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Identification
HMDB Protein ID HMDBP00237
Secondary Accession Numbers
  • 5469
  • HMDBP06414
Name Lipid phosphate phosphohydrolase 1
Synonyms
  1. PAP-2a
  2. PAP2-alpha
  3. PAP2a
  4. Phosphatidate phosphohydrolase type 2a
  5. Phosphatidic acid phosphatase 2a
Gene Name PPAP2A
Protein Type Unknown
Biological Properties
General Function Involved in catalytic activity
Specific Function Broad-specificity phosphohydrolase that dephosphorylates exogenous bioactive glycerolipids and sphingolipids. Catalyzes the conversion of phosphatidic acid (PA) to diacylglycerol (DG). Pivotal regulator of lysophosphatidic acid (LPA) signaling in the cardiovascular system. Major enzyme responsible of dephosphorylating LPA in platelets, which terminates signaling actions of LPA. May control circulating, and possibly also regulate localized, LPA levels resulting from platelet activation. It has little activity towards ceramide-1-phosphate (C-1-P) and sphingosine-1-phosphate (S-1-P). The relative catalytic efficiency is LPA > PA > S-1-P > C-1-P. It's down-regulation may contribute to the development of colon adenocarcinoma.
Pathways
  • D-glyceric acidura
  • Ether lipid metabolism
  • Fabry disease
  • Familial lipoprotein lipase deficiency
  • Fat digestion and absorption
  • Fc gamma R-mediated phagocytosis
  • Gaucher Disease
  • Globoid Cell Leukodystrophy
  • Glycerol Kinase Deficiency
  • Glycerolipid metabolism
  • Glycerolipid Metabolism
  • Glycerophospholipid metabolism
  • Krabbe disease
  • Metachromatic Leukodystrophy (MLD)
  • Phospholipid Biosynthesis
  • Plasmalogen Synthesis
  • Sphingolipid Metabolism
  • sphingolipid metabolism
Reactions
A 1,2-diacylglycerol 3-phosphate + Water → a 1,2-diacyl-sn-glycerol + Phosphoric acid details
Phosphatidate + Water → 1,2-Diacyl-sn-glycerol + Phosphoric acid details
2-Acyl-1-alkyl-sn-glycero-3-phosphate + Water → 1-Alkyl-2-acylglycerol + Phosphoric acid details
Sphinganine 1-phosphate + Water → Sphinganine + Phosphoric acid details
Sphingosine 1-phosphate + Water → Sphingosine + Phosphoric acid details
Ceramide 1-phosphate + Water → N-Acylsphingosine + Phosphoric acid details
GO Classification
Biological Process
small molecule metabolic process
phospholipid metabolic process
regulation of lipid metabolic process
sphingolipid biosynthetic process
phospholipid dephosphorylation
germ cell migration
protein kinase C-activating G-protein coupled receptor signaling pathway
negative regulation of cell proliferation
androgen receptor signaling pathway
Cellular Component
integral to plasma membrane
Component
membrane
cell part
Function
catalytic activity
Molecular Function
phosphatidate phosphatase activity
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location 5
Locus 5q11
SNPs PPAP2A
Gene Sequence
>855 bp
ATGTTCGACAAGACGCGGCTGCCGTACGTGGCCCTCGATGTGCTCTGCGTGTTGCTGGCT
GGATTGCCTTTTGCAATTCTTACTTCAAGGCATACCCCCTTCCAACGAGGAGTATTCTGT
AATGATGAGTCCATCAAGTACCCTTACAAAGAAGACACCATACCTTATGCGTTATTAGGT
GGAATAATCATTCCATTCAGTATTATCGTTATTATTCTTGGAGAAACCCTGTCTGTTTAC
TGTAACCTTTTGCACTCAAATTCCTTTATCAGGAATAACTACATAGCCACTATTTACAAA
GCCATTGGAACCTTTTTATTTGGTGCAGCTGCTAGTCAGTCCCTGACTGACATTGCCAAG
TATTCAATAGGCAGACTGCGGCCTCACTTCTTGGATGTTTGTGATCCAGATTGGTCAAAA
ATCAACTGCAGCGATGGTTACATTGAATACTACATATGTCGAGGGAATGCAGAAAGAGTT
AAGGAAGGCAGGTTGTCCTTCTATTCAGGCCACTCTTCGTTTTCCATGTACTGCATGCTG
TTTGTGGCACTTTATCTTCAAGCCAGGATGAAGGGAGACTGGGCAAGACTCTTACGCCCC
ACACTGCAATTTGGTCTTGTTGCCGTATCCATTTATGTGGGCCTTTCTCGAGTTTCTGAT
TATAAACACCACTGGAGCGATGTGTTGACTGGACTCATTCAGGGAGCTCTGGTTGCAATA
TTAGTTGCTGTATATGTATCGGATTTCTTCAAAGAAAGAACTTCTTTTAAAGAAAGAAAA
GAGGAGGACTCTCATACAACTCTGCATGAAACACCAACAACTGGGAATCACTATCCGAGC
AATCACCAGCCTTGA
Protein Properties
Number of Residues 284
Molecular Weight 32155.715
Theoretical pI 7.965
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Lipid phosphate phosphohydrolase 1
MFDKTRLPYVALDVLCVLLAGLPFAILTSRHTPFQRGVFCNDESIKYPYKEDTIPYALLG
GIIIPFSIIVIILGETLSVYCNLLHSNSFIRNNYIATIYKAIGTFLFGAAASQSLTDIAK
YSIGRLRPHFLDVCDPDWSKINCSDGYIEYYICRGNAERVKEGRLSFYSGHSSFSMYCML
FVALYLQARMKGDWARLLRPTLQFGLVAVSIYVGLSRVSDYKHHWSDVLTGLIQGALVAI
LVAVYVSDFFKERTSFKERKEEDSHTTLHETPTTGNHYPSNHQP
GenBank ID Protein 2467298
UniProtKB/Swiss-Prot ID O14494
UniProtKB/Swiss-Prot Entry Name LPP1_HUMAN
PDB IDs Not Available
GenBank Gene ID AB000888
GeneCard ID PPAP2A
GenAtlas ID PPAP2A
HGNC ID HGNC:9228
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Leung DW, Tompkins CK, 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. 1998 Apr;17(4):377-85. [PubMed:9570154 ]
  3. Roberts R, Sciorra VA, Morris AJ: 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. 1998 Aug 21;273(34):22059-67. [PubMed:9705349 ]
  4. Kai M, Wada I, Imai Si, Sakane F, Kanoh H: Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase. J Biol Chem. 1997 Sep 26;272(39):24572-8. [PubMed:9305923 ]
  5. Ulrix W, Swinnen JV, Heyns W, Verhoeven G: Identification of the phosphatidic acid phosphatase type 2a isozyme as an androgen-regulated gene in the human prostatic adenocarcinoma cell line LNCaP. J Biol Chem. 1998 Feb 20;273(8):4660-5. [PubMed:9468526 ]
  6. Smyth SS, Sciorra VA, Sigal YJ, Pamuklar Z, Wang Z, Xu Y, Prestwich GD, Morris AJ: Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity. J Biol Chem. 2003 Oct 31;278(44):43214-23. Epub 2003 Aug 8. [PubMed:12909631 ]