Q13822 (ENPP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
Short name=E-NPP 2
EC=3.1.4.39

Alternative name(s):
Autotaxin
Extracellular lysophospholipase D
Short name=LysoPLD

Gene names

Name:	ENPP2
Synonyms:	ATX, PDNP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	863 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.9 Ref.10 Ref.11 Ref.12
Catalytic activity	1-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-alkyl-sn-glycerol 3-phosphate + ethanolamine. Ref.12
Cofactor	Binds 2 zinc ions per subunit By similarity. Binds 1 calcium ion per subunit By similarity.
Enzyme regulation	Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA Probable. Ref.4 Ref.5 Ref.12
Subcellular location	Secreted. Note: Secreted by most body fluids including serum and CSF. Also by adipocytes and numerous cancer cells. Ref.4
Tissue specificity	Predominantly expressed in brain, placenta, ovary, and small intestine. Expressed in a number of carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma and non-small-cell lung cancer. Expressed in body fluids such as plasma, cerebral spinal fluid (CSF), saliva, follicular and amniotic fluids. Not detected in leukocytes. Isoform 1 is more highly expressed in peripheral tissues than in the central nervous system (CNS). Adipocytes only express isoform 1. Isoform 3 is more highly expressed in the brain than in peripheral tissues. Ref.2 Ref.3 Ref.5
Induction	Up-regulated in massively obese subjects with glucose intolerance, and during adipogenesis. Ref.4 Ref.5 Ref.11 Ref.12
Post-translational modification	N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity By similarity. 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.
Biophysicochemical properties	Kinetic parameters: KM=0.5 mM for 16:0-LPC (at pH 8.5) Ref.5 Ref.8 KM=5.5 mM for pNP-TMP (at pH 8.5) KM=11.3 mM for pNppp (isoform 1) KM=5.7 mM for pNppp (isoform 2) KM=19.8 mM for pNppp (isoform 3) Vmax=1.9 nmol/min/µg enzyme with pNppp as substrate (isoform 1) Vmax=0.67 nmol/min/µg enzyme with pNppp as substrate (isoform 2) Vmax=1.6 nmol/min/µg enzyme with pNppp as substrate (isoform 3) pH dependence: Optimum pH is 9.0 (isoform 1), 8.0 (isoform 3). Isoform 1 is less sensitive to pH. Isoform 1, isoform 2 and isoform 3 all retain some activity at pH 9.5. Temperature dependence: Isoform 1 and isoform 3 are active from 45 to 60 degrees Celsius.

Ontologies

Keywords
Biological process	Chemotaxis Lipid degradation Lipid metabolism
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Obesity
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement Ref.9. Source: ProtInc cellular component movement Traceable author statement Ref.9. Source: ProtInc chemotaxis Non-traceable author statement Ref.1. Source: UniProtKB immune response Inferred from electronic annotation. Source: InterPro phosphatidylcholine catabolic process Inferred from direct assay Ref.12. Source: UniProtKB regulation of cell migration Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	extracellular space Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.9. Source: ProtInc
Molecular_function	alkylglycerophosphoethanolamine phosphodiesterase activity Inferred from electronic annotation. Source: EC calcium ion binding Inferred from sequence or structural similarity. Source: UniProtKB lysophospholipase activity Inferred from direct assay Ref.12. Source: UniProtKB nucleic acid binding Inferred from electronic annotation. Source: InterPro nucleotide diphosphatase activity Traceable author statement Ref.3. Source: ProtInc phosphodiesterase I activity Traceable author statement Ref.1. Source: ProtInc polysaccharide binding Inferred from electronic annotation. Source: InterPro scavenger receptor activity Inferred from electronic annotation. Source: InterPro transcription factor binding Traceable author statement Ref.2. Source: ProtInc zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13822-1)

Also known as: ATXter; 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.

Isoform 2 (identifier: Q13822-2)

Also known as: ATXmel; Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     324-324: E → EESSYGSPFTPAKRPKRKVAPKRRQERPVAPPKKRRRKIHRMDHYAAETRQDK

Isoform 3 (identifier: Q13822-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     593-593: E → EAETRKYRGTRNENKENINGNFEPRK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	By similarity
	Propeptide	28 – 35	8	Removed by furin		PRO_0000281649
	Chain	36 – 863	828	Ectonucleotide pyrophosphatase/phosphodiesterase family member 2		PRO_0000188567
Regions
	Domain	55 – 98	44	SMB 1
	Domain	99 – 143	45	SMB 2
	Region	211 – 214	4	Substrate binding By similarity
	Region	244 – 255	12	Substrate binding By similarity
	Region	830 – 851	22	Required for secretion By similarity
	Motif	127 – 129	3	Cell attachment site Potential
Sites
	Active site	210	1	By similarity
	Metal binding	172	1	Zinc 1 By similarity
	Metal binding	210	1	Zinc 1 By similarity
	Metal binding	312	1	Zinc 2 By similarity
	Metal binding	316	1	Zinc 2 By similarity
	Metal binding	359	1	Zinc 1 By similarity
	Metal binding	360	1	Zinc 1 By similarity
	Metal binding	475	1	Zinc 2 By similarity
	Metal binding	740	1	Calcium By similarity
	Metal binding	744	1	Calcium By similarity
	Metal binding	746	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	748	1	Calcium By similarity
	Site	853	1	Essential for catalytic activity By similarity
Amino acid modifications
	Glycosylation	54	1	N-linked (GlcNAc...) Potential
	Glycosylation	411	1	N-linked (GlcNAc...) Potential
	Glycosylation	525	1	N-linked (GlcNAc...) Potential
	Glycosylation	807	1	N-linked (GlcNAc...) Potential
	Disulfide bond	59 ↔ 76		Alternate By similarity
	Disulfide bond	59 ↔ 63		Alternate By similarity
	Disulfide bond	63 ↔ 94		Alternate By similarity
	Disulfide bond	74 ↔ 87		Alternate By similarity
	Disulfide bond	74 ↔ 76		Alternate By similarity
	Disulfide bond	80 ↔ 86		By similarity
	Disulfide bond	87 ↔ 94		Alternate By similarity
	Disulfide bond	103 ↔ 120		Alternate By similarity
	Disulfide bond	103 ↔ 108		Alternate By similarity
	Disulfide bond	108 ↔ 138		Alternate By similarity
	Disulfide bond	118 ↔ 131		Alternate By similarity
	Disulfide bond	118 ↔ 120		Alternate By similarity
	Disulfide bond	124 ↔ 130		By similarity
	Disulfide bond	131 ↔ 138		Alternate By similarity
	Disulfide bond	149 ↔ 195		By similarity
	Disulfide bond	157 ↔ 351		By similarity
	Disulfide bond	367 ↔ 469		By similarity
	Disulfide bond	414 ↔ 806		By similarity
Natural variations
	Alternative sequence	324	1	E → EESSYGSPFTPAKRPKRKVA PKRRQERPVAPPKKRRRKIH RMDHYAAETRQDK in isoform 2.		VSP_006750
	Alternative sequence	593	1	E → EAETRKYRGTRNENKENING NFEPRK in isoform 3.		VSP_036398
	Natural variant	493	1	S → P. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.9 Corresponds to variant rs10283100 [ dbSNP | Ensembl ].		VAR_060469
	Natural variant	577	1	N → S. Corresponds to variant rs2289886 [ dbSNP | Ensembl ].		VAR_057472
	Natural variant	726	1	S → L. Corresponds to variant rs16892767 [ dbSNP | Ensembl ].		VAR_057473
Experimental info
	Mutagenesis	170	1	S → E: Reduces lysophospholipase activity by about 70%.
	Mutagenesis	210	1	T → A: Loss of lysophospholipase activity. Ref.12
	Mutagenesis	211	1	F → Y: Reduces lysophospholipase activity by about 70%. Ref.12
	Mutagenesis	218	1	A → V: Reduces lysophospholipase activity by about 50%. Ref.12
	Mutagenesis	231	1	N → A: Strongly reduced lysophospholipase activity. Ref.12
	Mutagenesis	307	1	Y → Q: Reduces lysophospholipase activity by about 70%. Ref.12
	Sequence conflict	23	1	N → S in AAA64785. Ref.1
	Sequence conflict	23	1	N → S in ABW38316. Ref.5
	Sequence conflict	73	1	D → H in BAA08260. Ref.2
	Sequence conflict	100	1	G → A in AAB00855. Ref.3
	Sequence conflict	291	1	Q → R in AAA64785. Ref.1
	Sequence conflict	291	1	Q → R in ABW38316. Ref.5
	Sequence conflict	349	1	H → R in AAA64785. Ref.1
	Sequence conflict	349	1	H → R in ABW38316. Ref.5
	Sequence conflict	457	1	K → P AA sequence Ref.9
	Sequence conflict	501	1	V → S AA sequence Ref.9
	Sequence conflict	508	1	E → N AA sequence Ref.9
	Sequence conflict	554	1	P → L AA sequence Ref.9
	Sequence conflict	629	1	P → L in AAA64785. Ref.1
	Sequence conflict	629	1	P → L in ABW38316. Ref.5
	Sequence conflict	644	1	S → R in BAA08260. Ref.2
	Sequence conflict	703	1	V → A in BAA08260. Ref.2
	Sequence conflict	769	1	Y → H in BAA08260. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ATXter) (Beta) [UniParc]. Last modified March 2, 2010. Version 3. Checksum: 94A7A2B3701F0993	FASTA	863	98,994
	10 20 30 40 50 60 MARRSSFQSC QIISLFTFAV GVNICLGFTA HRIKRAEGWE EGPPTVLSDS PWTNISGSCK 70 80 90 100 110 120 GRCFELQEAG PPDCRCDNLC KSYTSCCHDF DELCLKTARG WECTKDRCGE VRNEENACHC 130 140 150 160 170 180 SEDCLARGDC CTNYQVVCKG ESHWVDDDCE EIKAAECPAG FVRPPLIIFS VDGFRASYMK 190 200 210 220 230 240 KGSKVMPNIE KLRSCGTHSP YMRPVYPTKT FPNLYTLATG LYPESHGIVG NSMYDPVFDA 250 260 270 280 290 300 TFHLRGREKF NHRWWGGQPL WITATKQGVK AGTFFWSVVI PHERRILTIL QWLTLPDHER 310 320 330 340 350 360 PSVYAFYSEQ PDFSGHKYGP FGPEMTNPLR EIDKIVGQLM DGLKQLKLHR CVNVIFVGDH 370 380 390 400 410 420 GMEDVTCDRT EFLSNYLTNV DDITLVPGTL GRIRSKFSNN AKYDPKAIIA NLTCKKPDQH 430 440 450 460 470 480 FKPYLKQHLP KRLHYANNRR IEDIHLLVER RWHVARKPLD VYKKPSGKCF FQGDHGFDNK 490 500 510 520 530 540 VNSMQTVFVG YGSTFKYKTK VPPFENIELY NVMCDLLGLK PAPNNGTHGS LNHLLRTNTF 550 560 570 580 590 600 RPTMPEEVTR PNYPGIMYLQ SDFDLGCTCD DKVEPKNKLD ELNKRLHTKG STEERHLLYG 610 620 630 640 650 660 RPAVLYRTRY DILYHTDFES GYSEIFLMPL WTSYTVSKQA EVSSVPDHLT SCVRPDVRVS 670 680 690 700 710 720 PSFSQNCLAY KNDKQMSYGF LFPPYLSSSP EAKYDAFLVT NMVPMYPAFK RVWNYFQRVL 730 740 750 760 770 780 VKKYASERNG VNVISGPIFD YDYDGLHDTE DKIKQYVEGS SIPVPTHYYS IITSCLDFTQ 790 800 810 820 830 840 PADKCDGPLS VSSFILPHRP DNEESCNSSE DESKWVEELM KMHTARVRDI EHLTSLDFFR 850 860 KTSRSYPEIL TLKTYLHTYE SEI
	Isoform 2 (ATXmel) (Alpha) [UniParc]. Checksum: 30C7CB1E60101B75	FASTA	915	105,201
	10 20 30 40 50 60 MARRSSFQSC QIISLFTFAV GVNICLGFTA HRIKRAEGWE EGPPTVLSDS PWTNISGSCK 70 80 90 100 110 120 GRCFELQEAG PPDCRCDNLC KSYTSCCHDF DELCLKTARG WECTKDRCGE VRNEENACHC 130 140 150 160 170 180 SEDCLARGDC CTNYQVVCKG ESHWVDDDCE EIKAAECPAG FVRPPLIIFS VDGFRASYMK 190 200 210 220 230 240 KGSKVMPNIE KLRSCGTHSP YMRPVYPTKT FPNLYTLATG LYPESHGIVG NSMYDPVFDA 250 260 270 280 290 300 TFHLRGREKF NHRWWGGQPL WITATKQGVK AGTFFWSVVI PHERRILTIL QWLTLPDHER 310 320 330 340 350 360 PSVYAFYSEQ PDFSGHKYGP FGPEESSYGS PFTPAKRPKR KVAPKRRQER PVAPPKKRRR 370 380 390 400 410 420 KIHRMDHYAA ETRQDKMTNP LREIDKIVGQ LMDGLKQLKL HRCVNVIFVG DHGMEDVTCD 430 440 450 460 470 480 RTEFLSNYLT NVDDITLVPG TLGRIRSKFS NNAKYDPKAI IANLTCKKPD QHFKPYLKQH 490 500 510 520 530 540 LPKRLHYANN RRIEDIHLLV ERRWHVARKP LDVYKKPSGK CFFQGDHGFD NKVNSMQTVF 550 560 570 580 590 600 VGYGSTFKYK TKVPPFENIE LYNVMCDLLG LKPAPNNGTH GSLNHLLRTN TFRPTMPEEV 610 620 630 640 650 660 TRPNYPGIMY LQSDFDLGCT CDDKVEPKNK LDELNKRLHT KGSTEERHLL YGRPAVLYRT 670 680 690 700 710 720 RYDILYHTDF ESGYSEIFLM PLWTSYTVSK QAEVSSVPDH LTSCVRPDVR VSPSFSQNCL 730 740 750 760 770 780 AYKNDKQMSY GFLFPPYLSS SPEAKYDAFL VTNMVPMYPA FKRVWNYFQR VLVKKYASER 790 800 810 820 830 840 NGVNVISGPI FDYDYDGLHD TEDKIKQYVE GSSIPVPTHY YSIITSCLDF TQPADKCDGP 850 860 870 880 890 900 LSVSSFILPH RPDNEESCNS SEDESKWVEE LMKMHTARVR DIEHLTSLDF FRKTSRSYPE 910 ILTLKTYLHT YESEI
	Isoform 3 (Gamma) [UniParc]. Checksum: F06979D62CA31D12	FASTA	888	101,998
	10 20 30 40 50 60 MARRSSFQSC QIISLFTFAV GVNICLGFTA HRIKRAEGWE EGPPTVLSDS PWTNISGSCK 70 80 90 100 110 120 GRCFELQEAG PPDCRCDNLC KSYTSCCHDF DELCLKTARG WECTKDRCGE VRNEENACHC 130 140 150 160 170 180 SEDCLARGDC CTNYQVVCKG ESHWVDDDCE EIKAAECPAG FVRPPLIIFS VDGFRASYMK 190 200 210 220 230 240 KGSKVMPNIE KLRSCGTHSP YMRPVYPTKT FPNLYTLATG LYPESHGIVG NSMYDPVFDA 250 260 270 280 290 300 TFHLRGREKF NHRWWGGQPL WITATKQGVK AGTFFWSVVI PHERRILTIL QWLTLPDHER 310 320 330 340 350 360 PSVYAFYSEQ PDFSGHKYGP FGPEMTNPLR EIDKIVGQLM DGLKQLKLHR CVNVIFVGDH 370 380 390 400 410 420 GMEDVTCDRT EFLSNYLTNV DDITLVPGTL GRIRSKFSNN AKYDPKAIIA NLTCKKPDQH 430 440 450 460 470 480 FKPYLKQHLP KRLHYANNRR IEDIHLLVER RWHVARKPLD VYKKPSGKCF FQGDHGFDNK 490 500 510 520 530 540 VNSMQTVFVG YGSTFKYKTK VPPFENIELY NVMCDLLGLK PAPNNGTHGS LNHLLRTNTF 550 560 570 580 590 600 RPTMPEEVTR PNYPGIMYLQ SDFDLGCTCD DKVEPKNKLD ELNKRLHTKG STEAETRKYR 610 620 630 640 650 660 GTRNENKENI NGNFEPRKER HLLYGRPAVL YRTRYDILYH TDFESGYSEI FLMPLWTSYT 670 680 690 700 710 720 VSKQAEVSSV PDHLTSCVRP DVRVSPSFSQ NCLAYKNDKQ MSYGFLFPPY LSSSPEAKYD 730 740 750 760 770 780 AFLVTNMVPM YPAFKRVWNY FQRVLVKKYA SERNGVNVIS GPIFDYDYDG LHDTEDKIKQ 790 800 810 820 830 840 YVEGSSIPVP THYYSIITSC LDFTQPADKC DGPLSVSSFI LPHRPDNEES CNSSEDESKW 850 860 870 880 VEELMKMHTA RVRDIEHLTS LDFFRKTSRS YPEILTLKTY LHTYESEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases." Murata J., Lee H.Y., Clair T., Krutzsch H.C., Arestad A.A., Sobel M.E., Liotta L.A., Stracke M.L. J. Biol. Chem. 269:30479-30484(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION, VARIANT PRO-493. Tissue: Melanoma.
[2]	"Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)." Kawagoe H., Soma O., Goji J., Nishimura N., Narita M., Inazawa J., Nakamura H., Sano K. Genomics 30:380-384(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45, TISSUE SPECIFICITY, VARIANT PRO-493.
[3]	"Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells." Lee H.Y., Murata J., Clair T., Polymeropoulos M.H., Torres R., Manrow R.E., Liotta L.A., Stracke M.L. Biochem. Biophys. Res. Commun. 218:714-719(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT PRO-493. Tissue: Teratocarcinoma.
[4]	"Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate." van Meeteren L.A., Ruurs P., Christodoulou E., Goding J.W., Takakusa H., Kikuchi K., Perrakis A., Nagano T., Moolenaar W.H. J. Biol. Chem. 280:21155-21161(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, ENZYME REGULATION, VARIANT PRO-493.
[5]	"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), PROTEIN SEQUENCE OF 36-42 AND 49-54, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT PRO-493. Tissue: Brain and Melanoma.
[6]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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), VARIANT PRO-493. Tissue: Testis.
[8]	"Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase." Tokumura A., Majima E., Kariya Y., Tominaga K., Kogure K., Yasuda K., Fukuzawa K. J. Biol. Chem. 277:39436-39442(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 36-49; 318-330; 335-344; 440-450 AND 854-863, IDENTIFICATION, BIOPHYSICOCHEMICAL PROPERTIES.
[9]	"Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein." Stracke M.L., Krutzsch H.C., Unsworth E.J., Aarestad A., Cioce V., Schiffmann E., Liotta L.A. J. Biol. Chem. 267:2524-2529(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 256-266; 370-392; 457-463; 481-496; 501-510; 545-554; 639-643; 706-710 AND 829-840, FUNCTION, VARIANT PRO-493. Tissue: Melanoma.
[10]	"Autotaxin (NPP-2), a metastasis-enhancing mitogen, is an angiogenic factor." Nam S.W., Clair T., Kim Y.S., McMarlin A., Schiffmann E., Liotta L.A., Stracke M.L. Cancer Res. 61:6938-6944(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ANGIOGENESIS.
[11]	"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.
[12]	"Structural basis of substrate discrimination and integrin binding by autotaxin." Hausmann J., Kamtekar S., Christodoulou E., Day J.E., Wu T., Fulkerson Z., Albers H.M., van Meeteren L.A., Houben A.J., van Zeijl L., Jansen S., Andries M., Hall T., Pegg L.E., Benson T.E., Kasiem M., Harlos K., Kooi C.W. , Smyth S.S., Ovaa H., Bollen M., Morris A.J., Moolenaar W.H., Perrakis A. Nat. Struct. Mol. Biol. 18:198-204(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, MUTAGENESIS OF THR-210; PHE-211; ALA-218; ASN-231 AND TYR-307.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	L35594 mRNA. Translation: AAA64785.1. D45421 mRNA. Translation: BAA08260.1. D45914 Genomic DNA. Translation: BAA08342.1. L46720 mRNA. Translation: AAB00855.1. EU131011 mRNA. Translation: ABW38316.2. AC099818 Genomic DNA. No translation available. AC107960 Genomic DNA. No translation available. BC034961 mRNA. Translation: AAH34961.1.
IPI	IPI00156171. IPI00303210. IPI00878576.
PIR	A55144.
RefSeq	NP_001035181.1. NM_001040092.2. NP_001124335.1. NM_001130863.2. NP_006200.3. NM_006209.4.
UniGene	Hs.190977.
3D structure databases
ProteinModelPortal	Q13822.
SMR	Q13822. Positions 52-860.
ModBase	Search...
PTM databases
PhosphoSite	Q13822.
Polymorphism databases
DMDM	290457674.
Proteomic databases
PaxDb	Q13822.
PRIDE	Q13822.
Protocols and materials databases
DNASU	5168.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000075322; ENSP00000075322; ENSG00000136960. ENST00000259486; ENSP00000259486; ENSG00000136960.
GeneID	5168.
KEGG	hsa:5168.
UCSC	uc003yos.2. human. uc003yot.2. human.
Organism-specific databases
CTD	5168.
GeneCards	GC08M120569.
H-InvDB	HIX0025550.
HGNC	HGNC:3357. ENPP2.
HPA	HPA023700.
MIM	601060. gene.
neXtProt	NX_Q13822.
PharmGKB	PA27792.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1524.
HOVERGEN	HBG051484.
KO	K01122.
OMA	GDHGMED.
Enzyme and pathway databases
SABIO-RK	Q13822.
Gene expression databases
ArrayExpress	Q13822.
Bgee	Q13822.
CleanEx	HS_ENPP2.
Genevestigator	Q13822.
GermOnline	ENSG00000136960. Homo sapiens.
Family and domain databases
Gene3D	3.40.570.10. 1 hit. 3.40.720.10. 1 hit.
InterPro	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]
PANTHER	PTHR10151. PTHR10151. 1 hit.
Pfam	PF01223. Endonuclease_NS. 1 hit. PF01663. Phosphodiest. 2 hits. PF01033. Somatomedin_B. 2 hits. [Graphical view]
PRINTS	PR00022. SOMATOMEDINB.
SMART	SM00892. Endonuclease_NS. 1 hit. SM00477. NUC. 1 hit. SM00201. SO. 2 hits. [Graphical view]
SUPFAM	SSF53649. Alkaline_phosphatase_core. 1 hit.
PROSITE	PS00524. SMB_1. 2 hits. PS50958. SMB_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL3691.
ChiTaRS	ENPP2. human.
GenomeRNAi	5168.
NextBio	19994.
SOURCE	Search...

Entry information

Entry name

ENPP2_HUMAN

Accession

Primary (citable) accession number: Q13822
Secondary accession number(s): A8UHA1 , Q13827, Q14555, Q15117, Q9UCQ8, Q9UCR0, Q9UCR1, Q9UCR2, Q9UCR3, Q9UCR4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	March 2, 2010
Last modified:	April 3, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.