ENPP7_MOUSE
ID ENPP7_MOUSE Reviewed; 439 AA.
AC Q3TIW9; A2A5N7; D3Z6V6;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
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:21177474};
DE AltName: Full=Alkaline sphingomyelin phosphodiesterase;
DE AltName: Full=Intestinal alkaline sphingomyelinase {ECO:0000250|UniProtKB:Q6UWV6};
DE Short=Alk-SMase {ECO:0000250|UniProtKB:Q6UWV6};
DE Flags: Precursor;
GN Name=Enpp7 {ECO:0000312|MGI:MGI:3027917};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=21177474; DOI=10.1194/jlr.m012880;
RA Zhang Y., Cheng Y., Hansen G.H., Niels-Christiansen L.L., Koentgen F.,
RA Ohlsson L., Nilsson A., Duan R.D.;
RT "Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a
RT study on enzyme knockout mice.";
RL J. Lipid Res. 52:771-781(2011).
RN [5]
RP FUNCTION.
RX PubMed=24650549; DOI=10.1152/ajpgi.00319.2013;
RA Zhang P., Chen Y., Cheng Y., Hertervig E., Ohlsson L., Nilsson A.,
RA Duan R.D.;
RT "Alkaline sphingomyelinase (NPP7) promotes cholesterol absorption by
RT affecting sphingomyelin levels in the gut: A study with NPP7 knockout
RT mice.";
RL Am. J. Physiol. 306:G903-G908(2014).
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:21177474).
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. Does not have nucleotide
CC pyrophosphatase activity (By similarity). May promote cholesterol
CC absorption by affecting the levels of sphingomyelin derived from either
CC diet or endogenous sources, in the intestinal lumen (PubMed:24650549).
CC {ECO:0000250|UniProtKB:Q6UWV6, ECO:0000269|PubMed:21177474,
CC ECO:0000269|PubMed:24650549}.
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:21177474};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19254;
CC Evidence={ECO:0000305|PubMed:21177474};
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:0000250|UniProtKB:Q6UWV6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63381;
CC Evidence={ECO:0000250|UniProtKB:Q6UWV6};
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 -!- 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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6UWV6};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q6UWV6}.
CC Note=The catalytic domain is released into the extracellular medium
CC when cells are treated with trypsin. Localized at the surface of the
CC microvillar membrane in small intestine enterocytes, and in endosome-
CC like structures situated beneath the microvillar membrane, and in Golgi
CC complex. {ECO:0000250|UniProtKB:Q6UWV6}.
CC -!- TISSUE SPECIFICITY: Expressed in liver and small intestine.
CC {ECO:0000269|PubMed:21177474}.
CC -!- PTM: N-glycosylated; required for activity and transport to the plasma
CC membrane. {ECO:0000250|UniProtKB:Q6UWV6}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, are viable and fertile, are grown normally without obvious
CC abnormalities. Mice shown signs of hypertrophy of the intestinal
CC epithelium, as the widths of the villi and crypts, as well as the
CC thickness of muscle layer under the crypts appear increased. However,
CC no spontaneous tumorigenesis either in the small intestine or in the
CC colon is identifiedknockout mice up to the age of 10 months.
CC {ECO:0000269|PubMed:21177474}.
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DR EMBL; AK144474; BAE25908.1; -; mRNA.
DR EMBL; AK167678; BAE39727.1; -; mRNA.
DR EMBL; AL591544; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC141245; AAI41246.1; -; mRNA.
DR CCDS; CCDS88293.1; -.
DR RefSeq; XP_006533321.1; XM_006533258.2.
DR AlphaFoldDB; Q3TIW9; -.
DR SMR; Q3TIW9; -.
DR STRING; 10090.ENSMUSP00000090027; -.
DR GlyGen; Q3TIW9; 5 sites.
DR PhosphoSitePlus; Q3TIW9; -.
DR MaxQB; Q3TIW9; -.
DR ProteomicsDB; 324810; -.
DR ProteomicsDB; 347416; -.
DR Antibodypedia; 19751; 253 antibodies from 27 providers.
DR Ensembl; ENSMUST00000106273; ENSMUSP00000101880; ENSMUSG00000046697.
DR UCSC; uc007mpr.1; mouse.
DR UCSC; uc007mps.1; mouse.
DR MGI; MGI:3027917; Enpp7.
DR VEuPathDB; HostDB:ENSMUSG00000046697; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000159339; -.
DR HOGENOM; CLU_017594_1_0_1; -.
DR OrthoDB; 999163at2759; -.
DR TreeFam; TF330032; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR BioGRID-ORCS; 238011; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q3TIW9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR Bgee; ENSMUSG00000046697; Expressed in jejunum and 7 other tissues.
DR ExpressionAtlas; Q3TIW9; baseline and differential.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISS:UniProtKB.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IMP:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
DR GO; GO:0044241; P:lipid digestion; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0008156; P:negative regulation of DNA replication; ISO:MGI.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0045797; P:positive regulation of intestinal cholesterol absorption; IMP:UniProtKB.
DR GO; GO:2000755; P:positive regulation of sphingomyelin catabolic process; IMP:UniProtKB.
DR GO; GO:1904729; P:regulation of intestinal lipid absorption; IMP:UniProtKB.
DR GO; GO:0006685; P:sphingomyelin catabolic process; ISO:MGI.
DR GO; GO:0006684; P:sphingomyelin metabolic process; ISO:MGI.
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; Glycoprotein; Hydrolase; Lipid metabolism; Membrane;
KW Metal-binding; Reference proteome; Signal; Transmembrane;
KW 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 /evidence="ECO:0000255"
FT /id="PRO_5014309164"
FT TOPO_DOM 22..414
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..439
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 69..75
FT /note="Required for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT ACT_SITE 72
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 36
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 93
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 196
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 244
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT BINDING 350
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6UWV6"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 439 AA; 49618 MW; 5D6112A945136709 CRC64;
MGHSAVLLCV ALAILPACVT GAPVQRQHKL LLVSFDGFRW NYDQDVDTPN LDSMAQEGVK
AQYMTPAFVT MTSPCHFTLV TGKYIENHGV VHNMFYNTTS TVRLPYHATL GIQRWWDNGS
IPIWITAQRQ GLKTGSFFYP GGNVTYQGEA VTMSRKEGVL HNYKNETEWR GNVDTVMKWF
LEEDVSLVTL YFGEPDSTGH KYGPESQERK DMVKQVDRTV GYLRDSIKRH HLSDSLNLII
TSDHGMTTVN KKASDLVEFH KFSNFTFQDI QFELLDYGPI GMLIPKEGML EKVYSVLKDA
HPRLHVYKKE DFPKNFHYAN NPRITPLLMY SDLGYVIHGR VNVQFNNGEH GFNNQDMDMK
TIFRAVGPSF KAGLEVEPFE SVHVYELMCQ LLGIVPEPND GNPGILRPML RSGSASLLSS
QHHLVALLVG ILTCLAKVL
