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P97287 (MCL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Induced myeloid leukemia cell differentiation protein Mcl-1 homolog
Alternative name(s):
Bcl-2-related protein EAT/mcl1
Gene names
Name:Mcl1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length331 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 2 has antiapoptotic activity. Ref.2 Ref.7

Subunit structure

Interacts with BAD, BOK, BIK, BAX, BAK1, and TPT1. Interacts with BBC3, BFM and PMAIP1. Interacts with BOP. Interacts with BCL2L11; may sequester BCL2L11 to prevent its pro-apoptotic activity. Ref.7 Ref.8

Subcellular location

Membrane; Single-pass membrane protein By similarity. Cytoplasm By similarity. Mitochondrion. Nucleusnucleoplasm By similarity. Note: Cytoplasmic, associated with mitochondria.

Induction

Up-regulated by IL3 and CSF2. Up-regulated in murine embryonal carcinoma cells in response to retinoic acid treatment. Levels reach a maximum after 4 hours, are decreased after 8 hours and are back to maximum after 12 hours. Levels are decreased after 24 hours and back to basal levels after 48 hours. Expression remains constant in retinoic acid-treated embryonic stem cells. Ref.1 Ref.6

Post-translational modification

Cleaved by CASP3 during apoptosis, yielding a pro-apoptotic C-terminal fragment By similarity.

Rapidly degraded in the absence of phosphorylation in the PEST region By similarity.

Phosphorylated on Ser-140, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-140 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity. Treatment with taxol or okadaic acid induces phosphorylation on additional sites. Ref.7

Ubiquitinated. Ubiquitination is induced by phosphorylation at Ser-140 By similarity.

Sequence similarities

Belongs to the Bcl-2 family.

Ontologies

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

Inferred from direct assay Ref.2. Source: MGI

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

execution phase of apoptosis

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype Ref.7. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from direct assay PubMed 15901672. Source: MGI

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of anoikis

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 17289999. Source: UniProtKB

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

negative regulation of intrinsic apoptotic signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentBcl-2 family protein complex

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 20467439. Source: MGI

cytosol

Inferred from direct assay Ref.7. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay Ref.7. Source: UniProtKB

mitochondrial matrix

Inferred from direct assay PubMed 20627101. Source: MGI

mitochondrial outer membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitochondrion

Inferred from direct assay Ref.2PubMed 23926254. Source: MGI

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 15901672. Source: UniProtKB

protein heterodimerization activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein homodimerization activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BAK1Q166113EBI-707292,EBI-519866From a different organism.
BAXQ078122EBI-707292,EBI-516580From a different organism.
BBC3Q9BXH15EBI-707292,EBI-519884From a different organism.
BCL2L11O435217EBI-707292,EBI-526406From a different organism.
Bcl2l11O549184EBI-707292,EBI-526067
Pmaip1Q9JM544EBI-707292,EBI-709183

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P97287-1)

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: P97287-2)

Also known as: Mck-1V;

The sequence of this isoform differs from the canonical sequence as follows:
     18-63: Missing.
Note: This isoform is more stable than isoform 1 in cells undergoing apoptosis.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 331331Induced myeloid leukemia cell differentiation protein Mcl-1 homolog
PRO_0000143081

Regions

Transmembrane308 – 33023Helical; Potential
Region85 – 15672PEST-like By similarity
Motif190 – 20415BH3
Motif234 – 25320BH1
Motif285 – 30016BH2
Compositional bias149 – 1524Poly-Glu

Sites

Site108 – 1092Cleavage; by caspase-3 By similarity
Site138 – 1392Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue1021Phosphoserine By similarity
Modified residue1401Phosphoserine; by GSK3-alpha and GSK3-beta Ref.7
Modified residue1431Phosphoserine By similarity
Modified residue1441Phosphothreonine; by MAPK By similarity
Cross-link117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link178Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence18 – 6346Missing in isoform 2.
VSP_046443

Secondary structure

...................... 331
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 3.
Checksum: E4FD369DB0EC6723

FASTA33135,217
        10         20         30         40         50         60 
MFGLRRNAVI GLNLYCGGAS LGAGGGSPAG ARLVAEEAKA RREGGGEAAL LPGARVVARP 

        70         80         90        100        110        120 
PPVGAEDPDV TASAERRLHK SPGLLAVPPE EMAASAAAAI VSPEEELDGC EPEAIGKRPA 

       130        140        150        160        170        180 
VLPLLERVSE AAKSSGADGS LPSTPPPPEE EEDDLYRQSL EIISRYLREQ ATGSKDSKPL 

       190        200        210        220        230        240 
GEAGAAGRRA LETLRRVGDG VQRNHETAFQ GMLRKLDIKN EGDVKSFSRV MVHVFKDGVT 

       250        260        270        280        290        300 
NWGRIVTLIS FGAFVAKHLK SVNQESFIEP LAETITDVLV RTKRDWLVKQ RGWDGFVEFF 

       310        320        330 
HVQDLEGGIR NVLLAFAGVA GVGAGLAYLI R 

« Hide

Isoform 2 (Mck-1V) [UniParc].

Checksum: 73643EE7EE849B27
Show »

FASTA28530,930

References

« Hide 'large scale' references
[1]"Up-regulated expression of murine Mcl1/EAT, a bcl-2 related gene, in the early stage of differentiation of murine embryonal carcinoma cells and embryonic stem cells."
Okita H., Umezawa A., Suzuki A., Hata J.
Biochim. Biophys. Acta 1398:335-341(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION.
Tissue: Fetus.
[2]"MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair."
Kojima S., Hyakutake A., Koshikawa N., Nakagawara A., Takenaga K.
Biochem. Biophys. Res. Commun. 391:492-497(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCALIZATION.
Strain: C57BL/6.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Embryo and Embryonic stem cell.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"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).
Strain: Czech II and FVB/N.
Tissue: Mammary tumor and Salivary gland.
[6]"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: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65, INDUCTION.
Strain: 129/SvJ.
[7]"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-140 BY GSK3-ALPHA AND GSK3-BETA, INTERACTION WITH BCL2L11.
[8]"Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands."
Day C.L., Chen L., Richardson S.J., Harrison P.J., Huang D.C.S., Hinds M.G.
J. Biol. Chem. 280:4738-4744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 152-308, INTERACTION WITH BCL2L11; BMF AND PMAIP.
[9]"Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1."
Day C.L., Smits C., Fan F.C., Lee E.F., Fairlie W.D., Hinds M.G.
J. Mol. Biol. 380:958-971(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 148-308 IN COMPLEXES WITH WITH BBC3 AND PMAIP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U35623 mRNA. Translation: AAC31790.1.
GU182318 mRNA. Translation: ACZ54910.1.
AK010424 mRNA. Translation: BAB26927.1.
AK159504 mRNA. Translation: BAE35137.1.
AK160594 mRNA. Translation: BAE35901.1.
AC092479 Genomic DNA. No translation available.
FO082281 Genomic DNA. No translation available.
BC003839 mRNA. Translation: AAH03839.1.
BC005427 mRNA. Translation: AAH05427.1.
BC021638 mRNA. Translation: AAH21638.1.
AF063886 Genomic DNA. Translation: AAC27929.1.
RefSeqNP_032588.1. NM_008562.3.
UniGeneMm.1639.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WSXNMR-A152-308[»]
2JM6NMR-B152-308[»]
2NL9X-ray1.55A152-189[»]
2NLAX-ray2.80A152-189[»]
2ROCNMR-A152-308[»]
2RODNMR-A152-308[»]
3D7VX-ray2.03A152-247[»]
3IO9X-ray2.40A152-189[»]
4G35X-ray2.00A152-308[»]
ProteinModelPortalP97287.
SMRP97287. Positions 137-331.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201344. 10 interactions.
IntActP97287. 14 interactions.
MINTMINT-209660.

Chemistry

BindingDBP97287.
ChEMBLCHEMBL5768.

PTM databases

PhosphoSiteP97287.

Proteomic databases

PaxDbP97287.
PRIDEP97287.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000037947; ENSMUSP00000044048; ENSMUSG00000038612. [P97287-1]
ENSMUST00000178686; ENSMUSP00000135915; ENSMUSG00000038612. [P97287-2]
GeneID17210.
KEGGmmu:17210.
UCSCuc029unp.1. mouse. [P97287-1]

Organism-specific databases

CTD4170.
MGIMGI:101769. Mcl1.

Phylogenomic databases

eggNOGNOG282183.
GeneTreeENSGT00510000048923.
HOGENOMHOG000232116.
HOVERGENHBG003527.
InParanoidP97287.
KOK02539.
OMAKDTKPMG.
OrthoDBEOG7S2209.
PhylomeDBP97287.
TreeFamTF315834.

Gene expression databases

ArrayExpressP97287.
BgeeP97287.
CleanExMM_MCL1.
GenevestigatorP97287.

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. mouse.
EvolutionaryTraceP97287.
NextBio291598.
PROP97287.
SOURCESearch...

Entry information

Entry nameMCL1_MOUSE
AccessionPrimary (citable) accession number: P97287
Secondary accession number(s): D2K6L9 expand/collapse secondary AC list , Q3TUS0, Q792P0, Q9CRI4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot