ENPP6_RAT
ID ENPP6_RAT Reviewed; 440 AA.
AC B0BND0;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Glycerophosphocholine cholinephosphodiesterase ENPP6 {ECO:0000305};
DE Short=GPC-Cpde;
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q8BGN3};
DE EC=3.1.4.38 {ECO:0000250|UniProtKB:Q8BGN3};
DE AltName: Full=Choline-specific glycerophosphodiester phosphodiesterase {ECO:0000250|UniProtKB:Q8BGN3};
DE AltName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 6;
DE Short=E-NPP 6;
DE Short=NPP-6;
DE Flags: Precursor;
GN Name=Enpp6 {ECO:0000312|RGD:1311645};
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 [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-341, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Choline-specific glycerophosphodiesterase that hydrolyzes
CC glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and
CC contributes to supplying choline to the cells. Has a preference for LPC
CC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty
CC acids. In vitro, hydrolyzes only choline-containing lysophospholipids,
CC such as sphingosylphosphorylcholine (SPC), platelet-activating factor
CC (PAF) and lysoPAF, but not other lysophospholipids.
CC {ECO:0000250|UniProtKB:Q8BGN3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sn-glycerol 3-phosphocholine = glycerol + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:19545, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:295975; EC=3.1.4.38;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19546;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:44720,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58168,
CC ChEBI:CHEBI:64683, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44721;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-alkyl-sn-glycero-3-phosphocholine + H2O = 1-O-alkyl-sn-
CC glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:36083,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15850,
CC ChEBI:CHEBI:30909, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36084;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-dodecanoyl-sn-glycero-3-phosphocholine + H2O = 1-dodecanoyl-
CC sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:41127,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:74966,
CC ChEBI:CHEBI:75529, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41128;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
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:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41120;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine
CC + H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:41003, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:34071, ChEBI:CHEBI:74344,
CC ChEBI:CHEBI:295975; Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41004;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC tetradecanoyl-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:40999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64489, ChEBI:CHEBI:75536, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41000;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sphing-4-enine-phosphocholine = H(+) + phosphocholine +
CC sphing-4-enine; Xref=Rhea:RHEA:41095, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57756, ChEBI:CHEBI:58906,
CC ChEBI:CHEBI:295975; Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41096;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:41091, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28610, ChEBI:CHEBI:75757, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41092;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphocholine + H2O =
CC 1-(9Z,12Z-octadecadienoyl)-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:41115, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28733, ChEBI:CHEBI:75561, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41116;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycero-2-phosphocholine + H2O = glycerol + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:61684, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:144950,
CC ChEBI:CHEBI:295975; Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61685;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8BGN3};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q8BGN3};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and EGTA in vitro.
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Homotetramer. {ECO:0000250,
CC ECO:0000250|UniProtKB:Q8BGN3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; BC158772; AAI58773.1; -; mRNA.
DR RefSeq; XP_006253218.1; XM_006253156.3.
DR AlphaFoldDB; B0BND0; -.
DR SMR; B0BND0; -.
DR BioGRID; 258461; 1.
DR IntAct; B0BND0; 1.
DR MINT; B0BND0; -.
DR STRING; 10116.ENSRNOP00000013005; -.
DR GlyGen; B0BND0; 4 sites, 4 N-linked glycans (1 site).
DR iPTMnet; B0BND0; -.
DR PhosphoSitePlus; B0BND0; -.
DR PaxDb; B0BND0; -.
DR PRIDE; B0BND0; -.
DR Ensembl; ENSRNOT00000013005; ENSRNOP00000013005; ENSRNOG00000009660.
DR GeneID; 306460; -.
DR CTD; 133121; -.
DR RGD; 1311645; Enpp6.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000158457; -.
DR InParanoid; B0BND0; -.
DR OMA; KEAWQNG; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; B0BND0; -.
DR TreeFam; TF330032; -.
DR Reactome; R-RNO-6814848; Glycerophospholipid catabolism.
DR PRO; PR:B0BND0; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000009660; Expressed in adult mammalian kidney and 6 other tissues.
DR ExpressionAtlas; B0BND0; baseline and differential.
DR Genevisible; B0BND0; RN.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0047390; F:glycerophosphocholine cholinephosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0008889; F:glycerophosphodiester phosphodiesterase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISS:UniProtKB.
DR GO; GO:0019695; P:choline metabolic process; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR029889; ENPP6.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR PANTHER; PTHR10151:SF66; PTHR10151:SF66; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase;
KW Lipid degradation; Lipid metabolism; Lipoprotein; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..419
FT /note="Glycerophosphocholine cholinephosphodiesterase
FT ENPP6"
FT /id="PRO_0000366924"
FT PROPEP 420..440
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000420894"
FT ACT_SITE 71
FT /note="Nucleophile"
FT /evidence="ECO:0000255"
FT BINDING 32
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 32
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 71
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 193
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 354
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 354
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 419
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT DISULFID 142..154
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT DISULFID 412
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 440 AA; 50701 MW; 4A76DB3E3EF8AD08 CRC64;
MAGKLWTFLL LFGFSWVWPA SAHRKLLVLL LDGFRSDYIS EDALASLPGF REIVNRGVKV
DYLTPDFPSL SYPNYYTLMT GRHCEVHQMI GNYMWDPRTN KSFDIGVNRD SLMPLWWNGS
EPLWITLMKA RRKVYMYYWP GCEVEILGVR PTYCLEYKNV PTDINFANAV SDALDSLKSG
RADLAAIYHE RIDVEGHHYG PSSPQRKDAL KAVDTVLKYM TQWIQERGLQ NDLNVILFSD
HGMTDIFWMD KVIELSKYIS LDDLQQVKDQ GPVVSLWPVP EKHSEIYHKL RTVEHMTVYE
KEAIPNRFYY KKGKFVSPLT LVADEGWFIA ESREALPFWM NSTGKREGWQ HGWHGYDNEL
MDMRGIFLAF GPDFKSNFRA APIRSVDVYN IMCNVVGITP LPNNGSWSRV VCMLKSQTSS
SPSIPPNSCA LVLILLLYFV
