ENPP1
entrez
5167
canonical
uniprot
P22413
canonical
ensembl
ENSG00000197594
resolver
ensp
ENSP00000498074
resolver
enst
ENST00000647893
resolver
genesymbol
ENPP1
resolver
genesymbol_syn
M6S1
resolver
genesymbol_syn
NPPS
resolver
genesymbol_syn
PC1
resolver
genesymbol_syn
PDNP1
resolver
hgnc
HGNC:3356
resolver
uniprot
Q5T9R6
resolver
uniprot
Q9NPZ3
resolver
uniprot
Q9P1P6
resolver
uniprot
Q9UP61
resolver
uniprot
Q9Y6K3
resolver
uniprot_entry
ENPP1_HUMAN
resolver
uniprot_sec
Q5T9R6
resolver
uniprot_sec
Q9NPZ3
resolver
uniprot_sec
Q9P1P6
resolver
uniprot_sec
Q9UP61
resolver
uniprot_sec
Q9Y6K3
resolver
activity_regulation
ACTIVITY REGULATION: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis. {ECO:0000250|UniProtKB:P06802}.
uniprot
proteins
amino_acid_sequence
MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQAAASLLAPMDVGEEPLEKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFGNCRCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLTRSLCACSDDCKDKGDCCINYSSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLDGFRAEYLHTWGGLLPVISKLKKCGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPEWYKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFPDIYKMYNGSVPFEERILAVLQWLQLPKDERPHFYTLYLEEPDSSGHSYGPVSSEVIKALQRVDGMVGMLMDGLKELNLHRCLNLILISDHGMEQGSCKKYIYLNKYLGDVKNIKVIYGPAARLRPSDVPDKYYSFNYEGIARNLSCREPNQHFKPYLKHFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNVFSNMQALFVGYGPGFKHGIEADTFENIEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVYTPKHPKEVHPLVQCPFTRNPRDNLGCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYGRPRVLQKENTICLLSQHQFMSGYSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPLSPVHKCSFYKNNTKVSYGFLSPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTLLRKYAEERNGVNVVSGPVFDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKDTSQTPLHCENLDTLAFILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSFYQQRKEPVSDILKLKTHLPTFSQED
uniprot
proteins
disease_involvement
DISEASE: Ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]: A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis. {ECO:0000269|PubMed:10453738}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Arterial calcification of infancy, generalized, 1 (GACI1) [MIM:208000]: A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. {ECO:0000269|PubMed:12881724, ECO:0000269|PubMed:15605415, ECO:0000269|PubMed:15940697, ECO:0000269|PubMed:20016754, ECO:0000269|PubMed:22209248, ECO:0000269|PubMed:23430823, ECO:0000269|PubMed:27467858}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:16186408, ECO:0000269|PubMed:29958952}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2) [MIM:613312]: A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities. {ECO:0000269|PubMed:20137772, ECO:0000269|PubMed:20137773, ECO:0000269|PubMed:25741938}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cole disease (COLED) [MIM:615522]: A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy. {ECO:0000269|PubMed:24075184, ECO:0000269|PubMed:26617416, ECO:0000269|PubMed:28964717}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.4.1
uniprot
proteins
ec_number
3.6.1.9
uniprot
proteins
function
FUNCTION: Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:25344812, PubMed:27467858, PubMed:28011303, PubMed:35147247, PubMed:8001561). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2',3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2',3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812). {ECO:0000250|UniProtKB:P06802, ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:27467858, ECO:0000269|PubMed:28011303, ECO:0000269|PubMed:28964717, ECO:0000269|PubMed:35147247, ECO:0000269|PubMed:8001561, ECO:0000305|PubMed:11004006}.
uniprot
proteins
mass_dalton
104924
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity. {ECO:0000305|PubMed:7737162}.; PTM: N-glycosylated. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:8001561}.; PTM: The secreted form is produced through cleavage at Lys-103 by intracellular processing. {ECO:0000250|UniProtKB:P06802}.
uniprot
proteins
protein_family
Nucleotide pyrophosphatase/phosphodiesterase family
uniprot
proteins
pubmed
10453738
uniprot
proteins
pubmed
10480624
uniprot
proteins
pubmed
10615944
uniprot
proteins
pubmed
11004006
uniprot
proteins
pubmed
11598187
uniprot
proteins
pubmed
12881724
uniprot
proteins
pubmed
1315502
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
15072822
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15605415
uniprot
proteins
pubmed
15940697
uniprot
proteins
pubmed
16186408
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
20016754
uniprot
proteins
pubmed
20034067
uniprot
proteins
pubmed
20137772
uniprot
proteins
pubmed
20137773
uniprot
proteins
pubmed
2211644
uniprot
proteins
pubmed
22209248
uniprot
proteins
pubmed
23430823
uniprot
proteins
pubmed
24075184
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25344812
uniprot
proteins
pubmed
25741938
uniprot
proteins
pubmed
26617416
uniprot
proteins
pubmed
27467858
uniprot
proteins
pubmed
28011303
uniprot
proteins
pubmed
28964717
uniprot
proteins
pubmed
29958952
uniprot
proteins
pubmed
35147247
uniprot
proteins
pubmed
7737162
uniprot
proteins
pubmed
8001561
uniprot
proteins
pubmed
9344668
uniprot
proteins
sequence_length
925
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1]: Cell membrane {ECO:0000269|PubMed:15072822, ECO:0000269|PubMed:27467858, ECO:0000269|PubMed:8001561}; Single-pass type II membrane protein. Basolateral cell membrane {ECO:0000269|PubMed:11598187}; Single-pass type II membrane protein. Note=Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts (PubMed:11598187). In bile duct cells and cancer cells, located to the apical cytoplasmic side (PubMed:11598187). {ECO:0000269|PubMed:11598187}.; SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form]: Secreted {ECO:0000250|UniProtKB:P06802}. Note=Secreted following proteolytic cleavage. {ECO:0000250|UniProtKB:P06802}.
uniprot
proteins
transmembrane_region
TRANSMEM 77..97; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins