UniProtKB/Swiss-Prot P63104: Variant p.Gly53Arg

14-3-3 protein zeta/delta
Gene: YWHAZ
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Variant information Variant position:

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

US 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 Glycine (G) to Arginine (R) at position 53 (G53R, p.Gly53Arg). 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 glycine (G) 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:

Found in a patient with a neurodevelopmental disorder; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

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

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

GAELSNEERNLLSVAYKNVV G ARRSSWRVVSSIEQKTEGAE 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                         GAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Mouse                         GAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Rat                           GAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Bovine                        GAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Sheep                         GAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Chicken                       GAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Xenopus laevis                GGELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Xenopus tropicalis            GGELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAE

Drosophila                    GVELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTEASA

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 – 245	14-3-3 protein zeta/delta
Site	56 – 56	Interaction with phosphoserine on interacting protein
Modified residue	58 – 58	Phosphoserine; by PKA and PKB/AKT1
Modified residue	68 – 68	N6-acetyllysine
Alternative sequence	1 – 98	MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVL -> MSQPCRKLWRHNYETSSCIEFLK. In isoform 2.
Mutagenesis	49 – 49	K -> E. Loss of interaction with NOXA1.
Mutagenesis	58 – 58	S -> A. Loss of sphingosine-activated PKA phosphorylation. Promotes homodimerization and heterodimerization with YWHAE. Enhanced transcriptional activity of P53.
Mutagenesis	58 – 58	S -> E. Loss of homodimerization. Reduced dimerization with YWHAE. Significantly reduced interaction with P53. No enhancement of P53 transcriptional activity.
Helix	38 – 67

Literature citations
A YWHAZ variant associated with cardiofaciocutaneous syndrome activates the RAF-ERK pathway.
Popov I.K.; Hiatt S.M.; Whalen S.; Keren B.; Ruivenkamp C.; van Haeringen A.; Chen M.J.; Cooper G.M.; Korf B.R.; Chang C.;
Front. Physiol. 10:388-388(2019)
Cited for: VARIANTS 14-GLU--ASN-245 DEL; ARG-53; LEU-145 AND TRP-230; CHARACTERIZATION OF VARIANT TRP-230; FUNCTION; INTERACTION WITH BRAF AND RAF1; PHOSPHORYLATION AT THR-232 BY CK1; MUTAGENESIS OF THR-232;

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.