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P22413

- ENPP1_HUMAN

UniProt

P22413 - ENPP1_HUMAN

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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Gene
ENPP1, M6S1, NPPS, PC1, PDNP1
Organism
Homo sapiens (Human)
Status
Reviewed - 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 dinucleotide + H2O = 2 mononucleotides.1 Publication

Cofactori

Binds 2 zinc 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)LengthDescriptionGraphical viewFeature identifierActions
Sitei102 – 1032Cleavage By similarity
Metal bindingi218 – 2181Zinc 1; catalytic By similarity
Active sitei256 – 2561AMP-threonine intermediate By similarity
Metal bindingi256 – 2561Zinc 1; catalytic By similarity
Binding sitei277 – 2771Substrate By similarity
Binding sitei295 – 2951Substrate By similarity
Binding sitei340 – 3401Substrate By similarity
Metal bindingi376 – 3761Zinc 2; catalytic By similarity
Metal bindingi380 – 3801Zinc 2; via tele nitrogen; catalytic By similarity
Metal bindingi423 – 4231Zinc 1; catalytic By similarity
Metal bindingi424 – 4241Zinc 1; via tele nitrogen; catalytic By similarity
Metal bindingi535 – 5351Zinc 2; via tele nitrogen; catalytic By similarity
Metal bindingi800 – 8001Calcium By similarity
Metal bindingi802 – 8021Calcium By similarity
Metal bindingi804 – 8041Calcium By similarity
Metal bindingi806 – 8061Calcium; via carbonyl oxygen By similarity
Metal bindingi808 – 8081Calcium By similarity
Sitei915 – 9151Essential for catalytic activity By similarity

GO - Molecular functioni

  1. 3'-phosphoadenosine 5'-phosphosulfate binding Source: BHF-UCL
  2. ATP binding Source: BHF-UCL
  3. calcium ion binding Source: UniProtKB
  4. insulin receptor binding Source: BHF-UCL
  5. NADH pyrophosphatase activity Source: UniProtKB-EC
  6. nucleic acid binding Source: InterPro
  7. nucleoside-triphosphate diphosphatase activity Source: BHF-UCL
  8. nucleotide diphosphatase activity Source: BHF-UCL
  9. phosphodiesterase I activity Source: UniProtKB
  10. polysaccharide binding Source: InterPro
  11. protein binding Source: IntAct
  12. protein homodimerization activity Source: BHF-UCL
  13. scavenger receptor activity Source: InterPro
  14. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. 3'-phosphoadenosine 5'-phosphosulfate metabolic process Source: BHF-UCL
  2. ATP catabolic process Source: UniProtKB
  3. biomineral tissue development Source: UniProtKB-KW
  4. bone remodeling Source: Ensembl
  5. cellular phosphate ion homeostasis Source: BHF-UCL
  6. cellular response to insulin stimulus Source: BHF-UCL
  7. generation of precursor metabolites and energy Source: BHF-UCL
  8. immune response Source: InterPro
  9. inorganic diphosphate transport Source: BHF-UCL
  10. negative regulation of cell growth Source: BHF-UCL
  11. negative regulation of fat cell differentiation Source: BHF-UCL
  12. negative regulation of glucose import Source: BHF-UCL
  13. negative regulation of glycogen biosynthetic process Source: BHF-UCL
  14. negative regulation of insulin receptor signaling pathway Source: BHF-UCL
  15. negative regulation of ossification Source: Ensembl
  16. negative regulation of protein autophosphorylation Source: BHF-UCL
  17. nucleic acid phosphodiester bond hydrolysis Source: GOC
  18. nucleoside triphosphate catabolic process Source: BHF-UCL
  19. phosphate-containing compound metabolic process Source: BHF-UCL
  20. regulation of bone mineralization Source: BHF-UCL
  21. riboflavin metabolic process Source: Reactome
  22. sequestering of triglyceride Source: BHF-UCL
  23. small molecule metabolic process Source: Reactome
  24. vitamin metabolic process Source: Reactome
  25. water-soluble vitamin metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_11070. 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:3.1.4.1)
Nucleotide pyrophosphatase (EC:3.6.1.9)
Short name:
NPPase
Gene namesi
Name:ENPP1
Synonyms:M6S1, NPPS, PC1, PDNP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:3356. ENPP1.

Subcellular locationi

Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Secreted By similarity
Note: The proteolytically processed form is secreted By similarity. Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7676Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei77 – 9721Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini98 – 925828Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. basolateral plasma membrane Source: BHF-UCL
  2. cell surface Source: BHF-UCL
  3. extracellular space Source: BHF-UCL
  4. integral component of membrane Source: UniProtKB
  5. integral component of plasma membrane Source: UniProtKB
  6. lysosomal membrane Source: UniProtKB
  7. 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) [MIM:602475]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti91 – 911L → P in OPLL. 1 Publication
VAR_014141
Natural varianti287 – 2871S → F in OPLL. 1 Publication
Corresponds to variant rs190947144 [ dbSNP | Ensembl ].
VAR_014143
Arterial calcification of infancy, generalized, 1 (GACI1) [MIM:208000]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.4 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti250 – 2501P → L in GACI1. 1 Publication
VAR_067910
Natural varianti252 – 2521Missing in GACI1. 1 Publication
VAR_067911
Natural varianti305 – 3051P → T in GACI1. 1 Publication
VAR_067912
Natural varianti342 – 3421G → V in GACI1. 2 Publications
VAR_037433
Natural varianti371 – 3711Y → F in GACI1; unknown pathological significance. 2 Publications
VAR_037434
Natural varianti538 – 5381D → H in GACI1. 1 Publication
VAR_067913
Natural varianti579 – 5791L → F in GACI1. 1 Publication
VAR_018514
Natural varianti586 – 5861G → R in GACI1. 1 Publication
VAR_067914
Natural varianti774 – 7741R → C in GACI1; unknown pathological significance. 2 Publications
Corresponds to variant rs28933977 [ dbSNP | Ensembl ].
VAR_018515
Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti173 – 1731K → Q Associated with NIDDM. 4 Publications
Corresponds to variant rs1044498 [ dbSNP | Ensembl ].
VAR_008873
Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2) [MIM:613312]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti266 – 2661G → V in ARHR2. 1 Publication
Corresponds to variant rs121908248 [ dbSNP | Ensembl ].
VAR_063719
Natural varianti901 – 9011Y → S in ARHR2; loss of activity. 1 Publication
Corresponds to variant rs121908249 [ dbSNP | Ensembl ].
VAR_063720
Cole disease (COLED) [MIM:615522]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti149 – 1491C → S in COLED. 1 Publication
VAR_070782
Natural varianti164 – 1641C → S in COLED. 1 Publication
VAR_070783
Natural varianti177 – 1771C → Y in COLED. 1 Publication
VAR_070784

Keywords - Diseasei

Diabetes mellitus, Disease mutation, Obesity

Organism-specific databases

MIMi125853. phenotype.
208000. phenotype.
602475. phenotype.
613312. phenotype.
615522. phenotype.
Orphaneti289176. Autosomal recessive hypophosphatemic rickets.
51608. Generalized arterial calcification of infancy.
324561. Hypopigmentation-punctate palmoplantar keratoderma syndrome.
PharmGKBiPA27791.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 925925Ectonucleotide pyrophosphatase/phosphodiesterase family member 1PRO_0000188564Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi108 ↔ 122 By similarity
Disulfide bondi112 ↔ 140 By similarity
Disulfide bondi120 ↔ 133 By similarity
Disulfide bondi126 ↔ 132 By similarity
Disulfide bondi149 ↔ 166 By similarity
Disulfide bondi154 ↔ 184 By similarity
Disulfide bondi164 ↔ 177 By similarity
Disulfide bondi170 ↔ 176 By similarity
Glycosylationi179 – 1791N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi195 ↔ 241 By similarity
Disulfide bondi203 ↔ 415 By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...) Reviewed prediction
Glycosylationi341 – 3411N-linked (GlcNAc...)2 Publications
Disulfide bondi431 ↔ 530 By similarity
Glycosylationi477 – 4771N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi480 ↔ 868 By similarity
Glycosylationi585 – 5851N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi614 ↔ 672 By similarity
Disulfide bondi626 ↔ 726 By similarity
Disulfide bondi628 ↔ 711 By similarity
Glycosylationi643 – 6431N-linked (GlcNAc...)1 Publication
Glycosylationi700 – 7001N-linked (GlcNAc...) Reviewed prediction
Glycosylationi731 – 7311N-linked (GlcNAc...) Reviewed prediction
Glycosylationi748 – 7481N-linked (GlcNAc...)1 Publication
Disulfide bondi838 ↔ 848 By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP22413.
PaxDbiP22413.
PRIDEiP22413.

PTM databases

PhosphoSiteiP22413.

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

ArrayExpressiP22413.
BgeeiP22413.
CleanExiHS_ENPP1.
GenevestigatoriP22413.

Organism-specific databases

HPAiCAB032904.

Interactioni

Subunit structurei

The secreted form is monomeric By similarity. Homodimer. Interacts with INSR.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi111193. 3 interactions.
IntActiP22413. 3 interactions.
STRINGi9606.ENSP00000354238.

Structurei

Secondary structure

1
925
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni151 – 1555
Beta strandi163 – 1653
Helixi168 – 1736
Helixi180 – 1834

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YS0NMR-A147-189[»]
ProteinModelPortaliP22413.
SMRiP22413. Positions 106-922.

Miscellaneous databases

EvolutionaryTraceiP22413.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini104 – 14441SMB 1Add
BLAST
Domaini145 – 18945SMB 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni191 – 591401PhosphodiesteraseAdd
BLAST
Regioni597 – 64751Linker By similarityAdd
BLAST
Regioni654 – 925272NucleaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi45 – 528Di-leucine motif

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

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1524.
HOGENOMiHOG000037439.
HOVERGENiHBG051484.
InParanoidiP22413.
KOiK01513.
OMAiFEERILA.
OrthoDBiEOG7XM2X4.
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.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 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.
PROSITEiPS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P22413-1 [UniParc]FASTAAdd to Basket

« Hide

MERDGCAGGG SRGGEGGRAP REGPAGNGRD RGRSHAAEAP GDPQAAASLL    50
APMDVGEEPL EKAARARTAK DPNTYKVLSL VLSVCVLTTI LGCIFGLKPS 100
CAKEVKSCKG RCFERTFGNC RCDAACVELG NCCLDYQETC IEPEHIWTCN 150
KFRCGEKRLT RSLCACSDDC KDKGDCCINY SSVCQGEKSW VEEPCESINE 200
PQCPAGFETP PTLLFSLDGF RAEYLHTWGG LLPVISKLKK CGTYTKNMRP 250
VYPTKTFPNH YSIVTGLYPE SHGIIDNKMY DPKMNASFSL KSKEKFNPEW 300
YKGEPIWVTA KYQGLKSGTF FWPGSDVEIN GIFPDIYKMY NGSVPFEERI 350
LAVLQWLQLP KDERPHFYTL YLEEPDSSGH SYGPVSSEVI KALQRVDGMV 400
GMLMDGLKEL NLHRCLNLIL ISDHGMEQGS CKKYIYLNKY LGDVKNIKVI 450
YGPAARLRPS DVPDKYYSFN YEGIARNLSC REPNQHFKPY LKHFLPKRLH 500
FAKSDRIEPL TFYLDPQWQL ALNPSERKYC GSGFHGSDNV FSNMQALFVG 550
YGPGFKHGIE ADTFENIEVY NLMCDLLNLT PAPNNGTHGS LNHLLKNPVY 600
TPKHPKEVHP LVQCPFTRNP RDNLGCSCNP SILPIEDFQT QFNLTVAEEK 650
IIKHETLPYG RPRVLQKENT ICLLSQHQFM SGYSQDILMP LWTSYTVDRN 700
DSFSTEDFSN CLYQDFRIPL SPVHKCSFYK NNTKVSYGFL SPPQLNKNSS 750
GIYSEALLTT NIVPMYQSFQ VIWRYFHDTL LRKYAEERNG VNVVSGPVFD 800
FDYDGRCDSL ENLRQKRRVI RNQEILIPTH FFIVLTSCKD TSQTPLHCEN 850
LDTLAFILPH RTDNSESCVH GKHDSSWVEE LLMLHRARIT DVEHITGLSF 900
YQQRKEPVSD ILKLKTHLPT FSQED 925
Length:925
Mass (Da):104,924
Last modified:September 19, 2002 - v2
Checksum:i0ECAA063801CAFEB
GO

Sequence cautioni

The sequence AAA63237.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
The sequence AAH59375.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
The sequence BAA02054.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti91 – 911L → P in OPLL. 1 Publication
VAR_014141
Natural varianti149 – 1491C → S in COLED. 1 Publication
VAR_070782
Natural varianti164 – 1641C → S in COLED. 1 Publication
VAR_070783
Natural varianti173 – 1731K → Q Associated with NIDDM. 4 Publications
Corresponds to variant rs1044498 [ dbSNP | Ensembl ].
VAR_008873
Natural varianti177 – 1771C → Y in COLED. 1 Publication
VAR_070784
Natural varianti179 – 1791N → S.
Corresponds to variant rs2273411 [ dbSNP | Ensembl ].
VAR_037432
Natural varianti250 – 2501P → L in GACI1. 1 Publication
VAR_067910
Natural varianti252 – 2521Missing in GACI1. 1 Publication
VAR_067911
Natural varianti266 – 2661G → V in ARHR2. 1 Publication
Corresponds to variant rs121908248 [ dbSNP | Ensembl ].
VAR_063719
Natural varianti268 – 2681Y → H.1 Publication
Corresponds to variant rs1805139 [ dbSNP | Ensembl ].
VAR_014142
Natural varianti287 – 2871S → F in OPLL. 1 Publication
Corresponds to variant rs190947144 [ dbSNP | Ensembl ].
VAR_014143
Natural varianti305 – 3051P → T in GACI1. 1 Publication
VAR_067912
Natural varianti342 – 3421G → V in GACI1. 2 Publications
VAR_037433
Natural varianti371 – 3711Y → F in GACI1; unknown pathological significance. 2 Publications
VAR_037434
Natural varianti538 – 5381D → H in GACI1. 1 Publication
VAR_067913
Natural varianti579 – 5791L → F in GACI1. 1 Publication
VAR_018514
Natural varianti586 – 5861G → R in GACI1. 1 Publication
VAR_067914
Natural varianti774 – 7741R → C in GACI1; unknown pathological significance. 2 Publications
Corresponds to variant rs28933977 [ dbSNP | Ensembl ].
VAR_018515
Natural varianti779 – 7791T → P.1 Publication
Corresponds to variant rs1805138 [ dbSNP | Ensembl ].
VAR_014144
Natural varianti886 – 8861R → T.
Corresponds to variant rs8192683 [ dbSNP | Ensembl ].
VAR_037435
Natural varianti901 – 9011Y → S in ARHR2; loss of activity. 1 Publication
Corresponds to variant rs121908249 [ dbSNP | Ensembl ].
VAR_063720

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi23503088.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS5150.2.
PIRi A39216.
RefSeqi NP_006199.2. NM_006208.2.
UniGenei Hs.527295.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2YS0 NMR - A 147-189 [» ]
ProteinModelPortali P22413.
SMRi P22413. Positions 106-922.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111193. 3 interactions.
IntActi P22413. 3 interactions.
STRINGi 9606.ENSP00000354238.

Chemistry

BindingDBi P22413.
ChEMBLi CHEMBL5925.
DrugBanki DB01143. Amifostine.
DB00811. Ribavirin.

PTM databases

PhosphoSitei P22413.

Polymorphism databases

DMDMi 23503088.

Proteomic databases

MaxQBi P22413.
PaxDbi P22413.
PRIDEi P22413.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000360971 ; ENSP00000354238 ; ENSG00000197594 .
GeneIDi 5167.
KEGGi hsa:5167.
UCSCi uc011ecf.2. human.

Organism-specific databases

CTDi 5167.
GeneCardsi GC06P132129.
HGNCi HGNC:3356. ENPP1.
HPAi CAB032904.
MIMi 125853. phenotype.
173335. gene.
208000. phenotype.
602475. phenotype.
613312. phenotype.
615522. phenotype.
neXtProti NX_P22413.
Orphaneti 289176. Autosomal recessive hypophosphatemic rickets.
51608. Generalized arterial calcification of infancy.
324561. Hypopigmentation-punctate palmoplantar keratoderma syndrome.
PharmGKBi PA27791.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1524.
HOGENOMi HOG000037439.
HOVERGENi HBG051484.
InParanoidi P22413.
KOi K01513.
OMAi FEERILA.
OrthoDBi EOG7XM2X4.
PhylomeDBi P22413.
TreeFami TF330032.

Enzyme and pathway databases

Reactomei REACT_11070. Vitamin B2 (riboflavin) metabolism.
SABIO-RK P22413.

Miscellaneous databases

EvolutionaryTracei P22413.
GeneWikii Ectonucleotide_pyrophosphatase/phosphodiesterase_1.
GenomeRNAii 5167.
NextBioi 19990.
PROi P22413.
SOURCEi Search...

Gene expression databases

ArrayExpressi P22413.
Bgeei P22413.
CleanExi HS_ENPP1.
Genevestigatori P22413.

Family and domain databases

Gene3Di 3.40.570.10. 1 hit.
3.40.720.10. 1 hit.
InterProi IPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR001604. DNA/RNA_non-sp_Endonuclease.
IPR024873. E-NPP.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view ]
PANTHERi PTHR10151. PTHR10151. 1 hit.
Pfami PF01223. Endonuclease_NS. 1 hit.
PF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view ]
PRINTSi PR00022. SOMATOMEDINB.
SMARTi SM00892. Endonuclease_NS. 1 hit.
SM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view ]
SUPFAMi SSF53649. SSF53649. 1 hit.
PROSITEi PS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location."
    Buckley M.F., Loveland K.A., McKinstry W.J., Garson O.M., Goding J.W.
    J. Biol. Chem. 265:17506-17511(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skin fibroblast.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    Tissue: Skin fibroblast.
  3. "Genomic structure of the human PC1 gene."
    Bozzali M., Pizzuti A., Trischitta E.
    Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  6. "A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance."
    Pizzuti A., Frittitta L., Argiolas A., Baratta R., Goldfine I.D., Bozzali M., Ercolino T., Scarlato G., Iacoviello L., Vigneri R., Tassi V., Trischitta V.
    Diabetes 48:1881-1884(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 145-185, VARIANT GLN-173.
  7. "Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities."
    Belli S.I., Goding J.W.
    Eur. J. Biochem. 226:433-443(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOPOLOGY, CATALYTIC ACTIVITY, FUNCTION, GLYCOSYLATION.
  8. "Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site."
    Belli S.I., Mercuri F.A., Sali A., Goding J.W.
    Eur. J. Biochem. 228:669-676(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACTIVE SITE.
  9. "Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes."
    Piao J.-H., Goding J.W., Nakamura H., Sano K.
    Genomics 45:412-415(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  10. "Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit."
    Maddux B.A., Goldfine I.D.
    Diabetes 49:13-19(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INSR, FUNCTION IN INHIBITION OF INSR KINASE ACTIVITY.
  11. "Characterization of a di-leucine-based signal in the cytoplasmic tail of the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not endocytosis."
    Bello V., Goding J.W., Greengrass V., Sali A., Dubljevic V., Lenoir C., Trugnan G., Maurice M.
    Mol. Biol. Cell 12:3004-3015(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
  12. "Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases."
    Yano Y., Hayashi Y., Sano K., Nagano H., Nakaji M., Seo Y., Ninomiya T., Yoon S., Yokozaki H., Kasuga M.
    Cancer Lett. 207:139-147(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  13. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341.
    Tissue: Liver.
  14. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
    Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
    Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341; ASN-643 AND ASN-748.
    Tissue: Leukemic T-cell.
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  16. "Solution structure of the somatomedin B domain of human ectonucleotide pyrophosphatase/phosphodiesterase family member."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2007) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 147-189.
  17. "Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL)."
    Nakamura I., Ikegawa S., Okawa A., Okuda S., Koshizuka Y., Kawaguchi H., Nakamura K., Koyama T., Goto S., Toguchida J., Matsushita M., Ochi T., Takaoka K., Nakamura Y.
    Hum. Genet. 104:492-497(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS OPLL PRO-91 AND PHE-287, VARIANTS GLN-173; HIS-268 AND PRO-779.
  18. Cited for: VARIANTS GACI1 PHE-579 AND CYS-774.
  19. "Generalized arterial calcification of infancy: different clinical courses in two affected siblings."
    Cheng K.-S., Chen M.-R., Ruf N., Lin S.-P., Rutsch F.
    Am. J. Med. Genet. A 136:210-213(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GACI1 VAL-342 AND PHE-371.
  20. "The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction."
    Bacci S., Ludovico O., Prudente S., Zhang Y.Y., Di Paola R., Mangiacotti D., Rauseo A., Nolan D., Duffy J., Fini G., Salvemini L., Amico C., Vigna C., Pellegrini F., Menzaghi C., Doria A., Trischitta V.
    Diabetes 54:3021-3025(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GLN-173, ASSOCIATION WITH NIDDM.
  21. "The mutational spectrum oENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI)."
    Ruf N., Uhlenberg B., Terkeltaub R., Nurnberg P., Rutsch F.
    Hum. Mutat. 25:98-98(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GACI1 LEU-250; TYR-252 DEL; THR-305; VAL-342; PHE-371 AND CYS-774.
  22. "Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets."
    Lorenz-Depiereux B., Schnabel D., Tiosano D., Hausler G., Strom T.M.
    Am. J. Hum. Genet. 86:267-272(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARHR2 VAL-266.
  23. "Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene."
    Levy-Litan V., Hershkovitz E., Avizov L., Leventhal N., Bercovich D., Chalifa-Caspi V., Manor E., Buriakovsky S., Hadad Y., Goding J., Parvari R.
    Am. J. Hum. Genet. 86:273-278(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARHR2 SER-901, CHARACTERIZATION OF VARIANT ARHR2 SER-901.
  24. "An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy."
    Le Boulanger G., Labreze C., Croue A., Schurgers L.J., Chassaing N., Wittkampf T., Rutsch F., Martin L.
    Am. J. Med. Genet. A 152:118-123(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GLN-173.
  25. Cited for: VARIANTS GACI1 HIS-538 AND ARG-586.
  26. Cited for: VARIANTS COLED SER-149; SER-164 AND TYR-177.

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: September 3, 2014
This is version 163 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.

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

External Data

Dasty 3

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