Review. Comparative structures and evolution of mammalian lipase I (LIPI) genes and proteins: A close relative of vertebrate phospholipase LIPH

Roger S. Holmes, Laura A. Cox

Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, USA;.

DOI: 10.4236/ns.2012.412A142                

Abstract

Lipase I (enzyme name LIPI or LPDL) (gene name LIPI [human] or Lipi [mouse]) is a phospholipase which generates 2-acyl lysophosphatidic acid (LPA), a lipid mediator required for maintaining homeostasis of diverse biological functions and in activating cell surface recaptors. Bioinformatic methods were used to predict the amino acid sequences, secondary and tertiary structures and gene locations for LIPI genes and encoded proteins using data from several mammalian genome projects. LIPI is located on human chromosome 21 and is distinct from other phospholipase A1-like genes (LIPH and PS-PLA1). Mammalian LIPI genes contained 10 (human) or 11 (mouse) coding exons transcribed predominantly on the negative DNA strand. Mammalian LIPI protein subunits shared 61% - 99% sequence identities and exhibited sequence alignments and identities for key LIPI amino acid residues as well as extensive conservation of predicted secondary and tertiary structures with those previously reported for pancreatic lipase (PL), with “N-signal peptide”, “lipase” and “plat” structural domains. Comparative studies of mammalian LIPI sequences with LIPH, PS-PLA1 and pancreatic lipase (PL) confirmed predictions for LIPI N-terminal signal peptides (residues 1 - 15); predominantly conserved mammalian LIPI N-glycosylation sites (63NNSL and 396NISS for human LIPI); active site “triad” residues (Ser159; Asp183; His253); disulfide bond residues (238 - 251; 275 - 286; 289 - 297; 436 - 455); and a 12 residue “active site lid”, which is shorter than for other lipases examined. Phylogenetic analyses supported a hypothesis that LIPI arose from a vertebrate LIPH gene duplication event within a mammalian common ancestral genome. In addition, LIPI, LIPH and PL-PLA1 genes were distinct from the vascular lipase (LIPG, LIPC and LPL) and pancreatic lipase (PL) gene families.

Keywords

Mammalian LIPI Genes and Proteins; Amino Acid Sequence; Lipase I; Evolution; Phylogeny

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hiramatsu, T., Sonoda, H., Takanezawa, Y., Morikawa, R., Ishida, M., Kasahara, K., Sanai, Y., Taguchi, R., Aoki, J. and Arai, H. (2003) Biochemical and molecular characterization of two phosphatidic acid-selective phospholipase A1s, mPA-PLA1alpha and mPA-PLA1beta. Journal of Biological Chemistry, 278, 49438-49447. doi:10.1074/jbc.M213018200
[2]	Wen, X.Y., Hegele, R.A., Wang, J., Wang, D.Y., Cheung, J., Wilson, M., Yahyapour, M., Bai, Y., Zhuang, L., Skaug, J., Young, T.K., Connelly, P.W., Koop, B.F., Tsui, L.C. and Stewart, A.K. (2003) Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. Human Molecular Genetics, 12, 1131-1143. doi:10.1093/hmg/ddg124
[3]	Moolenaar, W.H. (1995) Lysophatidic acid, a multifunctional phospholipid messenger. The Journal of Biological Chemistry, 270, 12949-12952.
[4]	Hama, K. and Aoki, J. (2010) LPA3, a unique G protein- coupled receptor for lysophosphatidic acid. Progress in Lipid Research, 49, 335-342. doi:10.1016/j.plipres.2010.03.001
[5]	Aoki, J., Inoue, A. and Okudaira, S. (2008) Two pathways for lysophosphatidic acid production. Biochimica et Biophysica Acta, 1781, 513-518.
[6]	Shimomura, Y., Wajid, M., Petukhova, L., Shapiro, L. and Christiano, A.M. (2009) Mutations in the lipase H gene underlie autosomal recessive woolly hair/hypotrichosis. Journal of Investigative Dermatology, 129, 622- 628. doi:10.1038/jid.2008.290
[7]	Shinkuma, S., Akiyama, M., Inoue, A., Aoki, J., Natsuga, K., Nomura, T., Arita, K., Abe, R., Ito, K., Nakamura, H., Ujiie, H., Shibaki, A., Suga, H., Tsunemi, Y., Nishie, W. and Shimizu, H. (2010) Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA- PLA1alpha in autosomal recessive hypotrichosis. Human Mutation, 31, 602-610.
[8]	Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio, K., Doi, T., Arai, H. and Inoue, K. (1997) Serine phospholipid- specific phospholipase A that is secreted from activated platelets. The Journal of Biological Chemistry, 272, 2192- 2198. doi:10.1074/jbc.272.4.2192
[9]	Wen, X.Y., Hegele, R.A., Wang, J., Wang, D.Y., Cheung, J., Wilson, M., Yahyapour, M., Bai, Y., Zhuang, L., Skaug, J., Young, T.K., Connelly, P.W., Koop, B.F., Tsui, L.C. and Stewart, A.K. (2003) Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. Human Molecular Genetics, 12, 1131-1143. doi:10.1093/hmg/ddg124
[10]	Aoki, J., Inoue, A., Makide, K., Saiki, N. and Arai, H. (2007) Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family. Biochimie, 89, 197-204. doi:10.1016/j.biochi.2006.09.021
[11]	Schmiedel, B.J., Hutter, C., Hesse, M. and Staege, M.S. (2011) Expression of multiple membrane-associated phospholipase A1 beta transcript variants and lysophosphatidic acid receptors in Ewing tumour cells. Molecular Biology Reports, 38, 4619-4628. doi:10.1007/s11033-010-0595-z
[12]	Foell, J.L., Hesse, M., Volkmer, I., Schmiedel, B.J., Neumann, I. and Staege, M.S. (2008) Membrane-associated phospholipase A1 beta (LIPI) is an Ewing tumour-associated cancer-testis antigen. Pediatric Blood Cancer, 51, 228- 234. doi:10.1002/pbc.21602
[13]	Hattori, M., Fujiyama, A., Taylor, T.D., Watanabe, H., Yada, T., Park, H.S., Toyoda, A. and Ishii, K. (2000) The DNA sequence of human chromosome 21. Nature, 405, 311-319. doi:10.1038/35012518
[14]	Kent, W.J., Sugnet, C.W., Furey, T.S., Roskin, K.M., Pringle, T.H., Zahler, A.M. and Haussler, D. (2003) The human genome browser at UCSC. Genome Research, 12, 994- 1006.
[15]	Migdalska, A.M., van der Weyden, L., Inmail, O. and White, J.K. (2012) Modeling partial monosomy for human chromosome 21q11.2-q21.1 reveals haplosufficient genes influencing behaviour and fat deposition. PLoS One, 7, e29681. doi:10.1371/journal.pone.0029681
[16]	Hesse, M., Willscher, E., Schmiedel, B.J., Posch, S., Golbik, R.P. and Staege, M.S. (2012) Sequence and expression of the chicken membrane-associated phospholipases A1 alpha (LIPH) and beta (LIPI). Molecular Biology Reports, 39, 761-769. doi:10.1007/s11033-011-0796-0
[17]	Altschul, F., Vyas, V., Cornfield, A., Goodin, S., Ravikumar, T.S., Rubin, E.H. and Gupta, E. (1997) Basic local alignment search tool. Journal of Molecular Biology, 215, 403-410.
[18]	Holmes, R.S., VandeBerg, J.L. and Cox, L.A. (2011) Vertebrate endothelial lipase: Comparative studies of an ancient gene and protein in vertebrate evolution. Genetica, 139, 291-304. doi:10.1007/s10709-011-9549-1
[19]	Thierry-Mieg, D. and Thierry-Mieg, J. (2006) AceView: A comprehensive cDNA-supported gene and transcripts annotation. Genome Biology, 7, S12. doi:10.1186/gb-2006-7-s1-s12
[20]	Larkin, M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, G., Clustal, W. and Clustal, X. (2007) Version 2.0. Bioinformatics, 23, 2947-2948. doi:10.1093/bioinformatics/btm404
[21]	McGuffin, L.J., Bryson, K. and Jones, D.T. (2000) The PSIPRED protein structure prediction server. Bioinformatics, 16, 404-405. doi:10.1093/bioinformatics/16.4.404
[22]	Kopp, J. and Schwede, T. (2004) The SWISS-MODEL repository of annotated three-dimensional protein structure homology models. Nucleic Acids Research, 32, D230-D234. doi:10.1093/nar/gkh008
[23]	Bourne, Y., Martinez, C., Kerfelec, B., Lombardo, D., Chapus, C. and Cambillau, C. (1994) Horse pancreatic lipase. The crystal structure refined at 2.3-A resolution. Journal of Molecular Biology, 238, 709-732. doi:10.1006/jmbi.1994.1331
[24]	Emmanuelsson, O., Brunak, S., von Heijne, G. and Nielson, H. (2007) Locating proteins in the cell using TargetP, SignalP and related tools. Nature Protocols, 2, 953-971. doi:10.1038/nprot.2007.131
[25]	Saitou, N. and Nei, M. (1987) The neighbour-joining method: A new method for reconstructing phylogenetic trees. Molecular Biology and Evolution, 4, 406-411.
[26]	Felsenstein, J. (1985) Confidence limits on phylogenies: An approach using the bootstrap. Evolution, 39, 783-789. doi:10.2307/2408678
[27]	Emmerich, J., Beg, O.U., Peterson, J., Previato, L., Brunzell, J.D., Brewer Jr., H.B. and Santamarina-Fojo, S. (1992) Human lipoprotein lipase. Analysis of the catalytic triad by site-directed mutagenesis of Ser-132, Asp-156, and His-241. The Journal of Biological Chemistry, 267, 4161-4165.
[28]	Cygler, M., Schrag, J.D., Sussman, J.L., Harel, M., Silman, I., Gentry, M.K. and Dostor, B.P. (1993) Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases and related proteins. Protein Science, 2, 366-382. doi:10.1002/pro.5560020309
[29]	Laposata, E.A., Laboda, H.M., Glick, J.M. and Strauss, J.F. (1987) Hepatic lipase. Synthesis, processing, and secretion by isolated rat hepatocytes. The Journal of Biological Chemistry, 262, 5333-5338.
[30]	Kroetz, D.L., McBride, O.W. and Gonzalez, F.J. (1993) Glycosylation-dependent activity of Baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms. Biochemistry, 32, 11606-11617. doi:10.1021/bi00094a018
[31]	Matsuoka, S., Ballif, B.A., Smogorzewska, A., McDonald, E.R., Hurov, K.E., Luo, J., Bakalarski, C.E. and Zhao, Z. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science, 316, 1160-1166. doi:10.1126/science.1140321
[32]	Jin, W., Broedl, U.C., Monajemi, H., Glick, J.M., Rader, D.J. and Lipase, H. (2002) A new member of the triglyceride lipase family synthesized by the intestine. Genomics, 80, 268-273. doi:10.1006/geno.2002.6837
[33]	Jaye, M., Lynch, K.J., Krawiec, J., Marchadier, D., Maugeais, C., Doan, K., South, V., Amin, D., Perrone, M. and Rader, D.J. (1999) A novel endothelial-derived lipase that modulates HDL metabolism. Nature Genetics, 21, 424-428. doi:10.1038/7766
[34]	Martin, G.A., Busch, S.J., Meredith, G.D., Cardin, A.D., Blankenship, D.T., Mao, S.J.T., Rechtin, A.E., Woods, C.W., Racke, M.M., Schafer, M.P., Fitzgerald, M.C., Burke, D.M., Flanagan, M.A. and Jackson, R.L. (1988) Isolation and cDNA sequence of human postheparin plasma hepatic triglyceride lipase. The Journal of Biological Chemistry, 263, 10907-10914.
[35]	Wion, K.L., Kirchgessner, T.G., Lusis, A.J., Schotz, M.C. and Lawn, R.M. (1987) Human lipoprotein lipase complementary DNA sequence. Science, 235, 1638-1641. doi:10.1126/science.3823907
[36]	Lowe, M.E. (2002) The triglyceride lipases of the pancreas. The Journal of Lipid Research, 43, 2007-2016. doi:10.1194/jlr.R200012-JLR200
[37]	Hill, J.S., Yang, D., Nikazy, J., Curtiss, L.K., Sparrow, J.T. and Wong, H. (1998) Subdomain chimeras of hepatic lipase and lipoprotein lipase. Localization of heparin and cofactor binding. The Journal of Biological Chemistry, 273, 30979-30984. doi:10.1074/jbc.273.47.30979
[38]	Sendak, R.A. and Bensadoun, A. (1998) Identification of a heparin-binding domain in the distal carboxyl-terminal region of lipoprotein lipase by site-directed mutagenesis. The Journal of Lipid Research, 39, 1310-1315.
[39]	Winkler, F.K., D-Arcy, A. and Hunziker, W. (1990) Structure of human pancreatic lipase. Nature, 343, 771-774. doi:10.1038/343771a0
[40]	Bencharit, S., Morton, C.L., Xue, Y., Potter, P.M. and Redinbo, M.R. (2003) Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nature Structural & Molecular Biology, 10, 349- 356. doi:10.1038/nsb919
[41]	Datta, S., Luo, C.C., Li, W.H., Van Tuinen, P., Ledbetter, D.H., Brown, M.A., Chen, S.H., Liu, S. and Chan, L. (1988) Human hepatic lipase. Cloned cDNA sequence, restriction fragment length polymorphisms, chromosomal localization, and evolutionary relationships with lipoprotein lipase and pancreatic lipase. The Journal of Biological Chemistry, 263, 1107-1110.
[42]	Cai, S.J., Wong, D.M., Chen, S.H. and Chan, L. (1989) Structure of the human hepatic triglyceride lipase gene. Biochemistry, 28, 8966-8971. doi:10.1021/bi00449a002