UniProtKB/Swiss-Prot Q14145: Variant p.Val167Phe

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

167 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Valine (V) to Phenylalanine (F) at position 167 (V167F, p.Val167Phe). 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 medium size and hydrophobic (V) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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 patient. Any additional useful information about the variant.

Sequence information Variant position:

167 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:

MGEKCVLHVMNGAVMYQIDS V VRACSDFLVQQLDPSNAIGI 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                         MGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGI

Mouse                         VGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGI

Rat                           VGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGI

Pig                           MGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGI

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.

Type	Positions	Description
Chain	1 – 624	Kelch-like ECH-associated protein 1
Site	151 – 151	Sensor for electrophilic agents
Modified residue	151 – 151	S-(2,3-dicarboxypropyl)cysteine; alternate
Modified residue	151 – 151	S-(2-succinyl)cysteine; alternate
Modified residue	151 – 151	S-nitrosocysteine; alternate
Cross	151 – 151	N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Cys-Arg) (interchain with R-135 in KEAP1)
Mutagenesis	151 – 151	C -> SNDL. Substitution with a small side chain that prevents covalent modification by an electrophile; promotes constitutive ubiquitination of NFE2L2/NRF2 and subsequent repression of phase 2 detoxifying enzymes. Resistance of ubiquitination of PGAM5 to inhibition by oxidative stress and sulforaphane. Impaired interaction with CUL3. Reduced formation of a high-molecular mass KEAP1 molecule when methylglyoxal accumulates.
Mutagenesis	151 – 151	C -> WY. Substitution with a bulky side chain that mimicks covalent modification by an electrophile; prevents ubiquitination and degradation of NFE2L2/NRF2, leading to constitutive activation of NFE2L2/NRF2 and subsequent expression of phase 2 detoxifying enzymes.
Helix	165 – 177

Literature citations
Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer.
Singh A.; Misra V.; Thimmulappa R.K.; Lee H.; Ames S.; Hoque M.O.; Herman J.G.; Baylin S.B.; Sidransky D.; Gabrielson E.; Brock M.V.; Biswal S.;
PLoS Med. 3:1865-1876(2006)
Cited for: VARIANTS PHE-167; HIS-236; LEU-284; CYS-333 AND SER-350; CHARACTERIZATION OF VARIANTS HIS-236 AND CYS-333;

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.