Full text data of PPAP2A
PPAP2A
(LPP1)
[Confidence: low (only semi-automatic identification from reviews)]
Lipid phosphate phosphohydrolase 1; 3.1.3.4 (PAP2-alpha; Phosphatidate phosphohydrolase type 2a; Phosphatidic acid phosphatase 2a; PAP-2a; PAP2a)
Lipid phosphate phosphohydrolase 1; 3.1.3.4 (PAP2-alpha; Phosphatidate phosphohydrolase type 2a; Phosphatidic acid phosphatase 2a; PAP-2a; PAP2a)
UniProt
O14494
ID LPP1_HUMAN Reviewed; 284 AA.
AC O14494; B7ZKN8; G3XA95; O60457; O60463; Q17RZ4;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Lipid phosphate phosphohydrolase 1;
DE EC=3.1.3.4;
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=PPAP2A; Synonyms=LPP1;
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 -!- 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 (By similarity).
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 positions:
CC 55:V->A, 56:T->A, 69:I->V;
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.
CC -!- CAUTION: PubMed:9305923 states that this phosphatase does not
CC hydrolyze sphingosine 1-phosphate while PubMed:9705349 states that
CC it does.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_003702.2; NM_003711.3.
DR RefSeq; NP_795714.1; NM_176895.2.
DR UniGene; Hs.696231; -.
DR ProteinModelPortal; O14494; -.
DR SMR; O14494; 114-240.
DR IntAct; O14494; 3.
DR STRING; 9606.ENSP00000264775; -.
DR PhosphoSite; O14494; -.
DR PaxDb; O14494; -.
DR PRIDE; O14494; -.
DR DNASU; 8611; -.
DR Ensembl; ENST00000264775; ENSP00000264775; ENSG00000067113.
DR Ensembl; ENST00000307259; ENSP00000302229; ENSG00000067113.
DR GeneID; 8611; -.
DR KEGG; hsa:8611; -.
DR UCSC; uc003jqa.4; human.
DR CTD; 8611; -.
DR GeneCards; GC05M054756; -.
DR HGNC; HGNC:9228; PPAP2A.
DR HPA; CAB033331; -.
DR MIM; 607124; gene.
DR neXtProt; NX_O14494; -.
DR PharmGKB; PA33552; -.
DR eggNOG; COG0671; -.
DR HOGENOM; HOG000041307; -.
DR HOVERGEN; HBG002048; -.
DR KO; K01080; -.
DR OMA; SKINCSA; -.
DR OrthoDB; EOG7C5M9Q; -.
DR Reactome; REACT_111217; Metabolism.
DR GeneWiki; PPAP2A; -.
DR GenomeRNAi; 8611; -.
DR NextBio; 32263; -.
DR PRO; PR:O14494; -.
DR ArrayExpress; O14494; -.
DR Bgee; O14494; -.
DR CleanEx; HS_PPAP2A; -.
DR Genevestigator; O14494; -.
DR GO; GO:0005887; C:integral to plasma membrane; NAS:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0008354; P:germ cell migration; TAS: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: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:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR Gene3D; 1.20.144.10; -; 1.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
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 Lipid phosphate phosphohydrolase 1.
FT /FTId=PRO_0000220905.
FT TOPO_DOM 1 6 Cytoplasmic (Potential).
FT TRANSMEM 7 27 Helical; (Potential).
FT TOPO_DOM 28 53 Extracellular (Potential).
FT TRANSMEM 54 74 Helical; (Potential).
FT TOPO_DOM 75 94 Cytoplasmic (Potential).
FT TRANSMEM 95 115 Helical; (Potential).
FT TOPO_DOM 116 164 Extracellular (Potential).
FT TRANSMEM 165 185 Helical; (Potential).
FT TOPO_DOM 186 199 Cytoplasmic (Potential).
FT TRANSMEM 200 220 Helical; (Potential).
FT TOPO_DOM 221 229 Extracellular (Potential).
FT TRANSMEM 230 250 Helical; (Potential).
FT TOPO_DOM 251 284 Cytoplasmic (Potential).
FT CARBOHYD 142 142 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 21 70 GLPFAILTSRHTPFQRGVFCNDESIKYPYKEDTIPYALLGG
FT IIIPFSIIV -> SMPMAVLKLGQIYPFQRGFFCKDNSINY
FT PYHDSTVTSTVLILVGVGLPISS (in isoform 2).
FT /FTId=VSP_009651.
FT CONFLICT 27 27 L -> FTSRHI (in Ref. 4; AAC32041).
FT CONFLICT 91 91 R -> S (in Ref. 2; AAC16033).
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
//
ID LPP1_HUMAN Reviewed; 284 AA.
AC O14494; B7ZKN8; G3XA95; O60457; O60463; Q17RZ4;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Lipid phosphate phosphohydrolase 1;
DE EC=3.1.3.4;
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=PPAP2A; Synonyms=LPP1;
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 -!- 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 (By similarity).
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 positions:
CC 55:V->A, 56:T->A, 69:I->V;
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.
CC -!- CAUTION: PubMed:9305923 states that this phosphatase does not
CC hydrolyze sphingosine 1-phosphate while PubMed:9705349 states that
CC it does.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_003702.2; NM_003711.3.
DR RefSeq; NP_795714.1; NM_176895.2.
DR UniGene; Hs.696231; -.
DR ProteinModelPortal; O14494; -.
DR SMR; O14494; 114-240.
DR IntAct; O14494; 3.
DR STRING; 9606.ENSP00000264775; -.
DR PhosphoSite; O14494; -.
DR PaxDb; O14494; -.
DR PRIDE; O14494; -.
DR DNASU; 8611; -.
DR Ensembl; ENST00000264775; ENSP00000264775; ENSG00000067113.
DR Ensembl; ENST00000307259; ENSP00000302229; ENSG00000067113.
DR GeneID; 8611; -.
DR KEGG; hsa:8611; -.
DR UCSC; uc003jqa.4; human.
DR CTD; 8611; -.
DR GeneCards; GC05M054756; -.
DR HGNC; HGNC:9228; PPAP2A.
DR HPA; CAB033331; -.
DR MIM; 607124; gene.
DR neXtProt; NX_O14494; -.
DR PharmGKB; PA33552; -.
DR eggNOG; COG0671; -.
DR HOGENOM; HOG000041307; -.
DR HOVERGEN; HBG002048; -.
DR KO; K01080; -.
DR OMA; SKINCSA; -.
DR OrthoDB; EOG7C5M9Q; -.
DR Reactome; REACT_111217; Metabolism.
DR GeneWiki; PPAP2A; -.
DR GenomeRNAi; 8611; -.
DR NextBio; 32263; -.
DR PRO; PR:O14494; -.
DR ArrayExpress; O14494; -.
DR Bgee; O14494; -.
DR CleanEx; HS_PPAP2A; -.
DR Genevestigator; O14494; -.
DR GO; GO:0005887; C:integral to plasma membrane; NAS:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0008354; P:germ cell migration; TAS: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: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:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR Gene3D; 1.20.144.10; -; 1.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
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 Lipid phosphate phosphohydrolase 1.
FT /FTId=PRO_0000220905.
FT TOPO_DOM 1 6 Cytoplasmic (Potential).
FT TRANSMEM 7 27 Helical; (Potential).
FT TOPO_DOM 28 53 Extracellular (Potential).
FT TRANSMEM 54 74 Helical; (Potential).
FT TOPO_DOM 75 94 Cytoplasmic (Potential).
FT TRANSMEM 95 115 Helical; (Potential).
FT TOPO_DOM 116 164 Extracellular (Potential).
FT TRANSMEM 165 185 Helical; (Potential).
FT TOPO_DOM 186 199 Cytoplasmic (Potential).
FT TRANSMEM 200 220 Helical; (Potential).
FT TOPO_DOM 221 229 Extracellular (Potential).
FT TRANSMEM 230 250 Helical; (Potential).
FT TOPO_DOM 251 284 Cytoplasmic (Potential).
FT CARBOHYD 142 142 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 21 70 GLPFAILTSRHTPFQRGVFCNDESIKYPYKEDTIPYALLGG
FT IIIPFSIIV -> SMPMAVLKLGQIYPFQRGFFCKDNSINY
FT PYHDSTVTSTVLILVGVGLPISS (in isoform 2).
FT /FTId=VSP_009651.
FT CONFLICT 27 27 L -> FTSRHI (in Ref. 4; AAC32041).
FT CONFLICT 91 91 R -> S (in Ref. 2; AAC16033).
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
//
MIM
607124
*RECORD*
*FIELD* NO
607124
*FIELD* TI
*607124 PHOSPHATIDIC ACID PHOSPHATASE TYPE 2A; PPAP2A
;;PAP2A
*FIELD* TX
DESCRIPTION
read more
Phosphatidic acid phosphatase catalyzes the dephosphorylation of
phosphatidic acid (PA) to form diacylglycerol. It has a role in
metabolic pathways controlling the synthesis of glycerophospholipids and
triacylglycerols, and in receptor-activated signal transduction mediated
by phospholipase D (GPLD1; 602515).
CLONING
Using the mouse PAP sequence as query, Kai et al. (1997) identified an
EST containing PPAP2A and obtained the full-length cDNA by PCR and RACE
amplification of HepG2 total RNA. The deduced 284-amino acid protein has
a calculated molecular mass of about 32 kD. It shares 47% and 83%
sequence identity with human PPAP2B (607125) and mouse PAP,
respectively. Both PPAP2A and PPAP2B are predicted to contain 6
transmembrane regions and a single conserved N-glycosylation site.
Northern blot analysis detected a 1.74-kb transcript that was abundant
in prostate, intermediate in heart, brain, lung, liver, skeletal muscle,
kidney, pancreas, spleen, testis, ovary, small intestine, and colon, but
was undetectable in thymus, placenta, and leukocytes. Biochemical
analysis of PPAP2A expressed by transfected embryonic kidney cells
indicated that mature PPAP2A contains a high mannose-type
oligosaccharide.
Roberts et al. (1998) cloned PPAP2A from myeloid leukemia cells. The
deduced 289-amino acid protein has a calculated molecular mass of about
33 kD and shares 54% sequence identity with PPAP2C (607126). Roberts et
al. (1998) noted that the C-terminal 40 amino acids of PPAP2A, PPAP2B,
and PPAP2C show the greatest divergence and that all 3 proteins contain
a single consensus N-glycosylation site. Western blot analysis of
transfected HEK293 cells expressing PPAP2C detected bands at 33 and 37
kD.
Leung et al. (1998) cloned PPAP2A from a human lung cDNA library and
identified 2 splice variants, which they called PAP-alpha-1 and
PAP-alpha-2. The area of alternative exon usage was confined to the
coding region at amino acids 20 to 70. Northern blot analysis detected
ubiquitous expression of PPAP2A, with highest levels in heart, lung,
uterus, and bladder. With use of specific PCR primers, Leung et al.
(1998) found that the alpha-1 isoform is predominant in kidney, lung,
placenta, and liver, and the alpha-2 isoform is predominant in heart and
pancreas.
GENE FUNCTION
Through biochemical analysis of embryonic kidney cell membrane fractions
following transfection with PPAP2A, Kai et al. (1997) confirmed that
PPAP2A is a type 2 plasma membrane-bound enzyme. The phosphatase
activity against phosphatidic acid was independent of Mg(2+),
insensitive to N-ethylmaleimide treatment, and inhibited by propranolol
and sphingosine. PPAP2A also hydrolyzed lyso-PA and ceramide
1-phosphate, but was inactive against sphingosine-1-phosphate.
By biochemical analysis of recombinant PPAP2A expressed by intact sf9
insect cells, Roberts et al. (1998) determined that PPAP2A activity is
expressed at the extracellular membrane. They found Zn(2+) to be an
effective inhibitor of all 3 of the PPAP2 enzymes and, in contrast to
the results of Kai et al. (1997), they found that propranolol is only a
modest inhibitor. Using membranes harvested from transfected embryonic
kidney cells, Hooks et al. (1998) compared the enzymatic activities of
PPAP2A, PPAP2B, and PPAP2C. All 3 enzymes hydrolyzed PA, lyso-PA, and
N-oleoyl ethanolamine phosphatidic acid (NOEPA). All showed a high
affinity for NOEPA and similar affinities for PA, but differed in
affinity for lyso-PA.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PPAP2A
gene to chromosome 5 (TMAP WI-15758).
*FIELD* RF
1. Hooks, S.B.; Ragan, S. P.; Lynch, K. R.: Identification of a novel
human phosphatidic acid phosphatase type 2 isoform. FEBS Lett. 427:
188-192, 1998.
2. Kai, M.; Wada, I.; Imai, S.; Sakane, F.; Kanoh, H.: Cloning and
characterization of two human isozymes of Mg(2+)-independent phosphatidic
acid phosphatase. J. Biol. Chem. 272: 24572-24578, 1997.
3. Leung, D. W.; Tompkins, C. K.; White, T.: Molecular cloning of
two alternatively spliced forms of human phosphatidic acid phosphatase
cDNAs that are differentially expressed in normal and tumor cells. DNA
Cell Biol. 17: 377-385, 1998.
4. Roberts, R.; Sciorra, V. A.; Morris, A. J.: Human type 2 phosphatidic
acid phosphohydrolases: substrate specificity of the type 2a, 2b,
and 2c enzymes and cell surface activity of the 2a isoform. J. Biol.
Chem. 273: 22059-22067, 1998.
*FIELD* CD
Patricia A. Hartz: 7/30/2002
*FIELD* ED
carol: 07/30/2002
*RECORD*
*FIELD* NO
607124
*FIELD* TI
*607124 PHOSPHATIDIC ACID PHOSPHATASE TYPE 2A; PPAP2A
;;PAP2A
*FIELD* TX
DESCRIPTION
read more
Phosphatidic acid phosphatase catalyzes the dephosphorylation of
phosphatidic acid (PA) to form diacylglycerol. It has a role in
metabolic pathways controlling the synthesis of glycerophospholipids and
triacylglycerols, and in receptor-activated signal transduction mediated
by phospholipase D (GPLD1; 602515).
CLONING
Using the mouse PAP sequence as query, Kai et al. (1997) identified an
EST containing PPAP2A and obtained the full-length cDNA by PCR and RACE
amplification of HepG2 total RNA. The deduced 284-amino acid protein has
a calculated molecular mass of about 32 kD. It shares 47% and 83%
sequence identity with human PPAP2B (607125) and mouse PAP,
respectively. Both PPAP2A and PPAP2B are predicted to contain 6
transmembrane regions and a single conserved N-glycosylation site.
Northern blot analysis detected a 1.74-kb transcript that was abundant
in prostate, intermediate in heart, brain, lung, liver, skeletal muscle,
kidney, pancreas, spleen, testis, ovary, small intestine, and colon, but
was undetectable in thymus, placenta, and leukocytes. Biochemical
analysis of PPAP2A expressed by transfected embryonic kidney cells
indicated that mature PPAP2A contains a high mannose-type
oligosaccharide.
Roberts et al. (1998) cloned PPAP2A from myeloid leukemia cells. The
deduced 289-amino acid protein has a calculated molecular mass of about
33 kD and shares 54% sequence identity with PPAP2C (607126). Roberts et
al. (1998) noted that the C-terminal 40 amino acids of PPAP2A, PPAP2B,
and PPAP2C show the greatest divergence and that all 3 proteins contain
a single consensus N-glycosylation site. Western blot analysis of
transfected HEK293 cells expressing PPAP2C detected bands at 33 and 37
kD.
Leung et al. (1998) cloned PPAP2A from a human lung cDNA library and
identified 2 splice variants, which they called PAP-alpha-1 and
PAP-alpha-2. The area of alternative exon usage was confined to the
coding region at amino acids 20 to 70. Northern blot analysis detected
ubiquitous expression of PPAP2A, with highest levels in heart, lung,
uterus, and bladder. With use of specific PCR primers, Leung et al.
(1998) found that the alpha-1 isoform is predominant in kidney, lung,
placenta, and liver, and the alpha-2 isoform is predominant in heart and
pancreas.
GENE FUNCTION
Through biochemical analysis of embryonic kidney cell membrane fractions
following transfection with PPAP2A, Kai et al. (1997) confirmed that
PPAP2A is a type 2 plasma membrane-bound enzyme. The phosphatase
activity against phosphatidic acid was independent of Mg(2+),
insensitive to N-ethylmaleimide treatment, and inhibited by propranolol
and sphingosine. PPAP2A also hydrolyzed lyso-PA and ceramide
1-phosphate, but was inactive against sphingosine-1-phosphate.
By biochemical analysis of recombinant PPAP2A expressed by intact sf9
insect cells, Roberts et al. (1998) determined that PPAP2A activity is
expressed at the extracellular membrane. They found Zn(2+) to be an
effective inhibitor of all 3 of the PPAP2 enzymes and, in contrast to
the results of Kai et al. (1997), they found that propranolol is only a
modest inhibitor. Using membranes harvested from transfected embryonic
kidney cells, Hooks et al. (1998) compared the enzymatic activities of
PPAP2A, PPAP2B, and PPAP2C. All 3 enzymes hydrolyzed PA, lyso-PA, and
N-oleoyl ethanolamine phosphatidic acid (NOEPA). All showed a high
affinity for NOEPA and similar affinities for PA, but differed in
affinity for lyso-PA.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PPAP2A
gene to chromosome 5 (TMAP WI-15758).
*FIELD* RF
1. Hooks, S.B.; Ragan, S. P.; Lynch, K. R.: Identification of a novel
human phosphatidic acid phosphatase type 2 isoform. FEBS Lett. 427:
188-192, 1998.
2. Kai, M.; Wada, I.; Imai, S.; Sakane, F.; Kanoh, H.: Cloning and
characterization of two human isozymes of Mg(2+)-independent phosphatidic
acid phosphatase. J. Biol. Chem. 272: 24572-24578, 1997.
3. Leung, D. W.; Tompkins, C. K.; White, T.: Molecular cloning of
two alternatively spliced forms of human phosphatidic acid phosphatase
cDNAs that are differentially expressed in normal and tumor cells. DNA
Cell Biol. 17: 377-385, 1998.
4. Roberts, R.; Sciorra, V. A.; Morris, A. J.: Human type 2 phosphatidic
acid phosphohydrolases: substrate specificity of the type 2a, 2b,
and 2c enzymes and cell surface activity of the 2a isoform. J. Biol.
Chem. 273: 22059-22067, 1998.
*FIELD* CD
Patricia A. Hartz: 7/30/2002
*FIELD* ED
carol: 07/30/2002