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Q07820 (MCL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Induced myeloid leukemia cell differentiation protein Mcl-1
Alternative name(s):
Bcl-2-like protein 3
Short name=Bcl2-L-3
Bcl-2-related protein EAT/mcl1
mcl1/EAT
Gene names
Name:MCL1
Synonyms:BCL2L3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length350 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. Ref.4 Ref.20

Subunit structure

Interacts with BAD, BOK, BIK and BFM. Interacts with PMAIP1. Isoform 1 interacts with BAX, BAK1, TPT1 and BCL2L11. Heterodimer of isoform 1 and isoform 2. Homodimers of isoform 1 or isoform 2 are not detected. Isoform 2 does not interact with pro-apoptotic BCL2-related proteins. Interacts with BOP. Interacts with BCL2L11; may sequester BCL2L11 to prevent its pro-apoptotic activity. Ref.5 Ref.15 Ref.17 Ref.23

Subcellular location

Membrane; Single-pass membrane protein Potential. Cytoplasm. Mitochondrion. Nucleusnucleoplasm. Note: Cytoplasmic, associated with mitochondria. Ref.15 Ref.17 Ref.22

Induction

Expression increases early during phorbol ester-induced differentiation along the monocyte/macrophage pathway in myeloid leukemia cell line ML-1. Rapidly up-regulated by CSF2 in ML-1 cells. Up-regulated by heat shock-induced differentiation. Expression increases early during retinoic acid-induced differentiation. Ref.2 Ref.14

Post-translational modification

Cleaved by CASP3 during apoptosis. In intact cells cleavage occurs preferentially after Asp-127, yielding a pro-apoptotic 28 kDa C-terminal fragment.

Rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region.

Phosphorylated on Ser-159, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity. Treatment with taxol or okadaic acid induces phosphorylation on additional sites. Ref.16 Ref.18 Ref.20 Ref.22

Ubiquitinated. Ubiquitination is induced by phosphorylation at Ser-159. Ref.19 Ref.20

Sequence similarities

Belongs to the Bcl-2 family.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
   Cellular componentCytoplasm
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic mitochondrial changes

Inferred from electronic annotation. Source: Ensembl

cell fate determination

Non-traceable author statement Ref.5. Source: UniProtKB

cellular homeostasis

Non-traceable author statement Ref.5. Source: UniProtKB

execution phase of apoptosis

Inferred from direct assay Ref.5. Source: UniProtKB

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype Ref.20. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from Biological aspect of Ancestor. Source: RefGenome

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of anoikis

Inferred from mutant phenotype PubMed 22277751. Source: UniProtKB

negative regulation of execution phase of apoptosis

Traceable author statement Ref.5. Source: UniProtKB

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 20921992. Source: UniProtKB

negative regulation of intrinsic apoptotic signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein transmembrane transport

Traceable author statement Ref.5. Source: GOC

regulation of response to DNA damage stimulus

Inferred from mutant phenotype PubMed 20467439. Source: MGI

response to cytokine

Inferred from direct assay PubMed 9184696. Source: MGI

   Cellular_componentBcl-2 family protein complex

Inferred from direct assay PubMed 21199865. Source: UniProtKB

cytoplasm

Traceable author statement Ref.5. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial matrix

Inferred from electronic annotation. Source: Ensembl

mitochondrial outer membrane

Traceable author statement Ref.5. Source: UniProtKB

mitochondrion

Inferred from direct assay. Source: HPA

nucleoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 20467439. Source: MGI

   Molecular_functionBH3 domain binding

Inferred from physical interaction PubMed 21036904. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 15901672PubMed 16697956PubMed 17097560PubMed 17525735PubMed 19968986PubMed 20085765PubMed 21132008PubMed 21139567PubMed 21199865PubMed 21454712PubMed 21458670PubMed 21507240PubMed 22277751PubMed 22516262PubMed 23245996PubMed 23680104PubMed 19683529. Source: IntAct

protein channel activity

Traceable author statement Ref.5. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction Ref.5. Source: UniProtKB

protein homodimerization activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q07820-1)

Also known as: MCL1L; MCL-1L;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q07820-2)

Also known as: Delta S; MCL-1S; TM;

The sequence of this isoform differs from the canonical sequence as follows:
     231-271: MLRKLDIKNE...GRIVTLISFG → WVCGVLPCRG...FGISNKIALL
     272-350: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 350350Induced myeloid leukemia cell differentiation protein Mcl-1
PRO_0000143080

Regions

Transmembrane328 – 34821Helical; Potential
Region104 – 17572PEST-like
Motif209 – 22315BH3
Motif252 – 27221BH1
Motif304 – 31916BH2

Sites

Site127 – 1282Cleavage; by caspase-3
Site157 – 1582Cleavage; by caspase-3

Amino acid modifications

Modified residue1211Phosphoserine Ref.16
Modified residue1591Phosphoserine; by GSK3-alpha and GSK3-beta Ref.20
Modified residue1621Phosphoserine Ref.22
Modified residue1631Phosphothreonine; by MAPK Ref.16 Ref.18 Ref.22
Cross-link5Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link40Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link194Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link197Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Alternative sequence231 – 27141MLRKL…LISFG → WVCGVLPCRGPRRWHQECAA GFCRCCWSRSWFGISNKIAL L in isoform 2.
VSP_000532
Alternative sequence272 – 35079Missing in isoform 2.
VSP_000533
Natural variant1731E → D. Ref.1 Ref.4
Corresponds to variant rs2737820 [ dbSNP | Ensembl ].
VAR_024021
Natural variant2271A → V. Ref.7 Ref.8 Ref.12
Corresponds to variant rs11580946 [ dbSNP | Ensembl ].
VAR_024022
Natural variant2311M → L. Ref.26
VAR_054157

Experimental info

Mutagenesis51K → R: Reduced ubiquitination. Ref.19
Mutagenesis401K → R: Reduced ubiquitination. Ref.19
Mutagenesis1271D → A: Abolishes formation of 28 and 17 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-157. Ref.13
Mutagenesis1361K → R: Reduced ubiquitination. Ref.19
Mutagenesis1571D → A: Abolishes formation of 23 and 21 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-127. Ref.13
Mutagenesis1591S → A: Loss of phosphorylation by GSK3 and loss of ubiquitination increasing protein stability. Ref.20
Mutagenesis1621S → A: Abolishes mitochondrial localization and decreases stability. Ref.18 Ref.22
Mutagenesis1621S → A: No effect. Ref.18 Ref.22
Mutagenesis1631T → A or E: No effect on mitochondrial localization. Ref.18
Mutagenesis1631T → A: Abolishes phosphorylation by MAPK. No effect on phosphorylation induced by okadaic acid or taxol. Ref.18
Mutagenesis1941K → R: Reduced ubiquitination. Ref.19
Mutagenesis1971K → R: Reduced ubiquitination. Ref.19
Mutagenesis2081K → R: No effect on ubiquitination. Ref.19
Mutagenesis2341K → R: No effect on ubiquitination. Ref.19

Secondary structure

.................... 350
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MCL1L) (MCL-1L) [UniParc].

Last modified December 6, 2005. Version 3.
Checksum: D85821AC59275F1F

FASTA35037,337
        10         20         30         40         50         60 
MFGLKRNAVI GLNLYCGGAG LGAGSGGATR PGGRLLATEK EASARREIGG GEAGAVIGGS 

        70         80         90        100        110        120 
AGASPPSTLT PDSRRVARPP PIGAEVPDVT ATPARLLFFA PTRRAAPLEE MEAPAADAIM 

       130        140        150        160        170        180 
SPEEELDGYE PEPLGKRPAV LPLLELVGES GNNTSTDGSL PSTPPPAEEE EDELYRQSLE 

       190        200        210        220        230        240 
IISRYLREQA TGAKDTKPMG RSGATSRKAL ETLRRVGDGV QRNHETAFQG MLRKLDIKNE 

       250        260        270        280        290        300 
DDVKSLSRVM IHVFSDGVTN WGRIVTLISF GAFVAKHLKT INQESCIEPL AESITDVLVR 

       310        320        330        340        350 
TKRDWLVKQR GWDGFVEFFH VEDLEGGIRN VLLAFAGVAG VGAGLAYLIR 

« Hide

Isoform 2 (Delta S) (MCL-1S) (TM) [UniParc].

Checksum: FAE0BF9E126523EF
Show »

FASTA27128,662

References

« Hide 'large scale' references
[1]"MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2."
Kozopas K.M., Yang T., Buchan H.L., Zhou P., Craig R.W.
Proc. Natl. Acad. Sci. U.S.A. 90:3516-3520(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-173.
Tissue: Myeloid leukemia cell.
[2]"Induction of mcl1/EAT, Bcl-2 related gene, by retinoic acid or heat shock in the human embryonal carcinoma cells, NCR-G3."
Umezawa A., Maruyama T., Inazawa J., Imai S., Takano T., Hata J.
Cell Struct. Funct. 21:143-150(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION.
[3]"Functional analysis of the human MCL-1 gene."
Akgul C., Turner P.C., White M.R.H., Edwards S.W.
Cell. Mol. Life Sci. 57:684-691(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Exon skipping in Mcl-1 results in a Bcl-2 homology domain 3 only gene product that promotes cell death."
Bingle C.D., Craig R.W., Swales B.M., Singleton V., Zhou P., Whyte M.K.B.
J. Biol. Chem. 275:22136-22146(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT ASP-173, FUNCTION.
Tissue: Myeloid leukemia cell and Neuroblastoma.
[5]"MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain."
Bae J., Leo C.P., Hsu S.Y., Hsueh A.J.W.
J. Biol. Chem. 275:25255-25261(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH BAX; BAK1; BCL2L11 AND BETWEEN ISOFORMS 1 AND 2.
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-227.
Tissue: Thalamus.
[8]NIEHS SNPs program
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-227.
[9]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Mammary gland and Placenta.
[12]"Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions."
Okita H., Umezawa A., Fukuma M., Hata J.
Leuk. Res. 24:73-77(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 182-289 (ISOFORM 1), VARIANT VAL-227.
Tissue: Ewing sarcoma.
[13]"Mcl-1 is required for Akata6 B-lymphoma cell survival and is converted to a cell death molecule by efficient caspase-mediated cleavage."
Michels J., O'Neill J.W., Dallman C.L., Mouzakiti A., Habens F., Brimmell M., Zhang K.Y.J., Craig R.W., Marcusson E.G., Johnson P.W.M., Packham G.
Oncogene 23:4818-4827(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS OF FRAGMENTS OBTAINED BY CASPASE CLEAVAGE, MUTAGENESIS OF ASP-127 AND ASP-157.
[14]"Mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response."
Chao J.-R., Wang J.-M., Lee S.-F., Peng H.-W., Lin Y.-H., Chou C.-H., Li J.-C., Huang H.-M., Chou C.-K., Kuo M.-L., Yen J.J.-Y., Yang-Yen H.-F.
Mol. Cell. Biol. 18:4883-4898(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[15]"Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and fortilin. The potential role of MCL1 as a fortilin chaperone."
Zhang D., Li F., Weidner D., Mnjoyan Z.H., Fujise K.
J. Biol. Chem. 277:37430-37438(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TPT1, SUBCELLULAR LOCATION.
[16]"Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress."
Inoshita S., Takeda K., Hatai T., Terada Y., Sano M., Hata J., Umezawa A., Ichijo H.
J. Biol. Chem. 277:43730-43734(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-121 AND THR-163.
[17]"Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex."
Leu J.I.-J., Dumont P., Hafey M., Murphy M.E., George D.L.
Nat. Cell Biol. 6:443-450(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAK, SUBCELLULAR LOCATION.
[18]"MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol."
Domina A.M., Vrana J.A., Gregory M.A., Hann S.R., Craig R.W.
Oncogene 23:5301-5315(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-163, MUTAGENESIS OF SER-162 AND THR-163.
[19]"Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis."
Zhong Q., Gao W., Du F., Wang X.
Cell 121:1085-1095(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, MUTAGENESIS OF LYS-5; LYS-40; LYS-136; LYS-194; LYS-197; LYS-208 AND LYS-234.
[20]"Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1."
Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.
Mol. Cell 21:749-760(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS INHIBITOR OF APOPTOSIS, PHOSPHORYLATION AT SER-159 BY GSK3-ALPHA AND GSK3-BETA, UBIQUITINATION, MUTAGENESIS OF SER-159.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Serine 162, an essential residue for the mitochondrial localization, stability and anti-apoptotic function of Mcl-1."
Thomas L.W., Lam C., Clark R.E., White M.R., Spiller D.G., Moots R.J., Edwards S.W.
PLoS ONE 7:E45088-E45088(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-162 AND THR-163, MUTAGENESIS OF SER-162.
[23]"Human Bop is a novel BH3-only member of the Bcl-2 protein family."
Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L., Tang H.
Protein Cell 3:790-801(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BOP/C22ORF29.
[24]"Structural insights into the degradation of Mcl-1 induced by BH3 domains."
Czabotar P.E., Lee E.F., van Delft M.F., Day C.L., Smith B.J., Huang D.C.S., Fairlie W.D., Hinds M.G., Colman P.M.
Proc. Natl. Acad. Sci. U.S.A. 104:6217-6222(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 151-307 IN COMPLEXES WITH PMAIP1 AND BCL2L11.
[25]"The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer."
Stewart M.L., Fire E., Keating A.E., Walensky L.D.
Nat. Chem. Biol. 6:595-601(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 172-327 IN COMPLEX WITH BCL2L11.
[26]"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome."
Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. expand/collapse author list , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K.
Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-231.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L08246 mRNA. No translation available.
AF118124 mRNA. Translation: AAD13299.1.
AF147742 Genomic DNA. Translation: AAF74821.1.
AF198614 Genomic DNA. Translation: AAF64255.1.
AF198614 Genomic DNA. Translation: AAF64256.1.
AF162677, AF162676 Genomic DNA. Translation: AAG00896.1.
AF203373 mRNA. Translation: AAG00904.1.
BT006640 mRNA. Translation: AAP35286.1.
AK312508 mRNA. Translation: BAG35409.1.
DQ088966 Genomic DNA. Translation: AAY68220.1.
AL356356 Genomic DNA. Translation: CAI15503.1.
AL356356 Genomic DNA. Translation: CAI15504.1.
CH471121 Genomic DNA. Translation: EAW53538.1.
CH471121 Genomic DNA. Translation: EAW53539.1.
CH471121 Genomic DNA. Translation: EAW53540.1.
CH471121 Genomic DNA. Translation: EAW53541.1.
BC017197 mRNA. Translation: AAH17197.1.
BC071897 mRNA. Translation: AAH71897.1.
BC107735 mRNA. Translation: AAI07736.1.
AF118276 mRNA. Translation: AAF15309.1.
AF118277 mRNA. Translation: AAF15310.1.
AF118278 mRNA. Translation: AAF15311.1.
CCDSCCDS956.1. [Q07820-2]
CCDS957.1. [Q07820-1]
PIRA47476.
RefSeqNP_001184249.1. NM_001197320.1.
NP_068779.1. NM_021960.4. [Q07820-1]
NP_877495.1. NM_182763.2. [Q07820-2]
UniGeneHs.632486.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KBWNMR-A163-326[»]
2MHSNMR-A171-327[»]
2NL9X-ray1.55A209-327[»]
2NLAX-ray2.80A209-327[»]
2PQKX-ray2.00A172-327[»]
3D7VX-ray2.03A209-327[»]
3IO9X-ray2.40A209-327[»]
3KJ0X-ray1.70A172-327[»]
3KJ1X-ray1.94A172-327[»]
3KJ2X-ray2.35A172-327[»]
3KZ0X-ray2.35A/B172-327[»]
3MK8X-ray2.32A172-327[»]
B208-228[»]
3PK1X-ray2.49A/C174-326[»]
3TWUX-ray1.80B73-88[»]
3WIXX-ray1.90A/B/C/D172-327[»]
3WIYX-ray2.15A/B/C/D/E/F172-327[»]
4BPIX-ray1.98A209-327[»]
4BPJX-ray1.60A209-327[»]
4HW2X-ray2.80A/B/C/D/E/F172-323[»]
4HW3X-ray2.40A/B/C/D/E/F/G/H/I/J/K/L172-323[»]
4HW4X-ray1.53A/B172-327[»]
4OQ5X-ray2.86A/B/C/D/E/F174-326[»]
4OQ6X-ray1.81A/B174-326[»]
ProteinModelPortalQ07820.
SMRQ07820. Positions 133-324.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110338. 38 interactions.
DIPDIP-231N.
IntActQ07820. 25 interactions.
MINTMINT-89669.

Chemistry

BindingDBQ07820.
ChEMBLCHEMBL4361.

PTM databases

PhosphoSiteQ07820.

Polymorphism databases

DMDM83304396.

Proteomic databases

MaxQBQ07820.
PaxDbQ07820.
PRIDEQ07820.

Protocols and materials databases

DNASU4170.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307940; ENSP00000309973; ENSG00000143384. [Q07820-2]
ENST00000369026; ENSP00000358022; ENSG00000143384. [Q07820-1]
GeneID4170.
KEGGhsa:4170.
UCSCuc001euz.3. human. [Q07820-1]
uc001eva.3. human. [Q07820-2]

Organism-specific databases

CTD4170.
GeneCardsGC01M150547.
HGNCHGNC:6943. MCL1.
HPACAB002781.
HPA008455.
HPA031125.
MIM159552. gene.
neXtProtNX_Q07820.
PharmGKBPA30688.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282183.
HOVERGENHBG003527.
InParanoidQ07820.
KOK02539.
OMAKDTKPMG.
OrthoDBEOG7S2209.
PhylomeDBQ07820.
TreeFamTF315834.

Gene expression databases

ArrayExpressQ07820.
BgeeQ07820.
CleanExHS_MCL1.
GenevestigatorQ07820.

Family and domain databases

InterProIPR013281. Apop_reg_Mc1.
IPR002475. Bcl2-like.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR020728. Bcl2_BH3_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF6. PTHR11256:SF6. 1 hit.
PfamPF00452. Bcl-2. 1 hit.
[Graphical view]
PRINTSPR01866. APOPREGMCL1.
PR01862. BCL2FAMILY.
PROSITEPS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMCL1. human.
EvolutionaryTraceQ07820.
GeneWikiMCL1.
GenomeRNAi4170.
NextBio16422.
PMAP-CutDBQ07820.
PROQ07820.
SOURCESearch...

Entry information

Entry nameMCL1_HUMAN
AccessionPrimary (citable) accession number: Q07820
Secondary accession number(s): B2R6B2 expand/collapse secondary AC list , D3DV03, D3DV04, Q9HD91, Q9NRQ3, Q9NRQ4, Q9UHR7, Q9UHR8, Q9UHR9, Q9UNJ1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: December 6, 2005
Last modified: July 9, 2014
This is version 156 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM