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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

Gene

Enpp2

Organism
Mus musculus (Mouse)
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.2 Publications

Catalytic activityi

1-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-alkyl-sn-glycerol 3-phosphate + ethanolamine.2 Publications

Cofactori

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

Enzyme regulationi

Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) (By similarity). Inhibited by EDTA and EGTA.By similarity1 Publication

Kineticsi

  1. KM=12.9 mM for pNppp (isoform 1)1 Publication
  2. KM=4.4 mM for pNppp (isoform 2)1 Publication
  3. KM=11.8 mM for pNppp (isoform 3)1 Publication
  1. Vmax=1.9 nmol/min/µg enzyme with pNppp as substrate (isoform 1)1 Publication
  2. Vmax=0.35 nmol/min/µg enzyme with pNppp as substrate (isoform 2)1 Publication
  3. Vmax=1.8 nmol/min/µg enzyme with pNppp as substrate (isoform 3)1 Publication

pH dependencei

Optimum pH is 8.0 for isoforms 1, 2 and 3.1 Publication

Temperature dependencei

Isoforms 1 and 3 have maximum activity from 45 to 55 degrees Celsius.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi171 – 1711Zinc 1; catalytic
Active sitei209 – 2091NucleophileBy similarity
Metal bindingi209 – 2091Zinc 1; catalytic
Binding sitei230 – 2301Substrate
Binding sitei306 – 3061Substrate
Metal bindingi311 – 3111Zinc 2; catalytic
Metal bindingi315 – 3151Zinc 2; via tele nitrogen; catalytic
Metal bindingi358 – 3581Zinc 1; catalytic
Metal bindingi359 – 3591Zinc 1; via tele nitrogen; catalytic
Metal bindingi474 – 4741Zinc 2; via tele nitrogen; catalytic
Metal bindingi739 – 7391Calcium
Metal bindingi741 – 7411Calcium
Metal bindingi745 – 7451Calcium; via carbonyl oxygen
Metal bindingi747 – 7471Calcium
Sitei852 – 8521Essential for catalytic activity

GO - Molecular functioni

  • alkylglycerophosphoethanolamine phosphodiesterase activity Source: UniProtKB-EC
  • calcium ion binding Source: UniProtKB
  • lysophospholipase activity Source: UniProtKB
  • nucleic acid binding Source: InterPro
  • nucleotide diphosphatase activity Source: MGI
  • phosphodiesterase I activity Source: MGI
  • polysaccharide binding Source: InterPro
  • scavenger receptor activity Source: InterPro
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Chemotaxis, Lipid degradation, Lipid metabolism

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.1.4.39. 3474.
SABIO-RKQ9R1E6.

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
Synonyms:Npps2, Pdnp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1321390. Enpp2.

Subcellular locationi

  • Secreted 2 Publications

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

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

May contribute to obesity (PubMed:15700135).

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi12 – 2716Missing : Complete inhibition of secretion. 1 PublicationAdd
BLAST
Mutagenesisi12 – 2211Missing : Complete inhibition of secretion. 1 PublicationAdd
BLAST
Mutagenesisi23 – 275Missing : No effect on secretion. 1 Publication
Mutagenesisi23 – 231Missing : No effect on secretion.
Mutagenesisi25 – 251Missing : No effect on secretion. 1 Publication
Mutagenesisi27 – 359Missing : No effect on secretion nor lysophospholipase activity. 1 Publication
Mutagenesisi27 – 304Missing : No effect on secretion. 1 Publication
Mutagenesisi27 – 271Missing : No effect on secretion. 1 Publication
Mutagenesisi30 – 4112Missing : No effect on secretion nor lysophospholipase activity. 1 PublicationAdd
BLAST
Mutagenesisi30 – 334Missing : No effect on secretion nor lysophospholipase activity. 1 Publication
Mutagenesisi32 – 354Missing : No effect on secretion nor lysophospholipase activity. 1 Publication
Mutagenesisi36 – 405Missing : No effect on secretion nor lysophospholipase activity. 1 Publication
Mutagenesisi53 – 531Missing : No effect on secretion; slightly decreases lysophospholipase activity. Almost complete loss of lysophospholipase activity; when associated with N-410 del. 1 Publication
Mutagenesisi210 – 2101F → A: Reduced lysophospholipase activity. 1 Publication
Mutagenesisi213 – 2131L → A: Reduced lysophospholipase activity. 1 Publication
Mutagenesisi230 – 2301N → A: Reduced lysophospholipase activity. 1 Publication
Mutagenesisi243 – 2431L → A: Reduced lysophospholipase activity. 1 Publication
Mutagenesisi247 – 2471E → A: Reduced lysophospholipase activity. 1 Publication
Mutagenesisi249 – 2491F → A: Reduced lysophospholipase activity. 1 Publication
Mutagenesisi410 – 4101Missing : No effect on secretion; greatly inhibits lysoPLD activity. Inhibits secretion. Almost complete loss of lysoPLD activity; when associated with N-53 del. 1 Publication
Mutagenesisi512 – 5121M → A: Reduced lysophospholipase activity.
Mutagenesisi851 – 8533LKT → AAA, RRR or SSS: No catalytic activity. 1 Publication
Mutagenesisi851 – 8511L → A: No effect. 1 Publication
Mutagenesisi852 – 8521K → A or R: Strongly reduced catalytic activity. 1 Publication
Mutagenesisi853 – 8531T → A: No effect. 1 Publication

Keywords - Diseasei

Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727By similarityAdd
BLAST
Propeptidei28 – 358Removed by furinPRO_0000281650
Chaini36 – 862827Ectonucleotide pyrophosphatase/phosphodiesterase family member 2PRO_0000188568Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi53 – 531N-linked (GlcNAc...)2 Publications
Disulfide bondi58 ↔ 75
Disulfide bondi62 ↔ 93
Disulfide bondi73 ↔ 86
Disulfide bondi79 ↔ 85
Disulfide bondi102 ↔ 119
Disulfide bondi107 ↔ 137
Disulfide bondi117 ↔ 130
Disulfide bondi123 ↔ 129
Disulfide bondi148 ↔ 194
Disulfide bondi156 ↔ 350
Disulfide bondi366 ↔ 468
Glycosylationi410 – 4101N-linked (GlcNAc...)2 Publications
Disulfide bondi413 ↔ 805
Glycosylationi524 – 5241N-linked (GlcNAc...)2 Publications
Disulfide bondi566 ↔ 666
Disulfide bondi568 ↔ 651
Disulfide bondi774 ↔ 784
Glycosylationi806 – 8061N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity. Secretion requires simultaneous glycosylation on Asn-53 and Asn-410, while probable glycosylation of Asn-410 has a preferential role on lysoPLD activity. Not O-glycosylated.3 Publications
The interdomain disulfide bond between Cys-413 and Cys-805 is essential for catalytic activity.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9R1E6.
PRIDEiQ9R1E6.

PTM databases

PhosphoSiteiQ9R1E6.

Expressioni

Tissue specificityi

Expressed in brain and adipose tissue.1 Publication

Inductioni

Up-regulated in adipocytes of obese-diabetic db/db mice.1 Publication

Gene expression databases

BgeeiQ9R1E6.
ExpressionAtlasiQ9R1E6. baseline and differential.
GenevisibleiQ9R1E6. MM.

Interactioni

Chemistry

BindingDBiQ9R1E6.

Structurei

Secondary structure

1
862
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni59 – 635Combined sources
Helixi77 – 826Combined sources
Helixi89 – 935Combined sources
Helixi104 – 1063Combined sources
Beta strandi115 – 1184Combined sources
Helixi123 – 1264Combined sources
Helixi133 – 1375Combined sources
Helixi143 – 1453Combined sources
Beta strandi165 – 1717Combined sources
Helixi175 – 1839Combined sources
Helixi186 – 1949Combined sources
Beta strandi195 – 1973Combined sources
Helixi209 – 21810Combined sources
Helixi222 – 2254Combined sources
Beta strandi229 – 2346Combined sources
Turni235 – 2384Combined sources
Beta strandi239 – 2413Combined sources
Beta strandi243 – 2464Combined sources
Helixi247 – 2493Combined sources
Helixi251 – 2533Combined sources
Helixi259 – 2657Combined sources
Helixi281 – 29212Combined sources
Turni296 – 2983Combined sources
Beta strandi301 – 31010Combined sources
Helixi311 – 3177Combined sources
Beta strandi319 – 3213Combined sources
Helixi322 – 3243Combined sources
Helixi325 – 34420Combined sources
Turni348 – 3503Combined sources
Beta strandi352 – 3587Combined sources
Beta strandi368 – 3714Combined sources
Helixi372 – 3743Combined sources
Helixi379 – 3813Combined sources
Beta strandi382 – 3854Combined sources
Beta strandi387 – 39610Combined sources
Helixi404 – 4118Combined sources
Beta strandi420 – 4245Combined sources
Helixi425 – 4273Combined sources
Helixi430 – 4323Combined sources
Beta strandi438 – 4403Combined sources
Beta strandi442 – 4476Combined sources
Beta strandi452 – 4554Combined sources
Helixi457 – 4593Combined sources
Beta strandi471 – 4733Combined sources
Helixi481 – 4833Combined sources
Beta strandi487 – 4915Combined sources
Beta strandi496 – 4994Combined sources
Helixi505 – 5073Combined sources
Helixi508 – 5158Combined sources
Turni527 – 5304Combined sources
Helixi531 – 5333Combined sources
Beta strandi534 – 5363Combined sources
Beta strandi548 – 5514Combined sources
Helixi559 – 5613Combined sources
Helixi579 – 5813Combined sources
Turni583 – 5864Combined sources
Helixi591 – 5955Combined sources
Beta strandi609 – 6135Combined sources
Beta strandi618 – 6225Combined sources
Turni623 – 6264Combined sources
Beta strandi627 – 6359Combined sources
Helixi646 – 6483Combined sources
Helixi660 – 6623Combined sources
Helixi666 – 6716Combined sources
Beta strandi676 – 6816Combined sources
Helixi683 – 6853Combined sources
Turni689 – 6913Combined sources
Helixi692 – 6954Combined sources
Helixi698 – 7003Combined sources
Beta strandi701 – 7044Combined sources
Helixi706 – 71712Combined sources
Helixi719 – 7279Combined sources
Beta strandi729 – 7379Combined sources
Beta strandi743 – 7453Combined sources
Helixi749 – 7513Combined sources
Beta strandi759 – 7613Combined sources
Beta strandi765 – 77612Combined sources
Helixi781 – 7833Combined sources
Beta strandi788 – 7969Combined sources
Turni805 – 8084Combined sources
Helixi811 – 8133Combined sources
Helixi815 – 8217Combined sources
Helixi826 – 8338Combined sources
Helixi845 – 8539Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3NKMX-ray2.00A36-862[»]
3NKNX-ray1.80A36-862[»]
3NKOX-ray1.75A36-862[»]
3NKPX-ray1.75A36-862[»]
3NKQX-ray1.70A36-862[»]
3NKRX-ray1.70A36-862[»]
3WAVX-ray1.80A36-862[»]
3WAWX-ray1.95A36-862[»]
3WAXX-ray1.90A36-862[»]
3WAYX-ray1.75A36-862[»]
4GTWX-ray2.70A/B51-58[»]
4GTXX-ray3.20A/B51-58[»]
4GTYX-ray3.19A/B51-58[»]
4GTZX-ray3.19A/B51-58[»]
ProteinModelPortaliQ9R1E6.
SMRiQ9R1E6. Positions 51-859.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9R1E6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 9744SMB 1PROSITE-ProRule annotationAdd
BLAST
Domaini98 – 14245SMB 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni144 – 501358PhosphodiesteraseAdd
BLAST
Regioni210 – 2134Substrate binding
Regioni243 – 25412Substrate bindingAdd
BLAST
Regioni597 – 862266NucleaseAdd
BLAST
Regioni829 – 85022Required for secretionAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi126 – 1283Cell attachment siteSequence analysis

Sequence similaritiesi

Contains 2 SMB (somatomedin-B) domains.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

GeneTreeiENSGT00760000119157.
HOGENOMiHOG000037439.
HOVERGENiHBG051484.
InParanoidiQ9R1E6.
KOiK01122.
OMAiGMEDVTC.
OrthoDBiEOG7XM2X4.
PhylomeDBiQ9R1E6.
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. 1 hit.
PTHR10151:SF21. PTHR10151:SF21. 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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9R1E6-1) [UniParc]FASTAAdd to basket

Also known as: Beta

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.

« Hide

        10         20         30         40         50
MARQGCFGSY QVISLFTFAI GVNLCLGFTA SRIKRAEWDE GPPTVLSDSP
60 70 80 90 100
WTNTSGSCKG RCFELQEVGP PDCRCDNLCK SYSSCCHDFD ELCLKTARGW
110 120 130 140 150
ECTKDRCGEV RNEENACHCS EDCLSRGDCC TNYQVVCKGE SHWVDDDCEE
160 170 180 190 200
IRVPECPAGF VRPPLIIFSV DGFRASYMKK GSKVMPNIEK LRSCGTHAPY
210 220 230 240 250
MRPVYPTKTF PNLYTLATGL YPESHGIVGN SMYDPVFDAT FHLRGREKFN
260 270 280 290 300
HRWWGGQPLW ITATKQGVRA GTFFWSVSIP HERRILTILQ WLSLPDNERP
310 320 330 340 350
SVYAFYSEQP DFSGHKYGPF GPEMTNPLRE IDKTVGQLMD GLKQLKLHRC
360 370 380 390 400
VNVIFVGDHG MEDVTCDRTE FLSNYLTNVD DITLVPGTLG RIRPKIPNNL
410 420 430 440 450
KYDPKAIIAN LTCKKPDQHF KPYMKQHLPK RLHYANNRRI EDLHLLVERR
460 470 480 490 500
WHVARKPLDV YKKPSGKCFF QGDHGFDNKV NSMQTVFVGY GPTFKYRTKV
510 520 530 540 550
PPFENIELYN VMCDLLGLKP APNNGTHGSL NHLLRTNTFR PTLPEEVSRP
560 570 580 590 600
NYPGIMYLQS DFDLGCTCDD KVEPKNKLEE LNKRLHTKGS TEERHLLYGR
610 620 630 640 650
PAVLYRTSYD ILYHTDFESG YSEIFLMPLW TSYTISKQAE VSSIPEHLTN
660 670 680 690 700
CVRPDVRVSP GFSQNCLAYK NDKQMSYGFL FPPYLSSSPE AKYDAFLVTN
710 720 730 740 750
MVPMYPAFKR VWTYFQRVLV KKYASERNGV NVISGPIFDY NYNGLRDIED
760 770 780 790 800
EIKQYVEGSS IPVPTHYYSI ITSCLDFTQP ADKCDGPLSV SSFILPHRPD
810 820 830 840 850
NDESCNSSED ESKWVEELMK MHTARVRDIE HLTGLDFYRK TSRSYSEILT
860
LKTYLHTYES EI
Length:862
Mass (Da):98,885
Last modified:February 10, 2009 - v3
Checksum:i343D44DEAA8FA352
GO
Isoform 2 (identifier: Q9R1E6-2) [UniParc]FASTAAdd to basket

Also known as: Alpha

The sequence of this isoform differs from the canonical sequence as follows:
     323-323: E → EESSYGSPLTPAKRPKRKVAPKRRQERPVAPPKKRRRKLHRMDHYTAETRQDK

Show »
Length:914
Mass (Da):105,089
Checksum:iE36A577AB858AF02
GO
Isoform 3 (identifier: Q9R1E6-3) [UniParc]FASTAAdd to basket

Also known as: Gamma

The sequence of this isoform differs from the canonical sequence as follows:
     592-592: E → EAETGKFRGSKHENKKSLNGNVEPRK

Show »
Length:887
Mass (Da):101,680
Checksum:i599952429BBFBD6B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti103 – 1031T → I in ACD12866 (Ref. 3) Curated
Sequence conflicti517 – 5171G → S in AAD46480 (PubMed:10702660).Curated
Sequence conflicti550 – 5501P → T in AAD46480 (PubMed:10702660).Curated
Sequence conflicti573 – 5731E → K in AAD46480 (PubMed:10702660).Curated
Sequence conflicti743 – 7431N → D in ACD12866 (Ref. 3) Curated
Sequence conflicti743 – 7431N → D in AAH03264 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei323 – 3231E → EESSYGSPLTPAKRPKRKVA PKRRQERPVAPPKKRRRKLH RMDHYTAETRQDK in isoform 2. 1 PublicationVSP_036396
Alternative sequencei592 – 5921E → EAETGKFRGSKHENKKSLNG NVEPRK in isoform 3. 1 PublicationVSP_036397

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF123542 mRNA. Translation: AAD46480.1.
EU131009 mRNA. Translation: ABW38314.1.
EU131010 mRNA. Translation: ABW38315.1.
EU677474 Genomic DNA. Translation: ACD12865.1.
EU677475 Genomic DNA. Translation: ACD12866.1.
AK161144 mRNA. Translation: BAE36214.1.
CH466545 Genomic DNA. Translation: EDL29265.1.
BC003264 mRNA. Translation: AAH03264.1.
BC058759 mRNA. Translation: AAH58759.1.
CCDSiCCDS27472.1. [Q9R1E6-1]
CCDS49607.1. [Q9R1E6-2]
CCDS70628.1. [Q9R1E6-3]
RefSeqiNP_001129549.1. NM_001136077.3. [Q9R1E6-2]
NP_001272923.1. NM_001285994.2. [Q9R1E6-3]
NP_001272924.1. NM_001285995.2.
NP_056559.2. NM_015744.4. [Q9R1E6-1]
UniGeneiMm.250256.

Genome annotation databases

EnsembliENSMUST00000041591; ENSMUSP00000036180; ENSMUSG00000022425. [Q9R1E6-1]
ENSMUST00000167541; ENSMUSP00000132640; ENSMUSG00000022425. [Q9R1E6-3]
ENSMUST00000171545; ENSMUSP00000128941; ENSMUSG00000022425. [Q9R1E6-2]
GeneIDi18606.
KEGGimmu:18606.
UCSCiuc007vro.3. mouse. [Q9R1E6-1]
uc007vrq.3. mouse. [Q9R1E6-3]
uc011zsx.2. mouse. [Q9R1E6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF123542 mRNA. Translation: AAD46480.1.
EU131009 mRNA. Translation: ABW38314.1.
EU131010 mRNA. Translation: ABW38315.1.
EU677474 Genomic DNA. Translation: ACD12865.1.
EU677475 Genomic DNA. Translation: ACD12866.1.
AK161144 mRNA. Translation: BAE36214.1.
CH466545 Genomic DNA. Translation: EDL29265.1.
BC003264 mRNA. Translation: AAH03264.1.
BC058759 mRNA. Translation: AAH58759.1.
CCDSiCCDS27472.1. [Q9R1E6-1]
CCDS49607.1. [Q9R1E6-2]
CCDS70628.1. [Q9R1E6-3]
RefSeqiNP_001129549.1. NM_001136077.3. [Q9R1E6-2]
NP_001272923.1. NM_001285994.2. [Q9R1E6-3]
NP_001272924.1. NM_001285995.2.
NP_056559.2. NM_015744.4. [Q9R1E6-1]
UniGeneiMm.250256.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3NKMX-ray2.00A36-862[»]
3NKNX-ray1.80A36-862[»]
3NKOX-ray1.75A36-862[»]
3NKPX-ray1.75A36-862[»]
3NKQX-ray1.70A36-862[»]
3NKRX-ray1.70A36-862[»]
3WAVX-ray1.80A36-862[»]
3WAWX-ray1.95A36-862[»]
3WAXX-ray1.90A36-862[»]
3WAYX-ray1.75A36-862[»]
4GTWX-ray2.70A/B51-58[»]
4GTXX-ray3.20A/B51-58[»]
4GTYX-ray3.19A/B51-58[»]
4GTZX-ray3.19A/B51-58[»]
ProteinModelPortaliQ9R1E6.
SMRiQ9R1E6. Positions 51-859.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiQ9R1E6.

PTM databases

PhosphoSiteiQ9R1E6.

Proteomic databases

MaxQBiQ9R1E6.
PRIDEiQ9R1E6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041591; ENSMUSP00000036180; ENSMUSG00000022425. [Q9R1E6-1]
ENSMUST00000167541; ENSMUSP00000132640; ENSMUSG00000022425. [Q9R1E6-3]
ENSMUST00000171545; ENSMUSP00000128941; ENSMUSG00000022425. [Q9R1E6-2]
GeneIDi18606.
KEGGimmu:18606.
UCSCiuc007vro.3. mouse. [Q9R1E6-1]
uc007vrq.3. mouse. [Q9R1E6-3]
uc011zsx.2. mouse. [Q9R1E6-2]

Organism-specific databases

CTDi5168.
MGIiMGI:1321390. Enpp2.

Phylogenomic databases

GeneTreeiENSGT00760000119157.
HOGENOMiHOG000037439.
HOVERGENiHBG051484.
InParanoidiQ9R1E6.
KOiK01122.
OMAiGMEDVTC.
OrthoDBiEOG7XM2X4.
PhylomeDBiQ9R1E6.
TreeFamiTF330032.

Enzyme and pathway databases

BRENDAi3.1.4.39. 3474.
SABIO-RKQ9R1E6.

Miscellaneous databases

ChiTaRSiEnpp2. mouse.
EvolutionaryTraceiQ9R1E6.
NextBioi294522.
PROiQ9R1E6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9R1E6.
ExpressionAtlasiQ9R1E6. baseline and differential.
GenevisibleiQ9R1E6. MM.

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. 1 hit.
PTHR10151:SF21. PTHR10151:SF21. 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...

Publicationsi

« Hide 'large scale' publications
  1. "Assignment of Pdnp2, the gene encoding phosphodiesterase I/nucleotide pyrophosphatase 2, to mouse chromosome 15D2."
    Piao J.-H., Matsuda Y., Nakamura H., Sano K.
    Cytogenet. Cell Genet. 87:172-174(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
  2. "Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization."
    Giganti A., Rodriguez M., Fould B., Moulharat N., Coge F., Chomarat P., Galizzi J.-P., Valet P., Saulnier-Blache J.-S., Boutin J.A., Ferry G.
    J. Biol. Chem. 283:7776-7789(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
    Tissue: Adipocyte and Skeletal muscle.
  3. "Comparative genomics, experimental biology, and bioinformatics merge to narrow a QTL for HDL cholesterol on mouse chromosome 15 and human chromosome 8."
    Burgess-Herbert S.L., Shockley K., Sheehan S., Bickerstaff L., Harwood B.I.V., Shen Y., Li R., Churchill G.A., Paigen B.
    Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: MRL/MpJ.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Skin.
  5. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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] (ISOFORM 1).
    Strain: C57BL/6J and FVB/N.
    Tissue: Mammary gland and Retina.
  7. "Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression."
    Boucher J., Quilliot D., Pradere J.P., Simon M.F., Gres S., Guigne C., Prevot D., Ferry G., Boutin J.A., Carpene C., Valet P., Saulnier-Blache J.S.
    Diabetologia 48:569-577(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, POSSIBLE FUNCTION IN OBESITY.
  8. "Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase."
    Pradere J.P., Tarnus E., Gres S., Valet P., Saulnier-Blache J.S.
    Biochim. Biophys. Acta 1771:93-102(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, FUNCTION, GLYCOSYLATION, MUTAGENESIS OF 12-VAL--VAL-22; 12-VAL--GLY-27; 23-ASN--GLY-27; CYS-25; GLY-27; 27-GLY--ALA-30; 27-GLY--ARG-35; 30-ALA--ILE-33; 30-ALA--GLY-41; 32-ARG--ARG-35; 36-ALA--GLU-40; ASN-53 AND ASN-410.
  9. "Domain interplay mediated by an essential disulfide linkage is critical for the activity and secretion of the metastasis-promoting enzyme autotaxin."
    Jansen S., Andries M., Derua R., Waelkens E., Bollen M.
    J. Biol. Chem. 284:14296-14302(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERDOMAIN DISULFIDE BOND, MUTAGENESIS OF 851-LEU--THR-853; LEU-851; LYS-852 AND THR-853.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  11. "Crystal structure of autotaxin and insight into GPCR activation by lipid mediators."
    Nishimasu H., Okudaira S., Hama K., Mihara E., Dohmae N., Inoue A., Ishitani R., Takagi J., Aoki J., Nureki O.
    Nat. Struct. Mol. Biol. 18:205-212(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 36-862 IN COMPLEXES WITH LYSOPHOSPHATIDIC ACID; ZINC AND CALCIUM IONS, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DISULFIDE BONDS, GLYCOSYLATION AT ASN-53; ASN-410 AND ASN-524, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-210; LEU-213; ASN-230; LEU-243; GLU-247 AND PHE-249.
  12. "Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling."
    Kato K., Nishimasu H., Okudaira S., Mihara E., Ishitani R., Takagi J., Aoki J., Nureki O.
    Proc. Natl. Acad. Sci. U.S.A. 109:16876-16881(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 51-58.
  13. "Screening and X-ray crystal structure-based optimization of autotaxin (ENPP2) inhibitors, using a newly developed fluorescence probe."
    Kawaguchi M., Okabe T., Okudaira S., Nishimasu H., Ishitani R., Kojima H., Nureki O., Aoki J., Nagano T.
    ACS Chem. Biol. 8:1713-1721(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 36-862 IN COMPLEXES WITH INHIBITORS AND ZINC, GLYCOSYLATION AT ASN-53; ASN-410 AND ASN-524, CATALYTIC ACTIVITY, COFACTOR, DISULFIDE BOND.

Entry informationi

Entry nameiENPP2_MOUSE
AccessioniPrimary (citable) accession number: Q9R1E6
Secondary accession number(s): A8UH85
, A8UH93, B2ZP54, Q6PDE0, Q99LG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: February 10, 2009
Last modified: May 11, 2016
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.