MAP1LC3A explained

Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the MAP1LC3A gene.^{[1] [2] [3]} Two transcript variants encoding different isoforms have been found for this gene.

Function

MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B.^[3]

MAPLC3A is one of the mammalian homologues of yeast ATG8, an important marker and effector of autophagy.^[4]

Regulation

MAP1LC3A is regulated by several post-translational modifications. These include covalent linkage of the C-terminus to phosphatidylethanolamine in autophagic membranes, and phosphorylation by protein kinase A,^[5] which downregulates its autophagy functions. Noncovalent interactions are important for its cargo targeting functions in selective autophagy. For example, it has been shown to interact with sequestosome 1.^[6]

Further reading

• Snásel J, Pichová I . The cleavage of host cell proteins by HIV-1 protease. . Folia Biol. (Praha) . 42 . 5 . 227–30 . 1997 . 8997639 . 10.1007/BF02818986. 7617882 .
• Wallin M, Deinum J, Goobar L, Danielson UH . Proteolytic cleavage of microtubule-associated proteins by retroviral proteinases . J. Gen. Virol. . 71 . 9. 1985–91 . 1990 . 2212989 . 10.1099/0022-1317-71-9-1985 . free .
• Schoenfeld TA, McKerracher L, Obar R, Vallee RB . MAP 1A and MAP 1B are structurally related microtubule associated proteins with distinct developmental patterns in the CNS . J. Neurosci. . 9 . 5 . 1712–30 . 1989 . 2470876 . 6569839 . 10.1523/JNEUROSCI.09-05-01712.1989. free .
• Mann SS, Hammarback JA . Molecular characterization of light chain 3. A microtubule binding subunit of MAP1A and MAP1B . J. Biol. Chem. . 269 . 15 . 11492–7 . 1994 . 10.1016/S0021-9258(19)78150-2 . 7908909 . free .
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Wiemann S, Weil B, Wellenreuther R, etal . Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 .
• Bonnet C, Boucher D, Lazereg S, etal . Differential binding regulation of microtubule-associated proteins MAP1A, MAP1B, and MAP2 by tubulin polyglutamylation . J. Biol. Chem. . 276 . 16 . 12839–48 . 2001 . 11278895 . 10.1074/jbc.M011380200 . free .
• Deloukas P, Matthews LH, Ashurst J, etal . The DNA sequence and comparative analysis of human chromosome 20 . Nature . 414 . 6866 . 865–71 . 2002 . 11780052 . 10.1038/414865a . 2001Natur.414..865D . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• He H, Dang Y, Dai F, etal . Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B . J. Biol. Chem. . 278 . 31 . 29278–87 . 2003 . 12740394 . 10.1074/jbc.M303800200 . free .
• Tanida I, Sou YS, Ezaki J, etal . HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates . J. Biol. Chem. . 279 . 35 . 36268–76 . 2004 . 15187094 . 10.1074/jbc.M401461200 . free .
• Kouno T, Mizuguchi M, Tanida I, etal . 1H, 13C, and 15N resonance assignments of human microtubule-associated protein light chain-3 . J. Biomol. NMR . 29 . 3 . 415–6 . 2005 . 15213446 . 10.1023/B:JNMR.0000032505.99071.ea . 23561733 .
• Goehler H, Lalowski M, Stelzl U, etal . A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease . Mol. Cell . 15 . 6 . 853–65 . 2004 . 15383276 . 10.1016/j.molcel.2004.09.016 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Wiemann S, Arlt D, Huber W, etal . From ORFeome to Biology: A Functional Genomics Pipeline . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 10.1101/gr.2576704 . 528930 .
• Kouno T, Mizuguchi M, Tanida I, etal . Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains . J. Biol. Chem. . 280 . 26 . 24610–7 . 2005 . 15857831 . 10.1074/jbc.M413565200 . free .
• Sou YS, Tanida I, Komatsu M, etal . Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16 . J. Biol. Chem. . 281 . 6 . 3017–24 . 2006 . 16303767 . 10.1074/jbc.M505888200 . free .
• Mehrle A, Rosenfelder H, Schupp I, etal . The LIFEdb database in 2006 . Nucleic Acids Res. . 34 . Database issue . D415–8 . 2006 . 16381901 . 10.1093/nar/gkj139 . 1347501 .

Notes and References

1. Mann SS, Hammarback JA . Gene localization and developmental expression of light chain 3: a common subunit of microtubule-associated protein 1A(MAP1A) and MAP1B . J Neurosci Res . 43 . 5 . 535–44 . May 1997 . 8833088 . 10.1002/(SICI)1097-4547(19960301)43:5<535::AID-JNR3>3.0.CO;2-J . 23515321 .
2. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T . p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy . J Biol Chem . 282 . 33 . 24131–45 . Aug 2007 . 17580304 . 10.1074/jbc.M702824200 . free .
3. Web site: Entrez Gene: MAP1LC3A microtubule-associated protein 1 light chain 3 alpha.
4. 4127242. Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C . 2014. Biomed Res Int. 10.1155/2014/462658. 25136588. 2014. 462658. free.
5. Cherra SJ, Kulich SM, Uechi G, Balasubramani M, Mountzouris J, Day BW, Chu CT . Regulation of the autophagy protein LC3 by phosphorylation . J. Cell Biol. . 190 . 4 . 533–9 . August 2010 . 20713600 . 2928022 . 10.1083/jcb.201002108 .
6. Shvets E, Fass E, Scherz-Shouval R, Elazar Z . The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes . J. Cell Sci. . 121 . Pt 16 . 2685–95 . August 2008 . 18653543 . 10.1242/jcs.026005 . free .