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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

Gene

ENPP2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor (By similarity).By similarity

Catalytic activityi

1-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-alkyl-sn-glycerol 3-phosphate + ethanolamine.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity
  • Ca2+By similarityNote: Binds 1 Ca2+ ion per subunit.By similarity

Enzyme regulationi

Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi172 – 1721Zinc 1; catalyticBy similarity
Active sitei210 – 2101NucleophileBy similarity
Metal bindingi210 – 2101Zinc 1; catalyticBy similarity
Binding sitei231 – 2311SubstrateBy similarity
Binding sitei307 – 3071SubstrateBy similarity
Metal bindingi312 – 3121Zinc 2; catalyticBy similarity
Metal bindingi316 – 3161Zinc 2; catalyticBy similarity
Metal bindingi316 – 3161Zinc 2; via tele nitrogen; catalyticBy similarity
Metal bindingi359 – 3591Zinc 1; catalyticBy similarity
Metal bindingi360 – 3601Zinc 1; catalyticBy similarity
Metal bindingi360 – 3601Zinc 1; via tele nitrogen; catalyticBy similarity
Metal bindingi475 – 4751Zinc 2; catalyticBy similarity
Metal bindingi475 – 4751Zinc 2; via tele nitrogen; catalyticBy similarity
Metal bindingi765 – 7651CalciumBy similarity
Metal bindingi769 – 7691CalciumBy similarity
Metal bindingi771 – 7711Calcium; via carbonyl oxygenBy similarity
Metal bindingi773 – 7731CalciumBy similarity
Sitei878 – 8781Essential for catalytic activityBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Chemotaxis, Lipid degradation, Lipid metabolism

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (EC:3.1.4.39)
Short name:
E-NPP 2
Alternative name(s):
Autotaxin
Extracellular lysophospholipase D
Short name:
LysoPLD
Gene namesi
Name:ENPP2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 14

Subcellular locationi

  • Secreted

  • Note: Secreted by most body fluids including serum and CSF. Also by adipocytes and numerous cancer cells (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Obesity

Chemistry

ChEMBLiCHEMBL2021747.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727By similarityAdd
BLAST
Propeptidei28 – 358Removed by furinBy similarityPRO_0000281647
Chaini36 – 888853Ectonucleotide pyrophosphatase/phosphodiesterase family member 2PRO_0000281648Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence analysis
Disulfide bondi59 ↔ 76PROSITE-ProRule annotation
Disulfide bondi63 ↔ 94PROSITE-ProRule annotation
Disulfide bondi74 ↔ 87PROSITE-ProRule annotation
Disulfide bondi80 ↔ 86PROSITE-ProRule annotation
Disulfide bondi103 ↔ 120PROSITE-ProRule annotation
Disulfide bondi108 ↔ 138PROSITE-ProRule annotation
Disulfide bondi118 ↔ 131PROSITE-ProRule annotation
Disulfide bondi124 ↔ 130PROSITE-ProRule annotation
Disulfide bondi149 ↔ 195PROSITE-ProRule annotation
Disulfide bondi157 ↔ 351PROSITE-ProRule annotation
Disulfide bondi367 ↔ 469PROSITE-ProRule annotation
Glycosylationi411 – 4111N-linked (GlcNAc...)Sequence analysis
Disulfide bondi414 ↔ 831PROSITE-ProRule annotation
Glycosylationi525 – 5251N-linked (GlcNAc...)Sequence analysis
Disulfide bondi567 ↔ 692PROSITE-ProRule annotation
Disulfide bondi569 ↔ 677PROSITE-ProRule annotation
Disulfide bondi800 ↔ 810PROSITE-ProRule annotation
Glycosylationi832 – 8321N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiA1A4K5.
PRIDEiA1A4K5.

Expressioni

Gene expression databases

BgeeiENSBTAG00000013165.

Interactioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000036974.

Structurei

3D structure databases

ProteinModelPortaliA1A4K5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini55 – 9844SMB 1PROSITE-ProRule annotationAdd
BLAST
Domaini99 – 14345SMB 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni211 – 2144Substrate bindingBy similarity
Regioni244 – 25512Substrate bindingBy similarityAdd
BLAST
Regioni855 – 87622Required for secretionBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi127 – 1293Cell attachment siteSequence analysis

Sequence similaritiesi

Contains 2 SMB (somatomedin-B) domains.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG2645. Eukaryota.
COG1524. LUCA.
GeneTreeiENSGT00760000119157.
HOGENOMiHOG000037439.
HOVERGENiHBG051484.
InParanoidiA1A4K5.
KOiK01122.
OMAiGMEDVTC.
OrthoDBiEOG091G017X.
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.
IPR029881. ENPP2.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 2 hits.
PTHR10151:SF21. PTHR10151:SF21. 2 hits.
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.

Sequence processingi: The displayed sequence is further processed into a mature form.

A1A4K5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARRRSCQLH QVISLFTFAV GVNICLGVTA NRIKRAEGWG EGPPTVLSDS
60 70 80 90 100
PSINISGSCK GRCFELQEAG PPDCRCDNLC KSYSSCCLDF DELCLKTAGG
110 120 130 140 150
WECTKDRCGE VRNEDHACHC SEDCLARGDC CTNYQVVCKG ESHWVDDDCE
160 170 180 190 200
EIKTPECPAG FVRPPLIIFS VDGFRASYMK KGSKVMPNIE KLRSCGTHSP
210 220 230 240 250
YMRPVYPTKT FPNLYTLATG LYPESHGIVG NSMYDPVFDA HFNLRGREKF
260 270 280 290 300
NHRWWGGQPL WITATKQGVI AGTFFWPVVI PHERRILTIL QWLTLPDHER
310 320 330 340 350
PSVYAFYSEQ PDFSGHKYGP FGPEMTNPLR DIDKTVGQLM DGLKQLKLHR
360 370 380 390 400
CVNVIFVGDH GMEDVTCDRT EFLSNYLTNV DDIILVPGTL GRIRPKFNNH
410 420 430 440 450
AKYDPKVIIA NLTCKKPDQH FKPYLKQHLP KRLHYANNRR IEDVHLLVER
460 470 480 490 500
RWHVARKPLE VYKKPSGKCF FQGDHGFDNK VNSMQTVFVG YGPTFKYKTK
510 520 530 540 550
VPPFENIELY NVMCDLLGLK PAPNNGTHGS LNHLLRTNTF RPTVPEEVTR
560 570 580 590 600
PNYPGVMYLQ SDFDLGCTCD DKAEPKNKLD ELNKHLHIKE STEAETRKFR
610 620 630 640 650
GSKNEIKENV NGNFEPRKER HLLYGRPAVL YRTRYDILYH TDFESGYSEI
660 670 680 690 700
FLMPLWTSYT VSKQADVSDI PAHLTNCVRP DVRVSPSFSQ SCLAYKNDKQ
710 720 730 740 750
MSYGFLFPPY LSSSPEAKYD AFLVTNMVPM YPAFKRIWNY FQRVLVKKYA
760 770 780 790 800
SERNGVNVIS GPIFDYDYDG LHDTQDKIKQ YVEGSSVPVP THYYSILTSC
810 820 830 840 850
LDFTQPADRC DGPLSVSAFV LPHRPDNDES CNSSEDESKW VEELLKMHTA
860 870 880
RVRDIEHLTS LDFFRKTSRS YPEILTLKTY LQTYESEI
Length:888
Mass (Da):101,717
Last modified:January 23, 2007 - v1
Checksum:iC349950572B2BADF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti775 – 7751Q → E AA sequence (PubMed:12119361).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC126631 mRNA. Translation: AAI26632.1.
RefSeqiNP_001073762.1. NM_001080293.1.
UniGeneiBt.25525.

Genome annotation databases

EnsembliENSBTAT00000037135; ENSBTAP00000036974; ENSBTAG00000013165.
GeneIDi532663.
KEGGibta:532663.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC126631 mRNA. Translation: AAI26632.1.
RefSeqiNP_001073762.1. NM_001080293.1.
UniGeneiBt.25525.

3D structure databases

ProteinModelPortaliA1A4K5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000036974.

Chemistry

ChEMBLiCHEMBL2021747.

Proteomic databases

PaxDbiA1A4K5.
PRIDEiA1A4K5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000037135; ENSBTAP00000036974; ENSBTAG00000013165.
GeneIDi532663.
KEGGibta:532663.

Organism-specific databases

CTDi5168.

Phylogenomic databases

eggNOGiKOG2645. Eukaryota.
COG1524. LUCA.
GeneTreeiENSGT00760000119157.
HOGENOMiHOG000037439.
HOVERGENiHBG051484.
InParanoidiA1A4K5.
KOiK01122.
OMAiGMEDVTC.
OrthoDBiEOG091G017X.
TreeFamiTF330032.

Miscellaneous databases

PROiA1A4K5.

Gene expression databases

BgeeiENSBTAG00000013165.

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.
IPR029881. ENPP2.
IPR020821. Extracellular_endonuc_su_A.
IPR002591. Phosphodiest/P_Trfase.
IPR020436. Somatomedin_B_chordata.
IPR001212. Somatomedin_B_dom.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 2 hits.
PTHR10151:SF21. PTHR10151:SF21. 2 hits.
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 nameiENPP2_BOVIN
AccessioniPrimary (citable) accession number: A1A4K5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. 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.