Protein: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (E-NPP 1) (Alkaline phosphodiesterase I) (EC 3.1.4.1) (Nucleotide diphosphatase) (Nucleotide pyrophosphatase) (NPPase) (EC 3.6.1.9) (Phosphodiesterase I/nucleotide pyrophosphatase 1) (Plasma-cell membrane glycoprotein PC-1) [Cleaved into: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form] (Q924C3)
Organism: Rattus norvegicus (Rat)
Function: Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels. PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals. 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. 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. 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. 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 (By similarity). 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. Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-cGAMP (By similarity).
Subcellular location: [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1]: Cell membrane {ECO:0000250|UniProtKB:P06802}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:P06802}. Basolateral cell membrane {ECO:0000250|UniProtKB:P06802}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:P06802}. Note=Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. {ECO:0000250|UniProtKB:P06802}.; SUBCELLULAR LOCATION: [Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form]: Secreted {ECO:0000250|UniProtKB:P06802}. Note=Secreted following proteolytic cleavage. {ECO:0000250|UniProtKB:P06802}.
Interaction partners:
- 5'-nucleotidase
- Ectonucleoside triphosphate diphosphohydrolase 1
- 3',5'-cyclic-AMP phosphodiesterase 4B
- cGMP-dependent 3',5'-cyclic phosphodiesterase
- Bis
- Ectonucleoside triphosphate diphosphohydrolase 3
- NAD kinase
- Adenosine kinase
- Ectonucleoside triphosphate diphosphohydrolase 5
- Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
Sequence:
MERDGEQAGQGPRHGPAGNGRELESPAAASLLAPMDLGEEPLEKAERARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCAKEVKSCKGRCFERTFSNCRCDAACVSLGNCCLDFQETCVEPTHIWTCNKFRCGEKRLSRFVCSCADDCKAHNDCCINYSSVCQEKKSWVEEACETIDAPQCPAEFESPPTLLFSLDGFRAEYLHTWGGLLPVISKLKNCGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIIDNKMYDPKMNASFSLKSKEKFNPLWYKGQPIWVTANHQEVRSGTYFWPGSDVEIDGILPDIYKVYNGSVPFEERILAVLEWLQLPSYERPHFYTLYLEEPDSSGHSHGPVSSEVIKALQKVDHIVGMLMDGLKDLGLDKCLNLILISDHGMEQGSCKKYVYLNKYLGDVNNVKVVYGPAARLRPTEVPETYYSFNYEALAKNLSCRETNQHFRPYLKHFLPKRLHFAKNDRIEPLTFYLDPQWQLALNPSERKYCGSGFHGSDNLFSNMQALFIGYGPAFKHGAEVDSFENIEVYNLMCDLLGLIPAPNNESHGSLNHLLKKPIYTPSHPKEESFLSQCPIKSVSSDLGCTCDPSIVPIMDFEKQFNLTTDAVEDVYSMTVPNGRPRNLQKQHRVCLLHQQQFLTGYSLDLLMPLWTSYTFLSNDQFSTDDFSNCLYQDLRIPLSPMHKCSYYKSTSKLSYGFLTPPRLNRVSRQIYSEALLTSNIVPMYQSFQVIWQYLHDTVLRRYAQERNGVNVVSGPVFDFDYDGRYDSSEILKQNTRVIRSQENLIPTHFFIVLTSCKQLSESPLKCTALESSAFLLPHRPDNIESCTHGKQESAWVEELLALHRARVTDVELITGLSFYQDRQESVSELLRLKTHLPIFSQED