Home  |  Contact

UniProtKB/Swiss-Prot O43707: Variant p.Ser262Pro

Alpha-actinin-4
Gene: ACTN4
Variant information

Variant position:  262
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 Serine (S) to Proline (P) at position 262 (S262P, p.Ser262Pro).
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 small size and polar (S) to medium size and hydrophobic (P)
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 FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coactivator activity; dominant negative effect on nuclear receptors-mediated transcription; increased actin-binding affinity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  262
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  911
The length of the canonical sequence.

Location on the sequence:   DAEDIVNTARPDEKAIMTYV  S SFYHAFSGAQKAETAANRIC
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                         DAEDIVNTARPDEKAIMTYVSSFYHAFSGAQKAETAANRIC

Mouse                         DAEDIVNTARPDEKAIMTYVSSFYHAFSGAQKAETAANRIC

Rat                           DAEDIVNTARPDEKAIMTYVSSFYHAFSGAQKAETAANRIC

Bovine                        DAEDIVNTARPDEKAIMTYVSSFYHAFSGAQKAETAANRIC

Chicken                       DAEDIVNTARPDEKAIMTYVSSFYHAFSGAQKAETAANRIC

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 – 911 Alpha-actinin-4
Domain 163 – 269 Calponin-homology (CH) 2
Region 1 – 269 Actin-binding
Modified residue 249 – 249 Phosphothreonine
Alternative sequence 54 – 272 Missing. In isoform ACTN4ISO.
Alternative sequence 89 – 478 Missing. In isoform 3.
Helix 254 – 268


Literature citations

Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis.
Lee S.H.; Weins A.; Hayes D.B.; Pollak M.R.; Dominguez R.;
J. Mol. Biol. 376:317-324(2008)
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 47-271; CHARACTERIZATION OF VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262;

Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors.
Khurana S.; Chakraborty S.; Lam M.; Liu Y.; Su Y.T.; Zhao X.; Saleem M.A.; Mathieson P.W.; Bruggeman L.A.; Kao H.Y.;
J. Biol. Chem. 287:12027-12035(2012)
Cited for: CHARACTERIZATION OF VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262; FUNCTION; INTERACTION WITH PPARG AND RARA; MUTAGENESIS OF 87-LEU-LEU-88; DOMAIN; SUBCELLULAR LOCATION;

Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis.
Kaplan J.M.; Kim S.H.; North K.N.; Rennke H.; Correia L.A.; Tong H.-Q.; Mathis B.J.; Rodriguez-Perez J.-C.; Allen P.G.; Beggs A.H.; Pollak M.R.;
Nat. Genet. 24:251-256(2000)
Cited for: VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262;

Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis.
Barua M.; Brown E.J.; Charoonratana V.T.; Genovese G.; Sun H.; Pollak M.R.;
Kidney Int. 83:316-322(2013)
Cited for: VARIANTS FSGS1 ARG-59; GLN-72; LEU-153; GLU-255; ILE-259 AND PRO-262;

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.