UniProtKB/Swiss-Prot P27694: Variant p.Val227Ala

Replication protein A 70 kDa DNA-binding subunit
Gene: RPA1
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Variant information Variant position:

227 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Valine (V) to Alanine (A) at position 227 (V227A, p.Val227Ala). 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 (V) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 PFBMFT6; uncertain significance; increased single-stranded DNA binding; increased telomeric DNA binding; has no effect on the formation of canonical replication protein A complex. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs570041689 [ dbSNP | Ensembl ]

Sequence information Variant position:

227 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

616 The length of the canonical sequence.
Location on the sequence:

SQIRTWSNSRGEGKLFSLEL V DESGEIRATAFNEQVDKFFP 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                         SQIRTWSNSRGEGKLFSLELVDESGE-IRATAFNEQVDKFFP

Mouse                         SQIRTWSNSRGEGKLFSLELVDESGE-IRATAFNEQVDKFF

Chicken                       GQIRTWSNSRGEGKLFSIELVDESGE-IRATAFNDQADKFF

Xenopus laevis                GQIRTWSNSRGEGKLFSIEMVDESGE-IRATAFNEQADKFF

Xenopus tropicalis            GQIRTWSNSRGEGKLFSIEMVDESGE-IRATAFNEQADKFF

Zebrafish                     SAIRTWSNSRGDGKLFSMELVDESGE-IRATGFNNEVDKFF

Caenorhabditis elegans        EEIRTFPAK--NTKVFNFEITDSNGDTIRCTAFNEVAESLY

Drosophila                    SGIRTWSNARGEGKLFSMDLMDESGE-IRATAFKEQCDKFY

Baker's yeast                 GEIKTWHNQRGDGKLFNVNFLDTSGE-IRATAFNDFATKFN

Fission yeast                 SEVKHWHNQRGEGKLFSVNLLDESGE-IRATGFNDQVDAFY

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 – 616	Replication protein A 70 kDa DNA-binding subunit
Chain	2 – 616	Replication protein A 70 kDa DNA-binding subunit, N-terminally processed
DNA binding	197 – 281	OB
Cross	220 – 220	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	244 – 244	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Beta strand	218 – 227

Literature citations
Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue.
Sharma R.; Sahoo S.S.; Honda M.; Granger S.L.; Goodings C.; Sanchez L.; Kuenstner A.; Busch H.; Beier F.; Pruett-Miller S.M.; Valentine M.B.; Fernandez A.G.; Chang T.C.; Geli V.; Churikov D.; Hirschi S.; Pastor V.B.; Boerries M.; Lauten M.; Kelaidi C.; Cooper M.A.; Nicholas S.; Rosenfeld J.A.; Polychronopoulou S.; Kannengiesser C.; Saintome C.; Niemeyer C.M.; Revy P.; Wold M.S.; Spies M.; Erlacher M.; Coulon S.; Wlodarski M.W.;
Blood 139:1039-1051(2022)
Cited for: VARIANTS PFBMFT6 ALA-227; LYS-240 AND ALA-270; CHARACTERIZATION OF VARIANTS PFBMFT6 ALA-227; LYS-240 AND ALA-270; INVOLVEMENT IN PFBMFT6; FUNCTION; SUBUNIT;

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.