ID PLPP1_HUMAN Reviewed; 284 AA.
AC O14494; B7ZKN8; G3XA95; O60457; O60463; Q17RZ4;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 10-MAY-2017, entry version 151.
DE RecName: Full=Phospholipid phosphatase 1 {ECO:0000312|HGNC:HGNC:9228};
DE EC=3.1.3.4;
DE AltName: Full=Lipid phosphate phosphohydrolase 1;
DE AltName: Full=PAP2-alpha;
DE AltName: Full=Phosphatidate phosphohydrolase type 2a;
DE AltName: Full=Phosphatidic acid phosphatase 2a;
DE Short=PAP-2a;
DE Short=PAP2a;
GN Name=PLPP1 {ECO:0000312|HGNC:HGNC:9228}; Synonyms=LPP1, PPAP2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=9305923; DOI=10.1074/jbc.272.39.24572;
RA Kai M., Wada I., Imai S., Sakane F., Kanoh H.;
RT "Cloning and characterization of two human isozymes of Mg2+-
RT independent phosphatidic acid phosphatase.";
RL J. Biol. Chem. 272:24572-24578(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung;
RX PubMed=9570154; DOI=10.1089/dna.1998.17.377;
RA Leung D.W., Tompkins C.K., White T.;
RT "Molecular cloning of two alternatively spliced forms of human
RT phosphatidic acid phosphatase cDNAs that are differentially expressed
RT in normal and tumor cells.";
RL DNA Cell Biol. 17:377-385(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=9468526; DOI=10.1074/jbc.273.8.4660;
RA Ulrix W.E.J., Swinnen J., Heyns W., Verhoeven G.;
RT "Identification of the phosphatidic acid phosphatase type 2a isozyme
RT as an androgen-regulated gene in the human prostatic Adenocarcinoma
RT cell line LNCaP.";
RL J. Biol. Chem. 273:4660-4665(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=9705349; DOI=10.1074/jbc.273.34.22059;
RA Roberts R., Sciorra V.A., Morris A.J.;
RT "Human type 2 phosphatidic acid phosphohydrolases. Substrate
RT specificity of the type 2a, 2b, and 2c enzymes and cell surface
RT activity of the 2a isoform.";
RL J. Biol. Chem. 273:22059-22067(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION.
RX PubMed=12909631; DOI=10.1074/jbc.M306709200;
RA Smyth S.S., Sciorra V.A., Sigal Y.J., Pamulkar Z., Wang Z., Xu Y.,
RA Prestwich G.D., Morris A.J.;
RT "Lipid phosphate phosphatases regulate lysophosphatidic acid
RT production and signaling in platelets: studies using chemical
RT inhibitors of lipid phosphate phosphatase activity.";
RL J. Biol. Chem. 278:43214-43223(2003).
CC -!- FUNCTION: Broad-specificity phosphohydrolase that dephosphorylates
CC exogenous bioactive glycerolipids and sphingolipids. Catalyzes the
CC conversion of phosphatidic acid (PA) to diacylglycerol (DG).
CC Pivotal regulator of lysophosphatidic acid (LPA) signaling in the
CC cardiovascular system. Major enzyme responsible of
CC dephosphorylating LPA in platelets, which terminates signaling
CC actions of LPA. May control circulating, and possibly also
CC regulate localized, LPA levels resulting from platelet activation.
CC It has little activity towards ceramide-1-phosphate (C-1-P) and
CC sphingosine-1-phosphate (S-1-P). The relative catalytic efficiency
CC is LPA > PA > S-1-P > C-1-P. It's down-regulation may contribute
CC to the development of colon adenocarcinoma.
CC {ECO:0000269|PubMed:12909631}.
CC -!- CATALYTIC ACTIVITY: A 1,2-diacylglycerol 3-phosphate + H(2)O = a
CC 1,2-diacyl-sn-glycerol + phosphate.
CC -!- ENZYME REGULATION: Inhibited by sphingosine, zinc ions and
CC propanolol. Not inhibited by N-ethylmaleimide treatment.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=Alpha-1, hLPP1, PAP2-a1;
CC IsoId=O14494-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha-2, hLPP1-a, PAP2-a2;
CC IsoId=O14494-2; Sequence=VSP_009651;
CC Note=Ref.2 (AAC16033) sequence is in conflict in position:
CC 55:V->A. Ref.2 (AAC16033) sequence is in conflict in position:
CC 56:T->A. Ref.2 (AAC16033) sequence is in conflict in position:
CC 69:I->V. {ECO:0000305};
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest expression
CC found in prostate. Isoform 1 is predominant in kidney, lung,
CC placenta and liver. Isoform 2 is predominant in heart and
CC pancreas. Found to be down-regulated in colon adenocarcinomas.
CC -!- INDUCTION: By androgens.
CC -!- PTM: N-glycosylated. Contains high-mannose oligosaccharides.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
CC -!- CAUTION: PubMed:9305923 states that this phosphatase does not
CC hydrolyze sphingosine 1-phosphate while PubMed:9705349 states that
CC it does. {ECO:0000305}.
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DR EMBL; AB000888; BAA22593.1; -; mRNA.
DR EMBL; AF014402; AAC16032.1; -; mRNA.
DR EMBL; AF014403; AAC16033.1; -; mRNA.
DR EMBL; Y14436; CAC14588.1; -; mRNA.
DR EMBL; AF017116; AAC32041.1; -; mRNA.
DR EMBL; AC010480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471123; EAW54920.1; -; Genomic_DNA.
DR EMBL; CH471123; EAW54922.1; -; Genomic_DNA.
DR EMBL; BC039847; AAH39847.1; -; mRNA.
DR EMBL; BC117133; AAI17134.1; -; mRNA.
DR EMBL; BC143281; AAI43282.1; -; mRNA.
DR CCDS; CCDS34159.1; -. [O14494-1]
DR CCDS; CCDS34160.1; -. [O14494-2]
DR RefSeq; NP_003702.2; NM_003711.3. [O14494-1]
DR RefSeq; NP_795714.1; NM_176895.2. [O14494-2]
DR UniGene; Hs.696231; -.
DR ProteinModelPortal; O14494; -.
DR BioGrid; 114169; 8.
DR IntAct; O14494; 3.
DR SwissLipids; SLP:000000160; -.
DR DEPOD; O14494; -.
DR iPTMnet; O14494; -.
DR PhosphoSitePlus; O14494; -.
DR EPD; O14494; -.
DR MaxQB; O14494; -.
DR PeptideAtlas; O14494; -.
DR PRIDE; O14494; -.
DR DNASU; 8611; -.
DR Ensembl; ENST00000264775; ENSP00000264775; ENSG00000067113. [O14494-2]
DR Ensembl; ENST00000307259; ENSP00000302229; ENSG00000067113. [O14494-1]
DR GeneID; 8611; -.
DR KEGG; hsa:8611; -.
DR UCSC; uc003jpz.5; human. [O14494-1]
DR CTD; 8611; -.
DR DisGeNET; 8611; -.
DR GeneCards; PLPP1; -.
DR HGNC; HGNC:9228; PLPP1.
DR HPA; CAB033331; -.
DR HPA; HPA047815; -.
DR MIM; 607124; gene.
DR neXtProt; NX_O14494; -.
DR OpenTargets; ENSG00000067113; -.
DR PharmGKB; PA33552; -.
DR GeneTree; ENSGT00620000087654; -.
DR HOGENOM; HOG000041307; -.
DR HOVERGEN; HBG002048; -.
DR InParanoid; O14494; -.
DR KO; K01080; -.
DR OMA; RGLFCND; -.
DR PhylomeDB; O14494; -.
DR TreeFam; TF316040; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR ChiTaRS; PPAP2A; human.
DR GeneWiki; PPAP2A; -.
DR GenomeRNAi; 8611; -.
DR PRO; PR:O14494; -.
DR Proteomes; UP000005640; Chromosome 5.
DR Bgee; ENSG00000067113; -.
DR CleanEx; HS_PPAP2A; -.
DR ExpressionAtlas; O14494; baseline and differential.
DR Genevisible; O14494; HS.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042577; F:lipid phosphatase activity; IBA:GO_Central.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; TAS:Reactome.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0008354; P:germ cell migration; TAS:ProtInc.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR GO; GO:0008285; P:negative regulation of cell proliferation; NAS:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; TAS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0007205; P:protein kinase C-activating G-protein coupled receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; NAS:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR Gene3D; 1.20.144.10; -; 1.
DR InterPro; IPR028670; LPP1.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR PANTHER; PTHR10165:SF112; PTHR10165:SF112; 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; Complete proteome; Glycoprotein;
KW Hydrolase; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 284 Phospholipid phosphatase 1.
FT /FTId=PRO_0000220905.
FT TOPO_DOM 1 6 Cytoplasmic. {ECO:0000255}.
FT TRANSMEM 7 27 Helical. {ECO:0000255}.
FT TOPO_DOM 28 53 Extracellular. {ECO:0000255}.
FT TRANSMEM 54 74 Helical. {ECO:0000255}.
FT TOPO_DOM 75 94 Cytoplasmic. {ECO:0000255}.
FT TRANSMEM 95 115 Helical. {ECO:0000255}.
FT TOPO_DOM 116 164 Extracellular. {ECO:0000255}.
FT TRANSMEM 165 185 Helical. {ECO:0000255}.
FT TOPO_DOM 186 199 Cytoplasmic. {ECO:0000255}.
FT TRANSMEM 200 220 Helical. {ECO:0000255}.
FT TOPO_DOM 221 229 Extracellular. {ECO:0000255}.
FT TRANSMEM 230 250 Helical. {ECO:0000255}.
FT TOPO_DOM 251 284 Cytoplasmic. {ECO:0000255}.
FT CARBOHYD 142 142 N-linked (GlcNAc...) asparagine.
FT {ECO:0000255}.
FT VAR_SEQ 21 70 GLPFAILTSRHTPFQRGVFCNDESIKYPYKEDTIPYALLGG
FT IIIPFSIIV -> SMPMAVLKLGQIYPFQRGFFCKDNSINY
FT PYHDSTVTSTVLILVGVGLPISS (in isoform 2).
FT {ECO:0000303|PubMed:9570154}.
FT /FTId=VSP_009651.
FT CONFLICT 27 27 L -> FTSRHI (in Ref. 4; AAC32041).
FT {ECO:0000305}.
FT CONFLICT 91 91 R -> S (in Ref. 2; AAC16033).
FT {ECO:0000305}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 102 243 ismart:acidPPc [T]
FT MYHIT 104 247 ipfam:PAP2 [T]
SQ SEQUENCE 284 AA; 32156 MW; FC2F00617EE07EB3 CRC64;
MFDKTRLPYV ALDVLCVLLA GLPFAILTSR HTPFQRGVFC NDESIKYPYK EDTIPYALLG
GIIIPFSIIV IILGETLSVY CNLLHSNSFI RNNYIATIYK AIGTFLFGAA ASQSLTDIAK
YSIGRLRPHF LDVCDPDWSK INCSDGYIEY YICRGNAERV KEGRLSFYSG HSSFSMYCML
FVALYLQARM KGDWARLLRP TLQFGLVAVS IYVGLSRVSD YKHHWSDVLT GLIQGALVAI
LVAVYVSDFF KERTSFKERK EEDSHTTLHE TPTTGNHYPS NHQP
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