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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P38398: Variant p.Pro1749Arg

Breast cancer type 1 susceptibility protein
Gene: BRCA1
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Variant information Variant position: help 1749 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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: help From Proline (P) to Arginine (R) at position 1749 (P1749R, p.Pro1749Arg). 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: help Change from medium size and hydrophobic (P) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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: help In ovarian cancer; uncertain significance; abolishes ACACA binding and strongly reduces BRIP1 binding. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1749 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1863 The length of the canonical sequence.
Location on the sequence: help LNEHDFEVRGDVVNGRNHQG P KRARESQDRKIFRGLEICCY 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         LNEHDFEVR--GDVVNGR------NHQGPKRA-----RESQDRKIFRGLEICCY

Gorilla                       LNEHDFEVR--GDVVNGR------NHQGPKRA-----RESQ

                              LDEHDFEVR--GDVVNGR------NHQGPKRARESQDRESQ

Rhesus macaque                LNEHDFEVR--GDVVNGR------NHQGPKRA-----RESP

Chimpanzee                    LNEHDFEVR--GDVVNGR------NHQGPKRA-----RESQ

Mouse                         LNVHEFEVK--GDVVTGR------NHQGPRRS-----RESR

Rat                           LSVHEFEVK--GDVVTGS------NHQGPRRS-----RESQ

Bovine                        LDEHDFEVR--GDVVNGR------NHQGPKRA-----RESR

Caenorhabditis elegans        LSEADYTITSCSSTIPVKIPPSIGSEMGWLRS-----RNDE

Sequence annotation in neighborhood: help 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
Alternative sequence 64 – 1863 Missing. In isoform 2.
Mutagenesis 1738 – 1738 G -> E. Abolishes interaction with BRIP1.
Mutagenesis 1755 – 1755 S -> A. No effect on in vitro phosphorylation by ATR.
Helix 1748 – 1754



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: INTERACTION WITH BRIP1; CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749; CHARACTERIZATION OF VARIANT BC ARG-1775; 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; The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evidence for other ovarian cancer-susceptibility genes.
Gayther S.A.; Russell P.; Harrington P.; Antoniou A.C.; Easton D.F.; Ponder B.A.J.;
Am. J. Hum. Genet. 65:1021-1029(1999)
Cited for: VARIANT OVARIAN CANCER ARG-1749;
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.