ENPP7_HUMAN
ID ENPP7_HUMAN Reviewed; 458 AA.
AC Q6UWV6; Q6ZTS5; Q8IUS8;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 4.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 7;
DE Short=E-NPP 7;
DE Short=NPP-7;
DE EC=3.1.4.12 {ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:12885774, ECO:0000269|PubMed:15205117, ECO:0000269|PubMed:28292932};
DE AltName: Full=Alkaline sphingomyelin phosphodiesterase;
DE AltName: Full=Intestinal alkaline sphingomyelinase {ECO:0000303|PubMed:12671034, ECO:0000303|PubMed:12885774};
DE Short=Alk-SMase {ECO:0000303|PubMed:12885774, ECO:0000303|PubMed:28292932};
DE Flags: Precursor;
GN Name=ENPP7 {ECO:0000312|EMBL:AAH41453.2, ECO:0000312|HGNC:HGNC:23764};
GN ORFNames=UNQ3077/PRO9912;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP69661.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 137-151; 239-248; 256-271
RP AND 313-326, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Colon {ECO:0000269|PubMed:12885774},
RC Kidney {ECO:0000269|PubMed:12885774},
RC Small intestine {ECO:0000269|PubMed:12885774}, and
RC Stomach {ECO:0000269|PubMed:12885774};
RX PubMed=12885774; DOI=10.1074/jbc.m305437200;
RA Duan R.-D., Bergman T., Xu N., Wu J., Cheng Y., Duan J., Nelander S.,
RA Palmberg C., Nilsson A.;
RT "Identification of human intestinal alkaline sphingomyelinase as a novel
RT ecto-enzyme related to the nucleotide phosphodiesterase family.";
RL J. Biol. Chem. 278:38528-38536(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAQ88985.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAC86504.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver {ECO:0000312|EMBL:BAC86504.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH41453.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon {ECO:0000312|EMBL:AAH41453.2};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0000305}
RP PROTEIN SEQUENCE OF 22-36.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12671034; DOI=10.1194/jlr.m300037-jlr200;
RA Duan R.-D., Cheng Y., Hansen G., Hertervig E., Liu J.-J., Syk I.,
RA Sjostrom H., Nilsson A.;
RT "Purification, localization, and expression of human intestinal alkaline
RT sphingomyelinase.";
RL J. Lipid Res. 44:1241-1250(2003).
RN [7]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=15205117; DOI=10.1152/ajpgi.00190.2004;
RA Wu J., Liu F., Nilsson A., Duan R.D.;
RT "Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from
RT mucosa and enhances the sphingomyelinase activity.";
RL Am. J. Physiol. 287:G967-G973(2004).
RN [8] {ECO:0000305}
RP MUTAGENESIS OF HIS-353.
RX PubMed=15016655; DOI=10.1093/carcin/bgh140;
RA Wu J., Cheng Y., Nilsson A., Duan R.-D.;
RT "Identification of one exon deletion of intestinal alkaline
RT sphingomyelinase in colon cancer HT-29 cells and a differentiation-related
RT expression of the wild-type enzyme in Caco-2 cells.";
RL Carcinogenesis 25:1327-1333(2004).
RN [9] {ECO:0000305}
RP GLYCOSYLATION AT ASN-100; ASN-121; ASN-146; ASN-168 AND ASN-267, AND
RP MUTAGENESIS OF SER-76; CYS-78; ASN-100; ASN-121; ASN-146; ASN-168 AND
RP ASN-267.
RX PubMed=15458386; DOI=10.1042/bj20041455;
RA Wu J., Hansen G.H., Nilsson A., Duan R.-D.;
RT "Functional studies of human intestinal alkaline sphingomyelinase by
RT deglycosylation and mutagenesis.";
RL Biochem. J. 386:153-160(2005).
RN [10]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16255717; DOI=10.1042/bj20051121;
RA Wu J., Nilsson A., Joensson B.A., Stenstad H., Agace W., Cheng Y.,
RA Duan R.D.;
RT "Intestinal alkaline sphingomyelinase hydrolyses and inactivates platelet-
RT activating factor by a phospholipase C activity.";
RL Biochem. J. 394:299-308(2006).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-146.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12] {ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 17-433 IN COMPLEX WITH ZINC AND
RP PHOSPHOCHOLINE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, GLYCOSYLATION AT
RP ASN-100; ASN-121; ASN-146; ASN-168 AND ASN-267, AND MUTAGENESIS OF TYR-109;
RP TYR-166; ARG-271; ARG-343 AND 344-ILE--PHE-348.
RX PubMed=28292932; DOI=10.1074/jbc.m116.769273;
RA Gorelik A., Liu F., Illes K., Nagar B.;
RT "Crystal structure of the human alkaline sphingomyelinase provides insights
RT into substrate recognition.";
RL J. Biol. Chem. 292:7087-7094(2017).
CC -!- FUNCTION: Choline-specific phosphodiesterase that hydrolyzes
CC sphingomyelin releasing the ceramide and phosphocholine and therefore
CC is involved in sphingomyelin digestion, ceramide formation, and fatty
CC acid (FA) absorption in the gastrointestinal tract (PubMed:12885774,
CC PubMed:12671034, PubMed:15205117, PubMed:16255717, PubMed:28292932).
CC Has also phospholipase C activity and can also cleave phosphocholine
CC from palmitoyl lyso-phosphatidylcholine and platelet-activating factor
CC (PAF) leading to its inactivation (PubMed:16255717, PubMed:12885774).
CC Does not have nucleotide pyrophosphatase activity (PubMed:12885774).
CC May promote cholesterol absorption by affecting the levels of
CC sphingomyelin derived from either diet or endogenous sources, in the
CC intestinal lumen (By similarity). {ECO:0000250|UniProtKB:Q3TIW9,
CC ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:12885774,
CC ECO:0000269|PubMed:15205117, ECO:0000269|PubMed:16255717,
CC ECO:0000269|PubMed:28292932}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:295975; EC=3.1.4.12;
CC Evidence={ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:12885774,
CC ECO:0000269|PubMed:15205117, ECO:0000269|PubMed:16255717,
CC ECO:0000269|PubMed:28292932};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000269|PubMed:16255717};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:41119, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:75542, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:12885774};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41120;
CC Evidence={ECO:0000305|PubMed:12885774};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-
CC O-alkyl-2-acetyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:63380, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16291, ChEBI:CHEBI:36707, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000269|PubMed:16255717};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63381;
CC Evidence={ECO:0000269|PubMed:16255717};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-
CC O-octadecyl-2-acetyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:63384, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52450, ChEBI:CHEBI:147296, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q5EZ72};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63385;
CC Evidence={ECO:0000250|UniProtKB:Q5EZ72};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:28292932};
CC -!- ACTIVITY REGULATION: Inhibited in a dose dependent manner by ATP,
CC imidazole, orthovanadate and zinc ion. Not inhibited by ADP, AMP and
CC EDTA. {ECO:0000269|PubMed:12885774}.
CC -!- INTERACTION:
CC Q6UWV6; Q9BYV9: BACH2; NbExp=3; IntAct=EBI-12047821, EBI-1642333;
CC Q6UWV6; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12047821, EBI-618309;
CC Q6UWV6; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-12047821, EBI-3958099;
CC Q6UWV6; Q5JTD7: LRRC73; NbExp=3; IntAct=EBI-12047821, EBI-12003882;
CC Q6UWV6; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-12047821, EBI-11522433;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12671034,
CC ECO:0000269|PubMed:15205117}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:15205117}. Note=The
CC catalytic domain is released into the extracellular medium when cells
CC are treated with trypsin (PubMed:15205117). Localized at the surface of
CC the microvillar membrane in small intestine enterocytes, and in
CC endosome-like structures situated beneath the microvillar membrane, and
CC in Golgi complex (PubMed:12671034, PubMed:12885774).
CC {ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:12885774,
CC ECO:0000269|PubMed:15205117}.
CC -!- TISSUE SPECIFICITY: Detected in the colon (at protein level). Expressed
CC in the duodenum, jejunum and liver and at low levels in the ileum.
CC Expression was very low in the esophagus, stomach and colon.
CC {ECO:0000269|PubMed:12671034, ECO:0000269|PubMed:12885774}.
CC -!- PTM: N-glycosylated; required for activity and transport to the plasma
CC membrane. {ECO:0000269|PubMed:15458386, ECO:0000269|PubMed:19159218}.
CC -!- MISCELLANEOUS: Decreased levels of alkaline sphingomyelin
CC phosphodiesterase may be associated with colon cancer.
CC {ECO:0000303|PubMed:12671034, ECO:0000303|PubMed:15016655}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ENPP7ID44055ch17q25.html";
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DR EMBL; AY230663; AAP69661.1; -; mRNA.
DR EMBL; AY358622; AAQ88985.1; -; mRNA.
DR EMBL; AK126250; BAC86504.1; -; mRNA.
DR EMBL; BC041453; AAH41453.2; -; mRNA.
DR CCDS; CCDS11763.1; -.
DR RefSeq; NP_848638.3; NM_178543.4.
DR PDB; 5TCD; X-ray; 2.40 A; A=22-433.
DR PDB; 5UDY; X-ray; 2.60 A; A=22-433.
DR PDBsum; 5TCD; -.
DR PDBsum; 5UDY; -.
DR AlphaFoldDB; Q6UWV6; -.
DR SMR; Q6UWV6; -.
DR BioGRID; 130844; 30.
DR IntAct; Q6UWV6; 14.
DR STRING; 9606.ENSP00000332656; -.
DR ChEMBL; CHEMBL6058; -.
DR SwissLipids; SLP:000000173; -.
DR GlyGen; Q6UWV6; 5 sites.
DR iPTMnet; Q6UWV6; -.
DR PhosphoSitePlus; Q6UWV6; -.
DR BioMuta; ENPP7; -.
DR DMDM; 134047772; -.
DR jPOST; Q6UWV6; -.
DR MassIVE; Q6UWV6; -.
DR PaxDb; Q6UWV6; -.
DR PeptideAtlas; Q6UWV6; -.
DR PRIDE; Q6UWV6; -.
DR ProteomicsDB; 67528; -.
DR Antibodypedia; 19751; 253 antibodies from 27 providers.
DR DNASU; 339221; -.
DR Ensembl; ENST00000328313.10; ENSP00000332656.5; ENSG00000182156.10.
DR GeneID; 339221; -.
DR KEGG; hsa:339221; -.
DR MANE-Select; ENST00000328313.10; ENSP00000332656.5; NM_178543.5; NP_848638.3.
DR UCSC; uc002jxa.5; human.
DR CTD; 339221; -.
DR DisGeNET; 339221; -.
DR GeneCards; ENPP7; -.
DR HGNC; HGNC:23764; ENPP7.
DR HPA; ENSG00000182156; Tissue enriched (intestine).
DR MIM; 616997; gene.
DR neXtProt; NX_Q6UWV6; -.
DR OpenTargets; ENSG00000182156; -.
DR PharmGKB; PA134986550; -.
DR VEuPathDB; HostDB:ENSG00000182156; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000159339; -.
DR HOGENOM; CLU_017594_1_0_1; -.
DR InParanoid; Q6UWV6; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q6UWV6; -.
DR TreeFam; TF330032; -.
DR BRENDA; 3.1.4.12; 2681.
DR PathwayCommons; Q6UWV6; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SignaLink; Q6UWV6; -.
DR BioGRID-ORCS; 339221; 16 hits in 1070 CRISPR screens.
DR GeneWiki; ENPP7; -.
DR GenomeRNAi; 339221; -.
DR Pharos; Q6UWV6; Tbio.
DR PRO; PR:Q6UWV6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6UWV6; protein.
DR Bgee; ENSG00000182156; Expressed in jejunal mucosa and 74 other tissues.
DR ExpressionAtlas; Q6UWV6; baseline and differential.
DR Genevisible; Q6UWV6; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0044241; P:lipid digestion; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0008156; P:negative regulation of DNA replication; IDA:UniProtKB.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045797; P:positive regulation of intestinal cholesterol absorption; ISS:UniProtKB.
DR GO; GO:2000755; P:positive regulation of sphingomyelin catabolic process; ISS:UniProtKB.
DR GO; GO:1904729; P:regulation of intestinal lipid absorption; ISS:UniProtKB.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IEA:InterPro.
DR GO; GO:0006684; P:sphingomyelin metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR029895; ENPP7.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR PANTHER; PTHR10151:SF63; PTHR10151:SF63; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Glycoprotein;
KW Hydrolase; Lipid metabolism; Membrane; Metal-binding; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..21
FT /evidence="ECO:0000255, ECO:0000269|PubMed:15340161"
FT CHAIN 22..458
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 7"
FT /id="PRO_0000036403"
FT TOPO_DOM 22..433
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 72..78
FT /note="Required for enzyme activity"
FT /evidence="ECO:0000269|PubMed:15458386"
FT ACT_SITE 75
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:28292932"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT BINDING 96
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT BINDING 246
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT BINDING 247
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15458386,
FT ECO:0000269|PubMed:28292932, ECO:0007744|PDB:5TCD,
FT ECO:0007744|PDB:5UDY"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15458386,
FT ECO:0000269|PubMed:28292932, ECO:0007744|PDB:5TCD,
FT ECO:0007744|PDB:5UDY"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15458386,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:28292932,
FT ECO:0007744|PDB:5TCD, ECO:0007744|PDB:5UDY"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15458386,
FT ECO:0000269|PubMed:28292932, ECO:0007744|PDB:5TCD,
FT ECO:0007744|PDB:5UDY"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15458386,
FT ECO:0000269|PubMed:28292932, ECO:0007744|PDB:5TCD"
FT VARIANT 4
FT /note="P -> L (in dbSNP:rs8074547)"
FT /id="VAR_021506"
FT MUTAGEN 76
FT /note="S->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 78
FT /note="C->N: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 100
FT /note="N->Q: Strongly reduces N-glycosylation and enzyme
FT activity; when associated with Q-121; Q-146; Q-168 and Q-
FT 267."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 109
FT /note="Y->L: Decreased enzyme activity with sphingomyelin
FT and para-nitrophenylphosphorylcholine."
FT /evidence="ECO:0000269|PubMed:28292932"
FT MUTAGEN 121
FT /note="N->Q: Strongly reduces N-glycosylation and enzyme
FT activity; when associated with Q-100; Q-146; Q-168 and Q-
FT 267."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 146
FT /note="N->Q: Strongly reduces N-glycosylation and enzyme
FT activity; when associated with Q-100; Q-146; Q-168 and Q-
FT 267."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 166
FT /note="Y->L: Decreased enzyme activity with sphingomyelin
FT and para-nitrophenylphosphorylcholine."
FT /evidence="ECO:0000269|PubMed:28292932"
FT MUTAGEN 168
FT /note="N->Q: Strongly reduces N-glycosylation and enzyme
FT activity; when associated with Q-100; Q-121; Q-168 and Q-
FT 267."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 267
FT /note="N->Q: Strongly reduces N-glycosylation and enzyme
FT activity; when associated with Q-100; Q-121; Q-146 and Q-
FT 168."
FT /evidence="ECO:0000269|PubMed:15458386"
FT MUTAGEN 271
FT /note="R->E: Decreased enzyme activity; when associated
FT with E-343."
FT /evidence="ECO:0000269|PubMed:28292932"
FT MUTAGEN 343
FT /note="R->E: Decreased enzyme activity; when associated
FT with E-271."
FT /evidence="ECO:0000269|PubMed:28292932"
FT MUTAGEN 344..348
FT /note="INVQF->ENEQE: Loss of enzyme activity with
FT sphingomyelin."
FT /evidence="ECO:0000269|PubMed:28292932"
FT MUTAGEN 344..348
FT /note="INVQF->NNNQN: Loss of enzyme activity with
FT sphingomyelin."
FT /evidence="ECO:0000269|PubMed:28292932"
FT MUTAGEN 353
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15016655"
FT CONFLICT 101
FT /note="T -> I (in Ref. 2; AAQ88985)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="Y -> N (in Ref. 3; BAC86504)"
FT /evidence="ECO:0000305"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:5TCD"
FT TURN 43..48
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 75..84
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:5TCD"
FT TURN 101..104
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 126..131
FT /evidence="ECO:0007829|PDB:5TCD"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:5TCD"
FT TURN 143..146
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 169..185
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 199..205
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 210..232
FT /evidence="ECO:0007829|PDB:5TCD"
FT TURN 236..238
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 293..300
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:5TCD"
FT STRAND 375..379
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 387..395
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:5TCD"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:5TCD"
SQ SEQUENCE 458 AA; 51478 MW; A40560D61140F692 CRC64;
MRGPAVLLTV ALATLLAPGA GAPVQSQGSQ NKLLLVSFDG FRWNYDQDVD TPNLDAMARD
GVKARYMTPA FVTMTSPCHF TLVTGKYIEN HGVVHNMYYN TTSKVKLPYH ATLGIQRWWD
NGSVPIWITA QRQGLRAGSF FYPGGNVTYQ GVAVTRSRKE GIAHNYKNET EWRANIDTVM
AWFTEEDLDL VTLYFGEPDS TGHRYGPESP ERREMVRQVD RTVGYLRESI ARNHLTDRLN
LIITSDHGMT TVDKRAGDLV EFHKFPNFTF RDIEFELLDY GPNGMLLPKE GRLEKVYDAL
KDAHPKLHVY KKEAFPEAFH YANNPRVTPL LMYSDLGYVI HGRINVQFNN GEHGFDNKDM
DMKTIFRAVG PSFRAGLEVE PFESVHVYEL MCRLLGIVPE ANDGHLATLL PMLHTESALP
PDGRPTLLPK GRSALPPSSR PLLVMGLLGT VILLSEVA
