2000).
RN [32]
RP VARIANT HOPS SER-417.
RX PubMed=11745997; DOI=10.1002/ajmg.1541.abs;
RA Sergi C., Mornet E., Troeger J., Voigtlaender T.;
RT "Perinatal hypophosphatasia: radiology, pathology and molecular biology
RT studies in a family harboring a splicing mutation (648+1A) and a novel
RT missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase
RT (TNSALP) gene.";
RL Am. J. Med. Genet. 103:235-240(2001).
RN [33]
RP CHARACTERIZATION OF VARIANTS HOPS VAL-40; VAL-63; THR-116; LEU-181;
RP TRP-184; TRP-223; VAL-249; VAL-378; ILE-478 AND PHE-490.
RX PubMed=11479741; DOI=10.1007/s004390100546;
RA Lia-Baldini A.S., Muller F., Taillandier A., Gibrat J.F., Mouchard M.,
RA Robin B., Simon-Bouy B., Serre J.L., Aylsworth A.S., Bieth E., Delanote S.,
RA Freisinger P., Hu J.C.-C., Krohn H.-P., Nunes M.E., Mornet E.;
RT "A molecular approach to dominance in hypophosphatasia.";
RL Hum. Genet. 109:99-108(2001).
RN [34]
RP VARIANTS HPPI CYS-28 AND MET-459, AND VARIANTS HOPS VAL-40; VAL-51; HIS-71;
RP THR-116; HIS-136; HIS-152; THR-176; THR-179; LYS-191; ASP-211; VAL-220;
RP GLY-235; TYR-294; GLY-327; SER-399 AND ALA-423.
RX PubMed=11438998; DOI=10.1002/humu.1154;
RA Taillandier A., Lia-Baldini A.S., Mouchard M., Robin B., Muller F.,
RA Simon-Bouy B., Serre J.L., Bera-Louville A., Bonduelle M., Eckhardt J.,
RA Gaillard D., Myhre A.G., Koertge-Jung S., Larget-Piet L., Malou E.,
RA Sillence D., Temple I.K., Viot G., Mornet E.;
RT "Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene
RT (ALPL) in patients with various forms of hypophosphatasia.";
RL Hum. Mutat. 18:83-84(2001).
RN [35]
RP INVOLVEMENT IN HPPC, VARIANTS HPPC MET-68; SER-71; THR-177; TRP-223;
RP PRO-275 AND HIS-391, CHARACTERIZATION OF VARIANTS HPPC MET-68; SER-71;
RP THR-177; TRP-223; PRO-275 AND HIS-391, VARIANT ALA-522, AND
RP CHARACTERIZATION OF VARIANT ALA-522.
RX PubMed=11760847; DOI=10.1359/jbmr.2001.16.12.2313;
RA Orimo H., Girschick H.J., Goseki-Sone M., Ito M., Oda K., Shimada T.;
RT "Mutational analysis and functional correlation with phenotype in German
RT patients with childhood-type hypophosphatasia.";
RL J. Bone Miner. Res. 16:2313-2319(2001).
RN [36]
RP VARIANT HOPS VAL-132.
RX PubMed=11834095; DOI=10.1034/j.1601-0825.2001.00740.x;
RA Watanabe H., Hashimoto-Uoshima M., Goseki-Sone M., Orimo H., Ishikawa I.;
RT "A novel point mutation (C571T) in the tissue-non-specific alkaline
RT phosphatase gene in a case of adult-type hypophosphatasia.";
RL Oral Dis. 7:331-335(2001).
RN [37]
RP VARIANTS HOPS VAL-33; CYS-71; PRO-71; THR-111; VAL-132; THR-177; THR-179;
RP GLY-191; LYS-191; TRP-223; ALA-294; ASP-334; VAL-378; ILE-382 AND ARG-456,
RP VARIANT HPPI LYS-298, CHARACTERIZATION OF VARIANTS HOPS VAL-33; CYS-71;
RP PRO-71; THR-111; VAL-132; THR-177; THR-179; GLY-191; LYS-191; TRP-223;
RP ALA-294; ASP-334; VAL-378; ILE-382 AND ARG-456, CHARACTERIZATION OF VARIANT
RP HPPI LYS-298, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12162492; DOI=10.1359/jbmr.2002.17.8.1383;
RA Di Mauro S., Manes T., Hessle L., Kozlenkov A., Pizauro J.M.,
RA Hoylaerts M.F., Millan J.L.;
RT "Kinetic characterization of hypophosphatasia mutations with physiological
RT substrates.";
RL J. Bone Miner. Res. 17:1383-1391(2002).
RN [38]
RP VARIANTS HOPS LYS-291 AND ARG-326.
RX PubMed=11999978; DOI=10.1023/a:1015121414782;
RA Litmanovitz I., Reish O., Dolfin T., Arnon S., Regev R., Grinshpan G.,
RA Yamazaki M., Ozono K.;
RT "Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline
RT phosphatase gene in neonatal hypophosphatasia associated with
RT convulsions.";
RL J. Inherit. Metab. Dis. 25:35-40(2002).
RN [39]
RP VARIANTS HOPS SER-51; HIS-71; THR-111; MET-128; HIS-134; HIS-136; THR-176;
RP LYS-191; GLN-223; TRP-223; SER-246; ALA-294; PRO-299; PHE-327 DEL; ARG-339;
RP THR-348; VAL-378; MET-414; ASP-426 AND LYS-476, AND VARIANTS HIS-263 AND
RP ALA-522.
RX PubMed=11855933; DOI=10.1006/mgme.2001.3283;
RA Mumm S., Jones J., Finnegan P., Henthorn P.S., Podgornik M.N., Whyte M.P.;
RT "Denaturing gradient gel electrophoresis analysis of the tissue nonspecific
RT alkaline phosphatase isoenzyme gene in hypophosphatasia.";
RL Mol. Genet. Metab. 75:143-153(2002).
RN [40]
RP VARIANTS HOPS VAL-62; ARG-63; THR-111; ILE-148; SER-162; GLU-189; ALA-220;
RP LEU-272; GLY-293-294-ASP DEL; LYS-311; LYS-452 AND THR-468.
RX PubMed=12815606; DOI=10.1002/humu.9159;
RA Spentchian M., Merrien Y., Herasse M., Dobbie Z., Glaeser D., Holder S.E.,
RA Ivarsson S.-A., Kostiner D., Mansour S., Norman A., Roth J., Stipoljev F.,
RA Taillemite J.-L., van der Smagt J.J., Serre J.-L., Simon-Bouy B.,
RA Taillandier A., Mornet E.;
RT "Severe hypophosphatasia: characterization of fifteen novel mutations in
RT the ALPL gene.";
RL Hum. Mutat. 22:105-106(2003).
RN [41]
RP VARIANTS HOPS LEU-108; THR-116 AND MET-414, AND CHARACTERIZATION OF VARIANT
RP HOPS LEU-108.
RX PubMed=12920074; DOI=10.1136/jmg.40.8.605;
RA Herasse M., Spentchian M., Taillandier A., Keppler-Noreuil K.,
RA Fliorito A.N.M., Bergoffen J., Wallerstein R., Muti C., Simon-Bouy B.,
RA Mornet E.;
RT "Molecular study of three cases of odontohypophosphatasia resulting from
RT heterozygosity for mutations in the tissue non-specific alkaline
RT phosphatase gene.";
RL J. Med. Genet. 40:605-609(2003).
RN [42]
RP VARIANT HOPS GLY-114.
RX PubMed=15135428; DOI=10.1016/j.arcped.2004.02.018;
RA Draguet C., Gillerot Y., Mornet E.;
RT "Childhood hypophosphatasia: a case report due to a novel mutation.";
RL Arch. Pediatr. 11:440-443(2004).
RN [43]
RP VARIANTS HOPS VAL-33; HIS-136; GLN-223; TRP-223; HIS-272; THR-292; ALA-294;
RP THR-295; ASP-297; ASP-334 AND ALA-411, AND CHARACTERIZATION OF VARIANTS
RP HOPS VAL-33; HIS-272; THR-292; THR-295; ASP-297 AND ALA-411.
RX PubMed=15694177; DOI=10.1016/j.ymgme.2004.11.003;
RA Brun-Heath I., Taillandier A., Serre J.-L., Mornet E.;
RT "Characterization of 11 novel mutations in the tissue non-specific alkaline
RT phosphatase gene responsible for hypophosphatasia and genotype-phenotype
RT correlations.";
RL Mol. Genet. Metab. 84:273-277(2005).
RN [44]
RP VARIANTS HOPS CYS-71; HIS-71; THR-111; THR-176; LYS-191; ARG-334; ASP-334;
RP ARG-339; ILE-382; CYS-391; HIS-391; MET-414; ALA-420; LYS-452; LEU-459 AND
RP ALA-476, AND CHARACTERIZATION OF VARIANTS HOPS CYS-71; HIS-71; THR-111;
RP THR-176; LYS-191; ARG-334; ASP-334; ARG-339; ILE-382; CYS-391; HIS-391;
RP MET-414; LYS-452; LEU-459 AND ALA-476.
RX PubMed=19500388; DOI=10.1186/1471-2350-10-51;
RA Fauvert D., Brun-Heath I., Lia-Baldini A.S., Bellazi L., Taillandier A.,
RA Serre J.L., de Mazancourt P., Mornet E.;
RT "Mild forms of hypophosphatasia mostly result from dominant negative effect
RT of severe alleles or from compound heterozygosity for severe and moderate
RT alleles.";
RL BMC Med. Genet. 10:51-51(2009).
RN [45]
RP VARIANTS HOPS TYR-201 AND SER-489, AND CHARACTERIZATION OF VARIANTS HOPS
RP TYR-201 AND SER-489.
RX PubMed=22266140; DOI=10.1016/j.bbadis.2012.01.007;
RA Satou Y., Al-Shawafi H.A., Sultana S., Makita S., Sohda M., Oda K.;
RT "Disulfide bonds are critical for tissue-nonspecific alkaline phosphatase
RT function revealed by analysis of mutant proteins bearing a C(201)-Y or
RT C(489)-S substitution associated with severe hypophosphatasia.";
RL Biochim. Biophys. Acta 1822:581-588(2012).
RN [46]
RP CHARACTERIZATION OF VARIANTS HOPS SER-420 AND ALA-420, AND CATALYTIC
RP ACTIVITY.
RX PubMed=23039266; DOI=10.1111/febs.12022;
RA Makita S., Al-Shawafi H.A., Sultana S., Sohda M., Nomura S., Oda K.;
RT "A dimerization defect caused by a glycine substitution at position 420 by
RT serine in tissue-nonspecific alkaline phosphatase associated with perinatal
RT hypophosphatasia.";
RL FEBS J. 279:4327-4337(2012).
RN [47]
RP VARIANTS HOPS CYS-152 AND ASN-440 DEL.
RX PubMed=23791648; DOI=10.1016/j.bone.2013.06.010;
RA Martins L., Rodrigues T.L., Ribeiro M.M., Saito M.T., Giorgetti A.P.,
RA Casati M.Z., Sallum E.A., Foster B.L., Somerman M.J., Nociti F.H. Jr.;
RT "Novel ALPL genetic alteration associated with an odontohypophosphatasia
RT phenotype.";
RL Bone 56:390-397(2013).
RN [48]
RP CHARACTERIZATION OF VARIANT HOPS SER-417, SUBUNIT, SUBCELLULAR LOCATION,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23688511; DOI=10.1016/j.ymgme.2013.04.016;
RA Sultana S., Al-Shawafi H.A., Makita S., Sohda M., Amizuka N., Takagi R.,
RA Oda K.;
RT "An asparagine at position 417 of tissue-nonspecific alkaline phosphatase
RT is essential for its structure and function as revealed by analysis of the
RT N417S mutation associated with severe hypophosphatasia.";
RL Mol. Genet. Metab. 109:282-288(2013).
RN [49]
RP CHARACTERIZATION OF VARIANT HOPS LEU-108, SUBCELLULAR LOCATION, SUBUNIT,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25982064; DOI=10.1016/j.ymgme.2015.05.006;
RA Numa-Kinjoh N., Komaru K., Ishida Y., Sohda M., Oda K.;
RT "Molecular phenotype of tissue-nonspecific alkaline phosphatase with a
RT proline (108) to leucine substitution associated with dominant
RT odontohypophosphatasia.";
RL Mol. Genet. Metab. 115:180-185(2015).
RN [50]
RP VARIANT HOPS PRO-188.
RX PubMed=30083035; DOI=10.1297/cpe.27.179;
RA Oyachi M., Harada D., Sakamoto N., Ueyama K., Kondo K., Kishimoto K.,
RA Izui M., Nagamatsu Y., Kashiwagi H., Yamamuro M., Tamura M., Kikuchi S.,
RA Akiyama T., Michigami T., Seino Y., Namba N.;
RT "A case of perinatal hypophosphatasia with a novel mutation in the ALPL
RT gene: clinical course and review of the literature.";
RL Clin. Pediatr. Endocrinol. 27:179-186(2018).
RN [51]
RP VARIANT HOPS SER-218.
RX PubMed=32983484; DOI=10.1002/ccr3.2962;
RA Bisgin A., Boga I., Cetin C., Buyukkurt S.;
RT "Identification of a novel homozygous variant in the alkaline phosphate
RT (ALPL) gene associated with hypophosphatasia.";
RL Clin. Case Rep. 8:1719-1721(2020).
RN [52]
RP VARIANT HOPS ARG-82, CHARACTERIZATION OF VARIANT HOPS ARG-82, CATALYTIC
RP ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=33821301; DOI=10.1007/s00774-021-01219-0;
RA Kato M., Michigami T., Tachikawa K., Kato M., Yabe I., Shimizu T.,
RA Asaka T., Kitagawa Y., Atsumi T.;
RT "Novel mutation in the ALPL gene with a dominant negative effect in a
RT Japanese family.";
RL J. Bone Miner. Metab. 39:804-809(2021).
CC -!- FUNCTION: Alkaline phosphatase that metabolizes various phosphate
CC compounds and plays a key role in skeletal mineralization and adaptive
CC thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has
CC broad substrate specificity and can hydrolyze a considerable variety of
CC compounds: however, only a few substrates, such as diphosphate
CC (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-
CC phosphocreatine are natural substrates (PubMed:12162492,
CC PubMed:2220817). Plays an essential role in skeletal and dental
CC mineralization via its ability to hydrolyze extracellular diphosphate,
CC a potent mineralization inhibitor, to phosphate: it thereby promotes
CC hydroxyapatite crystal formation and increases inorganic phosphate
CC concentration (PubMed:23688511, PubMed:25982064). Acts in a non-
CC redundant manner with PHOSPHO1 in skeletal mineralization: while
CC PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in
CC the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of
CC hydroxyapatite crystallization in the extracellular matrix (By
CC similarity). Also promotes dephosphorylation of osteopontin (SSP1), an
CC inhibitor of hydroxyapatite crystallization in its phosphorylated
CC state; it is however unclear whether ALPL/TNAP mediates SSP1
CC dephosphorylation via a direct or indirect manner (By similarity).
CC Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable
CC form of vitamin B6, in order to provide a sufficient amount of PLP in
CC the brain, an essential cofactor for enzymes catalyzing the synthesis
CC of diverse neurotransmitters (PubMed:2220817, PubMed:20049532).
CC Additionally, also able to mediate ATP degradation in a stepwise manner
CC to adenosine, thereby regulating the availability of ligands for
CC purinergic receptors (By similarity). Also capable of dephosphorylating
CC microbial products, such as lipopolysaccharides (LPS) as well as other
CC phosphorylated small-molecules, such as poly-inosine:cytosine (poly
CC I:C) (PubMed:28448526). Acts as a key regulator of adaptive
CC thermogenesis as part of the futile creatine cycle: localizes to the
CC mitochondria of thermogenic fat cells and acts by mediating hydrolysis
CC of N-phosphocreatine to initiate a futile cycle of creatine
CC dephosphorylation and phosphorylation (By similarity). During the
CC futile creatine cycle, creatine and N-phosphocreatine are in a futile
CC cycle, which dissipates the high energy charge of N-phosphocreatine as
CC heat without performing any mechanical or chemical work (By
CC similarity). {ECO:0000250|UniProtKB:P09242,
CC ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:20049532,
CC ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23688511,
CC ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:28448526}.
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:12162492, ECO:0000269|PubMed:2220817,
CC ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511,
CC ECO:0000269|PubMed:25775211, ECO:0000269|PubMed:25982064,
CC ECO:0000269|PubMed:33821301};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15018;
CC Evidence={ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817,
CC ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511,
CC ECO:0000269|PubMed:25775211, ECO:0000269|PubMed:25982064,
CC ECO:0000269|PubMed:33821301};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000269|PubMed:12162492};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24577;
CC Evidence={ECO:0000269|PubMed:12162492};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + pyridoxal 5'-phosphate = phosphate + pyridoxal;
CC Xref=Rhea:RHEA:20533, ChEBI:CHEBI:15377, ChEBI:CHEBI:17310,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20534;
CC Evidence={ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + phosphoethanolamine = ethanolamine + phosphate;
CC Xref=Rhea:RHEA:16089, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:58190;
CC Evidence={ECO:0000269|PubMed:2220817};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16090;
CC Evidence={ECO:0000269|PubMed:2220817};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-phosphocreatine = creatine + phosphate;
CC Xref=Rhea:RHEA:12977, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57947, ChEBI:CHEBI:58092; EC=3.9.1.1;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12978;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP + H2O = AMP + H(+) + phosphate; Xref=Rhea:RHEA:61436,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61437;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + H2O = adenosine + phosphate; Xref=Rhea:RHEA:29375,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16335, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29376;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P05187};
CC Note=Binds 1 Mg(2+) ion. {ECO:0000250|UniProtKB:P05187};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:25775211};
CC Note=Binds 2 Zn(2+) ions. {ECO:0000269|PubMed:25775211};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:11395499, ECO:0000269|PubMed:25775211};
CC -!- ACTIVITY REGULATION: Phosphatase activity is specifically inhibited by
CC 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425).
CC {ECO:0000250|UniProtKB:P09242}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23688511,
CC ECO:0000269|PubMed:25982064}.
CC -!- INTERACTION:
CC P05186; Q99558: MAP3K14; NbExp=4; IntAct=EBI-1054354, EBI-358011;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2220817,
CC ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064,
CC ECO:0000269|PubMed:33821301}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064}.
CC Extracellular vesicle membrane {ECO:0000250|UniProtKB:P09242}; Lipid-
CC anchor, GPI-anchor {ECO:0000250|UniProtKB:P09242}. Mitochondrion
CC membrane {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P09242}. Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:P09242}. Note=Localizes to special class of
CC extracellular vesicles, named matrix vesicles (MVs), which are released
CC by osteogenic cells. Localizes to the mitochondria of thermogenic fat
CC cells: tethered to mitochondrial membranes via a GPI-anchor and
CC probably resides in the mitochondrion intermembrane space.
CC {ECO:0000250|UniProtKB:P09242}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P05186-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P05186-2; Sequence=VSP_042711;
CC Name=3;
CC IsoId=P05186-3; Sequence=VSP_044228;
CC -!- DOMAIN: Calcium-binding is structural and does not influence the
CC alkaline phosphatase activity (PubMed:25775211). At very high
CC concentrations, calcium can however substitute for zinc at zinc-binding
CC sites, leading to strongly reduced enzyme activity (PubMed:25775211).
CC {ECO:0000269|PubMed:25775211}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1458595,
CC ECO:0000269|PubMed:19159218}.
CC -!- DISEASE: Hypophosphatasia (HOPS) [MIM:146300]: A metabolic bone disease
CC characterized by defective skeletal mineralization and biochemically by
CC deficient activity of the tissue non-specific isoenzyme of alkaline
CC phosphatase. Four forms are distinguished, depending on the age of
CC onset: perinatal, infantile, childhood and adult type. The perinatal
CC form is the most severe and is almost always fatal. The adult form is
CC mild and characterized by recurrent fractures, osteomalacia, rickets,
CC and loss of teeth. Some cases are asymptomatic, while some patients
CC manifest dental features without skeletal manifestations
CC (odontohypophosphatasia). {ECO:0000269|PubMed:10094560,
CC ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:10679946,
CC ECO:0000269|PubMed:10690885, ECO:0000269|PubMed:10834525,
CC ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:11479741,
CC ECO:0000269|PubMed:11745997, ECO:0000269|PubMed:11760847,
CC ECO:0000269|PubMed:11834095, ECO:0000269|PubMed:11855933,
CC ECO:0000269|PubMed:11999978, ECO:0000269|PubMed:12162492,
CC ECO:0000269|PubMed:12815606, ECO:0000269|PubMed:12920074,
CC ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:15135428,
CC ECO:0000269|PubMed:15694177, ECO:0000269|PubMed:19500388,
CC ECO:0000269|PubMed:20049532, ECO:0000269|PubMed:22266140,
CC ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511,
CC ECO:0000269|PubMed:23791648, ECO:0000269|PubMed:25982064,
CC ECO:0000269|PubMed:30083035, ECO:0000269|PubMed:3174660,
CC ECO:0000269|PubMed:32983484, ECO:0000269|PubMed:33821301,
CC ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8406453,
CC ECO:0000269|PubMed:8954059, ECO:0000269|PubMed:9452105,
CC ECO:0000269|PubMed:9747027, ECO:0000269|PubMed:9781036}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hypophosphatasia, childhood (HPPC) [MIM:241510]: A bone
CC disease characterized by defective skeletal mineralization and
CC biochemically by deficient activity of the tissue non-specific
CC isoenzyme of alkaline phosphatase. {ECO:0000269|PubMed:11760847}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Hypophosphatasia, infantile (HPPI) [MIM:241500]: A severe bone
CC disease characterized by defective skeletal mineralization and
CC biochemically by deficient activity of the tissue non-specific
CC isoenzyme of alkaline phosphatase. Three more or less distinct types of
CC infantile hypophosphatasia can be identified: (1) type 1 with onset in
CC utero or in early postnatal life, craniostenosis, severe skeletal
CC abnormalities, hypercalcemia, and death in the first year or so of
CC life; (2) type 2 with later, more gradual development of symptoms,
CC moderately severe 'rachitic' skeletal changes and premature loss of
CC teeth; (3) type 3 with no symptoms, the condition being determined on
CC routine studies. {ECO:0000269|PubMed:10834525,
CC ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:12162492,
CC ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8954059}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the alkaline phosphatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93051.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=ALPL; Note=Tissue nonspecific alkaline phosphatase
CC gene mutations database;
CC URL="http://wp.hypophosphatasie.com/accueil/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alkaline phosphatase entry;
CC URL="https://en.wikipedia.org/wiki/Alkaline_phosphatase";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Constructive futility
CC - Issue 242 of December 2021;
CC URL="https://web.expasy.org/spotlight/back_issues/242/";
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DR EMBL; M24439; AAB59378.1; -; Genomic_DNA.
DR EMBL; M24429; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24430; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24431; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24432; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24433; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24434; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24435; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24436; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24437; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; M24438; AAB59378.1; JOINED; Genomic_DNA.
DR EMBL; X14174; CAA32376.1; -; mRNA.
DR EMBL; AB011406; BAA32129.1; -; mRNA.
DR EMBL; AK295608; BAH12123.1; -; mRNA.
DR EMBL; AK298085; BAH12722.1; -; mRNA.
DR EMBL; AB209814; BAD93051.1; ALT_INIT; mRNA.
DR EMBL; AL592309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359815; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471134; EAW94977.1; -; Genomic_DNA.
DR EMBL; BC021289; AAH21289.3; -; mRNA.
DR EMBL; BC066116; AAH66116.2; -; mRNA.
DR EMBL; BC090861; AAH90861.2; -; mRNA.
DR EMBL; BC110909; AAI10910.2; -; mRNA.
DR EMBL; BC126165; AAI26166.1; -; mRNA.
DR EMBL; BC136325; AAI36326.1; -; mRNA.
DR CCDS; CCDS217.1; -. [P05186-1]
DR CCDS; CCDS53274.1; -. [P05186-2]
DR CCDS; CCDS53275.1; -. [P05186-3]
DR PIR; S03613; PAHUH.
DR RefSeq; NP_000469.3; NM_000478.5. [P05186-1]
DR RefSeq; NP_001120973.2; NM_001127501.3. [P05186-3]
DR RefSeq; NP_001170991.1; NM_001177520.2. [P05186-2]
DR RefSeq; XP_005245875.1; XM_005245818.1.
DR RefSeq; XP_006710609.1; XM_006710546.2.
DR AlphaFoldDB; P05186; -.
DR SMR; P05186; -.
DR BioGRID; 106750; 28.
DR IntAct; P05186; 11.
DR MINT; P05186; -.
DR STRING; 9606.ENSP00000363973; -.
DR BindingDB; P05186; -.
DR ChEMBL; CHEMBL5979; -.
DR DrugBank; DB01143; Amifostine.
DR DrugBank; DB09338; Mersalyl.
DR DrugBank; DB00165; Pyridoxine.
DR DrugBank; DB09498; Strontium chloride Sr-89.
DR DrugCentral; P05186; -.
DR DEPOD; ALPL; -.
DR GlyConnect; 1916; 7 N-Linked glycans (2 sites).
DR GlyGen; P05186; 9 sites, 7 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P05186; -.
DR PhosphoSitePlus; P05186; -.
DR BioMuta; ALPL; -.
DR DMDM; 68067533; -.
DR EPD; P05186; -.
DR jPOST; P05186; -.
DR MassIVE; P05186; -.
DR MaxQB; P05186; -.
DR PaxDb; P05186; -.
DR PeptideAtlas; P05186; -.
DR PRIDE; P05186; -.
DR ProteomicsDB; 51821; -. [P05186-1]
DR ProteomicsDB; 51822; -. [P05186-2]
DR ProteomicsDB; 6645; -.
DR ABCD; P05186; 4 sequenced antibodies.
DR Antibodypedia; 2059; 1078 antibodies from 43 providers.
DR DNASU; 249; -.
DR Ensembl; ENST00000374832.5; ENSP00000363965.1; ENSG00000162551.14. [P05186-1]
DR Ensembl; ENST00000374840.8; ENSP00000363973.3; ENSG00000162551.14. [P05186-1]
DR Ensembl; ENST00000539907.5; ENSP00000437674.1; ENSG00000162551.14. [P05186-2]
DR Ensembl; ENST00000540617.5; ENSP00000442672.1; ENSG00000162551.14. [P05186-3]
DR GeneID; 249; -.
DR KEGG; hsa:249; -.
DR MANE-Select; ENST00000374840.8; ENSP00000363973.3; NM_000478.6; NP_000469.3.
DR UCSC; uc001bet.4; human. [P05186-1]
DR CTD; 249; -.
DR DisGeNET; 249; -.
DR GeneCards; ALPL; -.
DR GeneReviews; ALPL; -.
DR HGNC; HGNC:438; ALPL.
DR HPA; ENSG00000162551; Tissue enhanced (adrenal).
DR MalaCards; ALPL; -.
DR MIM; 146300; phenotype.
DR MIM; 171760; gene.
DR MIM; 241500; phenotype.
DR MIM; 241510; phenotype.
DR neXtProt; NX_P05186; -.
DR OpenTargets; ENSG00000162551; -.
DR Orphanet; 247676; Adult hypophosphatasia.
DR Orphanet; 247667; Childhood-onset hypophosphatasia.
DR Orphanet; 247651; Infantile hypophosphatasia.
DR Orphanet; 247685; Odontohypophosphatasia.
DR Orphanet; 247623; Perinatal lethal hypophosphatasia.
DR Orphanet; 247638; Prenatal benign hypophosphatasia.
DR PharmGKB; PA24729; -.
DR VEuPathDB; HostDB:ENSG00000162551; -.
DR eggNOG; KOG4126; Eukaryota.
DR GeneTree; ENSGT00950000183063; -.
DR HOGENOM; CLU_008539_4_0_1; -.
DR InParanoid; P05186; -.
DR OMA; RIMSKGM; -.
DR PhylomeDB; P05186; -.
DR TreeFam; TF323513; -.
DR BRENDA; 3.1.3.1; 2681.
DR PathwayCommons; P05186; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SABIO-RK; P05186; -.
DR SignaLink; P05186; -.
DR SIGNOR; P05186; -.
DR BioGRID-ORCS; 249; 4 hits in 1068 CRISPR screens.
DR ChiTaRS; ALPL; human.
DR GeneWiki; ALPL; -.
DR GenomeRNAi; 249; -.
DR Pharos; P05186; Tchem.
DR PRO; PR:P05186; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P05186; protein.
DR Bgee; ENSG00000162551; Expressed in right adrenal gland and 127 other tissues.
DR ExpressionAtlas; P05186; baseline and differential.
DR Genevisible; P05186; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043262; F:adenosine-diphosphatase activity; IEA:RHEA.
DR GO; GO:0004035; F:alkaline phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004427; F:inorganic diphosphatase activity; IEA:RHEA.
DR GO; GO:0050187; F:phosphoamidase activity; ISS:UniProtKB.
DR GO; GO:0052732; F:phosphoethanolamine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0033883; F:pyridoxal phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016462; F:pyrophosphatase activity; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; IDA:MGI.
DR GO; GO:0019725; P:cellular homeostasis; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0071529; P:cementum mineralization; IEA:Ensembl.
DR GO; GO:0016311; P:dephosphorylation; IBA:GO_Central.
DR GO; GO:0003006; P:developmental process involved in reproduction; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0010259; P:multicellular organism aging; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB.
DR GO; GO:0055062; P:phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:UniProtKB.
DR GO; GO:0042822; P:pyridoxal phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:1904383; P:response to sodium phosphate; IEA:Ensembl.
DR GO; GO:0034516; P:response to vitamin B6; IEA:Ensembl.
DR GO; GO:0033280; P:response to vitamin D; IEP:BHF-UCL.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
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 Alternative splicing; Biomineralization; Calcium; Cell membrane;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Mitochondrion; Phosphoprotein; Reference proteome; Signal; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:1458595,
FT ECO:0000269|PubMed:3954357"
FT CHAIN 18..501
FT /note="Alkaline phosphatase, tissue-nonspecific isozyme"
FT /id="PRO_0000024023"
FT PROPEP 502..524
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000024024"
FT ACT_SITE 110
FT /note="Phosphoserine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P05187,
FT ECO:0000255|PROSITE-ProRule:PRU10042"
FT BINDING 60
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:11395499"
FT BINDING 290
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:11395499"
FT BINDING 291
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:11395499"
FT BINDING 306
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:11395499"
FT BINDING 332
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 379
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 454
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09242"
FT LIPID 501
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 430
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 139..201
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT DISULFID 489..497
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT VAR_SEQ 1..99
FT /note="MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAK
FT NVIMFLGDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSK -> MPWSFRSS
FT TPTWLRMSSCSWEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042711"
FT VAR_SEQ 1..55
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044228"
FT VARIANT 17
FT /note="S -> F (in HOPS)"
FT /evidence="ECO:0000269|PubMed:9781036"
FT /id="VAR_025903"
FT VARIANT 28
FT /note="Y -> C (in HPPI; 7% of activity)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013972"
FT VARIANT 33
FT /note="A -> V (in HOPS; strongly reduced alkaline
FT phosphatase activity; dbSNP:rs121918005)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:15694177"
FT /id="VAR_006147"
FT VARIANT 40
FT /note="A -> V (in HOPS; 2% of activity; dbSNP:rs770093969)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:10679946, ECO:0000269|PubMed:11438998,
FT ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:9781036"
FT /id="VAR_011081"
FT VARIANT 51
FT /note="A -> S (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11855933"
FT /id="VAR_025904"
FT VARIANT 51
FT /note="A -> V (in HOPS; dbSNP:rs1470389268)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013973"
FT VARIANT 62
FT /note="M -> L (in HOPS; moderate; 27% of activity)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035"
FT /id="VAR_006148"
FT VARIANT 62
FT /note="M -> V (in HOPS)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025905"
FT VARIANT 63
FT /note="G -> R (in HOPS)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025906"
FT VARIANT 63
FT /note="G -> V (in HOPS; loss of activity)"
FT /evidence="ECO:0000269|PubMed:11479741"
FT /id="VAR_013974"
FT VARIANT 68
FT /note="T -> M (in HPPC; severe allele)"
FT /evidence="ECO:0000269|PubMed:11760847"
FT /id="VAR_025907"
FT VARIANT 71
FT /note="R -> C (in HOPS; abolished alkaline phosphatase
FT activity; dbSNP:rs121918001)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:19500388"
FT /id="VAR_006149"
FT VARIANT 71
FT /note="R -> H (in HOPS; loss of alkaline phosphatase
FT activity; dbSNP:rs121918003)"
FT /evidence="ECO:0000269|PubMed:11438998,
FT ECO:0000269|PubMed:11855933, ECO:0000269|PubMed:19500388"
FT /id="VAR_013975"
FT VARIANT 71
FT /note="R -> P (in HOPS; abolished alkaline phosphatase
FT activity; dbSNP:rs121918003)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:1409720"
FT /id="VAR_006150"
FT VARIANT 71
FT /note="R -> S (in HPPC; severe allele; dbSNP:rs121918001)"
FT /evidence="ECO:0000269|PubMed:11760847"
FT /id="VAR_025908"
FT VARIANT 75
FT /note="G -> S (in HOPS; severe; 3.5% of activity;
FT dbSNP:rs1304394441)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013976"
FT VARIANT 76
FT /note="Q -> R (in HOPS; dbSNP:rs1057521085)"
FT /id="VAR_025909"
FT VARIANT 82
FT /note="G -> R (in HOPS; dominant-negative mutant; abolished
FT alkaline phosphatase activity)"
FT /evidence="ECO:0000269|PubMed:33821301"
FT /id="VAR_085155"
FT VARIANT 108
FT /note="P -> L (in HOPS; 0.4% of alkaline phosphatase
FT activity; severe allele; no effect on subcellular location;
FT fails to assemble into dimeric structure; dominant negative
FT effect; dbSNP:rs121918015)"
FT /evidence="ECO:0000269|PubMed:12920074,
FT ECO:0000269|PubMed:25982064"
FT /id="VAR_025910"
FT VARIANT 111
FT /note="A -> T (in HOPS; odonto; abolished alkaline
FT phosphatase activity; dbSNP:rs773257111)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:10679946, ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:12815606,
FT ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:9452105"
FT /id="VAR_006151"
FT VARIANT 114
FT /note="A -> G (in HOPS)"
FT /evidence="ECO:0000269|PubMed:15135428"
FT /id="VAR_025911"
FT VARIANT 116
FT /note="A -> T (in HOPS; loss of alkaline phosphatase
FT activity; dbSNP:rs121918013)"
FT /evidence="ECO:0000269|PubMed:11438998,
FT ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:12920074,
FT ECO:0000269|PubMed:25982064"
FT /id="VAR_013977"
FT VARIANT 120
FT /note="G -> R (in HOPS; dbSNP:rs954135116)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013978"
FT VARIANT 128
FT /note="V -> M (in HOPS; dbSNP:rs1159854007)"
FT /evidence="ECO:0000269|PubMed:11855933"
FT /id="VAR_025912"
FT VARIANT 129
FT /note="G -> R (in HOPS)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013979"
FT VARIANT 132
FT /note="A -> V (in HOPS; strongly reduced alkaline
FT phosphatase activity)"
FT /evidence="ECO:0000269|PubMed:11834095,
FT ECO:0000269|PubMed:12162492"
FT /id="VAR_013146"
FT VARIANT 134
FT /note="T -> H (in HOPS; requires 2 nucleotide
FT substitutions; dbSNP:rs786204530)"
FT /evidence="ECO:0000269|PubMed:11855933"
FT /id="VAR_025913"
FT VARIANT 134
FT /note="T -> N (in HOPS; 9% of activity; dbSNP:rs780583917)"
FT /evidence="ECO:0000269|PubMed:10679946"
FT /id="VAR_011082"
FT VARIANT 136
FT /note="R -> H (in HOPS; moderate; 33% of activity;
FT dbSNP:rs121918011)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:11438998,
FT ECO:0000269|PubMed:11855933, ECO:0000269|PubMed:15694177"
FT /id="VAR_006152"
FT VARIANT 148
FT /note="T -> I (in HOPS; dbSNP:rs1376937780)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025914"
FT VARIANT 152
FT /note="R -> C (in HOPS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23791648"
FT /id="VAR_085156"
FT VARIANT 152
FT /note="R -> H (in HOPS; lethal form; benign variant;
FT dbSNP:rs149344982)"
FT /evidence="ECO:0000269|PubMed:11438998, ECO:0000269|Ref.6"
FT /id="VAR_013980"
FT VARIANT 162
FT /note="G -> S (in HOPS; dbSNP:rs760029254)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025915"
FT VARIANT 162
FT /note="G -> V (in HOPS; severe; 1% of activity;
FT dbSNP:rs121918012)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035"
FT /id="VAR_006153"
FT VARIANT 170
FT /note="N -> D (in HOPS)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013981"
FT VARIANT 171
FT /note="H -> R (in HOPS; dbSNP:rs778232217)"
FT /id="VAR_025916"
FT VARIANT 171
FT /note="H -> Y (in HOPS; severe; 2% of activity)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035"
FT /id="VAR_006154"
FT VARIANT 176
FT /note="A -> T (in HOPS; 30% of alkaline phosphatase
FT activity; dbSNP:rs121918019)"
FT /evidence="ECO:0000269|PubMed:10679946,
FT ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:19500388"
FT /id="VAR_011083"
FT VARIANT 177
FT /note="A -> T (in HOPS and HPPC; moderate allele; normal
FT alkaline phosphatase activity toward diphosphate and
FT increased activity toward pyridoxal 5'-phosphate;
FT dbSNP:rs199669988)"
FT /evidence="ECO:0000269|PubMed:11760847,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:9452105"
FT /id="VAR_006155"
FT VARIANT 179
FT /note="A -> T (in HOPS; reduced alkaline phosphatase
FT activity toward diphosphate and pyridoxal 5'-phosphate;
FT dbSNP:rs121918000)"
FT /evidence="ECO:0000269|PubMed:11438998,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:3174660"
FT /id="VAR_006156"
FT VARIANT 181
FT /note="S -> L (in HOPS; 1% of activity; dbSNP:rs199590449)"
FT /evidence="ECO:0000269|PubMed:11479741"
FT /id="VAR_013982"
FT VARIANT 184
FT /note="R -> W (in HOPS; loss of activity;
FT dbSNP:rs763159520)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:9781036"
FT /id="VAR_013983"
FT VARIANT 188
FT /note="S -> P (in HOPS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:30083035"
FT /id="VAR_085157"
FT VARIANT 189
FT /note="D -> E (in HOPS)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025917"
FT VARIANT 191
FT /note="E -> G (in HOPS; odonto; slightly reduced alkaline
FT phosphatase activity)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:9452105"
FT /id="VAR_006157"
FT VARIANT 191
FT /note="E -> K (in HOPS; moderate; frequent mutation in
FT European countries; slightly reduced alkaline phosphatase
FT activity; dbSNP:rs121918007)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:10679946,
FT ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:1409720,
FT ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:9781036"
FT /id="VAR_006158"
FT VARIANT 201
FT /note="C -> Y (in HOPS; weak alkaline phosphatase activity;
FT severely affects homodimerization; reduced cell surface
FT expression)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10679946, ECO:0000269|PubMed:22266140"
FT /id="VAR_006159"
FT VARIANT 207
FT /note="Q -> P (in HOPS; dbSNP:rs121918004)"
FT /evidence="ECO:0000269|PubMed:1409720"
FT /id="VAR_006160"
FT VARIANT 211
FT /note="N -> D (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013984"
FT VARIANT 212
FT /note="I -> F (in HOPS)"
FT /id="VAR_025918"
FT VARIANT 218
FT /note="I -> S (in HOPS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:32983484"
FT /id="VAR_085158"
FT VARIANT 220
FT /note="G -> A (in HOPS)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025919"
FT VARIANT 220
FT /note="G -> V (in HOPS; odonto)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013985"
FT VARIANT 223
FT /note="R -> Q (in HOPS; dbSNP:rs199665722)"
FT /evidence="ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:15694177"
FT /id="VAR_025920"
FT VARIANT 223
FT /note="R -> W (in HOPS and HPPC; severe allele; abolished
FT alkaline phosphatase activity; dbSNP:rs766076920)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:11760847,
FT ECO:0000269|PubMed:11855933, ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:15694177, ECO:0000269|PubMed:9781036"
FT /id="VAR_013986"
FT VARIANT 224
FT /note="K -> E (in HPPI; partial loss of activity;
FT dbSNP:rs1226800998)"
FT /evidence="ECO:0000269|PubMed:10834525"
FT /id="VAR_011084"
FT VARIANT 235
FT /note="E -> G (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013987"
FT VARIANT 246
FT /note="R -> S (in HOPS; 4% of activity;
FT dbSNP:rs1223142821)"
FT /evidence="ECO:0000269|PubMed:10679946,
FT ECO:0000269|PubMed:11855933"
FT /id="VAR_011085"
FT VARIANT 249
FT /note="G -> V (in HOPS; partial loss of activity;
FT dbSNP:rs121918018)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:11479741"
FT /id="VAR_013988"
FT VARIANT 263
FT /note="Y -> H (in dbSNP:rs3200254)"
FT /evidence="ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2928120, ECO:0000269|PubMed:9781036"
FT /id="VAR_006161"
FT VARIANT 272
FT /note="R -> H (in HOPS; 6.8% of wild-type activity;
FT dbSNP:rs781272386)"
FT /evidence="ECO:0000269|PubMed:15694177"
FT /id="VAR_025921"
FT VARIANT 272
FT /note="R -> L (in HOPS; dbSNP:rs781272386)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025922"
FT VARIANT 275
FT /note="L -> P (in HPPC; severe allele; dbSNP:rs1237252052)"
FT /evidence="ECO:0000269|PubMed:11760847"
FT /id="VAR_025923"
FT VARIANT 289
FT /note="L -> F (in HOPS)"
FT /evidence="ECO:0000269|PubMed:9747027"
FT /id="VAR_006162"
FT VARIANT 291
FT /note="E -> K (in HOPS; moderate; 8% of activity;
FT dbSNP:rs786204473)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:11999978, ECO:0000269|PubMed:9781036"
FT /id="VAR_013989"
FT VARIANT 292
FT /note="P -> T (in HOPS; 4% of wild-type activity;
FT dbSNP:rs765458125)"
FT /evidence="ECO:0000269|PubMed:15694177"
FT /id="VAR_025924"
FT VARIANT 293..294
FT /note="Missing (in HOPS)"
FT /id="VAR_025925"
FT VARIANT 294
FT /note="D -> A (in HOPS; reduced alkaline phosphatase toward
FT diphosphate and pyridoxal 5'-phosphate; dbSNP:rs121918002)"
FT /evidence="ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:1409720,
FT ECO:0000269|PubMed:15694177"
FT /id="VAR_006163"
FT VARIANT 294
FT /note="D -> Y (in HOPS; dbSNP:rs1553414079)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013990"
FT VARIANT 295
FT /note="M -> T (in HOPS; 8.5% of wild-type activity;
FT dbSNP:rs1220125702)"
FT /evidence="ECO:0000269|PubMed:15694177"
FT /id="VAR_025926"
FT VARIANT 297
FT /note="Y -> D (in HOPS; 1.3% of wild-type activity)"
FT /evidence="ECO:0000269|PubMed:15694177"
FT /id="VAR_025927"
FT VARIANT 298
FT /note="E -> K (in HPPI; does not affect alkaline
FT phosphatase activity; dbSNP:rs121918017)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:7833929"
FT /id="VAR_025928"
FT VARIANT 299
FT /note="L -> P (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11855933"
FT /id="VAR_025929"
FT VARIANT 306
FT /note="D -> V (in HOPS)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035"
FT /id="VAR_006164"
FT VARIANT 311
FT /note="E -> K (in HOPS; dbSNP:rs763457259)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025930"
FT VARIANT 326
FT /note="G -> R (in HOPS; in a patient carrying also K-291)"
FT /evidence="ECO:0000269|PubMed:11999978"
FT /id="VAR_013991"
FT VARIANT 327
FT /note="F -> G (in HOPS; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013992"
FT VARIANT 327
FT /note="F -> L (in HOPS and HPPI; dbSNP:rs121918010)"
FT /evidence="ECO:0000269|PubMed:8954059,
FT ECO:0000269|PubMed:9452105"
FT /id="VAR_006165"
FT VARIANT 327
FT /note="Missing (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11855933"
FT /id="VAR_025931"
FT VARIANT 334
FT /note="G -> D (in HOPS; abolished alkaline phosphatase
FT activity; dbSNP:rs121918009)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:15694177,
FT ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:8406453,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_006166"
FT VARIANT 334
FT /note="G -> R (in HOPS; weak alkaline phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19500388"
FT /id="VAR_075557"
FT VARIANT 339
FT /note="G -> R (in HOPS; loss of alkaline phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:19500388"
FT /id="VAR_025932"
FT VARIANT 348
FT /note="A -> T (in HOPS; dbSNP:rs1553414563)"
FT /evidence="ECO:0000269|PubMed:10679946,
FT ECO:0000269|PubMed:11855933"
FT /id="VAR_011086"
FT VARIANT 354
FT /note="E -> D (in HOPS; dbSNP:rs1553414568)"
FT /id="VAR_025933"
FT VARIANT 378
FT /note="D -> V (in HOPS; strongly reduced alkaline
FT phosphatase activity; dbSNP:rs121918008)"
FT /evidence="ECO:0000269|PubMed:10690885,
FT ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:1409720"
FT /id="VAR_006167"
FT VARIANT 381
FT /note="H -> R (in HOPS)"
FT /evidence="ECO:0000269|PubMed:10679946"
FT /id="VAR_011087"
FT VARIANT 382
FT /note="V -> I (in HOPS; abolished alkaline phosphatase
FT activity; dbSNP:rs771540767)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:9452105"
FT /id="VAR_006168"
FT VARIANT 391
FT /note="R -> C (in HOPS; moderate; 4-10% of alkaline
FT phosphatase activity; dbSNP:rs371243939)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:19500388"
FT /id="VAR_013993"
FT VARIANT 391
FT /note="R -> H (in HPPC and HOPS; severe allele; loss of
FT alkaline phosphatase activity; dbSNP:rs1442918125)"
FT /evidence="ECO:0000269|PubMed:11760847,
FT ECO:0000269|PubMed:19500388"
FT /id="VAR_025934"
FT VARIANT 399
FT /note="A -> S (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013994"
FT VARIANT 406
FT /note="D -> G (in HOPS; 15% of activity)"
FT /evidence="ECO:0000269|PubMed:10679946"
FT /id="VAR_011088"
FT VARIANT 411
FT /note="T -> A (in HOPS; absence of residual enzymatic
FT activity)"
FT /evidence="ECO:0000269|PubMed:15694177"
FT /id="VAR_025935"
FT VARIANT 414
FT /note="L -> M (in HOPS; loss of alkaline phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:11855933,
FT ECO:0000269|PubMed:12920074, ECO:0000269|PubMed:19500388"
FT /id="VAR_025936"
FT VARIANT 417
FT /note="N -> S (in HOPS; very low alkaline phosphatase
FT activity; does not affect subcellular location; fails to
FT assemble into dimeric structure; dbSNP:rs121918014)"
FT /evidence="ECO:0000269|PubMed:11745997,
FT ECO:0000269|PubMed:23688511"
FT /id="VAR_025937"
FT VARIANT 420
FT /note="G -> A (in HOPS; very low alkaline phosphatase
FT activity; does not affect subcellular location)"
FT /evidence="ECO:0000269|PubMed:19500388,
FT ECO:0000269|PubMed:23039266"
FT /id="VAR_075558"
FT VARIANT 420
FT /note="G -> S (in HOPS; very low alkaline phosphatase
FT activity; does not affect subcellular location)"
FT /evidence="ECO:0000269|PubMed:23039266"
FT /id="VAR_075559"
FT VARIANT 423
FT /note="V -> A (in HOPS; 16% alkaline of phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:11438998,
FT ECO:0000269|PubMed:23039266"
FT /id="VAR_013995"
FT VARIANT 426
FT /note="G -> C (in HPPI; partial loss of activity)"
FT /evidence="ECO:0000269|PubMed:10834525"
FT /id="VAR_011089"
FT VARIANT 426
FT /note="G -> D (in HOPS)"
FT /evidence="ECO:0000269|PubMed:11855933"
FT /id="VAR_025938"
FT VARIANT 436
FT /note="Y -> H (in HOPS; dbSNP:rs121918006)"
FT /evidence="ECO:0000269|PubMed:1409720"
FT /id="VAR_006169"
FT VARIANT 440
FT /note="Missing (in HOPS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23791648"
FT /id="VAR_085159"
FT VARIANT 445
FT /note="S -> P (in HOPS; severe; 2% of activity;
FT dbSNP:rs1553415041)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013996"
FT VARIANT 450
FT /note="R -> C (in HOPS; severe; 4% of activity;
FT dbSNP:rs138690664)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013997"
FT VARIANT 450
FT /note="R -> H (in HOPS; dbSNP:rs150799088)"
FT /evidence="ECO:0000269|PubMed:10679946"
FT /id="VAR_011090"
FT VARIANT 452
FT /note="E -> K (in HOPS; loss of alkaline phosphatase
FT activity; dbSNP:rs966212736)"
FT /evidence="ECO:0000269|PubMed:12815606,
FT ECO:0000269|PubMed:19500388"
FT /id="VAR_025939"
FT VARIANT 456
FT /note="G -> R (in HPPI and HOPS; strongly reduced alkaline
FT phosphatase activity; dbSNP:rs121918016)"
FT /evidence="ECO:0000269|PubMed:12162492,
FT ECO:0000269|PubMed:8954059"
FT /id="VAR_011091"
FT VARIANT 459
FT /note="V -> L (in HOPS; loss of alkaline phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19500388"
FT /id="VAR_075560"
FT VARIANT 459
FT /note="V -> M (in HPPI; dbSNP:rs1054159992)"
FT /evidence="ECO:0000269|PubMed:11438998"
FT /id="VAR_013998"
FT VARIANT 468
FT /note="A -> T (in HOPS; dbSNP:rs1196976671)"
FT /evidence="ECO:0000269|PubMed:12815606"
FT /id="VAR_025940"
FT VARIANT 473
FT /note="G -> S (in HOPS)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_013999"
FT VARIANT 476
FT /note="E -> A (in HOPS; loss of alkaline phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19500388"
FT /id="VAR_075561"
FT VARIANT 476
FT /note="E -> K (in HOPS)"
FT /evidence="ECO:0000269|PubMed:10094560,
FT ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:11855933"
FT /id="VAR_006170"
FT VARIANT 478
FT /note="N -> I (in HOPS; 9% of activity)"
FT /evidence="ECO:0000269|PubMed:10679946,
FT ECO:0000269|PubMed:11479741"
FT /id="VAR_011092"
FT VARIANT 489
FT /note="C -> S (in HOPS; reduces alkaline phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:10679946,
FT ECO:0000269|PubMed:22266140"
FT /id="VAR_011093"
FT VARIANT 490
FT /note="I -> F (in HOPS; odonto; partial loss of activity)"
FT /evidence="ECO:0000269|PubMed:11479741"
FT /id="VAR_014000"
FT VARIANT 491
FT /note="G -> R (in HOPS; dbSNP:rs1413274209)"
FT /evidence="ECO:0000269|PubMed:10332035,
FT ECO:0000269|PubMed:9781036"
FT /id="VAR_014001"
FT VARIANT 522
FT /note="V -> A (in dbSNP:rs34605986)"
FT /evidence="ECO:0000269|PubMed:10690885,
FT ECO:0000269|PubMed:11760847, ECO:0000269|PubMed:11855933"
FT /id="VAR_011094"
FT MUTAGEN 235
FT /note="E->A: Abolished alkaline phosphatase activity."
FT /evidence="ECO:0000269|PubMed:25775211"
FT MUTAGEN 270
FT /note="W->A: Reduced alkaline phosphatase activity."
FT /evidence="ECO:0000269|PubMed:25775211"
FT MUTAGEN 272
FT /note="R->A: Reduced alkaline phosphatase activity."
FT /evidence="ECO:0000269|PubMed:25775211"
FT MUTAGEN 290
FT /note="F->A: Abolished alkaline phosphatase activity."
FT /evidence="ECO:0000269|PubMed:25775211"
FT MUTAGEN 291
FT /note="E->A: Reduced alkaline phosphatase activity."
FT /evidence="ECO:0000269|PubMed:25775211"
FT MUTAGEN 306
FT /note="D->A: Abolished alkaline phosphatase activity."
FT /evidence="ECO:0000269|PubMed:25775211"
FT CONFLICT 29
FT /note="W -> A (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="N -> K (in Ref. 3; CAA32376)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="Q -> H (in Ref. 1; BAA32129)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="A -> P (in Ref. 1; BAA32129)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 524 AA; 57305 MW; 71B45F17F6211900 CRC64;
MISPFLVLAI GTCLTNSLVP EKEKDPKYWR DQAQETLKYA LELQKLNTNV AKNVIMFLGD
GMGVSTVTAA RILKGQLHHN PGEETRLEMD KFPFVALSKT YNTNAQVPDS AGTATAYLCG
VKANEGTVGV SAATERSRCN TTQGNEVTSI LRWAKDAGKS VGIVTTTRVN HATPSAAYAH
SADRDWYSDN EMPPEALSQG CKDIAYQLMH NIRDIDVIMG GGRKYMYPKN KTDVEYESDE
KARGTRLDGL DLVDTWKSFK PRYKHSHFIW NRTELLTLDP HNVDYLLGLF EPGDMQYELN
RNNVTDPSLS EMVVVAIQIL RKNPKGFFLL VEGGRIDHGH HEGKAKQALH EAVEMDRAIG
QAGSLTSSED TLTVVTADHS HVFTFGGYTP RGNSIFGLAP MLSDTDKKPF TAILYGNGPG
YKVVGGEREN VSMVDYAHNN YQAQSAVPLR HETHGGEDVA VFSKGPMAHL LHGVHEQNYV
PHVMAYAACI GANLGHCAPA SSAGSLAAGP LLLALALYPL SVLF
