InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ENPP1

Summary

InnateDB Protein

IDBP-96597.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ENPP1

Protein Name

ectonucleotide pyrophosphatase/phosphodiesterase 1

Synonyms

ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1; PDNP1;

Species

Homo sapiens

Ensembl Protein

ENSP00000354238

InnateDB Gene

IDBG-96591 (ENPP1)

Protein Structure

UniProt Annotation

Function

By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and 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. Appears to modulate insulin sensitivity and function. {ECO:0000269PubMed:10615944, ECO:0000269PubMed:8001561}.

Subcellular Localization

Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Secreted {ECO:0000250}. Note=The proteolytically processed form is secreted (By similarity). Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side. {ECO:0000250}.

Disease Associations

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:0000269PubMed:10453738}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:12881724, ECO:0000269PubMed:15605415, ECO:0000269PubMed:15940697, ECO:0000269PubMed:22209248}. Note=The disease is caused by mutations affecting the gene represented in this entry.Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.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:0000269PubMed:20137772, ECO:0000269PubMed:20137773}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:24075184}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis. {ECO:0000269PubMed:9344668}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.

Experimentally validated
Total	5 [view]
Protein-Protein	5 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003824	catalytic activity
GO:0004528	phosphodiesterase I activity
GO:0004551	nucleotide diphosphatase activity
GO:0005044	scavenger receptor activity
GO:0005158	insulin receptor binding
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0016787	hydrolase activity
GO:0030247	polysaccharide binding
GO:0035529	NADH pyrophosphatase activity
GO:0042803	protein homodimerization activity
GO:0046872	metal ion binding
GO:0047429	nucleoside-triphosphate diphosphatase activity
GO:0050656	3'-phosphoadenosine 5'-phosphosulfate binding

Biological Process

GO:0006091	generation of precursor metabolites and energy
GO:0006200	ATP catabolic process
GO:0006766	vitamin metabolic process
GO:0006767	water-soluble vitamin metabolic process
GO:0006771	riboflavin metabolic process
GO:0006796	phosphate-containing compound metabolic process
GO:0006898	receptor-mediated endocytosis
GO:0006955	immune response
GO:0008152	metabolic process
GO:0009143	nucleoside triphosphate catabolic process
GO:0030279	negative regulation of ossification
GO:0030308	negative regulation of cell growth
GO:0030500	regulation of bone mineralization
GO:0030505	inorganic diphosphate transport
GO:0030643	cellular phosphate ion homeostasis
GO:0030730	sequestering of triglyceride
GO:0031214	biomineral tissue development
GO:0031953	negative regulation of protein autophosphorylation
GO:0032869	cellular response to insulin stimulus
GO:0044281	small molecule metabolic process
GO:0045599	negative regulation of fat cell differentiation
GO:0045719	negative regulation of glycogen biosynthetic process
GO:0046325	negative regulation of glucose import
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0046849	bone remodeling
GO:0050427	3'-phosphoadenosine 5'-phosphosulfate metabolic process
GO:0090305	nucleic acid phosphodiester bond hydrolysis

Cellular Component

GO:0005615	extracellular space
GO:0005765	lysosomal membrane
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0016323	basolateral plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR001212 Somatomedin B domain
IPR001604 DNA/RNA non-specific endonuclease
IPR002591 Type I phosphodiesterase/nucleotide pyrophosphatase/phosphate transferase
IPR017850 Alkaline-phosphatase-like, core domain
IPR020436 Somatomedin B, chordata
IPR020821 Extracellular Endonuclease, subunit A

PFAM

PF01033
PF01223
PF01663

PRINTS

PR00022

PIRSF

SMART

SM00201
SM00892
SM00477

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt