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UniProtKB - P22413 (ENPP1_HUMAN)

Entry version 219 (07 Apr 2021)
Sequence version 2 (19 Sep 2002)
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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%5Fsection">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%5Fsection">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%5Fsection">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%5Fsection">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%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fmanual">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:ENSG00000197594.11

    <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%5Flocation%5Fsection">'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%5Flocation%5Fsection">'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%5Fprocessing%5Fsection">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%5Fprocessing%5Fsection">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, 9 sites

    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%5Fsection">'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%5Fsection">'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, 21 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%5Fand%5Fdomains%5Fsection">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>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    		DHTESCA

    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%5Flength">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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, 21 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, 9 sites
    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, 404 antibodies

    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:ENSG00000197594.11

    GenAtlas: human gene database

    More...    GenAtlasi    		Search...

    Phylogenomic databases

    eggNOGiKOG2645, Eukaryota
    GeneTreeiENSGT00940000156034
    HOGENOMiCLU_012256_0_1_1
    InParanoidiP22413
    OMAiDHTESCA
    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 990 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

    ProtoNet; Automatic hierarchical classification of proteins

    More...    ProtoNeti    		Search...

    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%5Fand%5Fisoforms">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: April 7, 2021
    This is version 219 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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