UniProtKB/SwissProt variant VAR

Variant information

Variant position:

47

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

Type of variant:

Disease [Disclaimer]

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 Proline (P) to Alanine (A) at position 47 (P47A, p.Pro47Ala).

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

Involvement in disease:

Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:14983014}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

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:

In BC; early onset; loss of ATPase and helicase activities.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28903098 [ dbSNP | Ensembl ]

Sequence information

Variant position:

47

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

Protein sequence length:

1249

The length of the canonical sequence.

Location on the sequence:

AMMNSILRGLNSKQHCLLES P TGSGKSLALLCSALAWQQSL

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                         AMMNSILRGLNSKQHCLLESPTGSGKSLALLCSALAWQQSL

Mouse                         AMMNSIVRGLNSSQHCLLESPTGSGKSLALLCSALAWQQSL

Chicken                       AMMNAIVKGLNNRQHCLLESPTGSGKSLALLCSALSWQQSL

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 – 1249	Fanconi anemia group J protein
Domain	11 – 442	Helicase ATP-binding
Mutagenesis	52 – 52	K -> R. Disrupts BRCA1-mediated double-strand break repair. Loss of ATPase and DNA helicase activities.

Literature citations

BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.
Cantor S.B.; Bell D.W.; Ganesan S.; Kass E.M.; Drapkin R.; Grossman S.; Wahrer D.C.R.; Sgroi D.C.; Lane W.S.; Haber D.A.; Livingston D.M.;
Cell 105:149-160(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); PROTEIN SEQUENCE OF 708-747; 765-790; 815-831; 1079-1085; 1169-1174 AND 1215-1225; FUNCTION; TISSUE SPECIFICITY; SUBCELLULAR LOCATION; INTERACTION WITH BRCA1; MUTAGENESIS OF LYS-52; VARIANTS BC ALA-47 AND ILE-299; VARIANTS ILE-193 AND PRO-919; IDENTIFICATION BY MASS SPECTROMETRY;

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations.
Cantor S.B.; Drapkin R.; Zhang F.; Lin Y.; Han J.; Pamidi S.; Livingston D.M.;
Proc. Natl. Acad. Sci. U.S.A. 101:2357-2362(2004)
Cited for: FUNCTION; MUTAGENESIS OF LYS-52; CHARACTERIZATION OF VARIANTS BC ALA-47 AND ILE-299;

UniProtKB/Swiss-Prot Q9BX63: Variant p.Pro47Ala