PLPP6_DANRE
ID PLPP6_DANRE Reviewed; 288 AA.
AC Q5TZ07; Q502I4; Q5TZD1;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-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=Phosphatidic acid phosphatase type 2 domain-containing protein 2;
DE AltName: Full=Phospholipid phosphatase 6 {ECO:0000305};
GN Name=plpp6; Synonyms=ppapdc2;
GN ORFNames=si:ch211-191d7.4, si:ch211-246k22.2, zgc:112181;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Magnesium-independent polyisoprenoid diphosphatase that
CC catalyzes the sequential dephosphorylation of presqualene, farnesyl,
CC geranyl and geranylgeranyl diphosphates. 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5TZ07-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5TZ07-2; Sequence=VSP_019222, VSP_019223;
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
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DR EMBL; BX255937; CAH68897.1; -; Genomic_DNA.
DR EMBL; BX548055; CAH68942.1; -; Genomic_DNA.
DR EMBL; BC095685; AAH95685.1; -; mRNA.
DR AlphaFoldDB; Q5TZ07; -.
DR SMR; Q5TZ07; -.
DR STRING; 7955.ENSDARP00000074783; -.
DR PaxDb; Q5TZ07; -.
DR Ensembl; ENSDART00000186381; ENSDARP00000146744; ENSDARG00000109634. [Q5TZ07-1]
DR Ensembl; ENSDART00000187072; ENSDARP00000152787; ENSDARG00000043527. [Q5TZ07-2]
DR ZFIN; ZDB-GENE-040724-247; plpp6.
DR eggNOG; KOG4268; Eukaryota.
DR GeneTree; ENSGT00940000160907; -.
DR HOGENOM; CLU_122903_0_0_1; -.
DR InParanoid; Q5TZ07; -.
DR PhylomeDB; Q5TZ07; -.
DR TreeFam; TF323272; -.
DR Reactome; R-DRE-191273; Cholesterol biosynthesis.
DR PRO; PR:Q5TZ07; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000043527; Expressed in early embryo and 18 other tissues.
DR ExpressionAtlas; Q5TZ07; baseline.
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:0042392; F:sphingosine-1-phosphate phosphatase activity; IBA:GO_Central.
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:0046839; P:phospholipid dephosphorylation; IBA:GO_Central.
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 Alternative splicing; Endoplasmic reticulum; Hydrolase; Lipid metabolism;
KW Membrane; Nucleus; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..288
FT /note="Polyisoprenoid diphosphate/phosphate
FT phosphohydrolase PLPP6"
FT /id="PRO_0000239399"
FT TOPO_DOM 1..127
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 128..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..161
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..255
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT REGION 1..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..187
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 206..209
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 244..255
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT COMPBIAS 63..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 209
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 251
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 255
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT VAR_SEQ 167..190
FT /note="ALVLDVVLVGVLKAVVRRRRPAHN -> DIPIFFFWTSLSLRRFQCQVYLQP
FT (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_019222"
FT VAR_SEQ 191..288
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_019223"
FT CONFLICT 200
FT /note="V -> M (in Ref. 1; CAH68897)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="N -> T (in Ref. 1; CAH68897)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 288 AA; 31284 MW; F91C07C3E6BD1BAC CRC64;
MPSPKARSGS GRSGSVPCPG GNGRYEFISL NRTPPSPVPP QLLQRQGSDP TTARLRASES
PVRRRGSGSS NSSTGGGGQQ LPEEDCMRLN PSFFGIALSS LLAIDLWLSK RLGVCACEDS
SWGSVRPLMK LIEVSGHGIP WLAGAAYCLY KSDSPAGQEV MLNLLMALVL DVVLVGVLKA
VVRRRRPAHN RMDMFATFSV DSYSFPSGHA TRAAMCARFL LNHLVLAAPL RVLVLLWATI
VGFSRVLLGR HNVTDVAFGF FMGYWQYNLV EMLWLSPVML QSAIGQLH
