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UniProtKB/Swiss-Prot P38398: Variant p.Met1775Arg

Breast cancer type 1 susceptibility protein
Gene: BRCA1
Variant information

Variant position:  1775
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Methionine (M) to Arginine (R) at position 1775 (M1775R, p.Met1775Arg).
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 (M) to large size and basic (R)
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 BC; alters protein stability and abolishes ACACA and BRIP1 binding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1775
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1863
The length of the canonical sequence.

Location on the sequence:   SQDRKIFRGLEICCYGPFTN  M PTDQLEWMVQLCGASVVKEL
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                         SQDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKEL

Gorilla                       SQDRKIFRGLDICCYGPFTNMPTDQLEWMVQL---CGASVV

                              SQDRKIFRGLEICCYGPFTNMPTDQLEWMVHL---CGASVV

Rhesus macaque                SPDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Chimpanzee                    SQDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Mouse                         SRE-KLFKGLQVYCCEPFTNMPKDELERMLQL---CGASVV

Rat                           SQE-KLFEGLQIYCCEPFTNMPKDELERMLQL---CGASVV

Bovine                        SRDKKIFKGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Caenorhabditis elegans        DEHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEIL

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 1 – 1863 Breast cancer type 1 susceptibility protein
Domain 1756 – 1855 BRCT 2
Alternative sequence 64 – 1863 Missing. In isoform 2.
Mutagenesis 1755 – 1755 S -> A. No effect on in vitro phosphorylation by ATR.
Beta strand 1773 – 1775


Literature citations

A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
Miki Y.; Swensen J.; Shattuck-Eidens D.; Futreal P.A.; Harshman K.; Tavtigian S.; Liu Q.; Cochran C.; Bennett L.M.; Ding W.; Bell R.; Rosenthal J.; Hussey C.; Tran T.; McClure M.; Frye C.; Hattier T.; Phelps R.; Haugen-Strano A.; Katcher H.; Yakumo K.; Gholami Z.; Shaffer D.; Stone S.; Bayer S.; Wray C.; Bogden R.; Dayananth P.; Ward J.; Tonin P.; Narod S.; Bristow P.K.; Norris F.H.; Helvering L.; Morrison P.; Rosteck P.; Lai M.; Barrett J.C.; Lewis C.; Neuhausen S.; Cannon-Albright L.; Godlgar D.; Wiseman R.; Kamb A.; Skolnick M.H.;
Science 266:66-71(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT BC ARG-1775;

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: INTERACTION WITH BRIP1; CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749; CHARACTERIZATION OF VARIANT BC ARG-1775;

Structural consequences of a cancer-causing BRCA1-BRCT missense mutation.
Williams R.S.; Glover J.N.;
J. Biol. Chem. 278:2630-2635(2003)
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1646-1859 OF VARIANT BC ARG-1775; CHARACTERIZATION OF VARIANT BC ARG-1775; CIRCULAR DICHROISM;

Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.
Clapperton J.A.; Manke I.A.; Lowery D.M.; Ho T.; Haire L.F.; Yaffe M.B.; Smerdon S.J.;
Nat. Struct. Mol. Biol. 11:512-518(2004)
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1649-1859 IN COMPLEX WITH PHOSPHORYLATED BRIP1 PEPTIDE; MUTAGENESIS OF SER-1655; LYS-1702 AND GLY-1738; CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749; CHARACTERIZATION OF VARIANT BC ARG-1775; SUBCELLULAR LOCATION; INTERACTION WITH PHOSPHORYLATED BRIP1;

BRCA1 mutations in primary breast and ovarian carcinomas.
Futreal P.A.; Liu Q.; Shattuck-Eidens D.; Cochran C.; Harshman K.; Tavtigian S.; Bennett L.M.; Haugen-Strano A.; Swensen J.; Miki Y.; Eddington K.; McClure M.; Frye C.; Weaver-Felhaus J.; Ding W.; Gholami Z.; Soederkvist P.; Terry L.; Jhanwar S.; Berchuk A.; Iglehart J.D.; Marks J.; Ballinger D.G.; Barrett J.C.; Skolnick M.H.; Kamb A.; Wiseman R.;
Science 266:120-122(1994)
Cited for: VARIANT BC ARG-1775; VARIANTS LEU-1637 AND GLU-1708;

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.