UniProtKB/Swiss-Prot P31751: Variant p.Arg274His

RAC-beta serine/threonine-protein kinase
Gene: AKT2
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Variant information Variant position:

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

LB/B 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 Arginine (R) to Histidine (H) at position 274 (R274H, p.Arg274His). 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 medium size and polar (H) 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:

Risk factor for T2D; typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121434593 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

FYGAEIVSALEYLHSRDVVY R DIKLENLMLDKDGHIKITDF 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                         FYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDF

Mouse                         FYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDF

Rat                           FYGAEIVSALEYLHSTDVVYRDIKLENLMLDKDGHIKITDF

Caenorhabditis elegans        FYGSEIILALGYLHHRNIVYRDMKLENLLLDRDGHIKITDF

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 – 481	RAC-beta serine/threonine-protein kinase
Domain	152 – 409	Protein kinase
Active site	275 – 275	Proton acceptor
Binding site	280 – 280
Binding site	293 – 293

Literature citations
A family with severe insulin resistance and diabetes due to a mutation in AKT2.
George S.; Rochford J.J.; Wolfrum C.; Gray S.L.; Schinner S.; Wilson J.C.; Soos M.A.; Murgatroyd P.R.; Williams R.M.; Acerini C.L.; Dunger D.B.; Barford D.; Umpleby A.M.; Wareham N.J.; Davies H.A.; Schafer A.J.; Stoffel M.; O'Rahilly S.; Barroso I.;
Science 304:1325-1328(2004)
Cited for: VARIANT HIS-274; INVOLVEMENT IN T2D; Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis.
Semple R.K.; Sleigh A.; Murgatroyd P.R.; Adams C.A.; Bluck L.; Jackson S.; Vottero A.; Kanabar D.; Charlton-Menys V.; Durrington P.; Soos M.A.; Carpenter T.A.; Lomas D.J.; Cochran E.K.; Gorden P.; O'Rahilly S.; Savage D.B.;
J. Clin. Invest. 119:315-322(2009)
Cited for: VARIANT HIS-274; INVOLVEMENT IN T2D;

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.