UniProtKB/SwissProt variant VAR

cAMP-dependent protein kinase catalytic subunit alpha
Gene: PRKACA
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Variant information Variant position:

206 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 Leucine (L) to Arginine (R) at position 206 (L206R, p.Leu206Arg). 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 medium size and hydrophobic (L) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 PPNAD4; somatic mutation; the mutation results in cAMP-independent basal protein kinase activity and constitutive activation of protein kinase A. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs386352352 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

FGFAKRVKGRTWTLCGTPEY L APEIILSKGYNKAVDWWALG 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                         FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

                              FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

Mouse                         FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

Rat                           FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

Pig                           FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

Bovine                        FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

Sheep                         FGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALG

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	2 – 351	cAMP-dependent protein kinase catalytic subunit alpha
Domain	44 – 298	Protein kinase
Modified residue	196 – 196	Phosphothreonine
Modified residue	198 – 198	Phosphothreonine; by PDPK1
Mutagenesis	195 – 195	R -> A. No phosphorylation.
Mutagenesis	201 – 201	G -> A. No phosphorylation.
Mutagenesis	202 – 202	T -> A. No phosphorylation.
Mutagenesis	205 – 205	Y -> A. Loss of allosteric regulation.

Literature citations
Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors.
Goh G.; Scholl U.I.; Healy J.M.; Choi M.; Prasad M.L.; Nelson-Williams C.; Kunstman J.W.; Kuntsman J.W.; Korah R.; Suttorp A.C.; Dietrich D.; Haase M.; Willenberg H.S.; Staalberg P.; Hellman P.; Akerstroem G.; Bjoerklund P.; Carling T.; Lifton R.P.;
Nat. Genet. 46:613-617(2014)
Cited for: INVOLVEMENT IN PPNAD4; VARIANT PPNAD4 ARG-206; CHARACTERIZATION OF VARIANT PPNAD4 ARG-206; Constitutive activation of PKA catalytic subunit in adrenal Cushing's syndrome.
Beuschlein F.; Fassnacht M.; Assie G.; Calebiro D.; Stratakis C.A.; Osswald A.; Ronchi C.L.; Wieland T.; Sbiera S.; Faucz F.R.; Schaak K.; Schmittfull A.; Schwarzmayr T.; Barreau O.; Vezzosi D.; Rizk-Rabin M.; Zabel U.; Szarek E.; Salpea P.; Forlino A.; Vetro A.; Zuffardi O.; Kisker C.; Diener S.; Meitinger T.; Lohse M.J.; Reincke M.; Bertherat J.; Strom T.M.; Allolio B.;
N. Engl. J. Med. 370:1019-1028(2014)
Cited for: VARIANT PPNAD4 ARG-206; CHARACTERIZATION OF VARIANT PPNAD4 ARG-206; Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome.
Cao Y.; He M.; Gao Z.; Peng Y.; Li Y.; Li L.; Zhou W.; Li X.; Zhong X.; Lei Y.; Su T.; Wang H.; Jiang Y.; Yang L.; Wei W.; Yang X.; Jiang X.; Liu L.; He J.; Ye J.; Wei Q.; Li Y.; Wang W.; Wang J.; Ning G.;
Science 344:913-917(2014)
Cited for: VARIANT PPNAD4 ARG-206; CHARACTERIZATION OF VARIANT PPNAD4 ARG-206; Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.
Sato Y.; Maekawa S.; Ishii R.; Sanada M.; Morikawa T.; Shiraishi Y.; Yoshida K.; Nagata Y.; Sato-Otsubo A.; Yoshizato T.; Suzuki H.; Shiozawa Y.; Kataoka K.; Kon A.; Aoki K.; Chiba K.; Tanaka H.; Kume H.; Miyano S.; Fukayama M.; Nureki O.; Homma Y.; Ogawa S.;
Science 344:917-920(2014)
Cited for: VARIANT PPNAD4 ARG-206; CHARACTERIZATION OF VARIANT PPNAD4 ARG-206;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17612: Variant p.Leu206Arg