Reviewed,
UniProtKB/Swiss-Prot P05186 (PPBT_HUMAN)
Last modified
November 3, 2009.
Version 129.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Alkaline phosphatase, tissue-nonspecific isozyme EC=3.1.3.1 Alternative name(s): AP-TNAP TNSALP Alkaline phosphatase liver/bone/kidney isozyme | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 524 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | This isozyme may play a role in skeletal mineralization. |
| Catalytic activity | A phosphate monoester + H2O = an alcohol + phosphate. |
| Cofactor | Binds 1 magnesium ion By similarity. Binds 2 zinc ions By similarity. |
| Subunit structure | Homodimer. |
| Subcellular location | |
| Post-translational modification | |
| Involvement in disease | Defects in ALPL are a cause of hypophosphatasia infantile (hypophosphatasia) [MIM:241500]; an inherited metabolic bone disease characterized by defective skeletal mineralization. Four hypophosphatasia forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. Patients with only premature loss of deciduous teeth, but with no bone disease are regarded as having odontohypophosphatasia (odonto). Defects in ALPL are a cause of hypophosphatasia childhood (hypophosphatasia) [MIM:241510]. Defects in ALPL are a cause of hypophosphatasia adult type (hypophosphatasia) [MIM:146300]. |
| Miscellaneous | In most mammals there are four different isozymes: placental, placental-like, intestinal and tissue non-specific (liver/bone/kidney). |
| Sequence similarities | Belongs to the alkaline phosphatase family. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 17 | 17 | Ref.9 Ref.8 | ||||||
| Chain | 18 – 502 | 485 | Alkaline phosphatase, tissue-nonspecific isozyme | PRO_0000024023 | |||||
| Propeptide | 503 – 524 | 22 | Removed in mature form Probable | PRO_0000024024 | |||||
Sites | |||||||||
| Active site | 110 | 1 | Phosphoserine intermediate | ||||||
| Metal binding | 60 | 1 | Magnesium Potential | ||||||
| Metal binding | 60 | 1 | Zinc 2 Potential | ||||||
| Metal binding | 173 | 1 | Magnesium Potential | ||||||
| Metal binding | 332 | 1 | Magnesium Potential | ||||||
| Metal binding | 337 | 1 | Zinc 1 Potential | ||||||
| Metal binding | 341 | 1 | Zinc 1 Potential | ||||||
| Metal binding | 378 | 1 | Zinc 2 Potential | ||||||
| Metal binding | 379 | 1 | Zinc 2 Potential | ||||||
| Metal binding | 454 | 1 | Zinc 1 Potential | ||||||
Amino acid modifications | |||||||||
| Lipidation | 502 | 1 | GPI-anchor amidated serine Probable | ||||||
| Glycosylation | 140 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 230 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 271 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 303 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 430 | 1 | N-linked (GlcNAc...) Ref.12 | ||||||
Natural variations | |||||||||
| Natural variant | 17 | 1 | S → F in hypophosphatasia. Ref.18 | VAR_025903 | |||||
| Natural variant | 28 | 1 | Y → C in hypophosphatasia; infantile; 7% of activity. Ref.27 | VAR_013972 | |||||
| Natural variant | 33 | 1 | A → V in hypophosphatasia; 7.2% of wild-type activity. Ref.14 Ref.35 | VAR_006147 | |||||
| Natural variant | 40 | 1 | A → V in hypophosphatasia; 2% of activity. Ref.18 Ref.27 Ref.20 Ref.23 Ref.26 | VAR_011081 | |||||
| Natural variant | 51 | 1 | A → S in hypophosphatasia. Ref.31 | VAR_025904 | |||||
| Natural variant | 51 | 1 | A → V in hypophosphatasia. Ref.27 | VAR_013973 | |||||
| Natural variant | 62 | 1 | M → L in hypophosphatasia; moderate; 27% of activity. Ref.20 Ref.21 | VAR_006148 | |||||
| Natural variant | 62 | 1 | M → V in hypophosphatasia. Ref.32 | VAR_025905 | |||||
| Natural variant | 63 | 1 | G → R in hypophosphatasia. Ref.32 | VAR_025906 | |||||
| Natural variant | 63 | 1 | G → V in hypophosphatasia; loss of activity. Ref.26 | VAR_013974 | |||||
| Natural variant | 68 | 1 | T → M in hypophosphatasia; childhood-type; severe allele. Ref.28 | VAR_025907 | |||||
| Natural variant | 71 | 1 | R → C in hypophosphatasia. Ref.14 | VAR_006149 | |||||
| Natural variant | 71 | 1 | R → H in hypophosphatasia. Ref.27 Ref.31 | VAR_013975 | |||||
| Natural variant | 71 | 1 | R → P in hypophosphatasia. Ref.14 | VAR_006150 | |||||
| Natural variant | 71 | 1 | R → S in hypophosphatasia; childhood-type; severe allele. Ref.28 | VAR_025908 | |||||
| Natural variant | 75 | 1 | G → S in hypophosphatasia; severe; 3.5% of activity. Ref.18 Ref.20 | VAR_013976 | |||||
| Natural variant | 76 | 1 | Q → R in hypophosphatasia. | VAR_025909 | |||||
| Natural variant | 108 | 1 | P → L in hypophosphatasia; 0.4% of wild-type activity; severe allele. Ref.33 | VAR_025910 | |||||
| Natural variant | 111 | 1 | A → T in hypophosphatasia; odonto. Ref.20 Ref.23 Ref.31 Ref.32 Ref.19 | VAR_006151 | |||||
| Natural variant | 114 | 1 | A → G in hypophosphatasia. Ref.34 | VAR_025911 | |||||
| Natural variant | 116 | 1 | A → T in hypophosphatasia; loss of activity. Ref.27 Ref.26 Ref.33 | VAR_013977 | |||||
| Natural variant | 120 | 1 | G → R in hypophosphatasia. Ref.18 Ref.20 | VAR_013978 | |||||
| Natural variant | 128 | 1 | V → M in hypophosphatasia. Ref.31 | VAR_025912 | |||||
| Natural variant | 129 | 1 | G → R in hypophosphatasia. Ref.18 Ref.20 | VAR_013979 | |||||
| Natural variant | 132 | 1 | A → V in hypophosphatasia. Ref.29 | VAR_013146 | |||||
| Natural variant | 134 | 1 | T → H in hypophosphatasia; requires 2 nucleotide substitutions. Ref.31 | VAR_025913 | |||||
| Natural variant | 134 | 1 | T → N in hypophosphatasia; 9% of activity. Ref.23 | VAR_011082 | |||||
| Natural variant | 136 | 1 | R → H in hypophosphatasia; moderate; 33% of activity. Ref.27 Ref.35 Ref.20 Ref.31 Ref.21 | VAR_006152 | |||||
| Natural variant | 148 | 1 | T → I in hypophosphatasia. Ref.32 | VAR_025914 | |||||
| Natural variant | 152 | 1 | R → H in hypophosphatasia. Ref.27 Ref.5 | VAR_013980 | |||||
| Natural variant | 162 | 1 | G → S in hypophosphatasia. Ref.32 | VAR_025915 | |||||
| Natural variant | 162 | 1 | G → V in hypophosphatasia; severe; 1% of activity. Ref.20 Ref.21 | VAR_006153 | |||||
| Natural variant | 170 | 1 | N → D in hypophosphatasia. Ref.18 Ref.20 | VAR_013981 | |||||
| Natural variant | 171 | 1 | H → R in hypophosphatasia. | VAR_025916 | |||||
| Natural variant | 171 | 1 | H → Y in hypophosphatasia; severe; 2% of activity. Ref.20 Ref.21 | VAR_006154 | |||||
| Natural variant | 176 | 1 | A → T in hypophosphatasia. Ref.27 Ref.23 Ref.31 | VAR_011083 | |||||
| Natural variant | 177 | 1 | A → T in hypophosphatasia; adult type; moderate allele. Ref.28 Ref.19 | VAR_006155 | |||||
| Natural variant | 179 | 1 | A → T in hypophosphatasia. Ref.27 Ref.13 | VAR_006156 | |||||
| Natural variant | 181 | 1 | S → L in hypophosphatasia; 1% OF activity. Ref.26 | VAR_013982 | |||||
| Natural variant | 184 | 1 | R → W in hypophosphatasia; loss of activity. Ref.18 Ref.20 Ref.26 | VAR_013983 | |||||
| Natural variant | 189 | 1 | D → E in hypophosphatasia. Ref.32 | VAR_025917 | |||||
| Natural variant | 191 | 1 | E → G in hypophosphatasia; odonto. Ref.19 | VAR_006157 | |||||
| Natural variant | 191 | 1 | E → K in hypophosphatasia; moderate; frequent mutation in European countries. Ref.18 Ref.27 Ref.14 Ref.20 Ref.23 Ref.31 Ref.21 | VAR_006158 | |||||
| Natural variant | 201 | 1 | C → Y in hypophosphatasia. Ref.23 Ref.21 | VAR_006159 | |||||
| Natural variant | 207 | 1 | Q → P in hypophosphatasia. Ref.14 | VAR_006160 | |||||
| Natural variant | 211 | 1 | N → D in hypophosphatasia. Ref.27 | VAR_013984 | |||||
| Natural variant | 212 | 1 | I → F in hypophosphatasia. | VAR_025918 | |||||
| Natural variant | 220 | 1 | G → A in hypophosphatasia. Ref.32 | VAR_025919 | |||||
| Natural variant | 220 | 1 | G → V in hypophosphatasia; odonto. Ref.27 | VAR_013985 | |||||
| Natural variant | 223 | 1 | R → Q in hypophosphatasia. Ref.35 Ref.31 | VAR_025920 | |||||
| Natural variant | 223 | 1 | R → W in hypophosphatasia; 3% of activity; severe allele. Ref.18 Ref.35 Ref.20 Ref.26 Ref.31 Ref.28 | VAR_013986 | |||||
| Natural variant | 224 | 1 | K → E in hypophosphatasia; infantile; partial loss of activity. Ref.22 | VAR_011084 | |||||
| Natural variant | 235 | 1 | E → G in hypophosphatasia. Ref.27 | VAR_013987 | |||||
| Natural variant | 246 | 1 | R → S in hypophosphatasia; 4% of activity. Ref.23 Ref.31 | VAR_011085 | |||||
| Natural variant | 249 | 1 | G → V in hypophosphatasia; partial loss of activity. Ref.20 Ref.26 Ref.21 | VAR_013988 | |||||
| Natural variant | 263 | 1 | Y → H Common polymorphism. dbSNP rs3200254. Ref.18 Ref.14 Ref.31 Ref.3 Ref.7 | VAR_006161 | |||||
| Natural variant | 272 | 1 | R → H in hypophosphatasia; 6.8% of wild-type activity. Ref.35 | VAR_025921 | |||||
| Natural variant | 272 | 1 | R → L in hypophosphatasia. Ref.32 | VAR_025922 | |||||
| Natural variant | 275 | 1 | L → P in hypophosphatasia; childhood-type; severe allele. Ref.28 | VAR_025923 | |||||
| Natural variant | 289 | 1 | L → F in hypophosphatasia. Ref.4 | VAR_006162 | |||||
| Natural variant | 291 | 1 | E → K in hypophosphatasia; moderate; 8% of activity. Ref.18 Ref.20 Ref.30 | VAR_013989 | |||||
| Natural variant | 292 | 1 | P → T in hypophosphatasia; 4% of wild-type activity. Ref.35 | VAR_025924 | |||||
| Natural variant | 293 – 294 | 2 | Missing in hypophosphatasia. | VAR_025925 | |||||
| Natural variant | 294 | 1 | D → A in hypophosphatasia. Ref.14 Ref.35 Ref.31 | VAR_006163 | |||||
| Natural variant | 294 | 1 | D → Y in hypophosphatasia. Ref.27 | VAR_013990 | |||||
| Natural variant | 295 | 1 | M → T in hypophosphatasia; 8.5% of wild-type activity. Ref.35 | VAR_025926 | |||||
| Natural variant | 297 | 1 | Y → D in hypophosphatasia; 1.3% of wild-type activity. Ref.35 | VAR_025927 | |||||
| Natural variant | 298 | 1 | E → K in hypophosphatasia. Ref.16 | VAR_025928 | |||||
| Natural variant | 299 | 1 | L → P in hypophosphatasia. Ref.31 | VAR_025929 | |||||
| Natural variant | 306 | 1 | D → V in hypophosphatasia. Ref.20 Ref.21 | VAR_006164 | |||||
| Natural variant | 311 | 1 | E → K in hypophosphatasia. Ref.32 | VAR_025930 | |||||
| Natural variant | 326 | 1 | G → R in hypophosphatasia; in a patient carrying also lys-291. Ref.30 | VAR_013991 | |||||
| Natural variant | 327 | 1 | F → G in hypophosphatasia; requires 2 nucleotide substitutions. Ref.27 | VAR_013992 | |||||
| Natural variant | 327 | 1 | F → L in hypophosphatasia; childhood. Ref.19 Ref.17 | VAR_006165 | |||||
| Natural variant | 327 | 1 | Missing in hypophosphatasia. | VAR_025931 | |||||
| Natural variant | 334 | 1 | G → D in hypophosphatasia. Ref.18 Ref.35 Ref.20 Ref.15 | VAR_006166 | |||||
| Natural variant | 339 | 1 | G → R in hypophosphatasia. Ref.31 | VAR_025932 | |||||
| Natural variant | 348 | 1 | A → T in hypophosphatasia. Ref.23 Ref.31 | VAR_011086 | |||||
| Natural variant | 354 | 1 | E → D in hypophosphatasia. | VAR_025933 | |||||
| Natural variant | 378 | 1 | D → V in hypophosphatasia; loss of activity. Ref.14 Ref.26 Ref.31 Ref.24 | VAR_006167 | |||||
| Natural variant | 381 | 1 | H → R in hypophosphatasia. Ref.23 | VAR_011087 | |||||
| Natural variant | 382 | 1 | V → I in hypophosphatasia. Ref.19 | VAR_006168 | |||||
| Natural variant | 391 | 1 | R → C in hypophosphatasia; moderate; 10% of activity. Ref.20 | VAR_013993 | |||||
| Natural variant | 391 | 1 | R → H in hypophosphatasia; childhood-type; severe allele. Ref.28 | VAR_025934 | |||||
| Natural variant | 399 | 1 | A → S in hypophosphatasia. Ref.27 | VAR_013994 | |||||
| Natural variant | 406 | 1 | D → G in hypophosphatasia; 15% of activity. Ref.23 | VAR_011088 | |||||
| Natural variant | 411 | 1 | T → A in hypophosphatasia; absence of residual enzymatic activity. Ref.35 | VAR_025935 | |||||
| Natural variant | 414 | 1 | L → M in hypophosphatasia. Ref.31 Ref.33 | VAR_025936 | |||||
| Natural variant | 417 | 1 | N → S in hypophosphatasia. Ref.25 | VAR_025937 | |||||
| Natural variant | 423 | 1 | V → A in hypophosphatasia; 16% of activity. Ref.27 | VAR_013995 | |||||
| Natural variant | 426 | 1 | G → C in hypophosphatasia; infantile; partial loss of activity. Ref.22 | VAR_011089 | |||||
| Natural variant | 426 | 1 | G → D in hypophosphatasia. Ref.31 | VAR_025938 | |||||
| Natural variant | 436 | 1 | Y → H in hypophosphatasia. Ref.14 | VAR_006169 | |||||
| Natural variant | 445 | 1 | S → P in hypophosphatasia; severe; 2% of activity. Ref.18 Ref.20 | VAR_013996 | |||||
| Natural variant | 450 | 1 | R → C in hypophosphatasia; severe; 4% of activity. Ref.18 Ref.20 | VAR_013997 | |||||
| Natural variant | 450 | 1 | R → H in hypophosphatasia. Ref.23 | VAR_011090 | |||||
| Natural variant | 452 | 1 | E → K in hypophosphatasia. Ref.32 | VAR_025939 | |||||
| Natural variant | 456 | 1 | G → R in hypophosphatasia; loss of activity. Ref.17 | VAR_011091 | |||||
| Natural variant | 459 | 1 | V → M in hypophosphatasia; infantile. Ref.27 | VAR_013998 | |||||
| Natural variant | 468 | 1 | A → T in hypophosphatasia. Ref.32 | VAR_025940 | |||||
| Natural variant | 473 | 1 | G → S in hypophosphatasia. Ref.18 Ref.20 | VAR_013999 | |||||
| Natural variant | 476 | 1 | E → K in hypophosphatasia. Ref.20 Ref.31 Ref.21 | VAR_006170 | |||||
| Natural variant | 478 | 1 | N → I in hypophosphatasia; 9% of activity. Ref.23 Ref.26 | VAR_011092 | |||||
| Natural variant | 489 | 1 | C → S in hypophosphatasia; 9% of activity. Ref.23 | VAR_011093 | |||||
| Natural variant | 490 | 1 | I → F in hypophosphatasia; odonto; partial loss of activity. Ref.26 | VAR_014000 | |||||
| Natural variant | 491 | 1 | G → R in hypophosphatasia. Ref.18 Ref.20 | VAR_014001 | |||||
| Natural variant | 522 | 1 | V → A: dbSNP rs34605986. Ref.31 Ref.28 Ref.24 | VAR_011094 | |||||
Experimental info | |||||||||
| Sequence conflict | 29 | 1 | W → A AA sequence Ref.8 | ||||||
| Sequence conflict | 104 | 1 | N → K in CAA32376. Ref.3 | ||||||
| Sequence conflict | 361 | 1 | Q → H in BAA32129. Ref.1 | ||||||
| Sequence conflict | 446 | 1 | A → P in BAA32129. Ref.1 | ||||||
Sequences
| ||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase." Weiss M.J., Henthorn P.S., Lafferty M.A., Slaughter C., Raducha M., Harris H. Proc. Natl. Acad. Sci. U.S.A. 83:7182-7186(1986) [PubMed: 3532105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Osteosarcoma. |
| [2] | "Structure of the human liver/bone/kidney alkaline phosphatase gene." Weiss M.J., Ray K., Henthorn P.S., Lamb B., Kadesch T., Harris H. J. Biol. Chem. 263:12002-12010(1988) [PubMed: 3165380] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Osteosarcoma. |
| [3] | "Nucleotide sequence of the human liver-type alkaline phosphatase cDNA." Kishi F., Matsuura S., Kajii T. Nucleic Acids Res. 17:2129-2129(1989) [PubMed: 2928120] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-263. Tissue: Liver. |
| [4] | "A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia." Sugimoto N., Iwamoto S., Hoshino Y., Kajii E. J. Hum. Genet. 43:160-164(1998) [PubMed: 9747027] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HYPOPHOSPHATASIA PHE-289. |
| [5] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-152. Tissue: Brain. |
| [6] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-263. Tissue: Brain, Cerebellum, Lymphoma and Peripheral nerve. |
| [8] | "Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme." Garattini E., Hua J.-C., Pan Y.C.E., Udenfriend S. Arch. Biochem. Biophys. 245:331-337(1986) [PubMed: 3954357] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-49. Tissue: Liver. |
| [9] | "Chemical nature of intestinal-type alkaline phosphatase in human kidney." Nishihara Y., Hayashi Y., Adachi T., Koyama I., Stigbrand T., Hirano K. Clin. Chem. 38:2539-2542(1992) [PubMed: 1458595] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32, GLYCOSYLATION. |
| [10] | "Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins." Elortza F., Nuehse T.S., Foster L.J., Stensballe A., Peck S.C., Jensen O.N. Mol. Cell. Proteomics 2:1261-1270(2003) [PubMed: 14517339] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [11] | "Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment." Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N. J. Proteome Res. 5:935-943(2006) [PubMed: 16602701] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [12] | "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-430, MASS SPECTROMETRY. Tissue: Liver. |
| [13] | "A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia." Weiss M.J., Cole D.E.C., Ray K., Whyte M.P., Lafferty M.A., Mulivor R.A., Harris H. Proc. Natl. Acad. Sci. U.S.A. 85:7666-7669(1988) [PubMed: 3174660] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA THR-179. |
| [14] | "Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia." Henthorn P.S., Raducha M., Fedde K.N., Lafferty M.A., Whyte M.P. Proc. Natl. Acad. Sci. U.S.A. 89:9924-9928(1992) [PubMed: 1409720] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-33; CYS-71; PRO-71; LYS-191; PRO-207; ALA-294; VAL-378 AND HIS-436, VARIANT HIS-263. |
| [15] | "A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites." Greenberg C.R., Taylor C.L., Haworth J.C., Seargeant L.E., Philipps S., Triggs-Raine B., Chodirker B.N. Genomics 17:215-217(1993) [PubMed: 8406453] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA ASP-334. |
| [16] | "Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia." Orimo H., Hayashi Z., Watanabe A., Hirayama T., Hirayama T., Shimada T. Hum. Mol. Genet. 3:1683-1684(1994) [PubMed: 7833929] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA LYS-298. |
| [17] | "Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia." Ozono K., Yamagata M., Michigami T., Nakajima S., Sakai N., Cai G., Satomura K., Yasui N., Okada S., Nakayama M. J. Clin. Endocrinol. Metab. 81:4458-4461(1996) [PubMed: 8954059] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LEU-327 AND ARG-456. |
| [18] | "Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia." Mornet E., Taillandier A., Peyramaure S., Kaper F., Muller F., Brenner R., Bussiere P., Freisinger P., Godard J., Le Merrer M., Oury J.F., Plauchu H., Puddu R., Rival J.M., Superti-Furga A., Touraine R.L., Serre J.L., Simon-Bouy B. Eur. J. Hum. Genet. 6:308-314(1998) [PubMed: 9781036] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA PHE-17; VAL-40; SER-75; ARG-120; ARG-129; ASP-170; TRP-184; LYS-191; TRP-223; LYS-291; ASP-334; PRO-445; CYS-450; SER-473 AND ARG-491, VARIANT HIS-263. |
| [19] | "Hypophosphatasia: identification of five novel missense mutations (G507A, G705A, A748G, T1155C, G1320A) in the tissue-nonspecific alkaline phosphatase gene among Japanese patients." Goseki-Sone M., Orimo H., Iimura T., Takagi Y., Watanabe H., Taketa K., Sato S., Mayanagi H., Shimada T., Oida S. Hum. Mutat. Suppl. 1:S263-S267(1998) [PubMed: 9452105] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA THR-111; THR-177; GLY-191; LEU-327 AND ILE-382. |
| [20] | "Correlations of genotype and phenotype in hypophosphatasia." Zurutuza L., Muller F., Gibrat J.F., Taillandier A., Simon-Bouy B., Serre J.L., Mornet E. Hum. Mol. Genet. 8:1039-1046(1999) [PubMed: 10332035] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-40; LEU-62; SER-75; THR-111; ARG-120; ARG-129; HIS-136; VAL-162; ASP-170; TYR-171; TRP-184; LYS-191; TRP-223; VAL-249; LYS-291; VAL-306; ASP-334; CYS-391; PRO-445; CYS-450; SER-473; LYS-476 AND ARG-491, 3D-STRUCTURE MODELING, CHARACTERIZATION OF VARIANTS. |
| [21] | "Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia." Taillandier A., Zurutuza L., Muller F., Simon-Bouy B., Serre J.L., Bird L., Brenner R., Boute O., Cousin J., Gaillard D., Heidemann P.H., Steinmann B., Wallot M., Mornet E. Hum. Mutat. 13:171-172(1999) [PubMed: 10094560] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LEU-62; HIS-136; VAL-162; TYR-171; LYS-191; TYR-201; VAL-249; VAL-306 AND LYS-476. |
| [22] | "Severe hypercalcaemia and respiratory insufficiency associated with infantile hypophosphatasia caused by two novel mutations of the tissue-nonspecific alkaline phosphatase gene." Mochizuki H., Saito M., Michigami T., Ohashi H., Koda N., Yamaguchi S., Ozono K. Eur. J. Pediatr. 159:375-379(2000) [PubMed: 10834525] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA GLU-224 AND CYS-426. |
| [23] | "Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia." Taillandier A., Cozien E., Muller F., Merrien Y., Bonnin E., Fribourg C., Simon-Bouy B., Serre J.L., Bieth E., Brenner R., Cordier M.P., De Bie S., Fellmann F., Freisinger P., Hesse V., Hennekam R.C.M., Josifova D., Kerzin-Storrar L. Mornet E.Hum. Mutat. 15:293-293(2000) [PubMed: 10679946] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-40; THR-111; ASN-134; THR-176; LYS-191; TYR-201; SER-246; THR-348; ARG-381; GLY-406; HIS-450; ILE-478 AND SER-489. |
| [24] | "Asp361Val mutant of alkaline phosphatase found in patients with dominantly inherited hypophosphatasia inhibits the activity of the wild-type enzyme." Mueller H.L., Yamazaki M., Michigami T., Kageyama T., Schoenau E., Schneider P., Ozono K. J. Clin. Endocrinol. Metab. 85:743-747(2000) [PubMed: 10690885] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA VAL-378, VARIANT ALA-522. |
| [25] | "Perinatal hypophosphatasia: radiology, pathology and molecular biology studies in a family harboring a splicing mutation (648+1A) and a novel missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene." Sergi C., Mornet E., Troeger J., Voigtlaender T. Am. J. Med. Genet. 103:235-240(2001) [PubMed: 11745997] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA SER-417. |
| [26] | "A molecular approach to dominance in hypophosphatasia." Lia-Baldini A.S., Muller F., Taillandier A., Gibrat J.F., Mouchard M., Robin B., Simon-Bouy B., Serre J.L., Aylsworth A.S., Bieth E., Delanote S., Freisinger P., Hu J.C.-C., Krohn H.-P., Nunes M.E., Mornet E. Hum. Genet. 109:99-108(2001) [PubMed: 11479741] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HYPOPHOSPHATASIA VAL-40; VAL-63; THR-116; LEU-181; TRP-184; TRP-223; VAL-249; VAL-378; ILE-478 AND PHE-490. |
| [27] | "Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia." Taillandier A., Lia-Baldini A.S., Mouchard M., Robin B., Muller F., Simon-Bouy B., Serre J.L., Bera-Louville A., Bonduelle M., Eckhardt J., Gaillard D., Myhre A.G., Koertge-Jung S., Larget-Piet L., Malou E., Sillence D., Temple I.K., Viot G., Mornet E. Hum. Mutat. 18:83-84(2001) [PubMed: 11438998] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA CYS-28; VAL-40; VAL-51; HIS-71; THR-116; HIS-136; HIS-152; THR-176; THR-179; LYS-191; ASP-211; VAL-220; GLY-235; TYR-294; GLY-327; SER-399; ALA-423 AND MET-459. |
| [28] | "Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia." Orimo H., Girschick H.J., Goseki-Sone M., Ito M., Oda K., Shimada T. J. Bone Miner. Res. 16:2313-2319(2001) [PubMed: 11760847] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA MET-68; SER-71; THR-177; TRP-223; PRO-275 AND HIS-391, CHARACTERIZATION OF VARIANTS HYPOPHOSPHATASIA MET-68; SER-71; THR-177; TRP-223; PRO-275 AND HIS-391, VARIANT ALA-522, CHARACTERIZATION OF VARIANT ALA-522. |
| [29] | "A novel point mutation (C571T) in the tissue-non-specific alkaline phosphatase gene in a case of adult-type hypophosphatasia." Watanabe H., Hashimoto-Uoshima M., Goseki-Sone M., Orimo H., Ishikawa I. Oral Dis. 7:331-335(2001) [PubMed: 11834095] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA VAL-132. |
| [30] | "Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions." Litmanovitz I., Reish O., Dolfin T., Arnon S., Regev R., Grinshpan G., Yamazaki M., Ozono K. J. Inherit. Metab. Dis. 25:35-40(2002) [PubMed: 11999978] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LYS-291 AND ARG-326. |
| [31] | "Denaturing gradient gel electrophoresis analysis of the tissue nonspecific alkaline phosphatase isoenzyme gene in hypophosphatasia." Mumm S., Jones J., Finnegan P., Henthorn P.S., Podgornik M.N., Whyte M.P. Mol. Genet. Metab. 75:143-153(2002) [PubMed: 11855933] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA SER-51; HIS-71; THR-111; MET-128; HIS-134; HIS-136; THR-176; LYS-191; GLN-223; TRP-223; SER-246; ALA-294; PRO-299; PHE-327 DEL; ARG-339; THR-348; VAL-378; MET-414; ASP-426 AND LYS-476, VARIANTS HIS-263 AND ALA-522. |
| [32] | "Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene." Spentchian M., Merrien Y., Herasse M., Dobbie Z., Glaeser D., Holder S.E., Ivarsson S.-A., Kostiner D., Mansour S., Norman A., Roth J., Stipoljev F., Taillemite J.-L., van der Smagt J.J., Serre J.-L., Simon-Bouy B., Taillandier A., Mornet E. Hum. Mutat. 22:105-106(2003) [PubMed: 12815606] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-62; ARG-63; THR-111; ILE-148; SER-162; GLU-189; ALA-220; LEU-272; GLY-293-294-ASP DEL; LYS-311; LYS-452 AND THR-468. |
| [33] | "Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene." Herasse M., Spentchian M., Taillandier A., Keppler-Noreuil K., Fliorito A.N.M., Bergoffen J., Wallerstein R., Muti C., Simon-Bouy B., Mornet E. J. Med. Genet. 40:605-609(2003) [PubMed: 12920074] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LEU-108; THR-116 AND MET-414, CHARACTERIZATION OF VARIANT HYPOPHOSPHATASIA LEU-108. |
| [34] | "Childhood hypophosphatasia: a case report due to a novel mutation." Draguet C., Gillerot Y., Mornet E. Arch. Pediatr. 11:440-443(2004) [PubMed: 15135428] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA GLY-114. |
| [35] | "Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations." Brun-Heath I., Taillandier A., Serre J.-L., Mornet E. Mol. Genet. Metab. 84:273-277(2005) [PubMed: 15694177] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-33; HIS-136; GLN-223; TRP-223; HIS-272; THR-292; ALA-294; THR-295; ASP-297; ASP-334 AND ALA-411, CHARACTERIZATION OF VARIANTS HYPOPHOSPHATASIA VAL-33; HIS-272; THR-292; THR-295; ASP-297 AND ALA-411. |
| + | Additional computationally mapped references. |
Web resources
| ALPL Tissue nonspecific alkaline phosphatase gene mutations database |
| GeneReviews |
| Wikipedia Alkaline phosphatase entry |
Cross-references
Sequence databases | |
|---|---|
M24439 M24438 Genomic DNA. Translation: AAB59378.1. X14174 mRNA. Translation: CAA32376.1. AB011406 mRNA. Translation: BAA32129.1. AB209814 mRNA. Translation: BAD93051.1. Different initiation. AL592309, AL359815 Genomic DNA. Translation: CAH72079.1. AL359815, AL592309 Genomic DNA. Translation: CAI16259.1. BC021289 mRNA. Translation: AAH21289.3. BC066116 mRNA. Translation: AAH66116.2. BC090861 mRNA. Translation: AAH90861.2. BC110909 mRNA. Translation: AAI10910.2. BC126165 mRNA. Translation: AAI26166.1. BC136325 mRNA. Translation: AAI36326.1. | |
| IPI | IPI00419916. |
| PIR | PAHUH. S03613. |
| RefSeq | NP_000469.3. NP_001120973.1. |
| UniGene | Hs.75431 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1EW2 based on UniProtKB P05187. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P05186. 1 interaction. |
| STRING | P05186. |
Proteomic databases | |
| PeptideAtlas | P05186. |
| PRIDE | P05186. |
Genome annotation databases | |
| Ensembl | ENST00000374829; ENSP00000363962; ENSG00000162551; Homo sapiens. [Genome view] ENST00000374830; ENSP00000363963; ENSG00000162551; Homo sapiens. [Genome view] ENST00000374832; ENSP00000363965; ENSG00000162551; Homo sapiens. [Genome view] ENST00000374840; ENSP00000363973; ENSG00000162551; Homo sapiens. [Genome view] ENST00000425315; ENSP00000394765; ENSG00000162551; Homo sapiens. [Genome view] |
| GeneID | 249. |
| KEGG | hsa:249. |
| NMPDR | fig|9606.3.peg.484. |
| UCSC | uc001bet.1. human. |
Organism-specific databases | |
| CTD | 249. |
| GeneCards | GC01P021708. |
| H-InvDB | HIX0000225. |
| HGNC | HGNC:438. ALPL. |
| HPA | CAB020829. HPA007105. HPA008765. |
| MIM | 146300. phenotype. 171760. gene. 241500. phenotype. 241510. phenotype. |
| Orphanet | 436. Hypophosphatasia. |
| PharmGKB | PA24729. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P05186. |
| OMA | MISPFLV. |
Enzyme and pathway databases | |
| BRENDA | 3.1.3.1. 247. |
Gene expression databases | |
| ArrayExpress | P05186. |
| Bgee | P05186. |
| Genevestigator | P05186. |
| GermOnline | ENSG00000162551. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR017849. Alkaline_Pase-like_a/b/a. IPR001952. Alkaline_phosphatase. IPR018299. Alkaline_phosphatase_AS. [Graphical view] |
| Gene3D | G3DSA:3.40.720.10. Alk_phosphtse. 1 hit. |
| Pfam | PF00245. Alk_phosphatase. 1 hit. [Graphical view] |
| PRINTS | PR00113. ALKPHPHTASE. |
| SMART | SM00098. alkPPc. 1 hit. [Graphical view] |
| PROSITE | PS00123. ALKALINE_PHOSPHATASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB01143. Amifostine. |
| NextBio | 997. |
| SOURCE | Search... |
Entry information
| Entry name | PPBT_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P05186 Secondary accession number(s): A1A4E7 Q9UBK0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


