Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Mcl1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Mcl1
  • participates in the following biological processes:
    • negative regulation of apoptotic process ^[5]
  • is located in the following cellular components:
    • cytoplasm ^[6]
    • mitochondrial matrix ^[3]
    • mitochondrion ^[5]
    • nucleus ^[6]
• The gene product of Mcl1 has been shown to bind to the gene products of Bak1, Bcl2l11, Pmaip1. ^{[1, 2, 4, 7, 8]} Researchers have inferred, based on physical interactions, that the gene product of Mcl1
  • performs the following molecular functions:
    • BH3 domain binding ^[8]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Mcl1
  • participates in the following biological processes:
    • negative regulation of apoptotic process ^{[7, 8]}

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Mcl1:
  • participates in the following biological processes:
    • apoptotic process
    • negative regulation of anoikis
    • negative regulation of apoptotic process
    • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
    • regulation of response to DNA damage stimulus
    • response to cytokine stimulus
  • performs the following molecular functions:
    • BH domain binding
    • BH3 domain binding
    • protein dimerization activity
    • protein heterodimerization activity
  • is located in the following cellular components:
    • Bcl-2 family protein complex
    • membrane
    • mitochondrion
    • nucleus

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Summary text based on GO annotations supported by structural data

• Mcl1 encodes a protein or proteins that contain the following InterPro domains: Apoptosis regulator, Bcl-2, BH1 motif, conserved site, Apoptosis regulator, Bcl-2, BH2 motif, conserved site, Apoptosis regulator, Bcl-2, BH3 motif, conserved site, Apoptosis regulator, Mcl-1, Bcl2-like, Blc2 family, indicating that the gene product:
  • participates in the following biological processes:
    • regulation of apoptotic process

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Mcl1 indicates that it:
  • participates in the following biological processes:
    • cell differentiation
    • multicellular organismal development
  • is located in the following cellular components:
    • integral to membrane

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References

1. Chen L et al. (2005) Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell, 17:393-403. (PubMed:15694340)
2. Du H et al. (2011) BH3 domains other than Bim and Bid can directly activate Bax/Bak. J Biol Chem, 286:491-501. (PubMed:21041309)
3. Huang CR et al. (2010) The fast-mobility isoform of mouse Mcl-1 is a mitochondrial matrix-localized protein with attenuated anti-apoptotic activity. FEBS Lett, 584:3323-30. (PubMed:20627101)
4. Jamil S et al. (2010) Prevention of cytokine withdrawal-induced apoptosis by Mcl-1 requires interaction between Mcl-1 and Bim. Biochem Cell Biol, 88:809-18. (PubMed:20921992)
5. Kojima S et al. (2010) MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair. Biochem Biophys Res Commun, 391:492-7. (PubMed:19919825)
6. Pawlikowska P et al. (2010) ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response. Cell Death Differ, 17:1739-50. (PubMed:20467439)
7. Willis SN et al. (2007) Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science, 315:856-9. (PubMed:17289999)
8. Willis SN et al. (2005) Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev, 19:1294-305. (PubMed:15901672)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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