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 27-MAR-2024, entry version 247. 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; 293-GLY-ASP-294 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 -!- 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7YIV; X-ray; 3.18 A; A/B/C/D/E/F/G/H=18-500. DR PDB; 7YIW; X-ray; 2.89 A; A/B/C/D/E/F/G/H=18-500. DR PDB; 7YIX; EM; 2.96 A; A/B=18-500. DR PDBsum; 7YIV; -. DR PDBsum; 7YIW; -. DR PDBsum; 7YIX; -. DR AlphaFoldDB; P05186; -. DR EMDB; EMD-33865; -. DR SMR; P05186; -. DR BioGRID; 106750; 29. DR IntAct; P05186; 9. 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 GlyCosmos; P05186; 6 sites, 8 glycans. DR GlyGen; P05186; 10 sites, 7 N-linked glycans (2 sites), 1 O-linked glycan (2 sites). 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; 9606-ENSP00000363973; -. DR PeptideAtlas; P05186; -. DR ProteomicsDB; 51821; -. [P05186-1] DR ProteomicsDB; 51822; -. [P05186-2] DR ProteomicsDB; 6645; -. DR Pumba; P05186; -. DR ABCD; P05186; 4 sequenced antibodies. DR Antibodypedia; 2059; 1198 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 AGR; HGNC:438; -. 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; LRYETHG; -. DR OrthoDB; 35876at2759; -. 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; 5 hits in 1161 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 129 other cell types or tissues. DR ExpressionAtlas; P05186; baseline and differential. 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:0098552; C:side of membrane; IEA:UniProtKB-KW. DR GO; GO:0043262; F:ADP phosphatase 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 diphosphate phosphatase 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:0140651; P:futile creatine cycle; IEA:Ensembl. DR GO; GO:0140928; P:inhibition of non-skeletal tissue mineralization; 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:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0036005; P:response to macrophage colony-stimulating factor; 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; Alkaline Phosphatase, subunit A; 1. DR InterPro; IPR001952; Alkaline_phosphatase. DR InterPro; IPR018299; Alkaline_phosphatase_AS. DR InterPro; IPR017850; Alkaline_phosphatase_core_sf. DR PANTHER; PTHR11596; ALKALINE PHOSPHATASE; 1. DR PANTHER; PTHR11596:SF74; ALKALINE PHOSPHATASE, TISSUE-NONSPECIFIC ISOZYME; 1. DR Pfam; PF00245; Alk_phosphatase; 1. DR PRINTS; PR00113; ALKPHPHTASE. DR SMART; SM00098; alkPPc; 1. DR SUPFAM; SSF53649; Alkaline phosphatase-like; 1. DR PROSITE; PS00123; ALKALINE_PHOSPHATASE; 1. DR Genevisible; P05186; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Biomineralization; Calcium; KW Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; KW Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Magnesium; Membrane; KW Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome; Signal; KW 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:23791648" FT /id="VAR_085156" FT VARIANT 152 FT /note="R -> H (in HOPS; benign; lethal form; 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; uncertain 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; uncertain 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; uncertain 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 //