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Database: UniProt
Entry: Q07820
LinkDB: Q07820
Original site: Q07820 
ID   MCL1_HUMAN              Reviewed;         350 AA.
AC   Q07820; B2R6B2; D3DV03; D3DV04; Q9HD91; Q9NRQ3; Q9NRQ4; Q9UHR7; Q9UHR8;
AC   Q9UHR9; Q9UNJ1;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   06-DEC-2005, sequence version 3.
DT   07-OCT-2020, entry version 218.
DE   RecName: Full=Induced myeloid leukemia cell differentiation protein Mcl-1;
DE   AltName: Full=Bcl-2-like protein 3;
DE            Short=Bcl2-L-3;
DE   AltName: Full=Bcl-2-related protein EAT/mcl1;
DE   AltName: Full=mcl1/EAT;
GN   Name=MCL1; Synonyms=BCL2L3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-173.
RC   TISSUE=Myeloid leukemia cell;
RX   PubMed=7682708; DOI=10.1073/pnas.90.8.3516;
RA   Kozopas K.M., Yang T., Buchan H.L., Zhou P., Craig R.W.;
RT   "MCL1, a gene expressed in programmed myeloid cell differentiation, has
RT   sequence similarity to BCL2.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:3516-3520(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION.
RX   PubMed=8790944; DOI=10.1247/csf.21.143;
RA   Umezawa A., Maruyama T., Inazawa J., Imai S., Takano T., Hata J.;
RT   "Induction of mcl1/EAT, Bcl-2 related gene, by retinoic acid or heat shock
RT   in the human embryonal carcinoma cells, NCR-G3.";
RL   Cell Struct. Funct. 21:143-150(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=11130466; DOI=10.1007/pl00000728;
RA   Akgul C., Turner P.C., White M.R.H., Edwards S.W.;
RT   "Functional analysis of the human MCL-1 gene.";
RL   Cell. Mol. Life Sci. 57:684-691(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT ASP-173, AND
RP   FUNCTION.
RC   TISSUE=Myeloid leukemia cell, and Neuroblastoma;
RX   PubMed=10766760; DOI=10.1074/jbc.m909572199;
RA   Bingle C.D., Craig R.W., Swales B.M., Singleton V., Zhou P., Whyte M.K.B.;
RT   "Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene
RT   product that promotes cell death.";
RL   J. Biol. Chem. 275:22136-22146(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH BAX; BAK1
RP   AND BCL2L11, AND DIMERIZATION OF ISOFORMS 1 AND 2.
RX   PubMed=10837489; DOI=10.1074/jbc.m909826199;
RA   Bae J., Leo C.P., Hsu S.Y., Hsueh A.J.W.;
RT   "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1,
RT   encodes a proapoptotic protein possessing only the BH3 domain.";
RL   J. Biol. Chem. 275:25255-25261(2000).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-227.
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-227.
RG   NIEHS SNPs program;
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Mammary gland, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 182-289 (ISOFORM 1), AND VARIANT VAL-227.
RC   TISSUE=Ewing sarcoma;
RX   PubMed=10634649; DOI=10.1016/s0145-2126(99)00137-x;
RA   Okita H., Umezawa A., Fukuma M., Hata J.;
RT   "Acute myeloid leukemia possessing jumping translocation is related to
RT   highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-
RT   apoptotic functions.";
RL   Leuk. Res. 24:73-77(2000).
RN   [13]
RP   PROTEIN SEQUENCE OF N-TERMINUS OF FRAGMENTS OBTAINED BY CASPASE CLEAVAGE,
RP   AND MUTAGENESIS OF ASP-127 AND ASP-157.
RX   PubMed=15122313; DOI=10.1038/sj.onc.1207648;
RA   Michels J., O'Neill J.W., Dallman C.L., Mouzakiti A., Habens F.,
RA   Brimmell M., Zhang K.Y.J., Craig R.W., Marcusson E.G., Johnson P.W.M.,
RA   Packham G.;
RT   "Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to
RT   a cell death molecule by efficient caspase-mediated cleavage.";
RL   Oncogene 23:4818-4827(2004).
RN   [14]
RP   INDUCTION.
RX   PubMed=9671497; DOI=10.1128/mcb.18.8.4883;
RA   Chao J.-R., Wang J.-M., Lee S.-F., Peng H.-W., Lin Y.-H., Chou C.-H.,
RA   Li J.-C., Huang H.-M., Chou C.-K., Kuo M.-L., Yen J.J.-Y., Yang-Yen H.-F.;
RT   "Mcl-1 is an immediate-early gene activated by the granulocyte-macrophage
RT   colony-stimulating factor (GM-CSF) signaling pathway and is one component
RT   of the GM-CSF viability response.";
RL   Mol. Cell. Biol. 18:4883-4898(1998).
RN   [15]
RP   INTERACTION WITH TPT1, AND SUBCELLULAR LOCATION.
RX   PubMed=12149273; DOI=10.1074/jbc.m207413200;
RA   Zhang D., Li F., Weidner D., Mnjoyan Z.H., Fujise K.;
RT   "Physical and functional interaction between myeloid cell leukemia 1
RT   protein (MCL1) and fortilin. The potential role of MCL1 as a fortilin
RT   chaperone.";
RL   J. Biol. Chem. 277:37430-37438(2002).
RN   [16]
RP   PHOSPHORYLATION AT SER-121 AND THR-163.
RX   PubMed=12223490; DOI=10.1074/jbc.m207951200;
RA   Inoshita S., Takeda K., Hatai T., Terada Y., Sano M., Hata J., Umezawa A.,
RA   Ichijo H.;
RT   "Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in
RT   response to oxidative stress.";
RL   J. Biol. Chem. 277:43730-43734(2002).
RN   [17]
RP   INTERACTION WITH BAK1, AND SUBCELLULAR LOCATION.
RX   PubMed=15077116; DOI=10.1038/ncb1123;
RA   Leu J.I.-J., Dumont P., Hafey M., Murphy M.E., George D.L.;
RT   "Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1
RT   complex.";
RL   Nat. Cell Biol. 6:443-450(2004).
RN   [18]
RP   PHOSPHORYLATION AT THR-163, AND MUTAGENESIS OF SER-162 AND THR-163.
RX   PubMed=15241487; DOI=10.1038/sj.onc.1207692;
RA   Domina A.M., Vrana J.A., Gregory M.A., Hann S.R., Craig R.W.;
RT   "MCL1 is phosphorylated in the PEST region and stabilized upon ERK
RT   activation in viable cells, and at additional sites with cytotoxic okadaic
RT   acid or taxol.";
RL   Oncogene 23:5301-5315(2004).
RN   [19]
RP   UBIQUITINATION, AND MUTAGENESIS OF LYS-5; LYS-40; LYS-136; LYS-194;
RP   LYS-197; LYS-208 AND LYS-234.
RX   PubMed=15989957; DOI=10.1016/j.cell.2005.06.009;
RA   Zhong Q., Gao W., Du F., Wang X.;
RT   "Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the
RT   polyubiquitination of Mcl-1 and regulates apoptosis.";
RL   Cell 121:1085-1095(2005).
RN   [20]
RP   FUNCTION AS INHIBITOR OF APOPTOSIS, PHOSPHORYLATION AT SER-159 BY
RP   GSK3-ALPHA AND GSK3-BETA, UBIQUITINATION, AND MUTAGENESIS OF SER-159.
RX   PubMed=16543145; DOI=10.1016/j.molcel.2006.02.009;
RA   Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.;
RT   "Glycogen synthase kinase-3 regulates mitochondrial outer membrane
RT   permeabilization and apoptosis by destabilization of MCL-1.";
RL   Mol. Cell 21:749-760(2006).
RN   [21]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [22]
RP   SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-162 AND THR-163, AND
RP   MUTAGENESIS OF SER-162.
RX   PubMed=23024798; DOI=10.1371/journal.pone.0045088;
RA   Thomas L.W., Lam C., Clark R.E., White M.R., Spiller D.G., Moots R.J.,
RA   Edwards S.W.;
RT   "Serine 162, an essential residue for the mitochondrial localization,
RT   stability and anti-apoptotic function of Mcl-1.";
RL   PLoS ONE 7:E45088-E45088(2012).
RN   [23]
RP   INTERACTION WITH RTL10/BOP.
RX   PubMed=23055042; DOI=10.1007/s13238-012-2069-7;
RA   Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L.,
RA   Tang H.;
RT   "Human Bop is a novel BH3-only member of the Bcl-2 protein family.";
RL   Protein Cell 3:790-801(2012).
RN   [24]
RP   INTERACTION WITH BCL2L11.
RX   PubMed=27013495; DOI=10.15252/embr.201541392;
RA   Weber A., Heinlein M., Dengjel J., Alber C., Singh P.K., Haecker G.;
RT   "The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances
RT   apoptosis.";
RL   EMBO Rep. 17:724-738(2016).
RN   [25]
RP   X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 151-307 IN COMPLEXES WITH PMAIP1
RP   AND BCL2L11.
RX   PubMed=17389404; DOI=10.1073/pnas.0701297104;
RA   Czabotar P.E., Lee E.F., van Delft M.F., Day C.L., Smith B.J.,
RA   Huang D.C.S., Fairlie W.D., Hinds M.G., Colman P.M.;
RT   "Structural insights into the degradation of Mcl-1 induced by BH3
RT   domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:6217-6222(2007).
RN   [26]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 172-327 IN COMPLEX WITH BCL2L11.
RX   PubMed=20562877; DOI=10.1038/nchembio.391;
RA   Stewart M.L., Fire E., Keating A.E., Walensky L.D.;
RT   "The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis
RT   sensitizer.";
RL   Nat. Chem. Biol. 6:595-601(2010).
RN   [27]
RP   VARIANT [LARGE SCALE ANALYSIS] LEU-231.
RX   PubMed=18987736; DOI=10.1038/nature07485;
RA   Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA   Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA   Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA   Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA   Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA   Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA   Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA   Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA   DiPersio J.F., Wilson R.K.;
RT   "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT   genome.";
RL   Nature 456:66-72(2008).
CC   -!- FUNCTION: Involved in the regulation of apoptosis versus cell survival,
CC       and in the maintenance of viability but not of proliferation. Mediates
CC       its effects by interactions with a number of other regulators of
CC       apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.
CC       {ECO:0000269|PubMed:10766760, ECO:0000269|PubMed:16543145}.
CC   -!- SUBUNIT: Interacts with HIF3A (via C-terminus domain) (By similarity).
CC       Interacts with BAD, BOK, BIK and BMF (By similarity). Interacts with
CC       PMAIP1 (PubMed:17389404). Interacts with BBC3 (By similarity). Isoform
CC       1 interacts with BAX, BAK1 and TPT1 (PubMed:10837489, PubMed:12149273,
CC       PubMed:15077116). Heterodimer of isoform 1 and isoform 2. Homodimers of
CC       isoform 1 or isoform 2 are not detected. Isoform 2 does not interact
CC       with pro-apoptotic BCL2-related proteins (PubMed:10837489). Interacts
CC       with RTL10/BOP (PubMed:23055042). Interacts with BCL2L11; may sequester
CC       BCL2L11 to prevent its pro-apoptotic activity (PubMed:10837489,
CC       PubMed:27013495, PubMed:17389404, PubMed:20562877). Interacts with
CC       GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and MCL1 is
CC       impaired in the absence of GIMAP5 (By similarity).
CC       {ECO:0000250|UniProtKB:P97287, ECO:0000250|UniProtKB:Q9Z1P3,
CC       ECO:0000269|PubMed:10837489, ECO:0000269|PubMed:12149273,
CC       ECO:0000269|PubMed:15077116, ECO:0000269|PubMed:17389404,
CC       ECO:0000269|PubMed:20562877, ECO:0000269|PubMed:23055042,
CC       ECO:0000269|PubMed:27013495}.
CC   -!- INTERACTION:
CC       Q07820; Q16611: BAK1; NbExp=17; IntAct=EBI-1003422, EBI-519866;
CC       Q07820; Q07812: BAX; NbExp=8; IntAct=EBI-1003422, EBI-516580;
CC       Q07820; Q9BXH1: BBC3; NbExp=5; IntAct=EBI-1003422, EBI-519884;
CC       Q07820; Q9BXH1-2: BBC3; NbExp=2; IntAct=EBI-1003422, EBI-519896;
CC       Q07820; O43521: BCL2L11; NbExp=15; IntAct=EBI-1003422, EBI-526406;
CC       Q07820; Q14457: BECN1; NbExp=2; IntAct=EBI-1003422, EBI-949378;
CC       Q07820; P55957: BID; NbExp=2; IntAct=EBI-1003422, EBI-519672;
CC       Q07820; Q96LC9: BMF; NbExp=3; IntAct=EBI-1003422, EBI-3919268;
CC       Q07820; Q03135: CAV1; NbExp=3; IntAct=EBI-1003422, EBI-603614;
CC       Q07820; Q7Z6Z7: HUWE1; NbExp=6; IntAct=EBI-1003422, EBI-625934;
CC       Q07820; Q9H3M0: KCNF1; NbExp=3; IntAct=EBI-1003422, EBI-6918743;
CC       Q07820; Q13794: PMAIP1; NbExp=5; IntAct=EBI-1003422, EBI-707392;
CC       Q07820; Q7L3V2: RTL10; NbExp=2; IntAct=EBI-1003422, EBI-10697720;
CC       Q07820; Q9UNK0: STX8; NbExp=3; IntAct=EBI-1003422, EBI-727240;
CC       Q07820; Q93008: USP9X; NbExp=10; IntAct=EBI-1003422, EBI-302524;
CC       Q07820; P49817: Cav1; Xeno; NbExp=3; IntAct=EBI-1003422, EBI-1161338;
CC       Q07820; Q9JM54: Pmaip1; Xeno; NbExp=2; IntAct=EBI-1003422, EBI-709183;
CC       Q07820; Q91AU0; Xeno; NbExp=2; IntAct=EBI-1003422, EBI-9657017;
CC       Q07820-1; Q07820-2: MCL1; NbExp=4; IntAct=EBI-7173045, EBI-1003451;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}. Cytoplasm. Mitochondrion. Nucleus, nucleoplasm.
CC       Note=Cytoplasmic, associated with mitochondria.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=MCL1L, MCL-1L;
CC         IsoId=Q07820-1; Sequence=Displayed;
CC       Name=2; Synonyms=Delta S, MCL-1S, TM;
CC         IsoId=Q07820-2; Sequence=VSP_000532, VSP_000533;
CC   -!- INDUCTION: Expression increases early during phorbol ester-induced
CC       differentiation along the monocyte/macrophage pathway in myeloid
CC       leukemia cell line ML-1. Rapidly up-regulated by CSF2 in ML-1 cells.
CC       Up-regulated by heat shock-induced differentiation. Expression
CC       increases early during retinoic acid-induced differentiation.
CC       {ECO:0000269|PubMed:8790944, ECO:0000269|PubMed:9671497}.
CC   -!- PTM: Cleaved by CASP3 during apoptosis. In intact cells cleavage occurs
CC       preferentially after Asp-127, yielding a pro-apoptotic 28 kDa C-
CC       terminal fragment.
CC   -!- PTM: Rapidly degraded in the absence of phosphorylation on Thr-163 in
CC       the PEST region. {ECO:0000269|PubMed:12223490,
CC       ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:23024798}.
CC   -!- PTM: Phosphorylated on Ser-159, by GSK3, in response to
CC       IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 induces
CC       ubiquitination and proteasomal degradation, abrogating the anti-
CC       apoptotic activity. Treatment with taxol or okadaic acid induces
CC       phosphorylation on additional sites. {ECO:0000269|PubMed:16543145}.
CC   -!- PTM: Ubiquitinated. Ubiquitination is induced by phosphorylation at
CC       Ser-159. {ECO:0000269|PubMed:16543145}.
CC   -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/mcl1/";
DR   EMBL; L08246; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AF118124; AAD13299.1; -; mRNA.
DR   EMBL; AF147742; AAF74821.1; -; Genomic_DNA.
DR   EMBL; AF198614; AAF64255.1; -; Genomic_DNA.
DR   EMBL; AF198614; AAF64256.1; -; Genomic_DNA.
DR   EMBL; AF162677; AAG00896.1; -; Genomic_DNA.
DR   EMBL; AF162676; AAG00896.1; JOINED; Genomic_DNA.
DR   EMBL; AF203373; AAG00904.1; -; mRNA.
DR   EMBL; BT006640; AAP35286.1; -; mRNA.
DR   EMBL; AK312508; BAG35409.1; -; mRNA.
DR   EMBL; DQ088966; AAY68220.1; -; Genomic_DNA.
DR   EMBL; AL356356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471121; EAW53538.1; -; Genomic_DNA.
DR   EMBL; CH471121; EAW53539.1; -; Genomic_DNA.
DR   EMBL; CH471121; EAW53540.1; -; Genomic_DNA.
DR   EMBL; CH471121; EAW53541.1; -; Genomic_DNA.
DR   EMBL; BC017197; AAH17197.1; -; mRNA.
DR   EMBL; BC071897; AAH71897.1; -; mRNA.
DR   EMBL; BC107735; AAI07736.1; -; mRNA.
DR   EMBL; AF118276; AAF15309.1; -; mRNA.
DR   EMBL; AF118277; AAF15310.1; -; mRNA.
DR   EMBL; AF118278; AAF15311.1; -; mRNA.
DR   CCDS; CCDS956.1; -. [Q07820-2]
DR   CCDS; CCDS957.1; -. [Q07820-1]
DR   PIR; A47476; A47476.
DR   RefSeq; NP_001184249.1; NM_001197320.1.
DR   RefSeq; NP_068779.1; NM_021960.4. [Q07820-1]
DR   RefSeq; NP_877495.1; NM_182763.2. [Q07820-2]
DR   PDB; 2KBW; NMR; -; A=163-326.
DR   PDB; 2MHS; NMR; -; A=171-327.
DR   PDB; 2NL9; X-ray; 1.55 A; A=209-327.
DR   PDB; 2NLA; X-ray; 2.80 A; A=209-327.
DR   PDB; 2PQK; X-ray; 2.00 A; A=172-327.
DR   PDB; 3D7V; X-ray; 2.03 A; A=209-327.
DR   PDB; 3IO9; X-ray; 2.40 A; A=209-327.
DR   PDB; 3KJ0; X-ray; 1.70 A; A=172-327.
DR   PDB; 3KJ1; X-ray; 1.94 A; A=172-327.
DR   PDB; 3KJ2; X-ray; 2.35 A; A=172-327.
DR   PDB; 3KZ0; X-ray; 2.35 A; A/B=172-327.
DR   PDB; 3MK8; X-ray; 2.32 A; A=172-327, B=208-228.
DR   PDB; 3PK1; X-ray; 2.49 A; A/C=174-326.
DR   PDB; 3TWU; X-ray; 1.80 A; B=73-88.
DR   PDB; 3WIX; X-ray; 1.90 A; A/B/C/D=172-327.
DR   PDB; 3WIY; X-ray; 2.15 A; A/B/C/D/E/F=172-327.
DR   PDB; 4BPI; X-ray; 1.98 A; A=209-327.
DR   PDB; 4BPJ; X-ray; 1.60 A; A=209-327.
DR   PDB; 4HW2; X-ray; 2.80 A; A/B/C/D/E/F=172-323.
DR   PDB; 4HW3; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L=172-323.
DR   PDB; 4HW4; X-ray; 1.53 A; A/B=172-327.
DR   PDB; 4OQ5; X-ray; 2.86 A; A/B/C/D/E/F=174-326.
DR   PDB; 4OQ6; X-ray; 1.81 A; A/B=174-326.
DR   PDB; 4WGI; X-ray; 1.85 A; A=173-321.
DR   PDB; 4WMR; X-ray; 1.70 A; A=173-321.
DR   PDB; 4WMS; X-ray; 1.90 A; A=174-321.
DR   PDB; 4WMT; X-ray; 2.35 A; A=174-321.
DR   PDB; 4WMU; X-ray; 1.55 A; A=174-321.
DR   PDB; 4WMV; X-ray; 2.40 A; A=174-321.
DR   PDB; 4WMW; X-ray; 1.90 A; A=174-321.
DR   PDB; 4WMX; X-ray; 2.00 A; A=174-321.
DR   PDB; 4ZBF; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=172-327.
DR   PDB; 4ZBI; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L=172-327.
DR   PDB; 5C3F; X-ray; 1.43 A; A=173-327.
DR   PDB; 5C6H; X-ray; 2.05 A; A/C/E/G/I/K/M/O/Q/S/U/W=171-327.
DR   PDB; 5FC4; X-ray; 1.50 A; A=172-320.
DR   PDB; 5FDO; X-ray; 2.80 A; A/B/C/D=172-320.
DR   PDB; 5FDR; X-ray; 2.60 A; A/B/C/D=172-327.
DR   PDB; 5IEZ; X-ray; 2.60 A; A/B/C/D=172-327.
DR   PDB; 5IF4; X-ray; 2.39 A; A/B=172-327.
DR   PDB; 5JSB; X-ray; 2.74 A; A/C/E/G/I/K=172-350.
DR   PDB; 5KU9; X-ray; 2.20 A; A/B=174-219, A/B=258-327.
DR   PDB; 5LOF; X-ray; 2.20 A; A=173-321.
DR   PDB; 5MES; X-ray; 2.24 A; A=241-327.
DR   PDB; 5MEV; X-ray; 2.94 A; A=241-327.
DR   PDB; 5UUM; X-ray; 2.35 A; A/B=172-325.
DR   PDB; 5VKC; X-ray; 2.31 A; A/B=174-326.
DR   PDB; 5VX2; X-ray; 1.85 A; A/C=241-327.
DR   PDB; 5W89; X-ray; 1.42 A; A=172-321.
DR   PDB; 5W8F; X-ray; 1.85 A; A=172-320.
DR   PDB; 6B4L; X-ray; 2.25 A; A/B=174-326.
DR   PDB; 6B4U; X-ray; 1.95 A; A=174-326.
DR   PDB; 6BW2; X-ray; 2.75 A; A/B/C/D=172-327.
DR   PDB; 6BW8; X-ray; 2.90 A; A/B/C/D=172-327.
DR   PDB; 6FS0; X-ray; 2.25 A; A=174-324.
DR   PDB; 6FS1; X-ray; 1.60 A; A/B=174-321.
DR   PDB; 6FS2; X-ray; 2.55 A; A=174-325, B=174-324.
DR   PDB; 6MBD; X-ray; 1.95 A; A/B=172-324.
DR   PDB; 6MBE; X-ray; 2.25 A; A=172-323.
DR   PDB; 6NE5; X-ray; 1.85 A; A/B/C/D=172-328.
DR   PDB; 6O4U; X-ray; 1.70 A; A/B=172-327.
DR   PDB; 6O6F; X-ray; 1.60 A; A/B=172-327.
DR   PDB; 6O6G; X-ray; 2.40 A; A=172-327.
DR   PDB; 6OQB; X-ray; 1.60 A; A=171-327.
DR   PDB; 6OQC; X-ray; 1.80 A; A/B=171-327.
DR   PDB; 6OQD; X-ray; 1.48 A; A=171-327.
DR   PDB; 6OQN; X-ray; 1.70 A; A/B=171-327.
DR   PDB; 6OVC; NMR; -; A=171-327.
DR   PDB; 6P3P; X-ray; 1.61 A; A=172-327.
DR   PDB; 6QB3; X-ray; 1.90 A; A=174-327.
DR   PDB; 6QB4; X-ray; 2.38 A; A=174-327.
DR   PDB; 6QB6; X-ray; 2.24 A; A=174-327.
DR   PDB; 6QFC; X-ray; 1.96 A; A=174-327.
DR   PDB; 6QFI; X-ray; 2.40 A; A=171-327.
DR   PDB; 6QFM; X-ray; 2.00 A; A=171-327.
DR   PDB; 6QFQ; X-ray; 1.60 A; A=171-327.
DR   PDB; 6QGD; X-ray; 1.80 A; A=173-321.
DR   PDB; 6QXJ; X-ray; 1.70 A; A=173-321.
DR   PDB; 6QYK; X-ray; 2.30 A; A=173-321.
DR   PDB; 6QYL; X-ray; 2.20 A; A=173-321.
DR   PDB; 6QYN; X-ray; 2.50 A; A=173-321.
DR   PDB; 6QYO; X-ray; 2.10 A; A=173-321.
DR   PDB; 6QYP; X-ray; 2.20 A; A=171-327.
DR   PDB; 6QZ5; X-ray; 2.00 A; A=171-327.
DR   PDB; 6QZ6; X-ray; 1.90 A; A=171-327.
DR   PDB; 6QZ7; X-ray; 2.20 A; A=173-321.
DR   PDB; 6QZ8; X-ray; 2.15 A; A=171-327.
DR   PDB; 6QZB; X-ray; 2.00 A; A=171-327.
DR   PDB; 6U63; X-ray; 2.75 A; A/B/C/D=171-323.
DR   PDB; 6U64; X-ray; 2.55 A; A=171-320.
DR   PDB; 6U65; X-ray; 2.09 A; A/B/C/D=171-323.
DR   PDB; 6U67; X-ray; 1.84 A; A/B=171-323.
DR   PDB; 6U6F; X-ray; 2.90 A; A/B/C=171-323.
DR   PDB; 6UD2; X-ray; 1.70 A; A=171-327.
DR   PDB; 6UDI; X-ray; 1.94 A; A=171-327.
DR   PDB; 6UDT; X-ray; 1.50 A; A=171-327.
DR   PDB; 6UDU; X-ray; 1.75 A; A=171-327.
DR   PDB; 6UDV; X-ray; 1.35 A; A=171-327.
DR   PDB; 6UDX; X-ray; 1.70 A; A/B=171-327.
DR   PDB; 6UDY; X-ray; 1.70 A; A/B=171-327.
DR   PDBsum; 2KBW; -.
DR   PDBsum; 2MHS; -.
DR   PDBsum; 2NL9; -.
DR   PDBsum; 2NLA; -.
DR   PDBsum; 2PQK; -.
DR   PDBsum; 3D7V; -.
DR   PDBsum; 3IO9; -.
DR   PDBsum; 3KJ0; -.
DR   PDBsum; 3KJ1; -.
DR   PDBsum; 3KJ2; -.
DR   PDBsum; 3KZ0; -.
DR   PDBsum; 3MK8; -.
DR   PDBsum; 3PK1; -.
DR   PDBsum; 3TWU; -.
DR   PDBsum; 3WIX; -.
DR   PDBsum; 3WIY; -.
DR   PDBsum; 4BPI; -.
DR   PDBsum; 4BPJ; -.
DR   PDBsum; 4HW2; -.
DR   PDBsum; 4HW3; -.
DR   PDBsum; 4HW4; -.
DR   PDBsum; 4OQ5; -.
DR   PDBsum; 4OQ6; -.
DR   PDBsum; 4WGI; -.
DR   PDBsum; 4WMR; -.
DR   PDBsum; 4WMS; -.
DR   PDBsum; 4WMT; -.
DR   PDBsum; 4WMU; -.
DR   PDBsum; 4WMV; -.
DR   PDBsum; 4WMW; -.
DR   PDBsum; 4WMX; -.
DR   PDBsum; 4ZBF; -.
DR   PDBsum; 4ZBI; -.
DR   PDBsum; 5C3F; -.
DR   PDBsum; 5C6H; -.
DR   PDBsum; 5FC4; -.
DR   PDBsum; 5FDO; -.
DR   PDBsum; 5FDR; -.
DR   PDBsum; 5IEZ; -.
DR   PDBsum; 5IF4; -.
DR   PDBsum; 5JSB; -.
DR   PDBsum; 5KU9; -.
DR   PDBsum; 5LOF; -.
DR   PDBsum; 5MES; -.
DR   PDBsum; 5MEV; -.
DR   PDBsum; 5UUM; -.
DR   PDBsum; 5VKC; -.
DR   PDBsum; 5VX2; -.
DR   PDBsum; 5W89; -.
DR   PDBsum; 5W8F; -.
DR   PDBsum; 6B4L; -.
DR   PDBsum; 6B4U; -.
DR   PDBsum; 6BW2; -.
DR   PDBsum; 6BW8; -.
DR   PDBsum; 6FS0; -.
DR   PDBsum; 6FS1; -.
DR   PDBsum; 6FS2; -.
DR   PDBsum; 6MBD; -.
DR   PDBsum; 6MBE; -.
DR   PDBsum; 6NE5; -.
DR   PDBsum; 6O4U; -.
DR   PDBsum; 6O6F; -.
DR   PDBsum; 6O6G; -.
DR   PDBsum; 6OQB; -.
DR   PDBsum; 6OQC; -.
DR   PDBsum; 6OQD; -.
DR   PDBsum; 6OQN; -.
DR   PDBsum; 6OVC; -.
DR   PDBsum; 6P3P; -.
DR   PDBsum; 6QB3; -.
DR   PDBsum; 6QB4; -.
DR   PDBsum; 6QB6; -.
DR   PDBsum; 6QFC; -.
DR   PDBsum; 6QFI; -.
DR   PDBsum; 6QFM; -.
DR   PDBsum; 6QFQ; -.
DR   PDBsum; 6QGD; -.
DR   PDBsum; 6QXJ; -.
DR   PDBsum; 6QYK; -.
DR   PDBsum; 6QYL; -.
DR   PDBsum; 6QYN; -.
DR   PDBsum; 6QYO; -.
DR   PDBsum; 6QYP; -.
DR   PDBsum; 6QZ5; -.
DR   PDBsum; 6QZ6; -.
DR   PDBsum; 6QZ7; -.
DR   PDBsum; 6QZ8; -.
DR   PDBsum; 6QZB; -.
DR   PDBsum; 6U63; -.
DR   PDBsum; 6U64; -.
DR   PDBsum; 6U65; -.
DR   PDBsum; 6U67; -.
DR   PDBsum; 6U6F; -.
DR   PDBsum; 6UD2; -.
DR   PDBsum; 6UDI; -.
DR   PDBsum; 6UDT; -.
DR   PDBsum; 6UDU; -.
DR   PDBsum; 6UDV; -.
DR   PDBsum; 6UDX; -.
DR   PDBsum; 6UDY; -.
DR   SMR; Q07820; -.
DR   BioGRID; 110338; 100.
DR   ComplexPortal; CPX-304; MCL1:PMAIP1 complex.
DR   ComplexPortal; CPX-481; MCL-1-BIM complex. [Q07820-1]
DR   CORUM; Q07820; -.
DR   DIP; DIP-231N; -.
DR   ELM; Q07820; -.
DR   IntAct; Q07820; 53.
DR   MINT; Q07820; -.
DR   STRING; 9606.ENSP00000358022; -.
DR   ChEMBL; CHEMBL4361; -.
DR   DrugBank; DB09401; Isosorbide.
DR   DrugCentral; Q07820; -.
DR   GuidetoPHARMACOLOGY; 2847; -.
DR   iPTMnet; Q07820; -.
DR   PhosphoSitePlus; Q07820; -.
DR   BioMuta; MCL1; -.
DR   DMDM; 83304396; -.
DR   EPD; Q07820; -.
DR   jPOST; Q07820; -.
DR   MassIVE; Q07820; -.
DR   MaxQB; Q07820; -.
DR   PaxDb; Q07820; -.
DR   PeptideAtlas; Q07820; -.
DR   PRIDE; Q07820; -.
DR   ProteomicsDB; 58540; -. [Q07820-1]
DR   ProteomicsDB; 58541; -. [Q07820-2]
DR   ABCD; Q07820; 1 sequenced antibody.
DR   Antibodypedia; 1508; 1358 antibodies.
DR   DNASU; 4170; -.
DR   Ensembl; ENST00000307940; ENSP00000309973; ENSG00000143384. [Q07820-2]
DR   Ensembl; ENST00000369026; ENSP00000358022; ENSG00000143384. [Q07820-1]
DR   GeneID; 4170; -.
DR   KEGG; hsa:4170; -.
DR   UCSC; uc001euz.4; human. [Q07820-1]
DR   CTD; 4170; -.
DR   DisGeNET; 4170; -.
DR   EuPathDB; HostDB:ENSG00000143384.12; -.
DR   GeneCards; MCL1; -.
DR   HGNC; HGNC:6943; MCL1.
DR   HPA; ENSG00000143384; Low tissue specificity.
DR   MIM; 159552; gene.
DR   neXtProt; NX_Q07820; -.
DR   OpenTargets; ENSG00000143384; -.
DR   PharmGKB; PA30688; -.
DR   eggNOG; KOG4728; Eukaryota.
DR   GeneTree; ENSGT01000000214591; -.
DR   HOGENOM; CLU_046711_0_0_1; -.
DR   InParanoid; Q07820; -.
DR   KO; K02539; -.
DR   OMA; KQKGWEG; -.
DR   OrthoDB; 1218929at2759; -.
DR   PhylomeDB; Q07820; -.
DR   TreeFam; TF315834; -.
DR   PathwayCommons; Q07820; -.
DR   Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR   SIGNOR; Q07820; -.
DR   BioGRID-ORCS; 4170; 271 hits in 878 CRISPR screens.
DR   ChiTaRS; MCL1; human.
DR   EvolutionaryTrace; Q07820; -.
DR   GeneWiki; MCL1; -.
DR   GenomeRNAi; 4170; -.
DR   Pharos; Q07820; Tchem.
DR   PRO; PR:Q07820; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q07820; protein.
DR   Bgee; ENSG00000143384; Expressed in epithelium of mammary gland and 246 other tissues.
DR   ExpressionAtlas; Q07820; baseline and differential.
DR   Genevisible; Q07820; HS.
DR   GO; GO:0097136; C:Bcl-2 family protein complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0051434; F:BH3 domain binding; IPI:BHF-UCL.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR   GO; GO:0008320; F:protein transmembrane transporter activity; TAS:UniProtKB.
DR   GO; GO:0001709; P:cell fate determination; NAS:UniProtKB.
DR   GO; GO:0019725; P:cellular homeostasis; NAS:UniProtKB.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR   GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW.
DR   GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:BHF-UCL.
DR   GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
DR   GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB.
DR   GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IGI:ParkinsonsUK-UCL.
DR   GO; GO:2001020; P:regulation of response to DNA damage stimulus; IMP:MGI.
DR   GO; GO:0034097; P:response to cytokine; IDA:MGI.
DR   Gene3D; 1.10.437.10; -; 1.
DR   InterPro; IPR013281; Apop_reg_Mc1.
DR   InterPro; IPR002475; Bcl2-like.
DR   InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR   InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR   InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR   InterPro; IPR036834; Blc2-like_sf.
DR   InterPro; IPR026298; Blc2_fam.
DR   PANTHER; PTHR11256; PTHR11256; 1.
DR   PANTHER; PTHR11256:SF46; PTHR11256:SF46; 1.
DR   Pfam; PF00452; Bcl-2; 1.
DR   PRINTS; PR01866; APOPREGMCL1.
DR   PRINTS; PR01862; BCL2FAMILY.
DR   SUPFAM; SSF56854; SSF56854; 1.
DR   PROSITE; PS50062; BCL2_FAMILY; 1.
DR   PROSITE; PS01080; BH1; 1.
DR   PROSITE; PS01258; BH2; 1.
DR   PROSITE; PS01259; BH3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Apoptosis; Cytoplasm;
KW   Developmental protein; Differentiation; Direct protein sequencing;
KW   Isopeptide bond; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Transmembrane; Transmembrane helix;
KW   Ubl conjugation.
FT   CHAIN           1..350
FT                   /note="Induced myeloid leukemia cell differentiation
FT                   protein Mcl-1"
FT                   /id="PRO_0000143080"
FT   TRANSMEM        328..348
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          104..175
FT                   /note="PEST-like"
FT   MOTIF           209..223
FT                   /note="BH3"
FT   MOTIF           252..272
FT                   /note="BH1"
FT   MOTIF           304..319
FT                   /note="BH2"
FT   SITE            127..128
FT                   /note="Cleavage; by caspase-3"
FT   SITE            157..158
FT                   /note="Cleavage; by caspase-3"
FT   MOD_RES         121
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:12223490"
FT   MOD_RES         159
FT                   /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT                   /evidence="ECO:0000269|PubMed:16543145"
FT   MOD_RES         162
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:23024798"
FT   MOD_RES         163
FT                   /note="Phosphothreonine; by MAPK"
FT                   /evidence="ECO:0000269|PubMed:12223490,
FT                   ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:23024798"
FT   CROSSLNK        5
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT   CROSSLNK        40
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT   CROSSLNK        136
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT   CROSSLNK        194
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT   CROSSLNK        197
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT   VAR_SEQ         231..271
FT                   /note="MLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFG -> WVCGVLP
FT                   CRGPRRWHQECAAGFCRCCWSRSWFGISNKIALL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10837489"
FT                   /id="VSP_000532"
FT   VAR_SEQ         272..350
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10837489"
FT                   /id="VSP_000533"
FT   VARIANT         173
FT                   /note="E -> D (in dbSNP:rs2737820)"
FT                   /evidence="ECO:0000269|PubMed:10766760,
FT                   ECO:0000269|PubMed:7682708"
FT                   /id="VAR_024021"
FT   VARIANT         227
FT                   /note="A -> V (in dbSNP:rs11580946)"
FT                   /evidence="ECO:0000269|PubMed:10634649,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|Ref.8"
FT                   /id="VAR_024022"
FT   VARIANT         231
FT                   /note="M -> L (in dbSNP:rs140449444)"
FT                   /evidence="ECO:0000269|PubMed:18987736"
FT                   /id="VAR_054157"
FT   MUTAGEN         5
FT                   /note="K->R: Reduced ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   MUTAGEN         40
FT                   /note="K->R: Reduced ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   MUTAGEN         127
FT                   /note="D->A: Abolishes formation of 28 and 17 kDa cleavage
FT                   products by CASP3. Abolishes cleavage by caspase-3; when
FT                   associated with A-157."
FT                   /evidence="ECO:0000269|PubMed:15122313"
FT   MUTAGEN         136
FT                   /note="K->R: Reduced ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   MUTAGEN         157
FT                   /note="D->A: Abolishes formation of 23 and 21 kDa cleavage
FT                   products by CASP3. Abolishes cleavage by caspase-3; when
FT                   associated with A-127."
FT                   /evidence="ECO:0000269|PubMed:15122313"
FT   MUTAGEN         159
FT                   /note="S->A: Loss of phosphorylation by GSK3 and loss of
FT                   ubiquitination increasing protein stability."
FT                   /evidence="ECO:0000269|PubMed:16543145"
FT   MUTAGEN         162
FT                   /note="S->A: Abolishes mitochondrial localization and
FT                   decreases stability."
FT                   /evidence="ECO:0000269|PubMed:15241487,
FT                   ECO:0000269|PubMed:23024798"
FT   MUTAGEN         162
FT                   /note="S->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:15241487,
FT                   ECO:0000269|PubMed:23024798"
FT   MUTAGEN         163
FT                   /note="T->A,E: No effect on mitochondrial localization."
FT                   /evidence="ECO:0000269|PubMed:15241487"
FT   MUTAGEN         163
FT                   /note="T->A: Abolishes phosphorylation by MAPK. No effect
FT                   on phosphorylation induced by okadaic acid or taxol."
FT                   /evidence="ECO:0000269|PubMed:15241487"
FT   MUTAGEN         194
FT                   /note="K->R: Reduced ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   MUTAGEN         197
FT                   /note="K->R: Reduced ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   MUTAGEN         208
FT                   /note="K->R: No effect on ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   MUTAGEN         234
FT                   /note="K->R: No effect on ubiquitination."
FT                   /evidence="ECO:0000269|PubMed:15989957"
FT   HELIX           173..191
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   STRAND          200..202
FT                   /evidence="ECO:0000244|PDB:6FS1"
FT   HELIX           203..223
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           225..235
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           240..244
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           246..253
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           254..256
FT                   /evidence="ECO:0000244|PDB:5C3F"
FT   HELIX           261..280
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           284..286
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           287..308
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           311..319
FT                   /evidence="ECO:0000244|PDB:6UDV"
FT   HELIX           323..325
FT                   /evidence="ECO:0000244|PDB:6OVC"
SQ   SEQUENCE   350 AA;  37337 MW;  D85821AC59275F1F CRC64;
     MFGLKRNAVI GLNLYCGGAG LGAGSGGATR PGGRLLATEK EASARREIGG GEAGAVIGGS
     AGASPPSTLT PDSRRVARPP PIGAEVPDVT ATPARLLFFA PTRRAAPLEE MEAPAADAIM
     SPEEELDGYE PEPLGKRPAV LPLLELVGES GNNTSTDGSL PSTPPPAEEE EDELYRQSLE
     IISRYLREQA TGAKDTKPMG RSGATSRKAL ETLRRVGDGV QRNHETAFQG MLRKLDIKNE
     DDVKSLSRVM IHVFSDGVTN WGRIVTLISF GAFVAKHLKT INQESCIEPL AESITDVLVR
     TKRDWLVKQR GWDGFVEFFH VEDLEGGIRN VLLAFAGVAG VGAGLAYLIR
//
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