ZDHHC9
Domain
The DHHC domain is required for palmitoyltransferase activity.
Function
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates, such as ADRB2, GSDMD, HRAS, NRAS and CGAS (PubMed:16000296, PubMed:27481942, PubMed:37802025, PubMed:38530158, PubMed:38599239). The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS (PubMed:16000296). May have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and therefore regulate G protein-coupled receptor signaling (PubMed:27481942). Acts as a regulator of innate immunity by catalyzing palmitoylation of CGAS, thereby promoting CGAS homodimerization and cyclic GMP-AMP synthase activity (PubMed:37802025). Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158, PubMed:38599239).
(Microbial infection) Through a sequential action with ZDHHC20, rapidly and efficiently palmitoylates SARS coronavirus-2/SARS-CoV-2 spike protein following its synthesis in the endoplasmic reticulum (ER). In the infected cell, promotes spike biogenesis by protecting it from premature ER degradation, increases half-life and controls the lipid organization of its immediate membrane environment. Once the virus has formed, spike palmitoylation controls fusion with the target cell.
Involvement in disease
Intellectual developmental disorder, X-linked, syndromic, Raymond type
MRXSR
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Some MRXSR patients show additional features, including marfanoid habitus, epilepsy, facial dysmorphism, hypotonia, and behavioral problems.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.
Tissue Specificity
Highly expressed in kidney, skeletal muscle, brain, lung and liver. Absent in thymus, spleen and leukocytes.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Golgi apparatus membrane
- Multi-pass membrane protein
Alternative names
CXorf11, ZDHHC10, ZNF379, ZNF380, CGI-89, UNQ261/PRO298, ZDHHC9, Palmitoyltransferase ZDHHC9, Zinc finger DHHC domain-containing protein 9, Zinc finger protein 379, Zinc finger protein 380, DHHC-9, DHHC9