COTL1 explained

Coactosin-like protein (COTL1 or CLP) is a protein that in humans is encoded by the COTL1 gene.^{[1] [2] [3] [4]}

Function

This gene encodes one of the numerous actin-binding proteins which regulate the actin cytoskeleton. This protein binds F-actin, and also interacts with and thereby stabilizes 5-lipoxygenase (ALOX5). Although this gene has been reported to map to chromosome 17 in the Smith-Magenis syndrome region, the best alignments for this gene are to chromosome 16. The Smith-Magenis syndrome region is the site of two related pseudogenes.

Interactions

COTL1 has been shown to interact with ALOX5.^[5] ALOX5 is the first committed enzyme in the metabolism of arachidonic acid to an array of biologically important cell signaling agents: a) the pro-inflammatory mediator, leukotriene B4 (LTB4); b) the airways constrictors, LTC4, LTD4, and LTE4; c) the 5-hydroxyeicosatetraenoic acid family of pro-inflammatory and pro-allergic reactions mediators, 5-HETE and 5-oxo-eicosatetraenoic acid. ALOX5 also contributes to the metabolism of arachidonic acid and other polyunsaturated fatty acids to agents which act block inflammation and allergic reactions, the specialized pro-resolving mediators of the lipoxin and resolvin subclasses. Based on in vitro studies, COTL1 serves to stabilize ALOX5, acting as a chaperone or scaffold, to avert the enzyme's inactivation and thereby to promote its metabolic activity.^[6]

Further reading

• Wu C, Friedlander P, Lamoureux C, Zannis-Hadjopoulos M, Price GB . cDNA clones contain autonomous replication activity . Biochim. Biophys. Acta . 1174 . 3 . 241–57 . 1993 . 7690594 . 10.1016/0167-4781(93)90193-h .
• Provost P, Doucet J, Hammarberg T, Gerisch G, Samuelsson B, Radmark O . 5-Lipoxygenase interacts with coactosin-like protein . J. Biol. Chem. . 276 . 19 . 16520–7 . 2001 . 11297527 . 10.1074/jbc.M011205200 . free .
• Provost P, Doucet J, Stock A, Gerisch G, Samuelsson B, Rådmark O . Coactosin-like protein, a human F-actin-binding protein: critical role of lysine-75 . Biochem. J. . 359 . Pt 2 . 255–63 . 2001 . 11583571 . 1222143 . 10.1042/0264-6021:3590255 .
• Nakatsura T, Senju S, Ito M, Nishimura Y, Itoh K . Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX method . Eur. J. Immunol. . 32 . 3 . 826–36 . 2002 . 11870627 . 10.1002/1521-4141(200203)32:3<826::AID-IMMU826>3.0.CO;2-Y . 21684580 . free .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nat. Biotechnol. . 21 . 5 . 566–9 . 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Dai H, Wu J, Xu Y, Yajun T, Husheng D, Shi Y . 1H, 13C and 15N resonance assignments and the secondary structures of human coactosin like protein (hCLP) D123N . J. Biomol. NMR . 29 . 3 . 455–6 . 2004 . 15213466 . 10.1023/B:JNMR.0000032550.18424.aa . 27858479 .
• Liu L, Wang Y, Zhang P, Cheng Z, Wan M, Zhou Z, Gong W . Expression, purification and preliminary crystallographic studies of human coactosin-like protein . Acta Crystallogr. D . 60 . Pt 9 . 1651–3 . 2004 . 15333945 . 10.1107/S0907444904016701 . 2004AcCrD..60.1651L .
• Li X, Liu X, Lou Z, Duan X, Wu H, Liu Y, Rao Z . Crystal structure of human coactosin-like protein at 1.9 A resolution . Protein Sci. . 13 . 11 . 2845–51 . 2004 . 15459340 . 2286586 . 10.1110/ps.04937304 .
• Li X, Liu X, Zhao Q, Liu Y, Duan X, Rao Z . Crystallization and preliminary crystallographic studies of human coactosin-like protein (CLP) . Acta Crystallogr. D . 60 . Pt 12 Pt 2 . 2387–8 . 2004 . 15583396 . 10.1107/S0907444904028112 . 2004AcCrD..60.2387L .
• Gevaert K, Staes A, Van Damme J, De Groot S, Hugelier K, Demol H, Martens L, Goethals M, Vandekerckhove J . Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC . Proteomics . 5 . 14 . 3589–99 . 2005 . 16097034 . 10.1002/pmic.200401217 . 895879 .
• Dai H, Huang W, Xu J, Yao B, Xiong S, Ding H, Tang Y, Liu H, Wu J, Shi Y . Binding model of human coactosin-like protein with filament actin revealed by mutagenesis . Biochim. Biophys. Acta . 1764 . 11 . 1688–700 . 2006 . 17070122 . 10.1016/j.bbapap.2006.06.017 .

Notes and References

1. Provost P, Samuelsson B, Rådmark O . Interaction of 5-lipoxygenase with cellular proteins . Proc. Natl. Acad. Sci. U.S.A. . 96 . 5 . 1881–5 . Apr 1999 . 10051563 . 26705 . 10.1073/pnas.96.5.1881 . 1999PNAS...96.1881P . free .
2. Chen KS, Manian P, Koeuth T, Potocki L, Zhao Q, Chinault AC, Lee CC, Lupski JR . Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome . Nat. Genet. . 17 . 2 . 154–63 . Nov 1997 . 9326934 . 10.1038/ng1097-154 . 27742511 .
3. Rakonjac M, Fischer L, Provost P, Werz O, Steinhilber D, Samuelsson B, Rådmark O . Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 production . Proc. Natl. Acad. Sci. U.S.A. . 103 . 35 . 13150–5 . Sep 2006 . 16924104 . 1559768 . 10.1073/pnas.0605150103 . 2006PNAS..10313150R . free .
4. Web site: Entrez Gene: COTL1 coactosin-like 1 (Dictyostelium).
5. Provost P, Doucet J, Hammarberg T, Gerisch G, Samuelsson B, Radmark O . 5-Lipoxygenase interacts with coactosin-like protein . J. Biol. Chem. . 276 . 19 . 16520–7 . May 2001 . 11297527 . 10.1074/jbc.M011205200 . free .
6. Anwar Y, Sabir JS, Qureshi MI, Saini KS . 5-lipoxygenase: a promising drug target against inflammatory diseases-biochemical and pharmacological regulation . Current Drug Targets . 15 . 4 . 410–22 . 2014 . 24313690 . 10.2174/1389450114666131209110745.