LYPLAL1 explained

Symbol:Lysophospholipase-like protein 1
Pfam:PF02230
Scop:3u0v
Cath:3u0v
Interpro:IPR029058

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] Structural comparisons have suggested that LYPLAL1 might be a protein deacetylase, but this has not been experimentally tested.[8]

Relationship to acyl-protein thioesterases

Sequence conservation and structural homology suggest a close relationship of LYPLAL1 proteins to acyl-protein thioesterases, and, therefore, it has been suggested that LYPLAL1 might be the third human acyl-protein thioesterase.[9] However, the major structural difference between both protein families has been established in the hydrophobic substrate binding tunnel, which has been identified in human acyl-protein thioesterases 1[10] and 2,[11] as well as in Zea mays acyl-protein thioesterase 2.[12] In LYPLAL1, this tunnel is closed due to a different loop conformation, changing the enzyme's substrate specificity to short acyl chains.

Notes and References

  1. Web site: Entrez Gene: Lysophospholipase-like 1. 2013-02-27 .
  2. Benjamin AM, Suchindran S, Pearce K, Rowell J, Lien LF, Guyton JR, McCarthy JJ . Gene by sex interaction for measures of obesity in the framingham heart study . Journal of Obesity . 2011 . 329038 . 2011 . 21253498 . 3021872 . 10.1155/2011/329038 . free .
  3. Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Mägi R, Workalemahu T, White CC, Bouatia-Naji N, Harris TB, Berndt SI, Ingelsson E, Willer CJ, Weedon MN, Luan J, Vedantam S, Esko T, Kilpeläinen TO, Kutalik Z, Li S, Monda KL, Dixon AL, Holmes CC, Kaplan LM, Liang L, Min JL, Moffatt MF, Molony C, Nicholson G, Schadt EE, Zondervan KT, Feitosa MF, Ferreira T, Lango Allen H, Weyant RJ, Wheeler E, Wood AR, Estrada K, Goddard ME, Lettre G, Mangino M, Nyholt DR, Purcell S, Smith AV, Visscher PM, Yang J, McCarroll SA, Nemesh J, Voight BF, Absher D, Amin N, Aspelund T, Coin L, Glazer NL, Hayward C, Heard-Costa NL, Hottenga JJ, Johansson A, Johnson T, Kaakinen M, Kapur K, Ketkar S, Knowles JW, Kraft P, Kraja AT, Lamina C, Leitzmann MF, McKnight B, Morris AP, Ong KK, Perry JR, Peters MJ, Polasek O, Prokopenko I, Rayner NW, Ripatti S, Rivadeneira F, Robertson NR, Sanna S, Sovio U, Surakka I, Teumer A, van Wingerden S, Vitart V, Zhao JH, Cavalcanti-Proença C, Chines PS, Fisher E, Kulzer JR, Lecoeur C, Narisu N, Sandholt C, Scott LJ, Silander K, Stark K, Tammesoo ML, Teslovich TM, Timpson NJ, Watanabe RM, Welch R, Chasman DI, Cooper MN, Jansson JO, Kettunen J, Lawrence RW, Pellikka N, Perola M, Vandenput L, Alavere H, Almgren P, Atwood LD, Bennett AJ, Biffar R, Bonnycastle LL, Bornstein SR, Buchanan TA, Campbell H, Day IN, Dei M, Dörr M, Elliott P, Erdos MR, Eriksson JG, Freimer NB, Fu M, Gaget S, Geus EJ, Gjesing AP, Grallert H, Grässler J, Groves CJ, Guiducci C, Hartikainen AL, Hassanali N, Havulinna AS, Herzig KH, Hicks AA, Hui J, Igl W, Jousilahti P, Jula A, Kajantie E, Kinnunen L, Kolcic I, Koskinen S, Kovacs P, Kroemer HK, Krzelj V, Kuusisto J, Kvaloy K, Laitinen J, Lantieri O, Lathrop GM, Lokki ML, Luben RN, Ludwig B, McArdle WL, McCarthy A, Morken MA, Nelis M, Neville MJ, Paré G, Parker AN, Peden JF, Pichler I, Pietiläinen KH, Platou CG, Pouta A, Ridderstråle M, Samani NJ, Saramies J, Sinisalo J, Smit JH, Strawbridge RJ, Stringham HM, Swift AJ, Teder-Laving M, Thomson B, Usala G, van Meurs JB, van Ommen GJ, Vatin V, Volpato CB, Wallaschofski H, Walters GB, Widen E, Wild SH, Willemsen G, Witte DR, Zgaga L, Zitting P, Beilby JP, James AL, Kähönen M, Lehtimäki T, Nieminen MS, Ohlsson C, Palmer LJ, Raitakari O, Ridker PM, Stumvoll M, Tönjes A, Viikari J, Balkau B, Ben-Shlomo Y, Bergman RN, Boeing H, Smith GD, Ebrahim S, Froguel P, Hansen T, Hengstenberg C, Hveem K, Isomaa B, Jørgensen T, Karpe F, Khaw KT, Laakso M, Lawlor DA, Marre M, Meitinger T, Metspalu A, Midthjell K, Pedersen O, Salomaa V, Schwarz PE, Tuomi T, Tuomilehto J, Valle TT, Wareham NJ, Arnold AM, Beckmann JS, Bergmann S, Boerwinkle E, Boomsma DI, Caulfield MJ, Collins FS, Eiriksdottir G, Gudnason V, Gyllensten U, Hamsten A, Hattersley AT, Hofman A, Hu FB, Illig T, Iribarren C, Jarvelin MR, Kao WH, Kaprio J, Launer LJ, Munroe PB, Oostra B, Penninx BW, Pramstaller PP, Psaty BM, Quertermous T, Rissanen A, Rudan I, Shuldiner AR, Soranzo N, Spector TD, Syvanen AC, Uda M, Uitterlinden A, Völzke H, Vollenweider P, Wilson JF, Witteman JC, Wright AF, Abecasis GR, Boehnke M, Borecki IB, Deloukas P, Frayling TM, Groop LC, Haritunians T, Hunter DJ, Kaplan RC, North KE, O'Connell JR, Peltonen L, Schlessinger D, Strachan DP, Hirschhorn JN, Assimes TL, Wichmann HE, Thorsteinsdottir U, van Duijn CM, Stefansson K, Cupples LA, Loos RJ, Barroso I, McCarthy MI, Fox CS, Mohlke KL, Lindgren CM . 6 . 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 . 949–60 . November 2010 . 20935629 . 3000924 . 10.1038/ng.685 .
  4. Steinberg GR, Kemp BE, Watt MJ . Adipocyte triglyceride lipase expression in human obesity . American Journal of Physiology. Endocrinology and Metabolism . 293 . 4 . E958-64 . October 2007 . 17609260 . 10.1152/ajpendo.00235.2007 .
  5. Tian L, McClafferty H, Knaus HG, Ruth P, Shipston MJ . Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels . The Journal of Biological Chemistry . 287 . 18 . 14718–25 . April 2012 . 22399288 . 3340283 . 10.1074/jbc.M111.335547 . free .
  6. Görmer K, Bürger M, Kruijtzer JA, Vetter I, Vartak N, Brunsveld L, Bastiaens PI, Liskamp RM, Triola G, Waldmann H . Chemical-biological exploration of the limits of the Ras de- and repalmitoylating machinery . ChemBioChem . 13 . 7 . 1017–23 . May 2012 . 22488913 . 10.1002/cbic.201200078 . 37748152 .
  7. Bürger M, Zimmermann TJ, Kondoh Y, Stege P, Watanabe N, Osada H, Waldmann H, Vetter IR . 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 . January 2012 . 22052940 . 3243480 . 10.1194/jlr.M019851 . free .
  8. Bürger M, Chory J . Structural and chemical biology of deacetylases for carbohydrates, proteins, small molecules and histones . Communications Biology . 1 . 217 . 2018 . 30534609 . 6281622 . 10.1038/s42003-018-0214-4 .
  9. Zeidman R, Jackson CS, Magee AI . Protein acyl thioesterases (Review) . Molecular Membrane Biology . 26 . 1 . 32–41 . January 2009 . 19115143 . 10.1080/09687680802629329 . 10044/1/1452 . 10591154 . free .
  10. Devedjiev Y, Dauter Z, Kuznetsov SR, Jones TL, Derewenda ZS . Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A . Structure . 8 . 11 . 1137–46 . November 2000 . 11080636 . 10.1016/s0969-2126(00)00529-3. free .
  11. Won SJ, Davda D, Labby KJ, Hwang SY, Pricer R, Majmudar JD, Armacost KA, Rodriguez LA, Rodriguez CL, Chong FS, Torossian KA, Palakurthi J, Hur ES, Meagher JL, Brooks CL, Stuckey JA, Martin BR . Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2) . ACS Chemical Biology . 11 . 12 . 3374–3382 . December 2016 . 27748579 . 5359770 . 10.1021/acschembio.6b00720 .
  12. Bürger M, Willige BC, Chory J . A hydrophobic anchor mechanism defines a deacetylase family that suppresses host response against YopJ effectors . Nature Communications . 8 . 1 . 2201 . December 2017 . 29259199 . 5736716 . 10.1038/s41467-017-02347-w . 2017NatCo...8.2201B .

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