UniProtKB/Swiss-Prot P00533: Variant p.Val674Ile

Epidermal growth factor receptor
Gene: EGFR
Chromosomal location: 7p12
Variant information

Variant position:  674
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Valine (V) to Isoleucine (I) at position 674 (V674I, p.Val674Ile).
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 hydrophobic.
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:  Slightly increased autophosphorylation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  674
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1210
The length of the canonical sequence.

Location on the sequence:   LLLLLVVALGIGLFMRRRHI  V RKRTLRRLLQERELVEPLTP
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                         LLLLLVVALGIGLFMRRRHIVRKRTLRRL---LQERELVEPLTP

Rhesus macaque                LLLLLVVALGIGLFMRRRHIVRKRTLRRL---LQERELVEP

Mouse                         LLFIVVVALGIGLFMRRRHIVRKRTLRRL---LQERELVEP

Drosophila                    VLVPTICILCVVTYICRQKQKAKKETVKMTMALSGCEDSEP

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 25 – 1210 Epidermal growth factor receptor
Topological domain 669 – 1210 Cytoplasmic
Modified residue 678 – 678 Phosphothreonine; by PKC and PKD/PRKD1
Modified residue 693 – 693 Phosphothreonine; by PKD/PRKD1
Alternative sequence 406 – 1210 Missing. In isoform 2.
Alternative sequence 628 – 705 CTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLR -> PGNESLKAMLFCLFKLSSCNQSNDGSVSHQSGSPAAQESCLGWIPSLLPSEFQLGWGGCSHLHAWPSASVIITASSCH. In isoform 3.
Alternative sequence 629 – 1210 Missing. In isoform 4.
Mutagenesis 688 – 688 L -> A. Strongly reduced phosphorylation.
Mutagenesis 689 – 689 V -> A. Reduced autophosphorylation.
Mutagenesis 689 – 689 V -> M. Constitutively activated kinase.
Mutagenesis 690 – 690 E -> A. Reduced phosphorylation.
Mutagenesis 692 – 692 L -> AP. Strongly reduced phosphorylation.
Mutagenesis 693 – 693 T -> A. Increased phosphorylation.
Mutagenesis 693 – 693 T -> D. Strongly reduced phosphorylation.
Mutagenesis 694 – 694 P -> A. Strongly reduced phosphorylation.


Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLN-98; ARG-266; LYS-521; ILE-674; GLY-962 AND PRO-988;

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.