Protein: Tegument protein ORF52 (Kaposi's sarcoma-associated herpesvirus inhibitor of cGAS) (KicGAS) (Q2HR80)
Organism: Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus)
Function: Plays a role in the inhibition of host innate immune system by targeting the CGAS enzymatic activity which is the principal cytosolic DNA sensor that detects invading viral DNA. Acts by inhibiting CGAS-DNA phase separation: directly binds double-stranded DNA (dsDNA) in a length dependent but sequence independent manner and is able to form DNA-induced phase separation in infected cells. DNA phase separation of ORF52 mediates disruption of liquid-like droplets in which CGAS is activated, thereby preventing CGAS activity. Targets also the HDP-RNP complex composed of DNA-PK subunits and paraspeckle proteins. This complex is a key nuclear regulator of DNA-mediated activation of innate immune response through the cGAS-STING pathway.
Subcellular location: Host cytoplasm {ECO:0000269|PubMed:26320998, ECO:0000269|PubMed:27009954}. Virion tegument {ECO:0000269|PubMed:27009954}.
Sequence: MAAPRGRPKKDLTMEDLTAKISQLTVENRELRKALGSTADPRDRPLTATEKEAQLTATVGALSAAAAKKIEARVRTIFSKVVTQKQVDDALKGLSLRIDVCMSDGGTAKPPPGANNRRRRGASTTRAGVDD
InterPro domains: - IPR008642: Herpesvirus BLRF2 (family) [11-126]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0016032 (viral process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019058 (viral life cycle), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019079 (viral genome replication), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0039693 (viral DNA genome replication), GO:0006139 (nucleobase-containing compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0006259 (DNA metabolic process), GO:0009059 (macromolecule biosynthetic process), GO:0039686 (bidirectional double-stranded viral DNA replication), GO:1901362 (organic cyclic compound biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0090304 (nucleic acid metabolic process), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0071897 (DNA biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0044423 (virion component), GO:0110165 (cellular anatomical entity), GO:0018995 (host cellular component), GO:0033643 (host cell part), GO:0043657 (host cell), GO:0033646 (host intracellular part), GO:0043656 (host intracellular region), GO:0033647 (host intracellular organelle), GO:0030430 (host cell cytoplasm), GO:0033648 (host intracellular membrane-bounded organelle), GO:0042025 (host cell nucleus)