UniProtKB/Swiss-Prot Q8N884: Variant p.Lys432Thr

Cyclic GMP-AMP synthase
Gene: CGAS
Feedback?

Variant information Variant position:

432 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 Lysine (K) to Threonine (T) at position 432 (K432T, p.Lys432Thr). 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 (K) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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 uterine endometrioid carcinoma; reduced nucleotidyltransferase activity. Any additional useful information about the variant.

Sequence information Variant position:

432 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:

LMKYLLEQLKERFKDKKHLD K FSSYHVKTAFFHVCTQNPQD 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                         LMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQD

Mouse                         LMKYLLEQLKKEF---QELDAFCSYHVKTAIFHMWTQDPQD

Pig                           LMKYLLEQLKKKFGNRRELAKFCSYHVKTAFFHVCTQDPHD

Bovine                        LMKYLLEQLKKKFGKQRGLDKFCSYHVKTAFLHVCTQNPHD

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
Binding site	414 – 414
Modified residue	414 – 414	N6-acetyllysine
Modified residue	434 – 434	Phosphoserine
Modified residue	435 – 435	Phosphoserine
Modified residue	451 – 451	(Microbial infection) Deamidated glutamine; by herpes simplex virus 1/HHV-1 UL37
Cross	414 – 414	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	427 – 427	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	428 – 428	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	414 – 414	K -> AE. Abolishes stimulation of interferon production.
Mutagenesis	414 – 414	K -> Q. Acetylation-mimetic mutant; reduced enzyme activity.
Mutagenesis	414 – 414	K -> R. Reduced enzyme activity. Decreased ubiquitination and SQSTM1-mediated autophagic degradation.
Mutagenesis	434 – 434	S -> C. Gains susceptibility to mouse-specific RU.521; when associated with H-482.
Mutagenesis	435 – 435	S -> A. Decreased cyclic GMP-AMP synthase activity.
Mutagenesis	435 – 435	S -> D. Phospho-mimetic mutant; increased cyclic GMP-AMP synthase activity.
Mutagenesis	436 – 436	Y -> I. Abolishes enzyme activity; when associated with Q-211 and I-376.
Turn	429 – 432

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.