Induced myeloid leukemia cell differentiation protein Mcl-1

Details

Name
Induced myeloid leukemia cell differentiation protein Mcl-1
Synonyms
  • Bcl-2-like protein 3
  • Bcl-2-related protein EAT/mcl1
  • Bcl2-L-3
  • BCL2L3
  • mcl1/EAT
Gene Name
MCL1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006783|Induced myeloid leukemia cell differentiation protein Mcl-1
MFGLKRNAVIGLNLYCGGAGLGAGSGGATRPGGRLLATEKEASARREIGGGEAGAVIGGS
AGASPPSTLTPDSRRVARPPPIGAEVPDVTATPARLLFFAPTRRAAPLEEMEAPAADAIM
SPEEELDGYEPEPLGKRPAVLPLLELVGESGNNTSTDGSLPSTPPPAEEEEDELYRQSLE
IISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNE
DDVKSLSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVR
TKRDWLVKQRGWDGFVEFFHVEDLEGGIRNVLLAFAGVAGVGAGLAYLIR
Number of residues
350
Molecular Weight
37336.975
Theoretical pI
5.34
GO Classification
Functions
BH3 domain binding / protein channel activity / protein heterodimerization activity / protein homodimerization activity
Processes
apoptotic mitochondrial changes / cell fate determination / cellular homeostasis / extrinsic apoptotic signaling pathway in absence of ligand / intrinsic apoptotic signaling pathway in response to DNA damage / multicellular organismal development / negative regulation of anoikis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of intrinsic apoptotic signaling pathway / positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / protein transmembrane transport / regulation of response to DNA damage stimulus / response to cytokine
Components
Bcl-2 family protein complex / cytoplasm / cytosol / integral component of membrane / membrane / mitochondrial matrix / mitochondrial outer membrane / mitochondrion / nucleoplasm / nucleus
General Function
Protein homodimerization activity
Specific Function
Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.
Pfam Domain Function
Transmembrane Regions
328-348
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0019430|Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)
ATGTTTGGCCTCAAAAGAAACGCGGTAATCGGACTCAACCTCTACTGTGGGGGGGCCGGC
TTGGGGGCCGGCAGCGGCGGCGCCACCCGCCCGGGAGGGCGACTTTTGGCCACCGGCGCC
AAGGACACAAAGCCAATGGGCAGGTCTGGGGCCACCAGCAGGAAGGCGCTGGAGACCTTA
CGACGGGTTGGGGATGGCGTGCAGCGCAACCACGAGACGGCCTTCCAAGGCATGCTTCGG
AAACTGGACATCAAAAACGAAGACGATGTGAAATCGTTGTCTCGAGTGATGATCCATGTT
TTCAGCGACGGCGTAACAAACTGGGGCAGGATTGTGACTCTCATTTCTTTTGGTGCCTTT
GTGGCTAAACACTTGAAGACCATAAACCAAGAAAGCTGCATCGAACCATTAGCAGAAAGT
ATCACAGACGTTCTCGTAAGGACAAAACGGGACTGGCTAGTTAAACAAAGAGGCTGGGAT
GGGTTTGTGGAGTTCTTCCATGTAGAGGACCTAGAAGGTGGCATCAGGAATGTGCTGCTG
GCTTTTGCAGGTGTTGCTGGAGTAGGAGCTGGTTTGGCATATCTAATAAGATAG
Chromosome Location
1
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ07820
UniProtKB Entry NameMCL1_HUMAN
GenBank Gene IDAF118278
GenAtlas IDMCL1
HGNC IDHGNC:6943
General References
  1. Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW: MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3516-20. [Article]
  2. Umezawa A, Maruyama T, Inazawa J, Imai S, Takano T, Hata J: Induction of mcl1/EAT, Bcl-2 related gene, by retinoic acid or heat shock in the human embryonal carcinoma cells, NCR-G3. Cell Struct Funct. 1996 Apr;21(2):143-50. [Article]
  3. Akgul C, Turner PC, White MR, Edwards SW: Functional analysis of the human MCL-1 gene. Cell Mol Life Sci. 2000 Apr;57(4):684-91. [Article]
  4. Bingle CD, Craig RW, Swales BM, Singleton V, Zhou P, Whyte MK: Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death. J Biol Chem. 2000 Jul 21;275(29):22136-46. [Article]
  5. Bae J, Leo CP, Hsu SY, Hsueh AJ: MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain. J Biol Chem. 2000 Aug 18;275(33):25255-61. [Article]
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  9. Okita H, Umezawa A, Fukuma M, Ando T, Urano F, Sano M, Nakata Y, Mori T, Hata J: Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions. Leuk Res. 2000 Jan;24(1):73-7. [Article]
  10. Michels J, O'Neill JW, Dallman CL, Mouzakiti A, Habens F, Brimmell M, Zhang KY, Craig RW, Marcusson EG, Johnson PW, Packham G: Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage. Oncogene. 2004 Jun 17;23(28):4818-27. [Article]
  11. Chao JR, Wang JM, Lee SF, Peng HW, Lin YH, Chou CH, Li JC, Huang HM, Chou CK, Kuo ML, Yen JJ, Yang-Yen HF: mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response. Mol Cell Biol. 1998 Aug;18(8):4883-98. [Article]
  12. Zhang D, Li F, Weidner D, Mnjoyan ZH, Fujise K: Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and Fortilin. The potential role of MCL1 as a fortilin chaperone. J Biol Chem. 2002 Oct 4;277(40):37430-8. Epub 2002 Jul 30. [Article]
  13. Inoshita S, Takeda K, Hatai T, Terada Y, Sano M, Hata J, Umezawa A, Ichijo H: Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress. J Biol Chem. 2002 Nov 15;277(46):43730-4. Epub 2002 Sep 9. [Article]
  14. Leu JI, Dumont P, Hafey M, Murphy ME, George DL: Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol. 2004 May;6(5):443-50. Epub 2004 Apr 11. [Article]
  15. Domina AM, Vrana JA, Gregory MA, Hann SR, Craig RW: MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol. Oncogene. 2004 Jul 8;23(31):5301-15. [Article]
  16. Zhong Q, Gao W, Du F, Wang X: Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell. 2005 Jul 1;121(7):1085-95. [Article]
  17. Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR: Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 2006 Mar 17;21(6):749-60. [Article]
  18. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  19. Thomas LW, Lam C, Clark RE, White MR, Spiller DG, Moots RJ, Edwards SW: Serine 162, an essential residue for the mitochondrial localization, stability and anti-apoptotic function of Mcl-1. PLoS One. 2012;7(9):e45088. Epub 2012 Sep 14. [Article]
  20. Zhang X, Weng C, Li Y, Wang X, Jiang C, Li X, Xu Y, Chen Q, Pan L, Tang H: Human Bop is a novel BH3-only member of the Bcl-2 protein family. Protein Cell. 2012 Oct;3(10):790-801. doi: 10.1007/s13238-012-2069-7. Epub 2012 Oct 11. [Article]
  21. Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC, Fairlie WD, Hinds MG, Colman PM: Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6217-22. Epub 2007 Mar 27. [Article]
  22. Stewart ML, Fire E, Keating AE, Walensky LD: The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat Chem Biol. 2010 Aug;6(8):595-601. doi: 10.1038/nchembio.391. Epub 2010 Jun 20. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails