LYPLAL1

Crystal structure of human LYPLAL1, PDB code 3u0v. Alpha helices are in red, beta strands in gold, catalytic site residues in black.
Identifiers
Symbol Lysophospholipase-like protein 1
Pfam PF02230
InterPro IPR029058
CATH 3u0v
SCOP 3u0v
SUPERFAMILY 3u0v

Lysophospholipase-like 1 is a protein in humans that is encoded by the LYPLAL1 gene. [1] The protein is a α/β-hydrolase of uncharacterized metabolic function. Genome-wide association studies in humans have linked the gene to fat distribution[2] and waist-to-hip ratio.[3] The protein's enzymatic function is unclear. LYPLAL1 was reported to act as a triglyceride lipase in adipose tissue[4] and another study suggested that the protein may play a role in the depalmitoylation of calcium-activated potassium channels.[5] However, LYPLAL1 does not depalmitoylate the oncogene Ras[6] and a structural and enzymatic study concluded that LYPLAL1 is generally unable to act as a lipase and is instead an esterase that prefers short-chain substrates, such as acetyl groups.[7]

Model organisms

Model organisms have been used in the study of LYPLAL1 function. A conditional knockout mouse line called Lyplal1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[8] Male and female animals underwent a standardized phenotypic screen[9] to determine the effects of deletion.[10][11][12][13] Additional screens performed: - In-depth immunological phenotyping[14]



References

  1. ↑ "Entrez Gene: Lysophospholipase-like 1". Retrieved 2013-02-27.
  2. ↑ Benjamin, Ashlee M.; Suchindran, Sunil; Pearce, Kaela; Rowell, Jennifer; Lien, Lillian F.; Guyton, John R.; McCarthy, Jeanette J. (2011). "Gene by sex interaction for measures of obesity in the framingham heart study". Journal of Obesity. 2011: 329038. ISSN 2090-0716. PMC 3021872 Freely accessible. PMID 21253498. doi:10.1155/2011/329038.
  3. ↑ Heid, Iris M.; Jackson, Anne U.; Randall, Joshua C.; Winkler, Thomas W.; Qi, Lu; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Zillikens, M. Carola; Speliotes, Elizabeth K. (November 2010). "Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution". Nature Genetics. 42 (11): 949–960. ISSN 1546-1718. PMC 3000924 Freely accessible. PMID 20935629. doi:10.1038/ng.685.
  4. ↑ Steinberg, Gregory R.; Kemp, Bruce E.; Watt, Matthew J. (October 2007). "Adipocyte triglyceride lipase expression in human obesity". American Journal of Physiology. Endocrinology and Metabolism. 293 (4): E958–964. ISSN 0193-1849. PMID 17609260. doi:10.1152/ajpendo.00235.2007.
  5. ↑ Tian, Lijun; McClafferty, Heather; Knaus, Hans-Guenther; Ruth, Peter; Shipston, Michael J. (2012-04-27). "Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels". The Journal of Biological Chemistry. 287 (18): 14718–14725. ISSN 1083-351X. PMC 3340283 Freely accessible. PMID 22399288. doi:10.1074/jbc.M111.335547.
  6. ↑ Görmer, Kristina; Bürger, Marco; Kruijtzer, John A. W.; Vetter, Ingrid; Vartak, Nachiket; Brunsveld, Lucas; Bastiaens, Philippe I. H.; Liskamp, Rob M. J.; Triola, Gemma (2012-05-07). "Chemical-biological exploration of the limits of the Ras de- and repalmitoylating machinery". Chembiochem: A European Journal of Chemical Biology. 13 (7): 1017–1023. ISSN 1439-7633. PMID 22488913. doi:10.1002/cbic.201200078.
  7. ↑ Bürger, Marco; Zimmermann, Tobias J.; Kondoh, Yasumitsu; Stege, Patricia; Watanabe, Nobumoto; Osada, Hiroyuki; Waldmann, Herbert; Vetter, Ingrid R. (January 2012). "Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity despite close relationship to acyl protein thioesterases". Journal of Lipid Research. 53 (1): 43–50. ISSN 1539-7262. PMC 3243480 Freely accessible. PMID 22052940. doi:10.1194/jlr.M019851.
  8. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  9. 1 2 "International Mouse Phenotyping Consortium".
  10. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. PMC 3572410 Freely accessible. PMID 21677750. doi:10.1038/nature10163.
  11. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. PMID 21677718. doi:10.1038/474262a.
  12. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. PMID 17218247. doi:10.1016/j.cell.2006.12.018.
  13. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. PMC 3717207 Freely accessible. PMID 23870131. doi:10.1016/j.cell.2013.06.022.
  14. 1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading


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