Enpp1
entrez
18605
canonical
uniprot
P06802
canonical
ensembl
ENSMUSG00000037370
resolver
ensp
ENSMUSP00000101159
resolver
ensp
ENSMUSP00000114273
resolver
enst
ENSMUST00000105520
resolver
enst
ENSMUST00000135846
resolver
genesymbol
Enpp1
resolver
genesymbol_syn
Npps
resolver
genesymbol_syn
Pc1
resolver
genesymbol_syn
Pdnp1
resolver
uniprot
A0A0R4J1Q7
resolver
uniprot
G3X9S2
resolver
uniprot
Q542E9
resolver
uniprot
Q924C4
resolver
uniprot_entry
A0A0R4J1Q7_MOUSE
resolver
uniprot_entry
ENPP1_MOUSE
resolver
uniprot_entry
G3X9S2_MOUSE
resolver
uniprot_sec
Q542E9
resolver
uniprot_sec
Q924C4
resolver
activity_regulation
ACTIVITY REGULATION: At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis. {ECO:0000269|PubMed:11027689}.
uniprot
proteins
amino_acid_sequence
MERDGDQAGHGPRHGSAGNGRELESPAAASLLAPMDLGEEPLEKAERARPAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFSNCRCDAACVSLGNCCLDFQETCVEPTHIWTCNKFRCGEKRLSRFVCSCADDCKTHNDCCINYSSVCQDKKSWVEETCESIDTPECPAEFESPPTLLFSLDGFRAEYLHTWGGLLPVISKLKNCGTYTKNMRPMYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPLWYKGQPIWVTANHQEVKSGTYFWPGSDVEIDGILPDIYKVYNGSVPFEERILAVLEWLQLPSHERPHFYTLYLEEPDSSGHSHGPVSSEVIKALQKVDRLVGMLMDGLKDLGLDKCLNLILISDHGMEQGSCKKYVYLNKYLGDVNNVKVVYGPAARLRPTDVPETYYSFNYEALAKNLSCREPNQHFRPYLKPFLPKRLHFAKSDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNLFSNMQALFIGYGPAFKHGAEVDSFENIEVYNLMCDLLGLIPAPNNGSHGSLNHLLKKPIYNPSHPKEEGFLSQCPIKSTSNDLGCTCDPWIVPIKDFEKQLNLTTEDVDDIYHMTVPYGRPRILLKQHHVCLLQQQQFLTGYSLDLLMPLWASYTFLRNDQFSRDDFSNCLYQDLRIPLSPVHKCSYYKSNSKLSYGFLTPPRLNRVSNHIYSEALLTSNIVPMYQSFQVIWHYLHDTLLQRYAHERNGINVVSGPVFDFDYDGRYDSLEILKQNSRVIRSQEILIPTHFFIVLTSCKQLSETPLECSALESSAYILPHRPDNIESCTHGKRESSWVEELLTLHRARVTDVELITGLSFYQDRQESVSELLRLKTHLPIFSQED
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Enpp1 are the cause of the tiptoe walking (ttw) phenotype. Ttw mice exhibit ossification of the spinal ligaments (PubMed:9662402). Mice display increased bone formation process in joints and develop spontaneous osteoarthritis-like changes (PubMed:22510396). {ECO:0000269|PubMed:22510396, ECO:0000269|PubMed:9662402}.; DISEASE: Note=Defects in Enpp1 are the cause of spontaneous asj-2J mutant characterized by gait due to stiffening of the joints (PubMed:25479107). Defects are caused by a significant reduction in the plasma diphosphate (PPi) concentration, leading to extensive aberrant mineralization affecting the arterial vasculature, a number of internal organs and the dermal sheath of vibrissae (PubMed:25479107). Asj-2J mice are used as a model for arterial calcification of infancy disorder (GACI1) (PubMed:25479107). Mice also show ectopic mineralization of cartilage and collagen-rich tendons and ligaments (PubMed:26910915). {ECO:0000269|PubMed:25479107, ECO:0000269|PubMed:26910915}.
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 (PubMed:10352096, PubMed:11004006, PubMed:12082181, PubMed:22510396, PubMed:25260930, PubMed:9662402). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:10352096, PubMed:11004006, PubMed:12082181, PubMed:19419305, PubMed:22510396, PubMed:25260930, PubMed:25479107, PubMed:26910915, PubMed:30111653, PubMed:35147247, PubMed:9662402). 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:11027689, PubMed:1647027, PubMed:23027977, PubMed:8223581). 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:1647027). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (PubMed:30111653). Appears to modulate insulin sensitivity (By similarity). Also involved in melanogenesis (By similarity). 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 (By similarity). Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3',3'-cGAMP (By similarity). {ECO:0000250|UniProtKB:P22413, ECO:0000269|PubMed:10352096, ECO:0000269|PubMed:11004006, ECO:0000269|PubMed:11027689, ECO:0000269|PubMed:12082181, ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:19419305, ECO:0000269|PubMed:22510396, ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:25260930, ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:25479107, ECO:0000269|PubMed:26910915, ECO:0000269|PubMed:30111653, ECO:0000269|PubMed:35147247, ECO:0000269|PubMed:8223581, ECO:0000269|PubMed:9662402}.
uniprot
proteins
mass_dalton
103176
uniprot
proteins
mutagenesis
MUTAGEN 28; /note="A->G: No effect on basolateral sorting in epithelial cells."; /evidence="ECO:0000269|PubMed:11598187"; MUTAGEN 30; /note="S->A,D: Little change in baolateral sorting in epithelial cells."; /evidence="ECO:0000269|PubMed:11598187"; MUTAGEN 31; /note="L->A: 60% of ENPP1 redirected to apical surface in epithelial cells. 75% of ENPP1 redirected to apical surface in epithelial cells; abrogation of increased NPP activity in oestoblastic matrix vesicles; when associated with A-32."; /evidence="ECO:0000269|PubMed:11598187, ECO:0000269|PubMed:15075217"; MUTAGEN 32; /note="L->A: 70% of ENPP1 redirected to apical surface in epithelial cells; abrogation of increased NPP activity in oestoblastic matrix vesicles. 75% of ENPP1 redirected to apical surface in epithelial cells; abrogation of increased NPP activity in oestoblastic matrix vesicles; when associated with A-31."; /evidence="ECO:0000269|PubMed:11598187, ECO:0000269|PubMed:15075217"; MUTAGEN 42; /note="L->A: No change in increased NPP activity in oestoblastic matrix vesicles."; /evidence="ECO:0000269|PubMed:15075217"; MUTAGEN 57; /note="Y->G: No change in increased NPP activity in oestoblastic matrix vesicles."; /evidence="ECO:0000269|PubMed:15075217"; MUTAGEN 200; /note="D->N: Decreases phosphodiesterase activity by 95%. Abolishes formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 237; /note="K->A: Decreases phosphodiesterase activity by 40%. Decreased formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 238; /note="T->A: Abolishes all phosphodiesterase activity. Abolishes formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689, ECO:0000269|PubMed:30356045"; MUTAGEN 238; /note="T->S: Decreases phosphodiesterase activity by 95%. Accumulates nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 239; /note="F->A: Decreases phosphodiesterase activity by 50%. Decreased formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689, ECO:0000269|PubMed:23027977"; MUTAGEN 242; /note="H->L: Strongly decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:23027977"; MUTAGEN 304..323; /note="Missing: Nearly abolishes activity with nucleotide phosphates. Confers very low activity with lysophospholipids."; /evidence="ECO:0000269|PubMed:23027977"; MUTAGEN 308; /note="D->A: Decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:23027977"; MUTAGEN 322; /note="Y->A: Strongly decreased phosphodiesterase activity."; /evidence="ECO:0000269|PubMed:23027977"; MUTAGEN 358; /note="D->Q: Decreases phosphodiesterase activity by 90%. Accumulates nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 362; /note="H->Q: Decreases phosphodiesterase activity by 95%. 65% activity can be restored by addition of Zn(2+) ions. Accumulates nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 397; /note="C->S: Mice display a low bone mass density and show a striking joint disease and calcification of blood vessels. Probably affects protein stability."; /evidence="ECO:0000269|PubMed:19419305"; MUTAGEN 405; /note="D->N: Abolishes all phosphodiesterase activity. 10% activity can be restored by addition of Zn(2+) ions. Abolishes formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 406; /note="H->Q: Abolishes all phosphodiesterase activity. 15% activity can be restored by addition of Zn(2+) ions. Abolishes formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689"; MUTAGEN 514; /note="S->L: Abolished ability to hydrolyze 2',3'-cGAMP without affecting ability to hydrolyze ATP."; /evidence="ECO:0000269|PubMed:30356045"; MUTAGEN 517; /note="H->Q: Abolishes all phosphodiesterase activity. 60% activity can be restored by addition of Zn(2+) ions. Abolishes formation of nucleotidylated intermediate."; /evidence="ECO:0000269|PubMed:11027689
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:19656770, ECO:0000269|PubMed:23027977, ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:8223581}.; PTM: The secreted form is produced through cleavage at Lys-85 by intracellular processing. {ECO:0000269|PubMed:23041369}.
uniprot
proteins
protein_family
Nucleotide pyrophosphatase/phosphodiesterase family
uniprot
proteins
pubmed
10352096
uniprot
proteins
pubmed
11004006
uniprot
proteins
pubmed
11027689
uniprot
proteins
pubmed
11598187
uniprot
proteins
pubmed
12082181
uniprot
proteins
pubmed
12121276
uniprot
proteins
pubmed
12533192
uniprot
proteins
pubmed
15075217
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
1647027
uniprot
proteins
pubmed
19419305
uniprot
proteins
pubmed
19656770
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
2211644
uniprot
proteins
pubmed
22510396
uniprot
proteins
pubmed
23027977
uniprot
proteins
pubmed
23041369
uniprot
proteins
pubmed
25260930
uniprot
proteins
pubmed
25344812
uniprot
proteins
pubmed
25479107
uniprot
proteins
pubmed
26910915
uniprot
proteins
pubmed
3001713
uniprot
proteins
pubmed
30111653
uniprot
proteins
pubmed
30356045
uniprot
proteins
pubmed
3104326
uniprot
proteins
pubmed
35147247
uniprot
proteins
pubmed
3917281
uniprot
proteins
pubmed
8223581
uniprot
proteins
pubmed
9662402
uniprot
proteins
sequence_length
906
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1]: Cell membrane {ECO:0000269|PubMed:1647027, ECO:0000269|PubMed:3104326, ECO:0000269|PubMed:3917281}; Single-pass type II membrane protein. Basolateral cell membrane {ECO:0000269|PubMed:11598187, ECO:0000269|PubMed:15075217}; 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. {ECO:0000269|PubMed:11598187, ECO:0000269|PubMed:15075217}.; SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form]: Secreted {ECO:0000269|PubMed:23041369, ECO:0000269|PubMed:8223581}. Note=Secreted following proteolytic cleavage. {ECO:0000269|PubMed:23041369}.
uniprot
proteins
transmembrane_region
TRANSMEM 59..79; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins