PLPP6_RAT
ID PLPP6_RAT Reviewed; 293 AA.
AC Q66H88;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000250|UniProtKB:Q8IY26};
DE EC=3.6.1.- {ECO:0000250|UniProtKB:Q8IY26};
DE EC=3.6.1.68 {ECO:0000250|UniProtKB:Q8IY26};
DE AltName: Full=Phospholipid phosphatase 6 {ECO:0000312|RGD:1566000};
GN Name=Plpp6 {ECO:0000312|RGD:1566000};
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=Lung;
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).
CC -!- FUNCTION: Magnesium-independent polyisoprenoid diphosphatase that
CC catalyzes the sequential dephosphorylation of presqualene, farnesyl,
CC geranyl and geranylgeranyl diphosphates. Functions in the innate immune
CC response through the dephosphorylation of presqualene diphosphate which
CC acts as a potent inhibitor of the signaling pathways contributing to
CC polymorphonuclear neutrophils activation. May regulate the biosynthesis
CC of cholesterol and related sterols by dephosphorylating presqualene and
CC farnesyl diphosphate, two key intermediates in this biosynthetic
CC pathway. May also play a role in protein prenylation by acting on
CC farnesyl diphosphate and its derivative geranylgeranyl diphosphate, two
CC precursors for the addition of isoprenoid anchors to membrane proteins.
CC Has a lower activity towards phosphatidic acid (PA), but through
CC phosphatidic acid dephosphorylation may participate in the biosynthesis
CC of phospholipids and triacylglycerols. May also act on ceramide-1-P,
CC lysophosphatidic acid (LPA) and sphing-4-enine 1-phosphate/sphingosine-
CC 1-phosphate. {ECO:0000250|UniProtKB:Q8IY26}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + presqualene diphosphate = H(+) + phosphate + presqualene
CC monophosphate; Xref=Rhea:RHEA:67968, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57310,
CC ChEBI:CHEBI:176803; Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67969;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + presqualene monophosphate = phosphate + presqualene
CC alcohol; Xref=Rhea:RHEA:68024, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:176803, ChEBI:CHEBI:176962;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68025;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + H2O = (2E,6E)-farnesyl
CC phosphate + H(+) + phosphate; Xref=Rhea:RHEA:48128,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:88226, ChEBI:CHEBI:175763;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48129;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl phosphate + H2O = (2E,6E)-farnesol +
CC phosphate; Xref=Rhea:RHEA:48132, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16619, ChEBI:CHEBI:43474, ChEBI:CHEBI:88226;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48133;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl diphosphate + H2O = (2E,6E,10E)-
CC geranylgeranyl phosphate + H(+) + phosphate; Xref=Rhea:RHEA:68008,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58756, ChEBI:CHEBI:144936;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68009;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl phosphate + H2O = (2E,6E,10E)-
CC geranylgeraniol + phosphate; Xref=Rhea:RHEA:68016, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:46762, ChEBI:CHEBI:144936;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68017;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl diphosphate + H2O = (2E)-geranyl phosphate + H(+)
CC + phosphate; Xref=Rhea:RHEA:47944, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:58057,
CC ChEBI:CHEBI:88107; EC=3.6.1.68;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47945;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl phosphate + H2O = (2E)-geraniol + phosphate;
CC Xref=Rhea:RHEA:68020, ChEBI:CHEBI:15377, ChEBI:CHEBI:17447,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:88107;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68021;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-
CC dihexadecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:43236,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72859,
CC ChEBI:CHEBI:82929; Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8IY26}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8IY26}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q8IY26}. Nucleus inner membrane
CC {ECO:0000250|UniProtKB:Q8IY26}.
CC -!- PTM: Phosphorylation by PKC activates the phosphatase activity towards
CC presqualene diphosphate. {ECO:0000250|UniProtKB:Q8IY26}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC081970; AAH81970.1; -; mRNA.
DR RefSeq; NP_001030026.1; NM_001034854.1.
DR AlphaFoldDB; Q66H88; -.
DR SMR; Q66H88; -.
DR STRING; 10116.ENSRNOP00000020475; -.
DR PaxDb; Q66H88; -.
DR PRIDE; Q66H88; -.
DR Ensembl; ENSRNOT00000020475; ENSRNOP00000020475; ENSRNOG00000015268.
DR GeneID; 619549; -.
DR KEGG; rno:619549; -.
DR UCSC; RGD:1566000; rat.
DR CTD; 403313; -.
DR RGD; 1566000; Plpp6.
DR eggNOG; KOG4268; Eukaryota.
DR GeneTree; ENSGT00940000160907; -.
DR HOGENOM; CLU_072573_4_0_1; -.
DR InParanoid; Q66H88; -.
DR OMA; GVCAGEN; -.
DR OrthoDB; 1356295at2759; -.
DR PhylomeDB; Q66H88; -.
DR TreeFam; TF323272; -.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR PRO; PR:Q66H88; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000015268; Expressed in jejunum and 20 other tissues.
DR Genevisible; Q66H88; RN.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR GO; GO:0106405; F:isoprenoid diphosphate phosphatase activity; ISO:RGD.
DR GO; GO:0042577; F:lipid phosphatase activity; ISO:RGD.
DR GO; GO:0052642; F:lysophosphatidic acid phosphatase activity; ISS:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; ISO:RGD.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; ISO:RGD.
DR GO; GO:0045339; P:farnesyl diphosphate catabolic process; ISS:UniProtKB.
DR GO; GO:0033383; P:geranyl diphosphate metabolic process; ISS:UniProtKB.
DR GO; GO:1902247; P:geranylgeranyl diphosphate catabolic process; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006720; P:isoprenoid metabolic process; ISS:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; ISO:RGD.
DR GO; GO:1902565; P:positive regulation of neutrophil activation; ISS:UniProtKB.
DR GO; GO:0018342; P:protein prenylation; ISS:UniProtKB.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Hydrolase; Immunity; Innate immunity;
KW Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..293
FT /note="Polyisoprenoid diphosphate/phosphate
FT phosphohydrolase PLPP6"
FT /id="PRO_0000239398"
FT TOPO_DOM 1..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..162
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..269
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..293
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..190
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 209..212
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 247..258
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 212
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 254
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 258
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D4F2"
SQ SEQUENCE 293 AA; 31700 MW; 96530C11EFEA0E26 CRC64;
MPSPRRTIEG RPLGSSGGSS VPGSPAHGGG GGGSGRFEFQ SLLSCRSGAD PACARLRASD
SPVHRRGSFP LAAACPAQVA PAPPPEDAGM NLNPSFLGIA LRSLLAIDLW LSKKLGVCAG
ESSAWGSVRP LMKLLEISGH GIPWLLGTLY CLLRSDSWAG REVLMNLLFA LLLDLLLVAV
IKGLVRRRRP AHNQMDMFFT LSVDKYSFPS GHATRAALVS RFILNHLVLA IPLRVLVVLW
AFVLGLSRVM LGRHNVTDVA FGFFLGYMQY SIVDYCWLSP LNVPVLFVLW NQQ
