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UniProtKB/Swiss-Prot Q14145: Variant p.Gly364Cys

Kelch-like ECH-associated protein 1
Gene: KEAP1
Variant information

Variant position:  364
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Glycine (G) to Cysteine (C) at position 364 (G364C, p.Gly364Cys).
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:  Change from glycine (G) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Variant description:  In a lung adenocarcinoma cell line; also in NSCLC cell lines; may be a polymorphism; strongly reduces interaction with NFE2L2/NRF2 and reduces repression of NFE2L2/NRF2-dependent gene expression.
Any additional useful information about the variant.

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



Sequence information

Variant position:  364
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  624
The length of the canonical sequence.

Location on the sequence:   AYNPSDGTWLRLADLQVPRS  G LAGCVVGGLLYAVGGRNNSP
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                         AYNPSDGTWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSP

Mouse                         AYNPSNGSWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSP

Rat                           AYNPSNGSWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSP

Pig                           AYNPSDGTWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSP

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.

TypePositionsDescription
Chain 1 – 624 Kelch-like ECH-associated protein 1
Repeat 327 – 372 Kelch 1
Mutagenesis 380 – 380 R -> A. Loss of interaction with NFE2L2/NRF2. Abolishes repression of NFE2L2/NRF2-dependent gene expression. Impaired interaction with SQSTM1/p62.
Mutagenesis 382 – 382 N -> A. Loss of interaction with NFE2L2/NRF2. Strongly reduces repression of NFE2L2/NRF2-dependent gene expression. Impaired interaction with SQSTM1/p62.
Beta strand 362 – 364


Literature citations

Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer.
Padmanabhan B.; Tong K.I.; Ohta T.; Nakamura Y.; Scharlock M.; Ohtsuji M.; Kang M.; Kobayashi A.; Yokoyama S.; Yamamoto M.;
Mol. Cell 21:689-700(2006)
Cited for: VARIANTS CYS-364 AND CYS-430; CHARACTERIZATION OF VARIANTS CYS-364 AND CYS-430;

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.