Variant position: 25 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 480 The length of the canonical sequence.
Location on the sequence:
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 AIVKEGWLHKRGEYIKTWRP RYFLLKNDGTFIGYKERPQDV
Mouse AIVKEGWLHKRGEYIKTWRP RYFLLKNDGTFIGYKERPQDV
Rat AIVKEGWLHKRGEYIKTWRP RYFLLKNDGTFIGYKERPQDV
Bovine AIVKEGWLHKRGEYIKTWRP RYFLLKNDGTFIGYKERPQDL
Xenopus laevis AIVKEGWLHKRGEYIKTWRP RYFLLKSDGTFIGYKERPQDV
Caenorhabditis elegans DVVIEGWLHKKGEHIRNWRP RYFMIFNDGALLGFRAKPKEG
Drosophila QVVKEGWLMKRGEHIKNWRQ RYFVLHSDGRLMGYRSKPADS
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
1 – 480 RAC-alpha serine/threonine-protein kinase
5 – 108 PH
23 – 25 Inositol-(1,3,4,5)-tetrakisphosphate binding
14 – 14 N6-acetyllysine
20 – 20 N6-acetyllysine
1 – 62 Missing. In isoform 2.
8 – 8 K -> R. Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation as well as IGF1-induced membrane recruitment. Decrease in ubiquitination and phosphorylation at T-308 as well as impaired association with the membrane; when associated with K-17.
14 – 14 K -> A. Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
14 – 14 K -> Q. Substantial reduction of phosphorylation at T-308 and S-473, loss of AKT activation, and loss of binding to PIP3 as well as IGF1-induced membrane recruitment.
14 – 14 K -> R. Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation, loss of binding to PIP3 as well as IGF1-induced membrane recruitment.
17 – 17 E -> K. No effect on membrane localization. Loss of membrane localization; when associated with Q-20.
20 – 20 K -> Q. Substantial reduction of phosphorylation at T-308 and S-473, reduced AKT activation, and reduced binding to PIP3 as well as IGF1-induced membrane recruitment. Loss of membrane localization; when associated with K-17.
20 – 20 K -> R. Slight increase of phosphorylation at T-308 and S-473.
25 – 25 R -> AC. Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
22 – 30
Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes.
Orloff M.S.; He X.; Peterson C.; Chen F.; Chen J.L.; Mester J.L.; Eng C.;
Am. J. Hum. Genet. 92:76-80(2013)
Cited for: VARIANTS CWS6 CYS-25 AND PRO-435;
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.