ENPP7_RAT
ID ENPP7_RAT Reviewed; 439 AA.
AC Q5EZ72;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 {ECO:0000305};
DE Short=E-NPP 7;
DE Short=NPP-7;
DE EC=3.1.4.12 {ECO:0000269|PubMed:15708357, ECO:0000269|PubMed:16255717};
DE AltName: Full=Alkaline sphingomyelin phosphodiesterase;
DE AltName: Full=Intestinal alkaline sphingomyelinase {ECO:0000303|PubMed:15205117, ECO:0000303|PubMed:15708357};
DE Short=Alk-SMase {ECO:0000250|UniProtKB:Q6UWV6};
DE Flags: Precursor;
GN Name=Enpp7 {ECO:0000312|RGD:1359324};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 32-40; 106-116; 204-211;
RP 221-226; 255-263 AND 317-342, IDENTIFICATION BY MASS SPECTROMETRY,
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Intestinal mucosa;
RX PubMed=15708357; DOI=10.1016/j.bbalip.2004.11.006;
RA Wu J., Cheng Y., Palmberg C., Bergman T., Nilsson A., Duan R.-D.;
RT "Cloning of alkaline sphingomyelinase from rat intestinal mucosa and
RT adjusting of the hypothetical protein XP_221184 in GenBank.";
RL Biochim. Biophys. Acta 1687:94-102(2005).
RN [2]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND TISSUE SPECIFICITY.
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 [3]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF ASP-198 AND ASP-245.
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).
CC -!- FUNCTION: Choline-specific phosphodiesterase that hydrolyzes
CC sphingomyelin (SM) releasing the ceramide and phosphocholine and
CC therefore is involved in sphingomyelin digestion, ceramide formation,
CC and fatty acid (FA) absorption in the gastrointestinal tract
CC (PubMed:16255717, PubMed:15708357). Has also phospholipase C activity
CC and can also cleave phosphocholine from palmitoyl lyso-
CC phosphatidylcholine and platelet-activating factor (PAF) leading to its
CC inactivation. Does not have nucleotide pyrophosphatase activity
CC (PubMed:16255717). May promote cholesterol absorption by affecting the
CC levels of sphingomyelin derived from either diet or endogenous sources,
CC in the intestinal lumen (By similarity). {ECO:0000250|UniProtKB:Q3TIW9,
CC ECO:0000269|PubMed:15708357, ECO:0000269|PubMed:16255717}.
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:15708357, ECO:0000269|PubMed:16255717};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000305|PubMed:15708357};
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:0000305|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:0000269|PubMed:16255717};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63385;
CC Evidence={ECO:0000305|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:0000250|UniProtKB:Q6UWV6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41120;
CC Evidence={ECO:0000250|UniProtKB:Q6UWV6};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q6UWV6};
CC -!- ACTIVITY REGULATION: platelet-activating factor hydrolysis is inhibited
CC by higher amount of sphingomyelin (PubMed:16255717). The hydrolysis of
CC platelet-activating factor and sphingomyelin can be inhibited by the
CC presence of sphingomyelin and platelet-activating factor respectively,
CC the inhibition of platelet-activating factor hydrolysis by
CC sphingomyelin being stronger (PubMed:16255717). PAF hydrolysis is dose-
CC dependently increased by both taurocholate (TC) and taurodeoxycholate
CC (TDC) (PubMed:16255717). Hydrolase activity against PAF is inhibited by
CC EDTA and stimulated by 0.1-0.25 mM Zn2+ (PubMed:16255717).
CC {ECO:0000269|PubMed:16255717}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.6 uM for 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine
CC {ECO:0000269|PubMed:16255717};
CC Vmax=374 umol/h/mg enzyme {ECO:0000269|PubMed:16255717};
CC pH dependence:
CC Optimum pH is 7.5 (PubMed:16255717). Optimum pH is 9
CC (PubMed:15708357). {ECO:0000269|PubMed:15708357,
CC ECO:0000269|PubMed:16255717};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15205117};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:15205117}.
CC Note=The catalytic domain is released into the extracellular medium
CC when cells are treated with trypsin (PubMed:15205117). Localized at the
CC surface of the microvillar membrane in small intestine enterocytes, and
CC in endosome-like structures situated beneath the microvillar membrane,
CC and in Golgi complex (By similarity). {ECO:0000250|UniProtKB:Q6UWV6,
CC ECO:0000269|PubMed:15205117}.
CC -!- TISSUE SPECIFICITY: Detected in small intestine (at protein level)
CC (PubMed:15205117). Highly expressed in the jejunum (PubMed:15708357).
CC {ECO:0000269|PubMed:15205117, ECO:0000269|PubMed:15708357}.
CC -!- PTM: N-glycosylated; required for activity and transport to the plasma
CC membrane. {ECO:0000250|UniProtKB:Q6UWV6}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; AY568760; AAU03450.1; -; mRNA.
DR RefSeq; NP_001012484.1; NM_001012466.1.
DR AlphaFoldDB; Q5EZ72; -.
DR SMR; Q5EZ72; -.
DR STRING; 10116.ENSRNOP00000064040; -.
DR GlyGen; Q5EZ72; 5 sites.
DR PhosphoSitePlus; Q5EZ72; -.
DR PaxDb; Q5EZ72; -.
DR PRIDE; Q5EZ72; -.
DR GeneID; 303729; -.
DR KEGG; rno:303729; -.
DR CTD; 339221; -.
DR RGD; 1359324; Enpp7.
DR eggNOG; KOG2645; Eukaryota.
DR InParanoid; Q5EZ72; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q5EZ72; -.
DR Reactome; R-RNO-1660662; Glycosphingolipid metabolism.
DR PRO; PR:Q5EZ72; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR GO; GO:0044241; P:lipid digestion; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0008156; P:negative regulation of DNA replication; ISO:RGD.
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; ISS: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 Cell membrane; Direct protein sequencing; Glycoprotein; Hydrolase;
KW Lipid metabolism; Membrane; Metal-binding; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..439
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 7"
FT /id="PRO_0000036404"
FT TOPO_DOM 22..422
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:15205117"
FT TRANSMEM 423..439
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 71..77
FT /note="Required for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT ACT_SITE 74
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 245
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 246
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 198
FT /note="D->A: Abolishes the phosphoric diester hydrolase
FT activity against PAF."
FT /evidence="ECO:0000269|PubMed:16255717"
FT MUTAGEN 245
FT /note="D->A: Abolishes the phosphoric diester hydrolase
FT activity against PAF."
FT /evidence="ECO:0000269|PubMed:16255717"
SQ SEQUENCE 439 AA; 49837 MW; 7CEABF0393C9480F CRC64;
MGHSAVLLSV ALVILPACVT GGPVQRQQQH KLLLVSFDGF RWNYDQDVET PNLDSMAQEG
VKARYMTPAF VTMTSPCHFT LVTGKYIENH GVVHNMFYNT TNKVRLPYHA TLGIQRWWDN
GSIPIWITAQ RQGLKTGSFF YPGGNVTYQG EAVTMSRKEG VLHNYKNETE WRANVDTVMK
WFTEEDVSLV TLYFGEPDST GHKYGPESQE RKDMVKQVDR TVGYLRDSIK RHHLTDSLNL
IITSDHGMTT VNKKASDLVE FHKFPNFTFR DIEFELLDYG PNGMLIPKEG MLEKVYSVLK
DAHPRLHVYK KEDFPKTFHY ANNPRITSLL MYSDLGYVIH GRVNVQFNSG EHGFDNQDMD
MKTIFRAVGP SFKAGLEVEP FESVHVYELM CQLLGIVPEP NDGHPGVLQP MLRSGSPLSR
QHHLVVVLMG ILTGLAKVV
