Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y243: Variant p.Arg465Trp

RAC-gamma serine/threonine-protein kinase
Gene: AKT3
Feedback?
Variant information Variant position: help 465 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Tryptophan (W) at position 465 (R465W, p.Arg465Trp). 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 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: help -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: help In MPPH2; disease phenotype overlaps with megalencephaly-capillary malformation syndrome. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 465 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 479 The length of the canonical sequence.
Location on the sequence: help TITPPEKYDEDGMDCMDNER R PHFPQFSYSASGRE 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                         TITPPEKYDEDGMDCMDNERRPHFPQFSYSASGRE

Mouse                         TITPPEKYDDDGMDGMDNERRPHFPQFSYSASGRE

Rat                           TITPPEKDDDDGMDCMDNERRPHFPQFSYSASGRE
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 2 – 479 RAC-gamma serine/threonine-protein kinase
Domain 406 – 479 AGC-kinase C-terminal
Region 458 – 479 Disordered
Modified residue 447 – 447 Phosphothreonine
Modified residue 472 – 472 Phosphoserine; by PKC/PRKCZ
Alternative sequence 452 – 479 YDEDGMDCMDNERRPHFPQFSYSASGRE -> CQQSDCGMLGNWKK. In isoform 2.
Mutagenesis 447 – 447 T -> A. No effect.
Mutagenesis 447 – 447 T -> D. No effect.
Mutagenesis 472 – 472 S -> A. 67% decrease of activity after pervanadate treatment.
Mutagenesis 472 – 472 S -> D. 1.4-fold increase of phosphorylation steady state level, 50% decrease of activity after pervanadate treatment.



Literature citations
De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.
Riviere J.B.; Mirzaa G.M.; O'Roak B.J.; Beddaoui M.; Alcantara D.; Conway R.L.; St-Onge J.; Schwartzentruber J.A.; Gripp K.W.; Nikkel S.M.; Worthylake T.; Sullivan C.T.; Ward T.R.; Butler H.E.; Kramer N.A.; Albrecht B.; Armour C.M.; Armstrong L.; Caluseriu O.; Cytrynbaum C.; Drolet B.A.; Innes A.M.; Lauzon J.L.; Lin A.E.; Mancini G.M.; Meschino W.S.; Reggin J.D.; Saggar A.K.; Lerman-Sagie T.; Uyanik G.; Weksberg R.; Zirn B.; Beaulieu C.L.; Majewski J.; Bulman D.E.; O'Driscoll M.; Shendure J.; Graham J.M. Jr.; Boycott K.M.; Dobyns W.B.;
Nat. Genet. 44:934-940(2012)
Cited for: VARIANTS MPPH2 SER-229 AND TRP-465;
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.