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UniProtKB - P22413 (ENPP1_HUMAN)

Entry version 221 (29 Sep 2021)
Sequence version 2 (19 Sep 2002)
Previous versions | rss
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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Gene

ENPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:27467858, PubMed:8001561, PubMed:25344812).

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).

By similarity1 Publication5 Publications

Caution

It is uncertain whether Met-1 or Met-53 is the initiator.Curated

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

  • Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.1 Publication EC:3.1.4.1

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.By similarity

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

Kcat is 4 sec(-1) with 2'-3'-cGAMP (PubMed:25344812). Kcat is 12 sec(-1) with ATP (PubMed:25344812).1 Publication
  1. KM=15 µM for 2'-3'-cGAMP1 Publication
  2. KM=20 µM for ATP1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi218Zinc 1; catalyticBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei256AMP-threonine intermediateBy similarity1
Metal bindingi256Zinc 1; catalyticBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei277SubstrateBy similarity1
Binding sitei295SubstrateBy similarity1
Binding sitei326SubstrateBy similarity1
Binding sitei340SubstrateBy similarity1
Metal bindingi376Zinc 2; catalyticBy similarity1
Metal bindingi380Zinc 2; via tele nitrogen; catalyticBy similarity1
Binding sitei380Substrate 2'-3'-cGAMPBy similarity1
Metal bindingi423Zinc 1; catalyticBy similarity1
Metal bindingi424Zinc 1; via tele nitrogen; catalyticBy similarity1
Binding sitei532Substrate 2'-3'-cGAMPBy similarity1
Metal bindingi535Zinc 2; via tele nitrogen; catalyticBy similarity1
Metal bindingi800CalciumBy similarity1
Metal bindingi802CalciumBy similarity1
Metal bindingi804CalciumBy similarity1
Metal bindingi806Calcium; via carbonyl oxygenBy similarity1
Metal bindingi808CalciumBy similarity1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei915Essential for catalytic activityBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase
Biological processBiomineralization
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		3.6.1.9, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P22413

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-196843, Vitamin B2 (riboflavin) metabolism
R-HSA-199220, Vitamin B5 (pantothenate) metabolism

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		P22413

SIGNOR Signaling Network Open Resource

More...SIGNORi		P22413

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Short name:
E-NPP 11 Publication
Alternative name(s):
Membrane component chromosome 6 surface marker 1
Phosphodiesterase I/nucleotide pyrophosphatase 1
Plasma-cell membrane glycoprotein PC-11 Publication
Cleaved into the following chain:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted formCurated
Including the following 2 domains:
Alkaline phosphodiesterase I1 Publication (EC:3.1.4.11 Publication)
Nucleotide pyrophosphatase1 Publication (EC:3.6.1.91 Publication)
Short name:
NPPase
Alternative name(s):
Nucleotide diphosphataseCurated
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ENPP1Imported
Synonyms:M6S1, NPPS1 Publication, PC11 Publication, PDNP1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:3356, ENPP1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		173335, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P22413

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000197594

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 76CytoplasmicSequence analysisAdd BLAST76
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei77 – 97Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini98 – 925ExtracellularSequence analysisAdd BLAST828

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Ossification of the posterior longitudinal ligament of the spine (OPLL)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_01414191L → P in OPLL. 1 Publication1
Natural variantiVAR_014143287S → F in OPLL. 1 PublicationCorresponds to variant dbSNP:rs190947144EnsemblClinVar.1
Arterial calcification of infancy, generalized, 1 (GACI1)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077256126C → R in GACI1. 1 Publication1
Natural variantiVAR_077259195C → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs763457176Ensembl.1
Natural variantiVAR_077260195C → S in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication1
Natural variantiVAR_077261216S → Y in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs760786509Ensembl.1
Natural variantiVAR_077262218D → V in GACI1. 1 PublicationCorresponds to variant dbSNP:rs1231182870Ensembl.1
Natural variantiVAR_077264242G → E in GACI1; unknown pathological significance. 1 Publication1
Natural variantiVAR_067910250P → L in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs754659608Ensembl.1
Natural variantiVAR_067911252Missing in GACI1. 1 Publication1
Natural variantiVAR_077265276D → N in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs143771474Ensembl.1
Natural variantiVAR_077266301Y → C in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication1
Natural variantiVAR_067912305P → T in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 3 PublicationsCorresponds to variant dbSNP:rs374270497EnsemblClinVar.1
Natural variantiVAR_037433342G → V in GACI1. 3 PublicationsCorresponds to variant dbSNP:rs121918025EnsemblClinVar.1
Natural variantiVAR_077267349R → K in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs764735802Ensembl.1
Natural variantiVAR_037434371Y → F in GACI1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs121918026EnsemblClinVar.1
Natural variantiVAR_077268456R → Q in GACI1. 1 PublicationCorresponds to variant dbSNP:rs765071179Ensembl.1
Natural variantiVAR_077269471Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs148462924Ensembl.1
Natural variantiVAR_077270481R → W in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs373044722EnsemblClinVar.1
Natural variantiVAR_077271500H → P in GACI1. 1 Publication1
Natural variantiVAR_077272504S → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 Publications1
Natural variantiVAR_077273513Y → C in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs1243920034Ensembl.1
Natural variantiVAR_067913538D → H in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs387906673EnsemblClinVar.1
Natural variantiVAR_077274570Y → C in GACI1. 1 PublicationCorresponds to variant dbSNP:rs140248167Ensembl.1
Natural variantiVAR_018514579L → F in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs121918024EnsemblClinVar.1
Natural variantiVAR_067914586G → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs777367269EnsemblClinVar.1
Natural variantiVAR_077276659Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs143393727Ensembl.1
Natural variantiVAR_077278726C → R in GACI1. 1 Publication1
Natural variantiVAR_077279777H → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs147346173EnsemblClinVar.1
Natural variantiVAR_077280792N → S in ARHR2 and GACI1. 2 PublicationsCorresponds to variant dbSNP:rs370184526Ensembl.1
Natural variantiVAR_077281804D → H in GACI1. 1 Publication1
Natural variantiVAR_077283888R → W in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs184483616Ensembl.1
Diabetes mellitus, non-insulin-dependent (NIDDM)2 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07725592G → D in ARHR2. 1 Publication1
Natural variantiVAR_077263219G → R in ARHR2; unknown pathological significance. 1 Publication1
Natural variantiVAR_063719266G → V in ARHR2. 1 PublicationCorresponds to variant dbSNP:rs121908248EnsemblClinVar.1
Natural variantiVAR_077280792N → S in ARHR2 and GACI1. 2 PublicationsCorresponds to variant dbSNP:rs370184526Ensembl.1
Natural variantiVAR_063720901Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121908249EnsemblClinVar.1
Cole disease (COLED)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_081644120C → R in COLED; impaired homodimerization. 1 Publication1
Natural variantiVAR_077257133C → R in COLED; impaired homodimerization. 2 Publications1
Natural variantiVAR_070782149C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518477EnsemblClinVar.1
Natural variantiVAR_070783164C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518476EnsemblClinVar.1
Natural variantiVAR_077258177C → S in COLED. 1 Publication1
Natural variantiVAR_070784177C → Y in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518475EnsemblClinVar.1

Keywords - Diseasei

Diabetes mellitus, Disease variant, Obesity

Organism-specific databases

DisGeNET

More...DisGeNETi		5167

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		ENPP1

MalaCards human disease database

More...MalaCardsi		ENPP1
MIMi125853, phenotype
208000, phenotype
602475, phenotype
613312, phenotype
615522, phenotype

Open Targets

More...OpenTargetsi		ENSG00000197594

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		289176, Autosomal recessive hypophosphatemic rickets
51608, Generalized arterial calcification of infancy
324561, Hypopigmentation-punctate palmoplantar keratoderma syndrome
758, Pseudoxanthoma elasticum

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA27791

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P22413, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL5925

Drug and drug target database

More...DrugBanki		DB13893, Crotalus adamanteus antivenin
DB11077, Polyethylene glycol 400
DB06408, Taribavirin

DrugCentral

More...DrugCentrali		P22413

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		ENPP1

Domain mapping of disease mutations (DMDM)

More...DMDMi		23503088

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001885641 – 925Ectonucleotide pyrophosphatase/phosphodiesterase family member 1Add BLAST925
ChainiPRO_0000447133103 – 925Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted formBy similarityAdd BLAST823

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi108 ↔ 122PROSITE-ProRule annotation
Disulfide bondi112 ↔ 140PROSITE-ProRule annotation
Disulfide bondi120 ↔ 133PROSITE-ProRule annotation
Disulfide bondi126 ↔ 132PROSITE-ProRule annotation
Disulfide bondi149 ↔ 166PROSITE-ProRule annotation
Disulfide bondi154 ↔ 184PROSITE-ProRule annotation
Disulfide bondi164 ↔ 177PROSITE-ProRule annotation
Disulfide bondi170 ↔ 176PROSITE-ProRule annotation
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi179N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi195 ↔ 241PROSITE-ProRule annotation
Disulfide bondi203 ↔ 415PROSITE-ProRule annotation
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei256PhosphothreonineBy similarity1
Glycosylationi285N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi341N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi431 ↔ 530PROSITE-ProRule annotation
Glycosylationi477N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi480 ↔ 868PROSITE-ProRule annotation
Glycosylationi585N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi614 ↔ 672PROSITE-ProRule annotation
Disulfide bondi626 ↔ 726PROSITE-ProRule annotation
Disulfide bondi628 ↔ 711PROSITE-ProRule annotation
Glycosylationi643N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi700N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi731N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi748N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi838 ↔ 848PROSITE-ProRule annotation

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity.1 Publication
N-glycosylated.3 Publications
The secreted form is produced through cleavage at Lys-103 by intracellular processing.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei102 – 103CleavageBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P22413

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P22413

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P22413

MaxQB - The MaxQuant DataBase

More...MaxQBi		P22413

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P22413

PeptideAtlas

More...PeptideAtlasi		P22413

PRoteomics IDEntifications database

More...PRIDEi		P22413

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		53988

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		1196, 19 N-Linked glycans (2 sites)

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P22413, 10 sites, 18 N-linked glycans (2 sites), 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P22413

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P22413

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis (PubMed:9344668). Expressed in melanocytes but not in keratinocytes (PubMed:28964717).2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000197594, Expressed in tibia and 210 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P22413, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P22413, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000197594, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (PubMed:28964717).

Interacts with INSR; leading to inhibit INSR autophosphorylation and subsequent activation of INSR kinase activity (PubMed:10615944).

2 Publications

Monomeric (By similarity).

By similarity

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		111193, 23 interactors

Protein interaction database and analysis system

More...IntActi		P22413, 13 interactors

Molecular INTeraction database

More...MINTi		P22413

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000354238

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P22413

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P22413, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1925
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Biological Magnetic Resonance Data Bank

More...BMRBi		P22413

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P22413

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P22413

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini104 – 144SMB 1PROSITE-ProRule annotationAdd BLAST41
Domaini145 – 189SMB 2PROSITE-ProRule annotationAdd BLAST45

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 43DisorderedSequence analysisAdd BLAST43
Regioni191 – 591PhosphodiesteraseBy similarityAdd BLAST401
Regioni597 – 647LinkerBy similarityAdd BLAST51
Regioni654 – 925NucleaseBy similarityAdd BLAST272

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi45 – 52Di-leucine motifBy similarity8

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.By similarity

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.Curated

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2645, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000156034

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_012256_0_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P22413

Identification of Orthologs from Complete Genome Data

More...OMAi		EHIWTCS

Database of Orthologous Groups

More...OrthoDBi		999163at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P22413

TreeFam database of animal gene trees

More...TreeFami		TF330032

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.40.720.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR017850, Alkaline_phosphatase_core_sf
IPR001604, DNA/RNA_non-sp_Endonuclease
IPR029890, ENPP1
IPR020821, Extracellular_endonuc_su_A
IPR002591, Phosphodiest/P_Trfase
IPR036024, Somatomedin_B-like_dom_sf
IPR020436, Somatomedin_B_chordata
IPR001212, Somatomedin_B_dom

The PANTHER Classification System

More...PANTHERi		PTHR10151:SF77, PTHR10151:SF77, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF01223, Endonuclease_NS, 1 hit
PF01663, Phosphodiest, 1 hit
PF01033, Somatomedin_B, 2 hits

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00022, SOMATOMEDINB

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00892, Endonuclease_NS, 1 hit
SM00477, NUC, 1 hit
SM00201, SO, 2 hits

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF53649, SSF53649, 1 hit
SSF90188, SSF90188, 2 hits

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00524, SMB_1, 2 hits
PS50958, SMB_2, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P22413-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MERDGCAGGG SRGGEGGRAP REGPAGNGRD RGRSHAAEAP GDPQAAASLL 
        60         70         80         90        100
APMDVGEEPL EKAARARTAK DPNTYKVLSL VLSVCVLTTI LGCIFGLKPS 
       110        120        130        140        150
CAKEVKSCKG RCFERTFGNC RCDAACVELG NCCLDYQETC IEPEHIWTCN 
       160        170        180        190        200
KFRCGEKRLT RSLCACSDDC KDKGDCCINY SSVCQGEKSW VEEPCESINE 
       210        220        230        240        250
PQCPAGFETP PTLLFSLDGF RAEYLHTWGG LLPVISKLKK CGTYTKNMRP 
       260        270        280        290        300
VYPTKTFPNH YSIVTGLYPE SHGIIDNKMY DPKMNASFSL KSKEKFNPEW 
       310        320        330        340        350
YKGEPIWVTA KYQGLKSGTF FWPGSDVEIN GIFPDIYKMY NGSVPFEERI 
       360        370        380        390        400
LAVLQWLQLP KDERPHFYTL YLEEPDSSGH SYGPVSSEVI KALQRVDGMV 
       410        420        430        440        450
GMLMDGLKEL NLHRCLNLIL ISDHGMEQGS CKKYIYLNKY LGDVKNIKVI 
       460        470        480        490        500
YGPAARLRPS DVPDKYYSFN YEGIARNLSC REPNQHFKPY LKHFLPKRLH 
       510        520        530        540        550
FAKSDRIEPL TFYLDPQWQL ALNPSERKYC GSGFHGSDNV FSNMQALFVG 
       560        570        580        590        600
YGPGFKHGIE ADTFENIEVY NLMCDLLNLT PAPNNGTHGS LNHLLKNPVY 
       610        620        630        640        650
TPKHPKEVHP LVQCPFTRNP RDNLGCSCNP SILPIEDFQT QFNLTVAEEK 
       660        670        680        690        700
IIKHETLPYG RPRVLQKENT ICLLSQHQFM SGYSQDILMP LWTSYTVDRN 
       710        720        730        740        750
DSFSTEDFSN CLYQDFRIPL SPVHKCSFYK NNTKVSYGFL SPPQLNKNSS 
       760        770        780        790        800
GIYSEALLTT NIVPMYQSFQ VIWRYFHDTL LRKYAEERNG VNVVSGPVFD 
       810        820        830        840        850
FDYDGRCDSL ENLRQKRRVI RNQEILIPTH FFIVLTSCKD TSQTPLHCEN 
       860        870        880        890        900
LDTLAFILPH RTDNSESCVH GKHDSSWVEE LLMLHRARIT DVEHITGLSF 
       910        920 
YQQRKEPVSD ILKLKTHLPT FSQED
Length:925
Mass (Da):104,924
Last modified:September 19, 2002 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i0ECAA063801CAFEB
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PE72E9PE72_HUMAN
Ectonucleotide pyrophosphatase/phos...
ENPP1
378Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A3B3IST7A0A3B3IST7_HUMAN
Ectonucleotide pyrophosphatase/phos...
ENPP1
56Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A3B3ISN7A0A3B3ISN7_HUMAN
Ectonucleotide pyrophosphatase/phos...
ENPP1
110Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A3B3IU14A0A3B3IU14_HUMAN
Ectonucleotide pyrophosphatase/phos...
ENPP1
68Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAA63237 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAH59375 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAA02054 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01414191L → P in OPLL. 1 Publication1
Natural variantiVAR_07725592G → D in ARHR2. 1 Publication1
Natural variantiVAR_081644120C → R in COLED; impaired homodimerization. 1 Publication1
Natural variantiVAR_077256126C → R in GACI1. 1 Publication1
Natural variantiVAR_077257133C → R in COLED; impaired homodimerization. 2 Publications1
Natural variantiVAR_070782149C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518477EnsemblClinVar.1
Natural variantiVAR_070783164C → S in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518476EnsemblClinVar.1
Natural variantiVAR_008873173K → Q Associated with NIDDM; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 6 PublicationsCorresponds to variant dbSNP:rs1044498EnsemblClinVar.1
Natural variantiVAR_077258177C → S in COLED. 1 Publication1
Natural variantiVAR_070784177C → Y in COLED. 1 PublicationCorresponds to variant dbSNP:rs397518475EnsemblClinVar.1
Natural variantiVAR_037432179N → S. Corresponds to variant dbSNP:rs2273411Ensembl.1
Natural variantiVAR_077259195C → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs763457176Ensembl.1
Natural variantiVAR_077260195C → S in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication1
Natural variantiVAR_077261216S → Y in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs760786509Ensembl.1
Natural variantiVAR_077262218D → V in GACI1. 1 PublicationCorresponds to variant dbSNP:rs1231182870Ensembl.1
Natural variantiVAR_077263219G → R in ARHR2; unknown pathological significance. 1 Publication1
Natural variantiVAR_077264242G → E in GACI1; unknown pathological significance. 1 Publication1
Natural variantiVAR_067910250P → L in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs754659608Ensembl.1
Natural variantiVAR_067911252Missing in GACI1. 1 Publication1
Natural variantiVAR_063719266G → V in ARHR2. 1 PublicationCorresponds to variant dbSNP:rs121908248EnsemblClinVar.1
Natural variantiVAR_014142268Y → H1 PublicationCorresponds to variant dbSNP:rs17847050EnsemblClinVar.1
Natural variantiVAR_077265276D → N in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs143771474Ensembl.1
Natural variantiVAR_014143287S → F in OPLL. 1 PublicationCorresponds to variant dbSNP:rs190947144EnsemblClinVar.1
Natural variantiVAR_077266301Y → C in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 1 Publication1
Natural variantiVAR_067912305P → T in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 3 PublicationsCorresponds to variant dbSNP:rs374270497EnsemblClinVar.1
Natural variantiVAR_037433342G → V in GACI1. 3 PublicationsCorresponds to variant dbSNP:rs121918025EnsemblClinVar.1
Natural variantiVAR_077267349R → K in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs764735802Ensembl.1
Natural variantiVAR_037434371Y → F in GACI1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs121918026EnsemblClinVar.1
Natural variantiVAR_077268456R → Q in GACI1. 1 PublicationCorresponds to variant dbSNP:rs765071179Ensembl.1
Natural variantiVAR_077269471Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs148462924Ensembl.1
Natural variantiVAR_077270481R → W in GACI1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs373044722EnsemblClinVar.1
Natural variantiVAR_077271500H → P in GACI1. 1 Publication1
Natural variantiVAR_077272504S → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 Publications1
Natural variantiVAR_077273513Y → C in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs1243920034Ensembl.1
Natural variantiVAR_067913538D → H in GACI1; loss of nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs387906673EnsemblClinVar.1
Natural variantiVAR_077274570Y → C in GACI1. 1 PublicationCorresponds to variant dbSNP:rs140248167Ensembl.1
Natural variantiVAR_018514579L → F in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs121918024EnsemblClinVar.1
Natural variantiVAR_067914586G → R in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs777367269EnsemblClinVar.1
Natural variantiVAR_077275611L → V1 PublicationCorresponds to variant dbSNP:rs79079368EnsemblClinVar.1
Natural variantiVAR_077276659Y → C in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs143393727Ensembl.1
Natural variantiVAR_077277668E → K No effect on nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs115371819EnsemblClinVar.1
Natural variantiVAR_077278726C → R in GACI1. 1 Publication1
Natural variantiVAR_018515774R → C Decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 4 PublicationsCorresponds to variant dbSNP:rs28933977EnsemblClinVar.1
Natural variantiVAR_077279777H → R in GACI1; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs147346173EnsemblClinVar.1
Natural variantiVAR_014144779T → P1 PublicationCorresponds to variant dbSNP:rs1805138EnsemblClinVar.1
Natural variantiVAR_077280792N → S in ARHR2 and GACI1. 2 PublicationsCorresponds to variant dbSNP:rs370184526Ensembl.1
Natural variantiVAR_077281804D → H in GACI1. 1 Publication1
Natural variantiVAR_077282821R → H Decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs367759638EnsemblClinVar.1
Natural variantiVAR_037435886R → T. Corresponds to variant dbSNP:rs8192683EnsemblClinVar.1
Natural variantiVAR_077283888R → W in GACI1; loss of nucleotide phosphodiesterase activity; loss of localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs184483616Ensembl.1
Natural variantiVAR_063720901Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121908249EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
M57736 mRNA Translation: AAA63237.1 Different initiation.
D12485 mRNA Translation: BAA02054.1 Different initiation.
AF110304 AF110303 Genomic DNA Translation: AAF36094.1
AJ242020 AJ242044 Genomic DNA Translation: CAC39442.1
AL117378 Genomic DNA No translation available.
AL139805 Genomic DNA No translation available.
BC059375 mRNA Translation: AAH59375.2 Different initiation.
AF067177 Genomic DNA Translation: AAD38420.1
AF067178 Genomic DNA Translation: AAD38421.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS5150.2

Protein sequence database of the Protein Information Resource

More...PIRi		A39216

NCBI Reference Sequences

More...RefSeqi		NP_006199.2, NM_006208.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000647893; ENSP00000498074; ENSG00000197594

Database of genes from NCBI RefSeq genomes

More...GeneIDi		5167

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:5167

UCSC genome browser

More...UCSCi		uc011ecf.2, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57736 mRNA Translation: AAA63237.1 Different initiation.
D12485 mRNA Translation: BAA02054.1 Different initiation.
AF110304 AF110303 Genomic DNA Translation: AAF36094.1
AJ242020 AJ242044 Genomic DNA Translation: CAC39442.1
AL117378 Genomic DNA No translation available.
AL139805 Genomic DNA No translation available.
BC059375 mRNA Translation: AAH59375.2 Different initiation.
AF067177 Genomic DNA Translation: AAD38420.1
AF067178 Genomic DNA Translation: AAD38421.1
CCDSiCCDS5150.2
PIRiA39216
RefSeqiNP_006199.2, NM_006208.2

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YS0NMR-A147-189[»]
6WETX-ray2.60AaA/BaB1-925[»]
6WEUX-ray2.65AbA/BbB1-925[»]
6WEVX-ray2.90AbA/BbB1-925[»]
6WEWX-ray2.73AbA/BaB1-925[»]
6WFJX-ray2.50AcA/BcB1-925[»]
BMRBiP22413
SMRiP22413
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi111193, 23 interactors
IntActiP22413, 13 interactors
MINTiP22413
STRINGi9606.ENSP00000354238

Chemistry databases

BindingDBiP22413
ChEMBLiCHEMBL5925
DrugBankiDB13893, Crotalus adamanteus antivenin
DB11077, Polyethylene glycol 400
DB06408, Taribavirin
DrugCentraliP22413

PTM databases

GlyConnecti1196, 19 N-Linked glycans (2 sites)
GlyGeniP22413, 10 sites, 18 N-linked glycans (2 sites), 1 O-linked glycan (1 site)
iPTMnetiP22413
PhosphoSitePlusiP22413

Genetic variation databases

BioMutaiENPP1
DMDMi23503088

Proteomic databases

EPDiP22413
jPOSTiP22413
MassIVEiP22413
MaxQBiP22413
PaxDbiP22413
PeptideAtlasiP22413
PRIDEiP22413
ProteomicsDBi53988

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		32916, 411 antibodies

The DNASU plasmid repository

More...DNASUi		5167

Genome annotation databases

EnsembliENST00000647893; ENSP00000498074; ENSG00000197594
GeneIDi5167
KEGGihsa:5167
UCSCiuc011ecf.2, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		5167
DisGeNETi5167

GeneCards: human genes, protein and diseases

More...GeneCardsi		ENPP1
GeneReviewsiENPP1
HGNCiHGNC:3356, ENPP1
HPAiENSG00000197594, Low tissue specificity
MalaCardsiENPP1
MIMi125853, phenotype
173335, gene
208000, phenotype
602475, phenotype
613312, phenotype
615522, phenotype
neXtProtiNX_P22413
OpenTargetsiENSG00000197594
Orphaneti289176, Autosomal recessive hypophosphatemic rickets
51608, Generalized arterial calcification of infancy
324561, Hypopigmentation-punctate palmoplantar keratoderma syndrome
758, Pseudoxanthoma elasticum
PharmGKBiPA27791
VEuPathDBiHostDB:ENSG00000197594

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2645, Eukaryota
GeneTreeiENSGT00940000156034
HOGENOMiCLU_012256_0_1_1
InParanoidiP22413
OMAiEHIWTCS
OrthoDBi999163at2759
PhylomeDBiP22413
TreeFamiTF330032

Enzyme and pathway databases

BRENDAi3.6.1.9, 2681
PathwayCommonsiP22413
ReactomeiR-HSA-196843, Vitamin B2 (riboflavin) metabolism
R-HSA-199220, Vitamin B5 (pantothenate) metabolism
SABIO-RKiP22413
SIGNORiP22413

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		5167, 5 hits in 1012 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		ENPP1, human
EvolutionaryTraceiP22413

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Ectonucleotide_pyrophosphatase/phosphodiesterase_1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		5167
PharosiP22413, Tchem

Protein Ontology

More...PROi		PR:P22413
RNActiP22413, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000197594, Expressed in tibia and 210 other tissues
ExpressionAtlasiP22413, baseline and differential
GenevisibleiP22413, HS

Family and domain databases

Gene3Di3.40.720.10, 1 hit
InterProiView protein in InterPro
IPR017850, Alkaline_phosphatase_core_sf
IPR001604, DNA/RNA_non-sp_Endonuclease
IPR029890, ENPP1
IPR020821, Extracellular_endonuc_su_A
IPR002591, Phosphodiest/P_Trfase
IPR036024, Somatomedin_B-like_dom_sf
IPR020436, Somatomedin_B_chordata
IPR001212, Somatomedin_B_dom
PANTHERiPTHR10151:SF77, PTHR10151:SF77, 1 hit
PfamiView protein in Pfam
PF01223, Endonuclease_NS, 1 hit
PF01663, Phosphodiest, 1 hit
PF01033, Somatomedin_B, 2 hits
PRINTSiPR00022, SOMATOMEDINB
SMARTiView protein in SMART
SM00892, Endonuclease_NS, 1 hit
SM00477, NUC, 1 hit
SM00201, SO, 2 hits
SUPFAMiSSF53649, SSF53649, 1 hit
SSF90188, SSF90188, 2 hits
PROSITEiView protein in PROSITE
PS00524, SMB_1, 2 hits
PS50958, SMB_2, 2 hits

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiENPP1_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P22413
Secondary accession number(s): Q5T9R6
, Q9NPZ3, Q9P1P6, Q9UP61, Q9Y6K3
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: September 19, 2002
Last modified: September 29, 2021
This is version 221 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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