PLPP5_HUMAN
ID PLPP5_HUMAN Reviewed; 264 AA.
AC Q8NEB5; C9JKF5; Q3KQX6; Q9BY45;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Phospholipid phosphatase 5 {ECO:0000312|HGNC:HGNC:25026};
DE EC=3.1.3.4 {ECO:0000269|PubMed:17590538};
DE EC=3.1.3.81 {ECO:0000269|PubMed:17590538};
DE AltName: Full=Phosphatidic acid phosphatase type 2 domain-containing protein 1B {ECO:0000312|HGNC:HGNC:25026};
GN Name=PLPP5 {ECO:0000312|HGNC:HGNC:25026};
GN Synonyms=DPPL1 {ECO:0000303|PubMed:17590538},
GN HTPAP {ECO:0000303|PubMed:16261160},
GN PPAPDC1B {ECO:0000312|HGNC:HGNC:25026};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP PATHWAY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, REGION, AND MUTAGENESIS
RP OF ARG-115; HIS-152 AND HIS-208.
RX PubMed=17590538; DOI=10.1016/j.gene.2007.05.009;
RA Takeuchi M., Harigai M., Momohara S., Ball E., Abe J., Furuichi K.,
RA Kamatani N.;
RT "Cloning and characterization of DPPL1 and DPPL2, representatives of a
RT novel type of mammalian phosphatidate phosphatase.";
RL Gene 399:174-180(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 4-264 (ISOFORM 2).
RC TISSUE=Lung, and Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 10-264 (ISOFORM 2).
RC TISSUE=Liver;
RA Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.;
RT "A novel gene expressed in human liver non-tumor tissue.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP MISCELLANEOUS.
RX PubMed=16261160; DOI=10.1038/sj.onc.1209191;
RA Wu X., Jia H.-L., Wang Y.-F., Ren N., Ye Q.-H., Sun H.-C., Wang L.,
RA Liu Y.-K., Tang Z.-Y., Qin L.-X.;
RT "HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human
RT hepatocellular carcinoma.";
RL Oncogene 25:1832-1840(2006).
CC -!- FUNCTION: Magnesium-independent phospholipid phosphatase with broad
CC substrate specificity (PubMed:17590538). Preferentially catalyzes the
CC conversion of diacylglycerol pyrophosphate into phosphatidate but can
CC also act on phosphatidate and lysophosphatidate (PubMed:17590538).
CC Phospholipid phosphatases are involved in both the synthesis of lipids
CC and the generation or degradation of lipid-signaling molecules
CC (PubMed:17590538). {ECO:0000269|PubMed:17590538,
CC ECO:0000303|PubMed:17590538}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacyl-
CC sn-glycero-3-phosphate + H(+) + phosphate; Xref=Rhea:RHEA:27449,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58608, ChEBI:CHEBI:59996; EC=3.1.3.81;
CC Evidence={ECO:0000269|PubMed:17590538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27450;
CC Evidence={ECO:0000305|PubMed:17590538};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:27429, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:43474, ChEBI:CHEBI:58608; EC=3.1.3.4;
CC Evidence={ECO:0000269|PubMed:17590538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000305|PubMed:17590538};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-diphosphate + H2O = 1,2-
CC dioctanoyl-sn-glycero-3-phosphate + H(+) + phosphate;
CC Xref=Rhea:RHEA:42856, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:78229, ChEBI:CHEBI:82765;
CC Evidence={ECO:0000269|PubMed:17590538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42857;
CC Evidence={ECO:0000305|PubMed:17590538};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phosphate + H2O = 1,2-dioctanoyl-
CC sn-glycerol + phosphate; Xref=Rhea:RHEA:42860, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:76979, ChEBI:CHEBI:78229;
CC Evidence={ECO:0000269|PubMed:17590538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42861;
CC Evidence={ECO:0000305|PubMed:17590538};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544,
CC ChEBI:CHEBI:75757; Evidence={ECO:0000269|PubMed:17590538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836;
CC Evidence={ECO:0000305|PubMed:17590538};
CC -!- ACTIVITY REGULATION: Magnesium-independent phospholipid phosphatase
CC (PubMed:17590538). Inhibited by N-ethylmaleimide (PubMed:17590538).
CC {ECO:0000269|PubMed:17590538}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=41 uM for 1,2-dioctanoyl-sn-glycero-3-diphosphate/diacylglycerol
CC pyrophosphate {ECO:0000269|PubMed:17590538};
CC KM=277 uM for 1,2-dioctanoyl-sn-glycero-3-phosphate/phosphatidate
CC {ECO:0000269|PubMed:17590538};
CC KM=295 uM for 1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphate/lysophosphatidate {ECO:0000269|PubMed:17590538};
CC -!- PATHWAY: Lipid metabolism; phospholipid metabolism.
CC {ECO:0000269|PubMed:17590538}.
CC -!- INTERACTION:
CC Q8NEB5; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-2803478, EBI-12019274;
CC Q8NEB5; Q96FB2; NbExp=3; IntAct=EBI-2803478, EBI-2857623;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:17590538};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q3UMZ3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8NEB5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NEB5-2; Sequence=VSP_025241, VSP_025242;
CC Name=3;
CC IsoId=Q8NEB5-3; Sequence=VSP_040055;
CC Name=4;
CC IsoId=Q8NEB5-4; Sequence=VSP_054076, VSP_054077;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:17590538}.
CC -!- MISCELLANEOUS: May be a metastatic suppressor for hepatocellular
CC carcinoma. {ECO:0000269|PubMed:16261160}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI06015.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK14924.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BD418664; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC087362; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033025; AAH33025.1; -; mRNA.
DR EMBL; BC106014; AAI06015.2; ALT_INIT; mRNA.
DR EMBL; AF212238; AAK14924.1; ALT_INIT; mRNA.
DR CCDS; CCDS47841.1; -. [Q8NEB5-1]
DR CCDS; CCDS47842.1; -. [Q8NEB5-2]
DR CCDS; CCDS47843.1; -. [Q8NEB5-4]
DR RefSeq; NP_001096029.1; NM_001102559.1. [Q8NEB5-1]
DR RefSeq; NP_001096030.1; NM_001102560.1. [Q8NEB5-4]
DR RefSeq; NP_115872.2; NM_032483.3. [Q8NEB5-2]
DR RefSeq; XP_011542973.1; XM_011544671.1. [Q8NEB5-3]
DR AlphaFoldDB; Q8NEB5; -.
DR BioGRID; 124107; 3.
DR IntAct; Q8NEB5; 3.
DR STRING; 9606.ENSP00000392553; -.
DR SwissLipids; SLP:000000604; -.
DR DEPOD; PLPP5; -.
DR iPTMnet; Q8NEB5; -.
DR PhosphoSitePlus; Q8NEB5; -.
DR BioMuta; PLPP5; -.
DR DMDM; 313104170; -.
DR EPD; Q8NEB5; -.
DR jPOST; Q8NEB5; -.
DR MassIVE; Q8NEB5; -.
DR MaxQB; Q8NEB5; -.
DR PaxDb; Q8NEB5; -.
DR PeptideAtlas; Q8NEB5; -.
DR PRIDE; Q8NEB5; -.
DR ProteomicsDB; 10577; -.
DR ProteomicsDB; 73143; -. [Q8NEB5-1]
DR ProteomicsDB; 73144; -. [Q8NEB5-2]
DR ProteomicsDB; 73145; -. [Q8NEB5-3]
DR Antibodypedia; 23567; 101 antibodies from 25 providers.
DR DNASU; 84513; -.
DR Ensembl; ENST00000419686.2; ENSP00000414522.2; ENSG00000147535.17. [Q8NEB5-4]
DR Ensembl; ENST00000422581.6; ENSP00000390622.2; ENSG00000147535.17. [Q8NEB5-2]
DR Ensembl; ENST00000424479.7; ENSP00000392553.2; ENSG00000147535.17. [Q8NEB5-1]
DR Ensembl; ENST00000529359.5; ENSP00000434916.1; ENSG00000147535.17. [Q8NEB5-3]
DR GeneID; 84513; -.
DR KEGG; hsa:84513; -.
DR MANE-Select; ENST00000424479.7; ENSP00000392553.2; NM_001102559.2; NP_001096029.1.
DR UCSC; uc003xle.5; human. [Q8NEB5-1]
DR CTD; 84513; -.
DR DisGeNET; 84513; -.
DR GeneCards; PLPP5; -.
DR HGNC; HGNC:25026; PLPP5.
DR HPA; ENSG00000147535; Low tissue specificity.
DR MIM; 610626; gene.
DR neXtProt; NX_Q8NEB5; -.
DR OpenTargets; ENSG00000147535; -.
DR PharmGKB; PA142671154; -.
DR VEuPathDB; HostDB:ENSG00000147535; -.
DR eggNOG; KOG3030; Eukaryota.
DR GeneTree; ENSGT00940000159772; -.
DR InParanoid; Q8NEB5; -.
DR OMA; CTPLIVI; -.
DR OrthoDB; 1621899at2759; -.
DR PhylomeDB; Q8NEB5; -.
DR TreeFam; TF323722; -.
DR BRENDA; 3.1.3.4; 2681.
DR BRENDA; 3.1.3.81; 2681.
DR PathwayCommons; Q8NEB5; -.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR SABIO-RK; Q8NEB5; -.
DR SignaLink; Q8NEB5; -.
DR UniPathway; UPA00085; -.
DR BioGRID-ORCS; 84513; 10 hits in 1066 CRISPR screens.
DR ChiTaRS; PLPP5; human.
DR GenomeRNAi; 84513; -.
DR Pharos; Q8NEB5; Tbio.
DR PRO; PR:Q8NEB5; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q8NEB5; protein.
DR Bgee; ENSG00000147535; Expressed in body of pancreas and 157 other tissues.
DR ExpressionAtlas; Q8NEB5; baseline and differential.
DR Genevisible; Q8NEB5; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR GO; GO:0000810; F:diacylglycerol diphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR InterPro; IPR043216; PA_PP_rel.
DR InterPro; IPR028668; PLPP4/5.
DR PANTHER; PTHR10165; PTHR10165; 1.
DR PANTHER; PTHR10165:SF87; PTHR10165:SF87; 1.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Hydrolase; Lipid metabolism; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Tumor suppressor.
FT CHAIN 1..264
FT /note="Phospholipid phosphatase 5"
FT /id="PRO_0000286945"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..54
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q3UMZ3"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 76..90
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q3UMZ3"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..154
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q3UMZ3"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..179
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q3UMZ3"
FT TRANSMEM 180..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 201..208
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q3UMZ3"
FT TRANSMEM 209..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q3UMZ3"
FT REGION 108..116
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000269|PubMed:17590538"
FT REGION 149..152
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000269|PubMed:17590538"
FT REGION 201..211
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000269|PubMed:17590538"
FT ACT_SITE 152
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 208
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 212
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT VAR_SEQ 1..41
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040055"
FT VAR_SEQ 155..176
FT /note="FAFAGLAFASFYLAGKLHCFTP -> CMNIIWTLPYACFHIIEFNLES (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_054076"
FT VAR_SEQ 177..264
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_054077"
FT VAR_SEQ 212..216
FT /note="DVLVG -> GPFKW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_025241"
FT VAR_SEQ 217..264
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_025242"
FT MUTAGEN 115
FT /note="R->A: Loss of phosphatase activity; when associated
FT with A-152 and with A-208."
FT /evidence="ECO:0000269|PubMed:17590538"
FT MUTAGEN 152
FT /note="H->A: Loss of phosphatase activity; when associated
FT with A-115 and with A-208."
FT /evidence="ECO:0000269|PubMed:17590538"
FT MUTAGEN 208
FT /note="H->A: Loss of phosphatase activity; when associated
FT with A-115 and with A-152."
FT /evidence="ECO:0000269|PubMed:17590538"
SQ SEQUENCE 264 AA; 29484 MW; 3682DA52B6F3C65B CRC64;
MGKAAAAVAF GAEVGVRLAL FAAFLVTELL PPFQRLIQPE EMWLYRNPYV EAEYFPTKPM
FVIAFLSPLS LIFLAKFLKK ADTRDSRQAC LAASLALALN GVFTNTIKLI VGRPRPDFFY
RCFPDGLAHS DLMCTGDKDV VNEGRKSFPS GHSSFAFAGL AFASFYLAGK LHCFTPQGRG
KSWRFCAFLS PLLFAAVIAL SRTCDYKHHW QDVLVGSMIG MTFAYVCYRQ YYPPLTDAEC
HKPFQDKLVL STAQKPGDSY CFDI
