ENPP6_BOVIN
ID ENPP6_BOVIN Reviewed; 445 AA.
AC F1N5C8;
DT 09-JAN-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 2.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Glycerophosphocholine choline phosphodiesterase ENPP6 {ECO:0000250|UniProtKB:Q6UWR7};
DE Short=GPC-Cpde {ECO:0000303|PubMed:23161088};
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q8BGN3};
DE EC=3.1.4.38 {ECO:0000269|PubMed:23161088};
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:0000250|UniProtKB:Q6UWR7};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19390049; DOI=10.1126/science.1169588;
RG The bovine genome sequencing and analysis consortium;
RT "The genome sequence of taurine cattle: a window to ruminant biology and
RT evolution.";
RL Science 324:522-528(2009).
RN [3]
RP PROTEIN SEQUENCE OF 23-51; 60-109; 113-129; 134-206; 212-222; 228-251;
RP 255-262; 271-289; 292-301; 315-363; 367-377 AND 387-417, FUNCTION,
RP HOMODIMERIZATION, DISULFIDE BONDS, BIOPHYSICOCHEMICAL PROPERTIES, SIGNAL
RP SEQUENCE CLEAVAGE SITE, GLYCOSYLATION AT ASN-100; ASN-118; ASN-341 AND
RP ASN-406, GPI-ANCHOR, AND CATALYTIC ACTIVITY.
RC TISSUE=Brain;
RX PubMed=23161088; DOI=10.1007/s11064-012-0921-z;
RA Greiner-Tollersrud L., Berg T., Stensland H.M., Evjen G.,
RA Greiner-Tollersrud O.K.;
RT "Bovine brain myelin glycerophosphocholine choline phosphodiesterase is an
RT alkaline lysosphingomyelinase of the eNPP-family, regulated by lysosomal
RT sorting.";
RL Neurochem. Res. 38:300-310(2013).
CC -!- FUNCTION: Choline-specific glycerophosphodiesterase that hydrolyzes
CC glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and
CC contributes to supplying choline to the cells (PubMed:23161088). Has a
CC preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2
CC and 20:4) fatty acids. In vitro, hydrolyzes only choline-containing
CC lysophospholipids, such as sphingosylphosphorylcholine (SPC), platelet-
CC activating factor (PAF) and lysoPAF, but not other lysophospholipids
CC (By similarity). {ECO:0000250|UniProtKB:Q8BGN3,
CC ECO:0000269|PubMed:23161088}.
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:0000269|PubMed:23161088};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19546;
CC Evidence={ECO:0000305|PubMed:23161088};
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:0000269|PubMed:23161088};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44721;
CC Evidence={ECO:0000305|PubMed:23161088};
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:0000269|PubMed:23161088};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41096;
CC Evidence={ECO:0000305|PubMed:23161088};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2000 uM for lysophosphatidylcholine {ECO:0000269|PubMed:23161088};
CC KM=5000 uM for glycerophosphocholine {ECO:0000269|PubMed:23161088};
CC KM=35 uM for p-nitrophenylphosphocholine
CC {ECO:0000269|PubMed:23161088};
CC KM=5 uM for lysosphingomyelin {ECO:0000269|PubMed:23161088};
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity) (PubMed:23161088).
CC Homotetramer (By similarity). {ECO:0000250|UniProtKB:Q8BGN3,
CC ECO:0000269|PubMed:23161088}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; DAAA02060163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02060164; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03002535; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03002537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03120609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005197234.1; XM_005197177.3.
DR RefSeq; XP_005226063.1; XM_005226006.3.
DR AlphaFoldDB; F1N5C8; -.
DR SMR; F1N5C8; -.
DR STRING; 9913.ENSBTAP00000015375; -.
DR iPTMnet; F1N5C8; -.
DR PaxDb; F1N5C8; -.
DR Ensembl; ENSBTAT00000015375; ENSBTAP00000015375; ENSBTAG00000011573.
DR GeneID; 537431; -.
DR KEGG; bta:537431; -.
DR CTD; 133121; -.
DR VEuPathDB; HostDB:ENSBTAG00000011573; -.
DR VGNC; VGNC:28507; ENPP6.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000158457; -.
DR HOGENOM; CLU_017594_2_0_1; -.
DR InParanoid; F1N5C8; -.
DR OMA; KEAWQNG; -.
DR OrthoDB; 999163at2759; -.
DR TreeFam; TF330032; -.
DR Reactome; R-BTA-6814848; Glycerophospholipid catabolism.
DR SABIO-RK; F1N5C8; -.
DR Proteomes; UP000009136; Chromosome 27.
DR Bgee; ENSBTAG00000011573; Expressed in uterine horn and 60 other tissues.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0047390; F:glycerophosphocholine cholinephosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0008889; F:glycerophosphodiester phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IBA:GO_Central.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipid degradation; Lipid metabolism; Lipoprotein;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:23161088"
FT CHAIN 23..421
FT /note="Glycerophosphocholine choline phosphodiesterase
FT ENPP6"
FT /id="PRO_0000420824"
FT PROPEP 422..445
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000420889"
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 356
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8BGN3"
FT BINDING 356
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:0000250|UniProtKB:B0BND0"
FT LIPID 421
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23161088"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23161088"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23161088"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23161088"
FT DISULFID 142..154
FT /evidence="ECO:0000269|PubMed:23161088"
FT DISULFID 414
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:23161088"
SQ SEQUENCE 445 AA; 50495 MW; 5D37CF112ACB6E8A CRC64;
MAGKLGVLLL ALVLSLAQPA SARRKLLVFL LDGFRADYIS DEALESLPGF KEIVSRGVKV
DYLTPDFPTL SYPNYYSLMT GRHCEVHQMT GNYMWDPDTN KSFDLGINRD SRLPLWWNGS
EPLWVTLTKA KRKVYMYYWP GCEVEILGVR PTYCLEYKSV PTDINFVNAV SGALDVFKSG
QADLAAIYYE RVDVEGHHYG PSSPQRKDAV KAVDTVMAYM TKWIQERDLQ DDLNVIIFSD
HGMTDISWTD KVIKLDNYIN LRDLQQLKGR GPVVSLWPAP GKHSEIYNKV RRVEHMTVYA
KEDIPSRFYY KKGKFVSPLT LVADEGWFIT ENRESLPFWM NSTVTRKPEG WQWGWHGYDN
ELRAMRGIFL AFGPDFKSDF RAAPIRVVDI YNLMCKVTGV TPLPNNGSWS RVMCMLKDPA
SSAPGAPPCA CALVTVLLVL LAILA
