MCL1_HUMAN
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 03-AUG-2022, entry version 226.
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/";
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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; 6STJ; X-ray; 2.20 A; A/B/C/D=173-327.
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; 6UA3; X-ray; 1.55 A; A=172-325.
DR PDB; 6UAB; X-ray; 2.10 A; A=172-325.
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 PDB; 6VBX; X-ray; 1.95 A; A=172-323.
DR PDB; 6YBG; X-ray; 2.10 A; A/B=171-327.
DR PDB; 6YBJ; X-ray; 2.50 A; A=173-321.
DR PDB; 6YBK; X-ray; 2.00 A; A=173-321.
DR PDB; 6YBL; X-ray; 2.10 A; A=173-321.
DR PDB; 6ZIE; X-ray; 2.30 A; B=172-327.
DR PDB; 7NB4; X-ray; 1.90 A; A=171-327.
DR PDB; 7NB7; X-ray; 2.82 A; A/B/C/D=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; 6STJ; -.
DR PDBsum; 6U63; -.
DR PDBsum; 6U64; -.
DR PDBsum; 6U65; -.
DR PDBsum; 6U67; -.
DR PDBsum; 6U6F; -.
DR PDBsum; 6UA3; -.
DR PDBsum; 6UAB; -.
DR PDBsum; 6UD2; -.
DR PDBsum; 6UDI; -.
DR PDBsum; 6UDT; -.
DR PDBsum; 6UDU; -.
DR PDBsum; 6UDV; -.
DR PDBsum; 6UDX; -.
DR PDBsum; 6UDY; -.
DR PDBsum; 6VBX; -.
DR PDBsum; 6YBG; -.
DR PDBsum; 6YBJ; -.
DR PDBsum; 6YBK; -.
DR PDBsum; 6YBL; -.
DR PDBsum; 6ZIE; -.
DR PDBsum; 7NB4; -.
DR PDBsum; 7NB7; -.
DR AlphaFoldDB; Q07820; -.
DR SMR; Q07820; -.
DR BioGRID; 110338; 122.
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; 57.
DR MINT; Q07820; -.
DR STRING; 9606.ENSP00000358022; -.
DR BindingDB; Q07820; -.
DR ChEMBL; CHEMBL4361; -.
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; 1456 antibodies from 50 providers.
DR DNASU; 4170; -.
DR Ensembl; ENST00000307940.3; ENSP00000309973.3; ENSG00000143384.14. [Q07820-2]
DR Ensembl; ENST00000369026.3; ENSP00000358022.2; ENSG00000143384.14. [Q07820-1]
DR Ensembl; ENST00000678770.1; ENSP00000502859.1; ENSG00000143384.14. [Q07820-1]
DR GeneID; 4170; -.
DR KEGG; hsa:4170; -.
DR MANE-Select; ENST00000369026.3; ENSP00000358022.2; NM_021960.5; NP_068779.1.
DR UCSC; uc001euz.4; human. [Q07820-1]
DR CTD; 4170; -.
DR DisGeNET; 4170; -.
DR GeneCards; MCL1; -.
DR HGNC; HGNC:6943; MCL1.
DR HPA; ENSG00000143384; Tissue enhanced (bone).
DR MIM; 159552; gene.
DR neXtProt; NX_Q07820; -.
DR OpenTargets; ENSG00000143384; -.
DR PharmGKB; PA30688; -.
DR VEuPathDB; HostDB:ENSG00000143384; -.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244872; -.
DR HOGENOM; CLU_046711_0_0_1; -.
DR InParanoid; Q07820; -.
DR OMA; TKPMGGS; -.
DR OrthoDB; 1218929at2759; -.
DR PhylomeDB; Q07820; -.
DR TreeFam; TF315834; -.
DR PathwayCommons; Q07820; -.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR SignaLink; Q07820; -.
DR SIGNOR; Q07820; -.
DR BioGRID-ORCS; 4170; 295 hits in 1097 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 visceral pleura and 211 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: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: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:0043065; P:positive regulation of apoptotic process; IDA:ComplexPortal.
DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:ComplexPortal.
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 CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013281; Apop_reg_Mc1.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
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 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 SMART; SM00337; BCL; 1.
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 Reference proteome; Transmembrane; Transmembrane helix; 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 47..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..175
FT /note="PEST-like"
FT REGION 148..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 209..223
FT /note="BH3"
FT MOTIF 252..272
FT /note="BH1"
FT MOTIF 304..319
FT /note="BH2"
FT COMPBIAS 148..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0007829|PDB:6UDV"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:6FS1"
FT HELIX 203..223
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 225..235
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 240..244
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:5C3F"
FT HELIX 261..280
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 287..308
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 311..319
FT /evidence="ECO:0007829|PDB:6UDV"
FT HELIX 323..325
FT /evidence="ECO:0007829|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
