UniProtKB/Swiss-Prot P04626: Variant p.Pro1170Ala

Receptor tyrosine-protein kinase erbB-2
Gene: ERBB2
Chromosomal location: 17q11.2-q12
Variant information

Variant position:  1170
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 Proline (P) to Alanine (A) at position 1170 (P1170A, p.Pro1170Ala).
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 (P) 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

Polymorphism:  There are four alleles due to the variations in positions 654 and 655. Allele B1 (Ile-654/Ile-655) has a frequency of 0.782; allele B2 (Ile-654/Val-655) has a frequency of 0.206; allele B3 (Val-654/Val-655) has a frequency of 0.012.
Additional information on the polymorphism described.

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



Sequence information

Variant position:  1170
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1255
The length of the canonical sequence.

Location on the sequence:   PSPREGPLPAARPAGATLER  P KTLSPGKNGVVKDVFAFGGA
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                         PSPREGPLPAARPAGATLERPKTLSP-----GKNGVVKDVFAFGGA

Mouse                         PLTPEGPPPPIRPAGATLERPKTLSP-----GKNGVVKDVF

Rat                           PLTPEGPLPPVRPAGATLERPKTLSP-----GKNGVVKDVF

Dog                           PLALEGPLPPSRPAGATLERPKTLSPKTLSPGKNGVVKDVF

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 23 – 1255 Receptor tyrosine-protein kinase erbB-2
Topological domain 676 – 1255 Cytoplasmic
Alternative sequence 884 – 1255 Missing. In isoform 6.


Literature citations

Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
Coussens L.; Yang-Feng T.L.; Liao Y.C.; Chen E.; Gray A.; McGrath J.; Seeburg P.H.; Libermann T.A.; Schlessinger J.; Francke U.; Levinson A.; Ullrich A.;
Science 230:1132-1139(1985)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); VARIANT ALA-1170;

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS CYS-452; VAL-655 AND ALA-1170;

Molecular cloning and sequencing of an intron of Her-2/neu (ERBB2) gene.
Sarkar F.H.; Ball D.E.; Li Y.W.; Crissman J.D.;
DNA Cell Biol. 12:611-615(1993)
Cited for: NUCLEOTIDE SEQUENCE OF 1081-1245; VARIANT ALA-1170;

Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-654; VAL-655; SER-768; SER-776; SER-857; ALA-1170 AND ASP-1216;

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.