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Reviewed, UniProtKB/Swiss-Prot Q924C3 (ENPP1_RAT)

Last modified September 2, 2008. Version 55. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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

Protein attributes

Sequence length906 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at transcript level.

General annotation (Comments)

Function

Involved primarily in ATP hydrolysis at the plasma membrane. Plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. In vitro, has a broad specificity, hydrolyzing 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 + H(2)O = 2 mononucleotides.

Cofactor

Binds 2 divalent metal cations per subunit Probable.

Enzyme regulation

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

Subunit structure

Homodimer; disulfide-linked By similarity.

Subcellular location

Membrane; Single-pass type II membrane protein. 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 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

It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.

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 componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal-anchor
Transmembrane
   LigandMetal-binding
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical termMultifunctional enzyme

Gene Ontology (GO)

None. [Check GOA]

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 view

Molecule processing

Chain1 – 906906Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

Regions

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

Sites

Active site2381AMP-threonine intermediate By similarity
Metal binding2001Divalent metal cation 2 Probable
Metal binding3581Divalent metal cation 1 Probable
Metal binding3621Divalent metal cation 1 Probable
Metal binding4051Divalent metal cation 2 Probable
Metal binding4061Divalent metal cation 2 Probable
Metal binding5171Divalent metal cation 1 Probable

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 ↔ 104Alternate By similarity
Disulfide bond90 ↔ 94Alternate By similarity
Disulfide bond94 ↔ 122Alternate By similarity
Disulfide bond102 ↔ 115Alternate By similarity
Disulfide bond102 ↔ 104Alternate By similarity
Disulfide bond108 ↔ 114 By similarity
Disulfide bond115 ↔ 122Alternate By similarity
Disulfide bond131 ↔ 148Alternate By similarity
Disulfide bond131 ↔ 136Alternate By similarity
Disulfide bond136 ↔ 166Alternate By similarity
Disulfide bond146 ↔ 159Alternate By similarity
Disulfide bond146 ↔ 148Alternate By similarity
Disulfide bond152 ↔ 158 By similarity
Disulfide bond159 ↔ 166Alternate By similarity

Natural variations

Alternative sequence6301Missing in isoform 1.
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 »

905102,843

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: 12121276] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS.
Strain: Lewis, Louvain and Wistar.

Cross-references

Sequence databases

AF340185 mRNA. Translation: AAK69653.1.
AF340186 mRNA. Translation: AAK69654.1.
AF320054 mRNA. Translation: AAL26912.1.
RefSeqNP_445987.1.
UniGeneRn.1199

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteQ924C3.

Genome annotation databases

EnsemblENSRNOG00000013994. Rattus norvegicus. [Contig view]
GeneID85496.
KEGGrno:85496.

Organism-specific databases

RGD628825. Enpp1.

Phylogenomic databases

HOVERGENQ924C3.

Gene expression databases

ArrayExpressQ924C3.
GermOnlineENSRNOG00000013994. Rattus norvegicus.

Family and domain databases

InterProIPR017849. Alkaline_Pase-like_a/b/a.
IPR001604. Endonuclease.
IPR002591. Phosphodiest/P_Trfase.
IPR001212. Somatomedin_B.
[Graphical view]
Gene3DG3DSA:3.40.720.10. Alk_phosphtse. 1 hit.
G3DSA:3.40.570.10. Endonuclease. 1 hit.
PfamPF01663. Phosphodiest. 1 hit.
PF01033. Somatomedin_B. 2 hits.
[Graphical view]
PRINTSPR00022. SOMATOMEDINB.
SMARTSM00477. NUC. 1 hit.
SM00201. SO. 2 hits.
[Graphical view]
PROSITEPS00524. SMB_1. 2 hits.
PS50958. SMB_2. 2 hits.
[Graphical view]
ProDomQ924C3.
[Graphical view] [Entries sharing at least one domain]
BLOCKSSearch...

Other Resources

ProtoNetSearch...

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: September 2, 2008
This is version 55 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents