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UniProtKB - P22413 (ENPP1_HUMAN)

Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Gene

ENPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Appears to modulate insulin sensitivity and function.3 Publications

Caution

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

Catalytic activityi

Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.1 Publication
A nucleoside triphosphate + H2O = a nucleotide + diphosphate.1 Publication

Cofactori

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

Activity regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi218Zinc 1; catalyticBy similarity1
Active sitei256AMP-threonine intermediateBy similarity1
Metal bindingi256Zinc 1; catalyticBy similarity1
Binding sitei277SubstrateBy similarity1
Binding sitei295SubstrateBy similarity1
Binding sitei340SubstrateBy similarity1
Metal bindingi376Zinc 2; catalyticBy similarity1
Metal bindingi380Zinc 2; via tele nitrogen; catalyticBy similarity1
Metal bindingi423Zinc 1; catalyticBy similarity1
Metal bindingi424Zinc 1; via tele nitrogen; catalyticBy 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
Sitei915Essential for catalytic activityBy similarity1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase
Biological processBiomineralization
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Short name:
E-NPP 1
Alternative name(s):
Membrane component chromosome 6 surface marker 1
Phosphodiesterase I/nucleotide pyrophosphatase 1
Plasma-cell membrane glycoprotein PC-1
Including the following 2 domains:
Alkaline phosphodiesterase I (EC:3.1.4.11 Publication)
Nucleotide pyrophosphatase (EC:3.6.1.91 Publication)
Short name:
NPPase
Alternative name(s):
Nucleotide diphosphataseCurated
Gene namesi
Name:ENPP1
Synonyms:M6S1, NPPS, PC1, PDNP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000197594.11
HGNCiHGNC:3356 ENPP1
MIMi173335 gene
neXtProtiNX_P22413

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 76CytoplasmicSequence analysisAdd BLAST76
Transmembranei77 – 97Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini98 – 925ExtracellularSequence analysisAdd BLAST828

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Ossification of the posterior longitudinal ligament of the spine (OPLL)1 Publication
The disease is caused by mutations 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.
See also OMIM:602475
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01414191L → P in OPLL. 1 Publication1
Natural variantiVAR_014143287S → F in OPLL. 1 PublicationCorresponds to variant dbSNP:rs190947144Ensembl.1
Arterial calcification of infancy, generalized, 1 (GACI1)7 Publications
The disease is caused by mutations 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.
See also OMIM:208000
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_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)1 Publication
Disease susceptibility is associated with variations 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.
See also OMIM:125853
Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2)3 Publications
The disease is caused by mutations 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.
See also OMIM:613312
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_063720901Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121908249EnsemblClinVar.1
Cole disease (COLED)2 Publications
The disease is caused by mutations 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.
See also OMIM:615522
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077257133C → R in COLED. 1 Publication1
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 mutation, Obesity

Organism-specific databases

DisGeNETi5167
MalaCardsiENPP1
MIMi125853 phenotype
208000 phenotype
602475 phenotype
613312 phenotype
615522 phenotype
OpenTargetsiENSG00000197594
Orphaneti289176 Autosomal recessive hypophosphatemic rickets
51608 Generalized arterial calcification of infancy
324561 Hypopigmentation-punctate palmoplantar keratoderma syndrome
758 Pseudoxanthoma elasticum
PharmGKBiPA27791

Chemistry databases

ChEMBLiCHEMBL5925
DrugBankiDB01143 Amifostine
DB00811 Ribavirin

Polymorphism and mutation databases

BioMutaiENPP1
DMDMi23503088

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001885641 – 925Ectonucleotide pyrophosphatase/phosphodiesterase family member 1Add BLAST925

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
Glycosylationi179N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi195 ↔ 241PROSITE-ProRule annotation
Disulfide bondi203 ↔ 415PROSITE-ProRule annotation
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

Post-translational modificationi

Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity.
N-glycosylated.3 Publications
A 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

EPDiP22413
MaxQBiP22413
PaxDbiP22413
PeptideAtlasiP22413
PRIDEiP22413
ProteomicsDBi53988

PTM databases

GlyConnecti1196
iPTMnetiP22413
PhosphoSitePlusiP22413

Expressioni

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.1 Publication

Gene expression databases

BgeeiENSG00000197594 Expressed in 192 organ(s), highest expression level in tibia
CleanExiHS_ENPP1
ExpressionAtlasiP22413 baseline and differential
GenevisibleiP22413 HS

Organism-specific databases

HPAiCAB032904
HPA062066

Interactioni

Subunit structurei

The secreted form is monomeric (By similarity). Homodimer. Interacts with INSR.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
INSRP062132EBI-3197846,EBI-475899

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111193, 15 interactors
IntActiP22413, 5 interactors
MINTiP22413
STRINGi9606.ENSP00000354238

Chemistry databases

BindingDBiP22413

Structurei

Secondary structure

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

3D structure databases

ProteinModelPortaliP22413
SMRiP22413
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22413

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini104 – 144SMB 1PROSITE-ProRule annotationAdd BLAST41
Domaini145 – 189SMB 2PROSITE-ProRule annotationAdd BLAST45

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni191 – 591PhosphodiesteraseAdd BLAST401
Regioni597 – 647LinkerBy similarityAdd BLAST51
Regioni654 – 925NucleaseAdd BLAST272

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi45 – 52Di-leucine motif8

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

Sequence similaritiesi

Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.Curated

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2645 Eukaryota
COG1524 LUCA
GeneTreeiENSGT00760000119157
HOGENOMiHOG000037439
HOVERGENiHBG051484
InParanoidiP22413
KOiK01513
OMAiRCDVACV
OrthoDBiEOG091G017X
PhylomeDBiP22413
TreeFamiTF330032

Family and domain databases

Gene3Di3.40.720.10, 1 hit
InterProiView protein in InterPro
IPR017849 Alkaline_Pase-like_a/b/a
IPR017850 Alkaline_phosphatase_core_sf
IPR001604 DNA/RNA_non-sp_Endonuclease
IPR020821 Extracellular_endonuc_su_A
IPR002591 Phosphodiest/P_Trfase
IPR036024 Somatomedin_B-like_dom_sf
IPR020436 Somatomedin_B_chordata
IPR001212 Somatomedin_B_dom
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is 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
Checksum:i0ECAA063801CAFEB
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PE72E9PE72_HUMAN
Ectonucleotide pyrophosphatase/phos...
ENPP1
378Annotation score:

Sequence cautioni

The sequence AAA63237 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH59375 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA02054 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.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_077256126C → R in GACI1. 1 Publication1
Natural variantiVAR_077257133C → R in COLED. 1 Publication1
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 Polymorphism; associated with NIDDM; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 5 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:rs190947144Ensembl.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 Polymorphism; 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 Polymorphism; 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 Polymorphism; decreased nucleotide phosphodiesterase activity; no effect on localization to plasma membrane. 2 PublicationsCorresponds to variant dbSNP:rs367759638Ensembl.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:
EMBLi
GenBanki
DDBJi
Links Updated
M57736 mRNA Translation: AAA63237.1 Different initiation.
D12485 mRNA Translation: BAA02054.1 Different initiation.
AF110304
, AF110280, AF110281, AF110283, AF110284, AF110285, AF110286, AF110287, AF110288, AF110289, AF110290, AF110291, AF110292, AF110293, AF110294, AF110295, AF110296, AF110297, AF110298, AF110299, AF110300, AF110301, AF110302, AF110303 Genomic DNA Translation: AAF36094.1
AJ242020
, AJ242021, AJ242022, AJ242023, AJ242024, AJ242025, AJ242026, AJ242027, AJ242028, AJ242029, AJ242030, AJ242031, AJ242032, AJ242033, AJ242034, AJ242035, AJ242036, AJ242037, AJ242038, AJ242039, AJ242040, AJ242041, AJ242042, AJ242043, 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
UniGeneiHs.527295

Genome annotation databases

EnsembliENST00000360971; ENSP00000354238; ENSG00000197594
GeneIDi5167
KEGGihsa:5167
UCSCiuc011ecf.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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
, AF110280, AF110281, AF110283, AF110284, AF110285, AF110286, AF110287, AF110288, AF110289, AF110290, AF110291, AF110292, AF110293, AF110294, AF110295, AF110296, AF110297, AF110298, AF110299, AF110300, AF110301, AF110302, AF110303 Genomic DNA Translation: AAF36094.1
AJ242020
, AJ242021, AJ242022, AJ242023, AJ242024, AJ242025, AJ242026, AJ242027, AJ242028, AJ242029, AJ242030, AJ242031, AJ242032, AJ242033, AJ242034, AJ242035, AJ242036, AJ242037, AJ242038, AJ242039, AJ242040, AJ242041, AJ242042, AJ242043, 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
UniGeneiHs.527295

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YS0NMR-A147-189[»]
ProteinModelPortaliP22413
SMRiP22413
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111193, 15 interactors
IntActiP22413, 5 interactors
MINTiP22413
STRINGi9606.ENSP00000354238

Chemistry databases

BindingDBiP22413
ChEMBLiCHEMBL5925
DrugBankiDB01143 Amifostine
DB00811 Ribavirin

PTM databases

GlyConnecti1196
iPTMnetiP22413
PhosphoSitePlusiP22413

Polymorphism and mutation databases

BioMutaiENPP1
DMDMi23503088

Proteomic databases

EPDiP22413
MaxQBiP22413
PaxDbiP22413
PeptideAtlasiP22413
PRIDEiP22413
ProteomicsDBi53988

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360971; ENSP00000354238; ENSG00000197594
GeneIDi5167
KEGGihsa:5167
UCSCiuc011ecf.2 human

Organism-specific databases

CTDi5167
DisGeNETi5167
EuPathDBiHostDB:ENSG00000197594.11
GeneCardsiENPP1
HGNCiHGNC:3356 ENPP1
HPAiCAB032904
HPA062066
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
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2645 Eukaryota
COG1524 LUCA
GeneTreeiENSGT00760000119157
HOGENOMiHOG000037439
HOVERGENiHBG051484
InParanoidiP22413
KOiK01513
OMAiRCDVACV
OrthoDBiEOG091G017X
PhylomeDBiP22413
TreeFamiTF330032

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP22413
GeneWikiiEctonucleotide_pyrophosphatase/phosphodiesterase_1
GenomeRNAii5167
PROiPR:P22413
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197594 Expressed in 192 organ(s), highest expression level in tibia
CleanExiHS_ENPP1
ExpressionAtlasiP22413 baseline and differential
GenevisibleiP22413 HS

Family and domain databases

Gene3Di3.40.720.10, 1 hit
InterProiView protein in InterPro
IPR017849 Alkaline_Pase-like_a/b/a
IPR017850 Alkaline_phosphatase_core_sf
IPR001604 DNA/RNA_non-sp_Endonuclease
IPR020821 Extracellular_endonuc_su_A
IPR002591 Phosphodiest/P_Trfase
IPR036024 Somatomedin_B-like_dom_sf
IPR020436 Somatomedin_B_chordata
IPR001212 Somatomedin_B_dom
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
ProtoNetiSearch...

Entry informationi

Entry nameiENPP1_HUMAN
AccessioniPrimary (citable) accession number: P22413
Secondary accession number(s): Q5T9R6
, Q9NPZ3, Q9P1P6, Q9UP61, Q9Y6K3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: September 19, 2002
Last modified: November 7, 2018
This is version 201 of the entry and version 2 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  7. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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