UniProtKB/Swiss-Prot P00533: Variant p.Glu709Ala

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

Variant position:  709
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 Alanine (A) at position 709 (E709A, p.Glu709Ala).
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 acidic (E) to small size and hydrophobic (A)
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

Involvement in disease:  Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. {ECO:0000269|PubMed:15118125, ECO:0000269|PubMed:16533793, ECO:0000269|PubMed:16672372}. Note=The gene represented in this entry is involved in disease pathogenesis.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  Found in a lung cancer sample; more sensitive to gefitinib than wild-type.
Any additional useful information about the variant.

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

Sequence information

Variant position:  709
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1210
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.





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 25 – 1210 Epidermal growth factor receptor
Topological domain 669 – 1210 Cytoplasmic
Modified residue 693 – 693 Phosphothreonine; by PKD/PRKD1
Modified residue 695 – 695 Phosphoserine
Cross 716 – 716 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence 406 – 1210 Missing. In isoform 2.
Alternative sequence 629 – 1210 Missing. In isoform 4.
Alternative sequence 706 – 1210 Missing. In isoform 3.
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.
Mutagenesis 699 – 699 P -> A. Reduced phosphorylation.
Mutagenesis 700 – 700 N -> A. Abolishes phosphorylation.
Mutagenesis 704 – 704 L -> A. Abolishes phosphorylation.
Mutagenesis 705 – 705 R -> A. Abolishes phosphorylation.
Mutagenesis 706 – 706 I -> A. Abolishes phosphorylation.
Helix 709 – 711

Literature citations

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.
Huang S.F.; Liu H.P.; Li L.H.; Ku Y.C.; Fu Y.N.; Tsai H.Y.; Chen Y.T.; Lin Y.F.; Chang W.C.; Kuo H.P.; Wu Y.C.; Chen Y.R.; Tsai S.F.;
Clin. Cancer Res. 10:8195-8203(2004)
Cited for: VARIANTS ALA-709; GLY-709; CYS-719; SER-719; 746-GLU--ALA-750 DEL; 746-GLU--THR-751 DELINS ALA; 746-GLU--SER-752 DELINS ASP; 747-LEU--THR-751 DEL; ILE-768; MET-769; VAL-833; LEU-835; VAL-838; ARG-858 AND GLN-861;

Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features.
Tam I.Y.S.; Chung L.P.; Suen W.S.; Wang E.; Wong M.C.M.; Ho K.K.; Lam W.K.; Chiu S.W.; Girard L.; Minna J.D.; Gazdar A.F.; Wong M.P.;
Clin. Cancer Res. 12:1647-1653(2006)
Cited for: VARIANTS ALA-709; LYS-709; ALA-719; ASP-719; CYS-719; SER-719; SER-724; LYS-734; GLU-746 DEL; PHE-747; 747-LEU--GLU-749 DEL; PRO-748; 752-SER--ILE-759 DEL; ARG-787; MET-790; VAL-833; LEU-834; MET-858; ARG-858; GLN-861 AND GLU-873; POSSIBLE INVOLVEMENT IN LUNG CANCER;

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants.
Chen Y.R.; Fu Y.N.; Lin C.H.; Yang S.T.; Hu S.F.; Chen Y.T.; Tsai S.F.; Huang S.F.;
Oncogene 25:1205-1215(2006)
Cited for: CHARACTERIZATION OF VARIANTS ALA-709; GLY-709; SER-719; ILE-768; VAL-833; LEU-835; VAL-838; ARG-858 AND GLN-861;

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.