ALPL
entrez
249
canonical
uniprot
P05186
canonical
ensembl
ENSG00000162551
resolver
ensp
ENSP00000363965
resolver
ensp
ENSP00000363973
resolver
ensp
ENSP00000437674
resolver
ensp
ENSP00000442672
resolver
ensp
ENSP00000656864
resolver
ensp
ENSP00000656865
resolver
genesymbol
ALPL
resolver
hgnc
HGNC:438
resolver
uniprot
A1A4E7
resolver
uniprot
B2RMP8
resolver
uniprot
B7Z387
resolver
uniprot
B7Z4Y6
resolver
uniprot
O75090
resolver
uniprot
Q2TAI7
resolver
uniprot
Q59EJ7
resolver
uniprot
Q5BKZ5
resolver
uniprot
Q5VTG5
resolver
uniprot
Q6NZI8
resolver
uniprot
Q8WU32
resolver
uniprot
Q9UBK0
resolver
uniprot_entry
PPBT_HUMAN
resolver
uniprot_sec
A1A4E7
resolver
uniprot_sec
B2RMP8
resolver
uniprot_sec
B7Z387
resolver
uniprot_sec
B7Z4Y6
resolver
uniprot_sec
O75090
resolver
uniprot_sec
Q2TAI7
resolver
uniprot_sec
Q59EJ7
resolver
uniprot_sec
Q5BKZ5
resolver
uniprot_sec
Q5VTG5
resolver
uniprot_sec
Q6NZI8
resolver
uniprot_sec
Q8WU32
resolver
uniprot_sec
Q9UBK0
resolver
activity_regulation
ACTIVITY REGULATION: Phosphatase activity is specifically inhibited by 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425). {ECO:0000250|UniProtKB:P09242}.
uniprot
proteins
amino_acid_sequence
MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAIQILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTADHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYAHNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHCAPASSAGSLAAGPLLLALALYPLSVLF
uniprot
proteins
disease_involvement
DISEASE: Hypophosphatasia (HOPS) [MIM:146300]: A metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four 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. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia). {ECO:0000269|PubMed:10094560, ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:10679946, ECO:0000269|PubMed:10690885, ECO:0000269|PubMed:10834525, ECO:0000269|PubMed:11395499, ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:11745997, ECO:0000269|PubMed:11760847, ECO:0000269|PubMed:11834095, ECO:0000269|PubMed:11855933, ECO:0000269|PubMed:11999978, ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:12230456, ECO:0000269|PubMed:12815606, ECO:0000269|PubMed:12920074, ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:15135428, ECO:0000269|PubMed:15694177, ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:20049532, ECO:0000269|PubMed:22266140, ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:23791648, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:30083035, ECO:0000269|PubMed:3174660, ECO:0000269|PubMed:32983484, ECO:0000269|PubMed:33821301, ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8406453, ECO:0000269|PubMed:8954059, ECO:0000269|PubMed:9452105, ECO:0000269|PubMed:9747027, ECO:0000269|PubMed:9781036}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypophosphatasia, childhood (HPPC) [MIM:241510]: A bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. {ECO:0000269|PubMed:11760847}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypophosphatasia, infantile (HPPI) [MIM:241500]: A severe bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Three more or less distinct types of infantile hypophosphatasia can be identified: (1) type 1 with onset in utero or in early postnatal life, craniostenosis, severe skeletal abnormalities, hypercalcemia, and death in the first year or so of life; (2) type 2 with later, more gradual development of symptoms, moderately severe 'rachitic' skeletal changes and premature loss of teeth; (3) type 3 with no symptoms, the condition being determined on routine studies. {ECO:0000269|PubMed:10834525, ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8954059}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.3.1
uniprot
proteins
ec_number
3.9.1.1
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P09242, ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:20049532, ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:28448526}.
uniprot
proteins
mass_dalton
57305
uniprot
proteins
mutagenesis
MUTAGEN 235; /note="E->A: Abolished alkaline phosphatase activity."; /evidence="ECO:0000269|PubMed:25775211"; MUTAGEN 270; /note="W->A: Reduced alkaline phosphatase activity."; /evidence="ECO:0000269|PubMed:25775211"; MUTAGEN 272; /note="R->A: Reduced alkaline phosphatase activity."; /evidence="ECO:0000269|PubMed:25775211"; MUTAGEN 290; /note="F->A: Abolished alkaline phosphatase activity."; /evidence="ECO:0000269|PubMed:25775211"; MUTAGEN 291; /note="E->A: Reduced alkaline phosphatase activity."; /evidence="ECO:0000269|PubMed:25775211"; MUTAGEN 306; /note="D->A: Abolished alkaline phosphatase activity."; /evidence="ECO:0000269|PubMed:25775211
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:1458595, ECO:0000269|PubMed:19159218}.
uniprot
proteins
protein_family
Alkaline phosphatase family
uniprot
proteins
pubmed
10094560
uniprot
proteins
pubmed
10332035
uniprot
proteins
pubmed
10679946
uniprot
proteins
pubmed
10690885
uniprot
proteins
pubmed
10834525
uniprot
proteins
pubmed
11395499
uniprot
proteins
pubmed
11438998
uniprot
proteins
pubmed
11479741
uniprot
proteins
pubmed
11745997
uniprot
proteins
pubmed
11760847
uniprot
proteins
pubmed
11834095
uniprot
proteins
pubmed
11855933
uniprot
proteins
pubmed
11999978
uniprot
proteins
pubmed
12162492
uniprot
proteins
pubmed
12230456
uniprot
proteins
pubmed
12815606
uniprot
proteins
pubmed
12920074
uniprot
proteins
pubmed
1409720
uniprot
proteins
pubmed
1458595
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15135428
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15694177
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17566972
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19500388
uniprot
proteins
pubmed
20049532
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
2220817
uniprot
proteins
pubmed
22266140
uniprot
proteins
pubmed
23039266
uniprot
proteins
pubmed
23688511
uniprot
proteins
pubmed
23791648
uniprot
proteins
pubmed
25775211
uniprot
proteins
pubmed
25982064
uniprot
proteins
pubmed
28448526
uniprot
proteins
pubmed
2928120
uniprot
proteins
pubmed
30083035
uniprot
proteins
pubmed
3165380
uniprot
proteins
pubmed
3174660
uniprot
proteins
pubmed
32983484
uniprot
proteins
pubmed
33821301
uniprot
proteins
pubmed
3532105
uniprot
proteins
pubmed
3954357
uniprot
proteins
pubmed
7833929
uniprot
proteins
pubmed
8406453
uniprot
proteins
pubmed
8954059
uniprot
proteins
pubmed
9452105
uniprot
proteins
pubmed
9747027
uniprot
proteins
pubmed
9781036
uniprot
proteins
sequence_length
524
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:33821301}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064}. Extracellular vesicle membrane {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P09242}. Mitochondrion membrane {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P09242}. Mitochondrion intermembrane space {ECO:0000250|UniProtKB:P09242}. Note=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. {ECO:0000250|UniProtKB:P09242}.
uniprot
proteins