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Q924C3 (ENPP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Short name=E-NPP 1
Alternative name(s):
Phosphodiesterase I/nucleotide pyrophosphatase 1
Plasma-cell membrane glycoprotein PC-1

Including the following 2 domains:

  1. Alkaline phosphodiesterase I
    EC=3.1.4.1
  2. Nucleotide pyrophosphatase
    Short name=NPPase
    EC=3.6.1.9
Gene names
Name:Enpp1
Synonyms:Npps, Pc1, Pdnp1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length906 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Catalytic activity

Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.

A dinucleotide + H2O = 2 mononucleotides.

Cofactor

Binds 2 zinc ions per subunit By similarity.

Enzyme regulation

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

Subunit structure

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

Subcellular location

Cell membrane; Single-pass type II membrane protein By similarity. Basolateral cell membrane; Single-pass type II membrane protein By similarity. Secreted By similarity. Note: 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. The proteolytically processed form is secreted By similarity.

Domain

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

Post-translational modification

A secreted form is produced through cleavage at Lys-85 by intracellular processing By similarity.

Sequence similarities

Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

Contains 2 SMB (somatomedin-B) domains.

Caution

It is uncertain whether Met-1 or Met-35 is the initiator.

Ontologies

Keywords
   Biological processBiomineralization
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal-anchor
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

biomineral tissue development

Inferred from electronic annotation. Source: UniProtKB-KW

immune response

Inferred from electronic annotation. Source: InterPro

nucleic acid phosphodiester bond hydrolysis

Inferred from sequence or structural similarity. Source: GOC

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19474315. Source: MGI

   Molecular_functionNADH pyrophosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

nucleic acid binding

Inferred from electronic annotation. Source: InterPro

nucleotide diphosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphodiesterase I activity

Inferred from sequence or structural similarity. Source: UniProtKB

polysaccharide binding

Inferred from electronic annotation. Source: InterPro

scavenger receptor activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: Q924C3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1 (identifier: Q924C3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     630-630: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 906906Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
PRO_0000188566

Regions

Topological domain1 – 5858Cytoplasmic Potential
Transmembrane59 – 7921Helical; Signal-anchor for type II membrane protein; Potential
Topological domain80 – 906827Extracellular Potential
Domain86 – 12641SMB 1
Domain127 – 17044SMB 2
Region173 – 573401Phosphodiesterase
Region579 – 62850Linker By similarity
Region635 – 906272Nuclease
Motif27 – 348Di-leucine motif

Sites

Active site2381AMP-threonine intermediate By similarity
Metal binding2001Zinc 1; catalytic By similarity
Metal binding2381Zinc 1; catalytic By similarity
Metal binding3581Zinc 2; catalytic By similarity
Metal binding3621Zinc 2; via tele nitrogen; catalytic By similarity
Metal binding4051Zinc 1; catalytic By similarity
Metal binding4061Zinc 1; via tele nitrogen; catalytic By similarity
Metal binding5171Zinc 2; via tele nitrogen; catalytic By similarity
Metal binding7811Calcium By similarity
Metal binding7831Calcium By similarity
Metal binding7851Calcium By similarity
Metal binding7871Calcium; via carbonyl oxygen By similarity
Metal binding7891Calcium By similarity
Binding site2591Substrate By similarity
Binding site2771Substrate By similarity
Binding site3221Substrate By similarity
Site84 – 852Cleavage By similarity
Site8961Essential for catalytic activity By similarity

Amino acid modifications

Glycosylation1611N-linked (GlcNAc...) Potential
Glycosylation2671N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Glycosylation4591N-linked (GlcNAc...) Potential
Glycosylation5671N-linked (GlcNAc...) Potential
Glycosylation6241N-linked (GlcNAc...) Potential
Disulfide bond90 ↔ 104 By similarity
Disulfide bond94 ↔ 122 By similarity
Disulfide bond102 ↔ 115 By similarity
Disulfide bond108 ↔ 114 By similarity
Disulfide bond131 ↔ 148 By similarity
Disulfide bond136 ↔ 166 By similarity
Disulfide bond146 ↔ 159 By similarity
Disulfide bond152 ↔ 158 By similarity
Disulfide bond177 ↔ 223 By similarity
Disulfide bond185 ↔ 397 By similarity
Disulfide bond413 ↔ 512 By similarity
Disulfide bond462 ↔ 849 By similarity
Disulfide bond596 ↔ 653 By similarity
Disulfide bond607 ↔ 707 By similarity
Disulfide bond609 ↔ 692 By similarity
Disulfide bond819 ↔ 829 By similarity

Natural variations

Alternative sequence6301Missing in isoform 1.
VSP_006749
Natural variant440 – 4423RPT → NPP in strain: Wistar.
Natural variant4571A → T in strain: Lewis.
Natural variant5551M → I in strain: Lewis.
Natural variant5681E → G in strain: Wistar.
Natural variant5831T → I in strain: Lewis.
Natural variant5921F → V in strain: Lewis.
Natural variant6241N → K in strain: Lewis.
Natural variant6401N → H in strain: Lewis.
Natural variant7741V → I in strain: Lewis.
Natural variant8061N → I in strain: Lewis.
Natural variant8501T → I in strain: Lewis.
Natural variant8981H → Q in strain: Lewis.

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 71F56780B279A919

FASTA906102,942
        10         20         30         40         50         60 
MERDGEQAGQ GPRHGPAGNG RELESPAAAS LLAPMDLGEE PLEKAERART AKDPNTYKVL 

        70         80         90        100        110        120 
SLVLSVCVLT TILGCIFGLK PSCAKEVKSC KGRCFERTFS NCRCDAACVS LGNCCLDFQE 

       130        140        150        160        170        180 
TCVEPTHIWT CNKFRCGEKR LSRFVCSCAD DCKAHNDCCI NYSSVCQEKK SWVEEACETI 

       190        200        210        220        230        240 
DAPQCPAEFE SPPTLLFSLD GFRAEYLHTW GGLLPVISKL KNCGTYTKNM RPVYPTKTFP 

       250        260        270        280        290        300 
NHYSIVTGLY PESHGIIDNK MYDPKMNASF SLKSKEKFNP LWYKGQPIWV TANHQEVRSG 

       310        320        330        340        350        360 
TYFWPGSDVE IDGILPDIYK VYNGSVPFEE RILAVLEWLQ LPSYERPHFY TLYLEEPDSS 

       370        380        390        400        410        420 
GHSHGPVSSE VIKALQKVDH IVGMLMDGLK DLGLDKCLNL ILISDHGMEQ GSCKKYVYLN 

       430        440        450        460        470        480 
KYLGDVNNVK VVYGPAARLR PTEVPETYYS FNYEALAKNL SCRETNQHFR PYLKHFLPKR 

       490        500        510        520        530        540 
LHFAKNDRIE PLTFYLDPQW QLALNPSERK YCGSGFHGSD NLFSNMQALF IGYGPAFKHG 

       550        560        570        580        590        600 
AEVDSFENIE VYNLMCDLLG LIPAPNNESH GSLNHLLKKP IYTPSHPKEE SFLSQCPIKS 

       610        620        630        640        650        660 
VSSDLGCTCD PSIVPIMDFE KQFNLTTDAV EDVYSMTVPN GRPRNLQKQH RVCLLHQQQF 

       670        680        690        700        710        720 
LTGYSLDLLM PLWTSYTFLS NDQFSTDDFS NCLYQDLRIP LSPMHKCSYY KSTSKLSYGF 

       730        740        750        760        770        780 
LTPPRLNRVS RQIYSEALLT SNIVPMYQSF QVIWQYLHDT VLRRYAQERN GVNVVSGPVF 

       790        800        810        820        830        840 
DFDYDGRYDS SEILKQNTRV IRSQENLIPT HFFIVLTSCK QLSESPLKCT ALESSAFLLP 

       850        860        870        880        890        900 
HRPDNIESCT HGKQESAWVE ELLALHRARV TDVELITGLS FYQDRQESVS ELLRLKTHLP 


IFSQED 

« Hide

Isoform 1 [UniParc].

Checksum: 46EE88917B4BBCD3
Show »

FASTA905102,843

References

« Hide 'large scale' references
[1]"Structural basis of allotypes of ecto-nucleotide pyrophosphatase/phosphodiesterase (plasma cell membrane glycoprotein PC-1) in the mouse and rat, and analysis of allele-specific xenogeneic antibodies."
Banakh I., Sali A., Dubljevic V., Grobben B., Slegers H., Goding J.W.
Eur. J. Immunogenet. 29:307-313(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS.
Strain: Lewis, Louvain and Wistar.
[2]"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF340185 mRNA. Translation: AAK69653.1.
AF340186 mRNA. Translation: AAK69654.1.
AF320054 mRNA. Translation: AAL26912.1.
RefSeqNP_445987.1. NM_053535.1. [Q924C3-1]
UniGeneRn.1199.

3D structure databases

ProteinModelPortalQ924C3.
SMRQ924C3. Positions 129-171.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4997931.

PTM databases

PhosphoSiteQ924C3.

Proteomic databases

PaxDbQ924C3.
PRIDEQ924C3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID85496.
KEGGrno:85496.

Organism-specific databases

CTD5167.
RGD628825. Enpp1.

Phylogenomic databases

eggNOGCOG1524.
HOGENOMHOG000037439.
HOVERGENHBG051484.
InParanoidQ924C3.
KOK01513.
PhylomeDBQ924C3.

Enzyme and pathway databases

SABIO-RKQ924C3.

Gene expression databases

GenevestigatorQ924C3.

Family and domain databases

Gene3D3.40.570.10. 1 hit.
3.40.720.10. 1 hit.
InterProIPR017849. 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]
PANTHERPTHR10151. PTHR10151. 1 hit.
PfamPF01223. Endonuclease_NS. 1 hit.
PF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view]
PRINTSPR00022. SOMATOMEDINB.
SMARTSM00892. Endonuclease_NS. 1 hit.
SM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view]
SUPFAMSSF53649. SSF53649. 1 hit.
PROSITEPS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio617598.
PROQ924C3.

Entry information

Entry nameENPP1_RAT
AccessionPrimary (citable) accession number: Q924C3
Secondary accession number(s): Q91XQ3, Q920C8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: September 19, 2002
Last modified: May 14, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families