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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-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.2 Publications

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

Enzyme 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

  • 3'-phosphoadenosine 5'-phosphosulfate binding Source: BHF-UCL
  • ATP binding Source: BHF-UCL
  • calcium ion binding Source: UniProtKB
  • insulin receptor binding Source: BHF-UCL
  • NADH pyrophosphatase activity Source: UniProtKB-EC
  • nucleic acid binding Source: InterPro
  • nucleoside-triphosphate diphosphatase activity Source: BHF-UCL
  • nucleotide diphosphatase activity Source: BHF-UCL
  • phosphodiesterase I activity Source: UniProtKB
  • polysaccharide binding Source: InterPro
  • protein homodimerization activity Source: BHF-UCL
  • scavenger receptor activity Source: InterPro
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • 3'-phosphoadenosine 5'-phosphosulfate metabolic process Source: BHF-UCL
  • biomineral tissue development Source: UniProtKB-KW
  • cellular phosphate ion homeostasis Source: BHF-UCL
  • cellular response to insulin stimulus Source: BHF-UCL
  • generation of precursor metabolites and energy Source: BHF-UCL
  • immune response Source: InterPro
  • inorganic diphosphate transport Source: BHF-UCL
  • negative regulation of cell growth Source: BHF-UCL
  • negative regulation of fat cell differentiation Source: BHF-UCL
  • negative regulation of glucose import Source: BHF-UCL
  • negative regulation of glycogen biosynthetic process Source: BHF-UCL
  • negative regulation of insulin receptor signaling pathway Source: BHF-UCL
  • negative regulation of protein autophosphorylation Source: BHF-UCL
  • nucleoside triphosphate catabolic process Source: BHF-UCL
  • phosphate-containing compound metabolic process Source: BHF-UCL
  • regulation of bone mineralization Source: BHF-UCL
  • riboflavin metabolic process Source: Reactome
  • sequestering of triglyceride Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS03544-MONOMER.
BRENDAi3.6.1.9. 2681.
ReactomeiR-HSA-196843. Vitamin B2 (riboflavin) metabolism.
SABIO-RKP22413.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3356. ENPP1.

Subcellular locationi

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

GO - Cellular componenti

  • basolateral plasma membrane Source: BHF-UCL
  • cell surface Source: BHF-UCL
  • extracellular space Source: BHF-UCL
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

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 rs190947144dbSNPEnsembl.1
Arterial calcification of infancy, generalized, 1 (GACI1)4 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_067910250P → L in GACI1. 1 PublicationCorresponds to variant rs754659608dbSNPEnsembl.1
Natural variantiVAR_067911252Missing in GACI1. 1 Publication1
Natural variantiVAR_067912305P → T in GACI1. 1 PublicationCorresponds to variant rs374270497dbSNPEnsembl.1
Natural variantiVAR_037433342G → V in GACI1. 2 PublicationsCorresponds to variant rs121918025dbSNPEnsembl.1
Natural variantiVAR_037434371Y → F in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant rs121918026dbSNPEnsembl.1
Natural variantiVAR_067913538D → H in GACI1. 1 PublicationCorresponds to variant rs387906673dbSNPEnsembl.1
Natural variantiVAR_018514579L → F in GACI1. 1 PublicationCorresponds to variant rs121918024dbSNPEnsembl.1
Natural variantiVAR_067914586G → R in GACI1. 1 Publication1
Natural variantiVAR_018515774R → C in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant rs28933977dbSNPEnsembl.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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_008873173K → Q Associated with NIDDM. 4 PublicationsCorresponds to variant rs1044498dbSNPEnsembl.1
Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2)2 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_063719266G → V in ARHR2. 1 PublicationCorresponds to variant rs121908248dbSNPEnsembl.1
Natural variantiVAR_063720901Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant rs121908249dbSNPEnsembl.1
Cole disease (COLED)1 Publication
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_070782149C → S in COLED. 1 PublicationCorresponds to variant rs397518477dbSNPEnsembl.1
Natural variantiVAR_070783164C → S in COLED. 1 PublicationCorresponds to variant rs397518476dbSNPEnsembl.1
Natural variantiVAR_070784177C → Y in COLED. 1 PublicationCorresponds to variant rs397518475dbSNPEnsembl.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.
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...)Sequence analysis1
Disulfide bondi195 ↔ 241PROSITE-ProRule annotation
Disulfide bondi203 ↔ 415PROSITE-ProRule annotation
Modified residuei256PhosphothreonineBy similarity1
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Glycosylationi341N-linked (GlcNAc...)2 Publications1
Disulfide bondi431 ↔ 530PROSITE-ProRule annotation
Glycosylationi477N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi480 ↔ 868PROSITE-ProRule annotation
Glycosylationi585N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi614 ↔ 672PROSITE-ProRule annotation
Disulfide bondi626 ↔ 726PROSITE-ProRule annotation
Disulfide bondi628 ↔ 711PROSITE-ProRule annotation
Glycosylationi643N-linked (GlcNAc...)1 Publication1
Glycosylationi700N-linked (GlcNAc...)Sequence analysis1
Glycosylationi731N-linked (GlcNAc...)Sequence analysis1
Glycosylationi748N-linked (GlcNAc...)1 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.

PTM databases

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.
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

  • insulin receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi111193. 11 interactors.
IntActiP22413. 4 interactors.
STRINGi9606.ENSP00000354238.

Chemistry databases

BindingDBiP22413.

Structurei

Secondary structure

1925
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni151 – 155Combined sources5
Beta strandi163 – 165Combined sources3
Helixi168 – 173Combined sources6
Helixi180 – 183Combined sources4

3D structure databases

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

Contains 2 SMB (somatomedin-B) domains.Curated

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.570.10. 1 hit.
3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR001604. DNA/RNA_non-sp_Endonuclease.
IPR024873. E-NPP.
IPR029890. ENPP1.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 1 hit.
PTHR10151:SF77. PTHR10151:SF77. 1 hit.
PfamiPF01223. Endonuclease_NS. 1 hit.
PF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view]
PRINTSiPR00022. SOMATOMEDINB.
SMARTiSM00892. Endonuclease_NS. 1 hit.
SM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.
SSF90188. SSF90188. 2 hits.
PROSITEiPS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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_070782149C → S in COLED. 1 PublicationCorresponds to variant rs397518477dbSNPEnsembl.1
Natural variantiVAR_070783164C → S in COLED. 1 PublicationCorresponds to variant rs397518476dbSNPEnsembl.1
Natural variantiVAR_008873173K → Q Associated with NIDDM. 4 PublicationsCorresponds to variant rs1044498dbSNPEnsembl.1
Natural variantiVAR_070784177C → Y in COLED. 1 PublicationCorresponds to variant rs397518475dbSNPEnsembl.1
Natural variantiVAR_037432179N → S.Corresponds to variant rs2273411dbSNPEnsembl.1
Natural variantiVAR_067910250P → L in GACI1. 1 PublicationCorresponds to variant rs754659608dbSNPEnsembl.1
Natural variantiVAR_067911252Missing in GACI1. 1 Publication1
Natural variantiVAR_063719266G → V in ARHR2. 1 PublicationCorresponds to variant rs121908248dbSNPEnsembl.1
Natural variantiVAR_014142268Y → H.1 PublicationCorresponds to variant rs17847050dbSNPEnsembl.1
Natural variantiVAR_014143287S → F in OPLL. 1 PublicationCorresponds to variant rs190947144dbSNPEnsembl.1
Natural variantiVAR_067912305P → T in GACI1. 1 PublicationCorresponds to variant rs374270497dbSNPEnsembl.1
Natural variantiVAR_037433342G → V in GACI1. 2 PublicationsCorresponds to variant rs121918025dbSNPEnsembl.1
Natural variantiVAR_037434371Y → F in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant rs121918026dbSNPEnsembl.1
Natural variantiVAR_067913538D → H in GACI1. 1 PublicationCorresponds to variant rs387906673dbSNPEnsembl.1
Natural variantiVAR_018514579L → F in GACI1. 1 PublicationCorresponds to variant rs121918024dbSNPEnsembl.1
Natural variantiVAR_067914586G → R in GACI1. 1 Publication1
Natural variantiVAR_018515774R → C in GACI1; unknown pathological significance. 2 PublicationsCorresponds to variant rs28933977dbSNPEnsembl.1
Natural variantiVAR_014144779T → P.1 PublicationCorresponds to variant rs1805138dbSNPEnsembl.1
Natural variantiVAR_037435886R → T.Corresponds to variant rs8192683dbSNPEnsembl.1
Natural variantiVAR_063720901Y → S in ARHR2; loss of activity. 1 PublicationCorresponds to variant rs121908249dbSNPEnsembl.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, AL139805 Genomic DNA. Translation: CAI19514.1.
AL139805, AL117378 Genomic DNA. Translation: CAI20161.1.
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

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, AL139805 Genomic DNA. Translation: CAI19514.1.
AL139805, AL117378 Genomic DNA. Translation: CAI20161.1.
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. 11 interactors.
IntActiP22413. 4 interactors.
STRINGi9606.ENSP00000354238.

Chemistry databases

BindingDBiP22413.
ChEMBLiCHEMBL5925.
DrugBankiDB01143. Amifostine.
DB00811. Ribavirin.

PTM databases

iPTMnetiP22413.
PhosphoSitePlusiP22413.

Polymorphism and mutation databases

BioMutaiENPP1.
DMDMi23503088.

Proteomic databases

EPDiP22413.
MaxQBiP22413.
PaxDbiP22413.
PeptideAtlasiP22413.
PRIDEiP22413.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5167.
DisGeNETi5167.
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.
PharmGKBiPA27791.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS03544-MONOMER.
BRENDAi3.6.1.9. 2681.
ReactomeiR-HSA-196843. Vitamin B2 (riboflavin) metabolism.
SABIO-RKP22413.

Miscellaneous databases

EvolutionaryTraceiP22413.
GeneWikiiEctonucleotide_pyrophosphatase/phosphodiesterase_1.
GenomeRNAii5167.
PROiP22413.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197594.
CleanExiHS_ENPP1.
ExpressionAtlasiP22413. baseline and differential.
GenevisibleiP22413. HS.

Family and domain databases

Gene3Di3.40.570.10. 1 hit.
3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR001604. DNA/RNA_non-sp_Endonuclease.
IPR024873. E-NPP.
IPR029890. ENPP1.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 1 hit.
PTHR10151:SF77. PTHR10151:SF77. 1 hit.
PfamiPF01223. Endonuclease_NS. 1 hit.
PF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view]
PRINTSiPR00022. SOMATOMEDINB.
SMARTiSM00892. Endonuclease_NS. 1 hit.
SM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.
SSF90188. SSF90188. 2 hits.
PROSITEiPS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiENPP1_HUMAN
AccessioniPrimary (citable) accession number: P22413
Secondary accession number(s): Q5T9R6
, Q9NPZ3, Q9P1P6, Q9UP61, Q9Y6K3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: September 19, 2002
Last modified: November 2, 2016
This is version 185 of the entry and version 2 of the sequence. [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

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, 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 polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.