UniProtKB/Swiss-Prot Q8N884: Variant p.Gly303Glu

Cyclic GMP-AMP synthase
Gene: CGAS
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Variant information Variant position:

303 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 Glutamate (E) at position 303 (G303E, p.Gly303Glu). 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 medium size and acidic (E) 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 patients with tumors; dominant mutation; reduced nucleotidyltransferase activity. Any additional useful information about the variant.

Sequence information Variant position:

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

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

IIKEEINDIKDTDVIMKRKR G GSPAVTLLISEKISVDITLA 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                         IIKEEINDIKDTDVIMKRKRGGSPAVTLLIS--EKISVDITLA

Mouse                         IIKEEVKEIKDIDVSVEKEKPGSPAVTLLIRNPEEISVDII

Pig                           IIKEEIKNIE--GVTVERKRRGSPAVTLLISKPKEISVDII

Bovine                        IIKEEIKHIEDTDVIMERKKRGSPAVTLLIRKPREISVDII

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 – 522	Cyclic GMP-AMP synthase
Motif	295 – 305	Nuclear localization signal
Binding site	319 – 319
Binding site	319 – 319
Binding site	319 – 319
Modified residue	286 – 286	5-glutamyl polyglutamate
Modified residue	305 – 305	Phosphoserine; by CDK1 and PKB
Modified residue	314 – 314	5-glutamyl glutamate
Cross	285 – 285	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	285 – 285	K -> E. Strongly reduced nucleotidyltransferase activity. Abolished nucleotidyltransferase activity; when associated with E-275.
Mutagenesis	295 – 305	Missing. Abolished nuclear localization.
Mutagenesis	300 – 300	R -> E. Reduced nucleotidyltransferase activity.
Mutagenesis	305 – 305	S -> A. Enhanced stimulation of interferon production. Does not affect chromosome localization.
Mutagenesis	305 – 305	S -> D. Phospho-mimetic mutant; decreased ability to trigger type-I interferon production.
Mutagenesis	319 – 319	D -> A. Abolishes enzyme activity. Does not affect translocation to the nucleus following treatment with etoposide. Abolished cleavage by CASP3.

Literature citations
Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation.
Xie W.; Lama L.; Adura C.; Tomita D.; Glickman J.F.; Tuschl T.; Patel D.J.;
Proc. Natl. Acad. Sci. U.S.A. 116:11946-11955(2019)
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 152-522 IN COMPLEX WITH DNA AND ZINC; FUNCTION; CATALYTIC ACTIVITY; DNA-BINDING; COFACTOR; SUBUNIT; MUTAGENESIS OF LYS-275; 279-LYS--LYS-282; LYS-279; LYS-285; 300-ARG-LYS-301; ARG-300 AND 427-LYS-LYS-428; CHARACTERIZATION OF VARIANT THR-432; VARIANT GLU-303;

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.