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Details on Person UniProt:P05186-1 ALPL
| Class:Id | ReferenceIsoform:8977150 |
|---|---|
| _chainChangeLog | signal peptide:1-17 added on Fri February 17 2017;chain:18-502 added on Fri February 17 2017;propeptide:503-524 added on Fri February 17 2017 |
| _displayName | UniProt:P05186-1 ALPL |
| _timestamp | 2025-02-21 19:52:35 |
| chain | signal peptide:1-17 chain:18-501 propeptide:502-524 |
| checksum | 71B45F17F6211900 |
| comment | FUNCTION Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:12162492, PubMed:2220817). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:23688511, PubMed:25982064). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (By similarity). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:20049532, PubMed:2220817). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (By similarity). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (PubMed:28448526). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity).CATALYTIC ACTIVITY a phosphate monoester + H2O = an alcohol + phosphateCATALYTIC ACTIVITY diphosphate + H2O = 2 phosphate + H(+)CATALYTIC ACTIVITY pyridoxal 5'-phosphate + H2O = pyridoxal + phosphateCATALYTIC ACTIVITY phosphoethanolamine + H2O = ethanolamine + phosphateCATALYTIC ACTIVITY N-phosphocreatine + H2O = creatine + phosphateCATALYTIC ACTIVITY ATP + H2O = ADP + phosphate + H(+)CATALYTIC ACTIVITY ADP + H2O = AMP + phosphate + H(+)CATALYTIC ACTIVITY AMP + H2O = adenosine + phosphateCOFACTOR Binds 1 Mg(2+) ion.COFACTOR Binds 2 Zn(2+) ions.COFACTOR Phosphatase activity is specifically inhibited by 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425).SUBUNIT Homodimer.SUBCELLULAR LOCATION Localizes to special class of extracellular vesicles, named matrix vesicles (MVs), which are released by osteogenic cells. Localizes to the mitochondria of thermogenic fat cells: tethered to mitochondrial membranes via a GPI-anchor and probably resides in the mitochondrion intermembrane space.ALTERNATIVE PRODUCTS Calcium-binding is structural and does not influence the alkaline phosphatase activity (PubMed:25775211). At very high concentrations, calcium can however substitute for zinc at zinc-binding sites, leading to strongly reduced enzyme activity (PubMed:25775211).PTM N-glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP).SIMILARITY Belongs to the alkaline phosphatase family.SEQUENCE CAUTION Extended N-terminus.ONLINE INFORMATION Tissue nonspecific alkaline phosphatase gene mutations databaseONLINE INFORMATION Alkaline phosphatase entryONLINE INFORMATION Constructive futility - Issue 242 of December 2021 |
| created | [InstanceEdit:8964659] Weiser, JD |
| description | recommendedName: fullName evidence="52"Alkaline phosphatase, tissue-nonspecific isozyme shortName: AP-TNAP shortName evidence="52"TNS-ALP shortName: TNSALP ecNumber evidence="30 32 33 36"3.1.3.1 alternativeName: fullName evidence="53"Alkaline phosphatase liver/bone/kidney isozyme alternativeName: fullName evidence="55"Phosphoamidase alternativeName: fullName evidence="2"Phosphocreatine phosphatase ecNumber evidence="2"3.9.1.1 |
| geneName | ALPL |
| identifier | P05186 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Biomineralization Calcium Cell membrane Direct protein sequencing Disease variant Disulfide bond Glycoprotein GPI-anchor Hydrolase Lipoprotein Magnesium Membrane Metal-binding Mitochondrion Phosphoprotein Proteomics identification Reference proteome Signal Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | ALPL |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9004324] ENSEMBL:ENSG00000162551 ALPL [Homo sapiens] |
| secondaryIdentifier | PPBT_HUMAN A1A4E7 B2RMP8 B7Z387 B7Z4Y6 O75090 Q2TAI7 Q59EJ7 Q5BKZ5 Q5VTG5 Q6NZI8 Q8WU32 Q9UBK0 |
| sequenceLength | 524 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P05186-1 |
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No pathways have been reviewed or authored by UniProt:P05186-1 ALPL (8977150)
