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 28-JAN-2026, entry version 243. 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 DEUBIQUITINATION BY USP20. RX PubMed=35063767; DOI=10.1016/j.bbrc.2022.01.019; RA Feng J., Liu P., Li X., Zhang D., Lin H., Hou Z., Guo C., Niu Y., Dai B., RA Wang O., Qi M., Wang H., Zhou H.; RT "The deubiquitinating enzyme USP20 regulates the stability of the MCL1 RT protein."; RL Biochem. Biophys. Res. Commun. 593:122-128(2022). RN [26] 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 [27] 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 [28] 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:17389404, PubMed:20562877, PubMed:27013495). 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; P31749: AKT1; NbExp=3; IntAct=EBI-1003422, EBI-296087; CC Q07820; Q16611: BAK1; NbExp=20; IntAct=EBI-1003422, EBI-519866; CC Q07820; Q07812: BAX; NbExp=11; IntAct=EBI-1003422, EBI-516580; CC Q07820; Q9BXH1: BBC3; NbExp=6; IntAct=EBI-1003422, EBI-519884; CC Q07820; Q9BXH1-2: BBC3; NbExp=2; IntAct=EBI-1003422, EBI-519896; CC Q07820; O43521: BCL2L11; NbExp=20; IntAct=EBI-1003422, EBI-526406; CC Q07820; Q14457: BECN1; NbExp=2; IntAct=EBI-1003422, EBI-949378; CC Q07820; P55957: BID; NbExp=3; 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=12; IntAct=EBI-1003422, EBI-625934; CC Q07820; Q9H3M0: KCNF1; NbExp=3; IntAct=EBI-1003422, EBI-6918743; CC Q07820; Q13794: PMAIP1; NbExp=6; 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 (PubMed:16543145). Deubiquitinated by USP20; leading to CC increased stability (PubMed:35063767). {ECO:0000269|PubMed:16543145, CC ECO:0000269|PubMed:35063767}. CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_021960.5. [Q07820-1] DR RefSeq; NP_877495.1; NM_182763.3. [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 PDB; 7XGE; X-ray; 2.38 A; B/D/F/H=172-321. DR PDB; 8AV9; X-ray; 1.99 A; A=174-327. DR PDB; 8EKX; X-ray; 1.55 A; A=173-321. DR PDB; 8EL0; X-ray; 1.92 A; A=173-321. DR PDB; 8EL1; X-ray; 2.41 A; A/B/C/D=173-321. DR PDB; 8G3S; X-ray; 1.40 A; A=173-321. DR PDB; 8G3T; X-ray; 1.83 A; A=173-321. DR PDB; 8G3U; X-ray; 1.94 A; A=173-321. DR PDB; 8G3W; X-ray; 1.78 A; A=173-321. DR PDB; 8G3X; X-ray; 1.46 A; A=173-321. DR PDB; 8G3Y; X-ray; 1.70 A; A=173-321. DR PDB; 8H7B; X-ray; 1.46 A; A/B=172-322. DR PDB; 8IQM; X-ray; 1.97 A; A=171-327. DR PDB; 8QSO; X-ray; 2.11 A; A=173-321. DR PDB; 8SVY; X-ray; 1.47 A; A=173-321. DR PDB; 8T6F; X-ray; 1.56 A; A=174-321. DR PDB; 8VJP; X-ray; 1.13 A; A=172-323. DR PDB; 8X62; X-ray; 2.80 A; A/B=172-321. DR PDB; 8Y1Y; X-ray; 2.01 A; A=171-327. DR PDB; 8Y1Z; X-ray; 1.91 A; A=171-327. DR PDB; 8Y20; X-ray; 2.23 A; A=173-321. DR PDB; 8ZCS; X-ray; 2.79 A; A/B=173-321. DR PDB; 9BCG; X-ray; 1.90 A; A=173-320. DR PDB; 9CKN; X-ray; 1.50 A; A/B=172-323. DR PDB; 9UGP; X-ray; 1.39 A; A=171-322. 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 PDBsum; 7XGE; -. DR PDBsum; 8AV9; -. DR PDBsum; 8EKX; -. DR PDBsum; 8EL0; -. DR PDBsum; 8EL1; -. DR PDBsum; 8G3S; -. DR PDBsum; 8G3T; -. DR PDBsum; 8G3U; -. DR PDBsum; 8G3W; -. DR PDBsum; 8G3X; -. DR PDBsum; 8G3Y; -. DR PDBsum; 8H7B; -. DR PDBsum; 8IQM; -. DR PDBsum; 8QSO; -. DR PDBsum; 8SVY; -. DR PDBsum; 8T6F; -. DR PDBsum; 8VJP; -. DR PDBsum; 8X62; -. DR PDBsum; 8Y1Y; -. DR PDBsum; 8Y1Z; -. DR PDBsum; 8Y20; -. DR PDBsum; 8ZCS; -. DR PDBsum; 9BCG; -. DR PDBsum; 9CKN; -. DR PDBsum; 9UGP; -. DR AlphaFoldDB; Q07820; -. DR SMR; Q07820; -. DR BioGRID; 110338; 147. 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 FunCoup; Q07820; 1501. DR IntAct; Q07820; 90. DR MINT; Q07820; -. DR STRING; 9606.ENSP00000358022; -. DR BindingDB; Q07820; -. DR ChEMBL; CHEMBL4361; -. DR DrugBank; DB04813; Bithionol. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB16770; Morin. DR DrugBank; DB17977; Murizatoclax. DR DrugBank; DB12191; Obatoclax. DR DrugBank; DB16865; Rosmarinic acid. DR DrugBank; DB17166; Tapotoclax. DR DrugBank; DB17059; TW-37. DR DrugCentral; Q07820; -. DR GuidetoPHARMACOLOGY; 2847; -. DR iPTMnet; Q07820; -. DR PhosphoSitePlus; Q07820; -. DR BioMuta; MCL1; -. DR DMDM; 83304396; -. DR jPOST; Q07820; -. DR MassIVE; Q07820; -. DR PaxDb; 9606-ENSP00000358022; -. DR PeptideAtlas; Q07820; -. DR ProteomicsDB; 58540; -. [Q07820-1] DR ProteomicsDB; 58541; -. [Q07820-2] DR Pumba; Q07820; -. DR ABCD; Q07820; 1 sequenced antibody. DR Antibodypedia; 1508; 1455 antibodies from 49 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 AGR; HGNC:6943; -. DR CIViC; 4170; 1 evidence item across 1 molecular profile. DR ClinPGx; PA30688; -. DR CTD; 4170; -. DR DisGeNET; 4170; -. DR GeneCards; MCL1; -. DR HGNC; HGNC:6943; MCL1. DR HPA; ENSG00000143384; Tissue enhanced (bone). DR MalaCards; MCL1; -. DR MIM; 159552; gene. DR OpenTargets; ENSG00000143384; -. DR VEuPathDB; HostDB:ENSG00000143384; -. DR eggNOG; KOG4728; Eukaryota. DR GeneTree; ENSGT01130000278292; -. DR HOGENOM; CLU_046711_0_0_1; -. DR InParanoid; Q07820; -. DR OMA; FFAPTRC; -. DR OrthoDB; 8932147at2759; -. DR PAN-GO; Q07820; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q07820; -. DR PathwayCommons; Q07820; -. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; Q07820; -. DR SIGNOR; Q07820; -. DR Agora; ENSG00000143384; -. DR BioGRID-ORCS; 4170; 304 hits in 1183 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 213 other cell types or tissues. DR ExpressionAtlas; Q07820; baseline and differential. 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: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:0015267; F:channel activity; IBA:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. 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:0006974; P:DNA damage response; IMP:MGI. 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:0008053; P:mitochondrial fusion; 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:0043065; P:positive regulation of apoptotic process; IDA:ComplexPortal. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; 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:0042981; P:regulation of apoptotic process; IDA:ComplexPortal. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IBA:GO_Central. DR GO; GO:0034097; P:response to cytokine; IDA:MGI. DR CDD; cd06845; Bcl-2_like; 1. DR DisProt; DP03697; -. DR FunFam; 1.10.437.10:FF:000002; Induced myeloid leukemia cell differentiation protein Mcl-1; 1. DR Gene3D; 1.10.437.10; Blc2-like; 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; BCL-2 RELATED; 1. DR PANTHER; PTHR11256:SF46; INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN MCL-1; 1. DR Pfam; PF00452; Bcl-2; 1. DR PRINTS; PR01866; APOPREGMCL1. DR PRINTS; PR01862; BCL2FAMILY. DR SMART; SM00337; BCL; 1. DR SUPFAM; SSF56854; Bcl-2 inhibitors of programmed cell death; 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 Proteomics identification; Reference proteome; Transmembrane; KW 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 50..61 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 150..161 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 //