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UniProtKB/Swiss-Prot Q07820: Variant p.Glu173Asp

Induced myeloid leukemia cell differentiation protein Mcl-1
Gene: MCL1
Variant information

Variant position:  173
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glutamate (E) to Aspartate (D) at position 173 (E173D, p.Glu173Asp).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Similar physico-chemical property. Both residues are medium size and acidic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  173
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  350
The length of the canonical sequence.

The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         NTSTDGSLPSTP------------------------------------PPAEE-----EEDELYRQSLEIISR-YLREQATGA


Mouse                         SSGADGSLPSTP-----------------------------

Rat                           SSGADGSLPSTP-----------------------------

Cat                           GPGTDGSLPSTP-----------------------------


Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

Chain 1 – 350 Induced myeloid leukemia cell differentiation protein Mcl-1
Region 104 – 175 PEST-like
Modified residue 159 – 159 Phosphoserine; by GSK3-alpha and GSK3-beta
Modified residue 162 – 162 Phosphoserine
Modified residue 163 – 163 Phosphothreonine; by MAPK
Mutagenesis 157 – 157 D -> A. Abolishes formation of 23 and 21 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-127.
Mutagenesis 159 – 159 S -> A. Loss of phosphorylation by GSK3 and loss of ubiquitination increasing protein stability.
Mutagenesis 162 – 162 S -> A. Abolishes mitochondrial localization and decreases stability.
Mutagenesis 162 – 162 S -> A. No effect.
Mutagenesis 163 – 163 T -> AE. No effect on mitochondrial localization.
Mutagenesis 163 – 163 T -> A. Abolishes phosphorylation by MAPK. No effect on phosphorylation induced by okadaic acid or taxol.
Helix 173 – 187

Literature citations

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)

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)

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.