MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
3.1.4.1	Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases; phosphodiesterase I
3.6.1.9	Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides; nucleotide diphosphatase

Structure

PDB	Resolution (Å)	PDB name
2YS0		Solution structure of the Somatomedin B domain of human Ectonucleotide pyrophosphatase/phosphodiesterase family member
6WET	2.6	Crystal structures of human E-NPP 1: apo
6WEU	2.65	Crystal structures of human E-NPP 1: bound to adenosine-5'-thio-monophosphate
6WEV	2.9	Crystal structures of human E-NPP 1: bound to N-{[1-(6,7-dimethoxy-5,8-dihydroquinazolin-4-yl)piperidin-4-yl]methyl}sulfuric diamide
6WEW	2.73	Crystal structures of human E-NPP 1: bound to N-{4-[(7-methoxyquinolin-4-yl)oxy]phenyl}sulfuric diamide
6WFJ	2.5	Crystal structures of human E-NPP 1: apo

GO term

GO ontology	GO term	GO description
Biological Process	GO:0050427	3'-phosphoadenosine 5'-phosphosulfate metabolic process
Biological Process	GO:0046034	ATP metabolic process
Biological Process	GO:0030282	bone mineralization
Biological Process	GO:0032869	cellular response to insulin stimulus
Biological Process	GO:0010467	gene expression
Biological Process	GO:0006091	generation of precursor metabolites and energy
Biological Process	GO:0006955	immune response
Biological Process	GO:0030505	inorganic diphosphate transport
Biological Process	GO:0030643	intracellular phosphate ion homeostasis
Biological Process	GO:0030318	melanocyte differentiation
Biological Process	GO:0030502	negative regulation of bone mineralization
Biological Process	GO:0030308	negative regulation of cell growth
Biological Process	GO:0045599	negative regulation of fat cell differentiation
Biological Process	GO:0046325	negative regulation of glucose import
Biological Process	GO:0045719	negative regulation of glycogen biosynthetic process
Biological Process	GO:1990787	negative regulation of hh target transcription factor activity
Biological Process	GO:0046627	negative regulation of insulin receptor signaling pathway
Biological Process	GO:0031953	negative regulation of protein autophosphorylation
Biological Process	GO:0090305	nucleic acid phosphodiester bond hydrolysis
Biological Process	GO:0009143	nucleoside triphosphate catabolic process
Biological Process	GO:0055062	phosphate ion homeostasis
Biological Process	GO:0006796	phosphate-containing compound metabolic process
Biological Process	GO:0030500	regulation of bone mineralization
Biological Process	GO:0033198	response to ATP
Biological Process	GO:0010035	response to inorganic substance
Biological Process	GO:0030730	sequestering of triglyceride
Molecular Function	GO:0004115	3',5'-cyclic-AMP phosphodiesterase activity
Molecular Function	GO:0050656	3'-phosphoadenosine 5'-phosphosulfate binding
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0047693	ATP diphosphatase activity
Molecular Function	GO:0036219	GTP diphosphatase activity
Molecular Function	GO:0036221	UTP diphosphatase activity
Molecular Function	GO:0005509	calcium ion binding
Molecular Function	GO:0106177	cyclic-GMP-AMP hydrolase activity
Molecular Function	GO:0004551	dinucleotide phosphatase activity
Molecular Function	GO:0004527	exonuclease activity
Molecular Function	GO:0005158	insulin receptor binding
Molecular Function	GO:0003676	nucleic acid binding
Molecular Function	GO:0047429	nucleoside triphosphate diphosphatase activity
Molecular Function	GO:0016791	phosphatase activity
Molecular Function	GO:0004528	phosphodiesterase I activity
Molecular Function	GO:0030247	polysaccharide binding
Molecular Function	GO:0042803	protein homodimerization activity
Molecular Function	GO:0005044	scavenger receptor activity
Molecular Function	GO:0008270	zinc ion binding
Cellular Component	GO:0016323	basolateral plasma membrane
Cellular Component	GO:0009986	cell surface
Cellular Component	GO:0005615	extracellular space
Cellular Component	GO:0005765	lysosomal membrane
Cellular Component	GO:0016020	membrane
Cellular Component	GO:0005886	plasma membrane

InterPro / Pfam

InterPro	InterPro name
IPR001212	Somatomedin B domain
IPR001604	DNA/RNA non-specific endonuclease
IPR002591	Type I phosphodiesterase/nucleotide pyrophosphatase/phosphate transferase
IPR017850	Alkaline-phosphatase-like, core domain superfamily
IPR020436	Somatomedin B domain, chordata
IPR020821	Extracellular Endonuclease, subunit A
IPR036024	Somatomedin B-like domain superfamily
IPR044925	His-Me finger superfamily
IPR044929	DNA/RNA non-specific endonuclease superfamily

Pfam	Pfam name
PF01033	Somatomedin B domain
PF01223	DNA/RNA non-specific endonuclease
PF01663	Type I phosphodiesterase / nucleotide pyrophosphatase

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-196843	Vitamin B2 (riboflavin) metabolism	Leaf	R-HSA-1430728	Metabolism
R-HSA-199220	Vitamin B5 (pantothenate) metabolism	Internal node	R-HSA-1430728	Metabolism

Subcellular location

Location	ECO term	Pubmed
Basolateral cell membrane	ECO:0000269	PubMed:11598187
Cell membrane	ECO:0000269	PubMed:15072822
Cell membrane	ECO:0000269	PubMed:27467858
Cell membrane	ECO:0000269	PubMed:8001561
Secreted	ECO:0000250

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0002326	Transient ischemic attack
HP:0100679	Lack of skin elasticity
HP:0012052	Low serum calcitriol
HP:0011463	Childhood onset
HP:0000505	Visual impairment
HP:0000218	High palate
HP:0001945	Fever
HP:0007392	Excessive wrinkled skin
HP:0003416	Spinal canal stenosis
HP:0002013	Vomiting
HP:0100559	Lower limb asymmetry
HP:0001658	Myocardial infarction
HP:0004966	Medial calcification of large arteries
HP:0010639	Elevated alkaline phosphatase of bone origin
HP:0007530	Punctate palmoplantar hyperkeratosis
HP:0000006	Autosomal dominant inheritance
HP:0001324	Muscle weakness
HP:0002092	Pulmonary arterial hypertension
HP:0002652	Skeletal dysplasia
HP:0001561	Polyhydramnios
HP:0003836	Stippled calcification of the shoulder
HP:0005764	Polyarticular arthritis
HP:0003941	Stippled calcification of the elbow
HP:0008732	Renal hypophosphatemia
HP:0000121	Nephrocalcinosis
HP:0000670	Carious teeth
HP:0003020	Enlargement of the wrists
HP:0025169	Left ventricular systolic dysfunction
HP:0002098	Respiratory distress
HP:0002024	Malabsorption
HP:0025116	Fetal distress
HP:0000737	Irritability
HP:0001717	Coronary artery calcification
HP:0003584	Late onset
HP:0002970	Genu varum
HP:0004912	Hypophosphatemic rickets
HP:0025477	Periarticular calcification
HP:0001513	Obesity
HP:0001723	Restrictive cardiomyopathy
HP:0020073	Hypopigmented macule
HP:0000962	Hyperkeratosis
HP:0000365	Hearing impairment
HP:0003577	Congenital onset
HP:0002172	Postural instability
HP:0000989	Pruritus
HP:0000592	Blue sclerae
HP:0012508	Metamorphopsia
HP:0002829	Arthralgia
HP:0000573	Retinal hemorrhage
HP:0000545	Myopia
HP:0025114	Hypergranulosis
HP:0000684	Delayed eruption of teeth
HP:0031313	Abdominal aortic calcification
HP:0002750	Delayed skeletal maturation
HP:0001642	Pulmonic stenosis
HP:0001698	Pericardial effusion
HP:0001597	Abnormality of the nail
HP:0000974	Hyperextensible skin
HP:0030680	Abnormality of cardiovascular system morphology
HP:0000961	Cyanosis
HP:0004374	Hemiplegia/hemiparesis
HP:0002650	Scoliosis
HP:0012409	Cortical nephrocalcinosis
HP:0000988	Skin rash
HP:0001872	Abnormality of thrombocytes
HP:0031314	Carotid artery calcification
HP:0006559	Hepatic calcification
HP:0000407	Sensorineural hearing impairment
HP:0001634	Mitral valve prolapse
HP:0011001	Increased bone mineral density
HP:0012408	Medullary nephrocalcinosis
HP:0002814	Abnormality of the lower limb
HP:0002617	Vascular dilatation
HP:0002812	Coxa vara
HP:0001644	Dilated cardiomyopathy
HP:0010766	Ectopic calcification
HP:0001531	Failure to thrive in infancy
HP:0002514	Cerebral calcification
HP:0030757	Tooth abscess
HP:0040162	Orthokeratosis
HP:0000117	Renal phosphate wasting
HP:0002621	Atherosclerosis
HP:0001640	Cardiomegaly
HP:0001595	Abnormal hair morphology
HP:0011036	Abnormality of renal excretion
HP:0001920	Renal artery stenosis
HP:0003621	Juvenile onset
HP:0100671	Abnormal trabecular bone morphology
HP:0001012	Multiple lipomas
HP:0100758	Gangrene
HP:0100036	Pseudo-fractures
HP:0001681	Angina pectoris
HP:0006690	Myocardial calcification
HP:0002643	Neonatal respiratory distress
HP:0001250	Seizure
HP:0000765	Abnormal thorax morphology
HP:0004322	Short stature
HP:0002239	Gastrointestinal hemorrhage
HP:0011506	Choroidal neovascularization
HP:0005103	Calcification of the auricular cartilage
HP:0100686	Enthesitis
HP:0001065	Striae distensae
HP:0001541	Ascites
HP:0003593	Infantile onset
HP:0004940	Generalized arterial calcification
HP:0000969	Edema
HP:0040197	Encephalomalacia
HP:0001507	Growth abnormality
HP:0002857	Genu valgum
HP:0000855	Insulin resistance
HP:0000410	Mixed hearing impairment
HP:0000381	Stapes ankylosis
HP:0009164	Abnormal calcification of the carpal bones
HP:0100585	Telangiectasia of the skin
HP:0001102	Angioid streaks of the fundus
HP:0025092	Epidermal acanthosis
HP:0002815	Abnormality of the knee
HP:0003207	Arterial calcification
HP:0100659	Abnormal cerebral vascular morphology
HP:0001714	Ventricular hypertrophy
HP:0000474	Thickened nuchal skin fold
HP:0001363	Craniosynostosis
HP:0002647	Aortic dissection
HP:0025520	Calcinosis cutis
HP:0002653	Bone pain
HP:0001297	Stroke
HP:0001061	Acne
HP:0011968	Feeding difficulties
HP:0000978	Bruising susceptibility
HP:0001635	Congestive heart failure
HP:0100529	Abnormal blood phosphate concentration
HP:0031819	Increased waist to hip ratio
HP:0100511	Abnormality of vitamin D metabolism
HP:0012340	Decreased resting energy expenditure
HP:0001510	Growth delay
HP:0012457	Medial calcification of medium-sized arteries
HP:0005692	Joint hyperflexibility
HP:0031013	Ankylosis
HP:0000982	Palmoplantar keratoderma
HP:0001645	Sudden cardiac death
HP:0100781	Abnormal sacroiliac joint morphology
HP:0004963	Calcification of the aorta
HP:0005978	Type II diabetes mellitus
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0002949	Fused cervical vertebrae
HP:0000630	Abnormal retinal artery morphology
HP:0003109	Hyperphosphaturia
HP:0010982	Polygenic inheritance
HP:0001482	Subcutaneous nodule
HP:0003074	Hyperglycemia
HP:0100545	Arterial stenosis
HP:0000822	Hypertension
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0002749	Osteomalacia
HP:0005096	Distal femoral bowing
HP:0003623	Neonatal onset
HP:0000821	Hypothyroidism
HP:0010512	Adrenal calcification
HP:0005213	Pancreatic calcification
HP:0002982	Tibial bowing
HP:0002673	Coxa valga
HP:0000405	Conductive hearing impairment
HP:0003472	Hypocalcemic tetany
HP:0011344	Severe global developmental delay
HP:0000951	Abnormality of the skin
HP:0004306	Abnormal endocardium morphology
HP:0001384	Abnormal hip joint morphology
HP:0004576	Sclerotic vertebral endplates
HP:0006463	Rickets of the lower limbs
HP:0001789	Hydrops fetalis
HP:0000685	Hypoplasia of teeth
HP:0000488	Retinopathy
HP:0032553	Weak pulse

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
appendix	endocrine cells	Low	Enhanced
appendix	enterocytes	Low	Enhanced
appendix	germinal center cells	Medium	Enhanced
appendix	goblet cells	Low	Enhanced
breast	glandular cells	Low	Enhanced
caudate	neuronal cells	Low	Enhanced
cerebral cortex	endothelial cells	Low	Enhanced
cerebral cortex	neuropil	Low	Enhanced
cervix	glandular cells	Low	Enhanced
cervix	squamous epithelial cells	Low	Enhanced
colon	endothelial cells	Low	Enhanced
colon	enterocytes	Low	Enhanced
colon	enterocytes - Microvilli	Low	Enhanced
colon	goblet cells	Low	Enhanced
duodenum	paneth cells	Low	Enhanced
endometrium 1	cells in endometrial stroma	Low	Enhanced
epididymis	glandular cells	Low	Enhanced
gallbladder	glandular cells	Medium	Enhanced
kidney	distal tubules	Medium	Enhanced
kidney	proximal tubules (cell body)	Medium	Enhanced
liver	hepatocytes	Medium	Enhanced
lung	macrophages	Low	Enhanced
ovary	ovarian stroma cells	Low	Enhanced
pancreas	exocrine glandular cells	Medium	Enhanced
parathyroid gland	glandular cells	High	Enhanced
rectum	enterocytes	Low	Enhanced
rectum	enterocytes - Microvilli	Low	Enhanced
rectum	goblet cells	Low	Enhanced
seminal vesicle	glandular cells	Low	Enhanced
skin 1	cells in corneal layer	Medium	Enhanced
skin 1	cells in granular layer	Medium	Enhanced
skin 1	cells in spinous layer	Medium	Enhanced
skin 1	endothelial cells	Low	Enhanced
skin 1	fibrohistiocytic cells	Low	Enhanced
skin 1	langerhans cells	Medium	Enhanced
skin 2	cells in corneal layer	Medium	Enhanced
skin 2	cells in granular layer	Medium	Enhanced
skin 2	cells in spinous layer	Medium	Enhanced
skin 2	endothelial cells	Low	Enhanced
skin 2	fibrohistiocytic cells	Low	Enhanced
skin 2	langerhans cells	Medium	Enhanced
skin 2	lymphocytes	Low	Enhanced
small intestine	enterocytes	Low	Enhanced
small intestine	goblet cells	Low	Enhanced
small intestine	paneth cells	Low	Enhanced
smooth muscle	smooth muscle cells	Low	Enhanced
stomach 1	glandular cells	Medium	Enhanced
stomach 2	glandular cells	Medium	Enhanced
testis	Leydig cells	Medium	Enhanced
thyroid gland	glandular cells	High	Enhanced
vagina	squamous epithelial cells	Low	Enhanced

Disease

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
type 2 diabetes mellitus	MONDO:0005148	E11	chapter4, Endocrine, nutritional and metabolic diseases	OMIM:125853
arterial calcification, generalized, of infancy, 1	MONDO:0008817	Q28	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:208000
autosomal recessive inherited pseudoxanthoma elasticum	MONDO:0009925	Q82	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:264800	Orphanet:758
ossification of the posterior longitudinal ligament of the spine	MONDO:0011230	M48	chapter13, Diseases of the musculoskeletal system and connective tissue	OMIM:602475
hypophosphatemic rickets, autosomal recessive, 2	MONDO:0013219	E83	chapter4, Endocrine, nutritional and metabolic diseases	OMIM:613312
hypopigmentation-punctate palmoplantar keratoderma syndrome	MONDO:0014227	Q82	chapter17, Congenital malformations, deformations and chromosomal abnormalities	OMIM:615522	Orphanet:324561

Summary of P22413

Gene: ENPP1, M6S1, NPPS, PC1, PDNP1
Protein: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P22413

Gene: ENPP1, M6S1, NPPS, PC1, PDNP1 Protein: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: ENPP1, M6S1, NPPS, PC1, PDNP1
Protein: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1