UniProtKB/Swiss-Prot Q9NZC9: Variant p.Arg586Trp

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1
Gene: SMARCAL1
Chromosomal location: 2q35
Variant information

Variant position:  586
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 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 Arginine (R) to Tryptophan (W) at position 586 (R586W, p.Arg586Trp).
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 large size and basic (R) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 SIOD; impairs without abolishing annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage.
Any additional useful information about the variant.



Sequence information

Variant position:  586
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  954
The length of the canonical sequence.

Location on the sequence:   MPVLKVAKRVILLSGTPAMS  R PAELYTQIIAVKPTFFPQFH
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                         MPVLKVAKRVILLSGTPAMSRPAELYTQIIAVKPTFFPQFH

Mouse                         VPILKVAKRVILLSGTPAMSRPAELYTQIIAVKPTFFPQFH

Rat                           VPILKVAKRVILLSGTPAMSRPAELYTQIIAVKPTFFPQFH

Bovine                        MPLLKVAKRVILLSGTPAMSRPAELYTQILAVRPTFFPQFH

Xenopus laevis                MPLLKSAKRVMLLSGTPAMSRPAELYTQIAAVRPTFFPRFH

Xenopus tropicalis            MPLLKSAKRVMLLSGTPAMSRPAELYTQIAAVRPSFFPRFH

Zebrafish                     LPLLKTAKRVILLSGTPAMSRPAELYTQIQAVRPALFPRFH

Caenorhabditis elegans        TDLSKVALHVILLSGTPALSRPSELFTQIRLIDHKLFTNFH

Drosophila                    KRLTDQAKRVVLLSGTPALSRPLELFTQLQMIDGKFM-NFM

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 2 – 954 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1
Domain 445 – 600 Helicase ATP-binding


Literature citations

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.
Boerkoel C.F.; Takashima H.; John J.; Yan J.; Stankiewicz P.; Rosenbarker L.; Andre J.-L.; Bogdanovic R.; Burguet A.; Cockfield S.; Cordeiro I.; Frund S.; Illies F.; Joseph M.; Kaitila I.; Lama G.; Loirat C.; McLeod D.R.; Milford D.V.; Petty E.M.; Rodrigo F.; Saraiva J.M.; Schmidt B.; Smith G.C.; Spranger J.; Stein A.; Thiele H.; Tizard J.; Weksberg R.; Lupski J.R.; Stockton D.W.;
Nat. Genet. 30:215-220(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; TISSUE SPECIFICITY; VARIANTS SIOD PRO-468; ASN-548; LEU-579; TRP-586; TRP-644; CYS-645; GLN-647; THR-647; ILE-705; GLN-764 AND HIS-820;

The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart.
Ciccia A.; Bredemeyer A.L.; Sowa M.E.; Terret M.E.; Jallepalli P.V.; Harper J.W.; Elledge S.J.;
Genes Dev. 23:2415-2425(2009)
Cited for: FUNCTION IN DNA REPLICATION; INTERACTION WITH RPA2 AND THE RPA COMPLEX; REGION; SUBCELLULAR LOCATION; MUTAGENESIS OF 17-ARG--LYS-19; CHARACTERIZATION OF VARIANTS SIOD TRP-586 AND GLN-764;

HARP is an ATP-driven annealing helicase.
Yusufzai T.; Kadonaga J.T.;
Science 322:748-750(2008)
Cited for: CHARACTERIZATION OF VARIANTS SIOD TRP-586 AND GLN-764; FUNCTION; DNA-BINDING;

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.