MORC2
Function
Essential for epigenetic silencing by the HUSH (human silencing hub) complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing (PubMed:28581500, PubMed:29440755, PubMed:32693025). Represses germ cell-related genes and L1 retrotransposons in collaboration with SETDB1 and the HUSH complex, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). During DNA damage response, regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, is phosphorylated by PAK1, both colocalize to chromatin and induce H2AX expression. ATPase activity is required and dependent of phosphorylation by PAK1 and presence of DNA (PubMed:23260667). Recruits histone deacetylases, such as HDAC4, to promoter regions, causing local histone H3 deacetylation and transcriptional repression of genes such as CA9 (PubMed:20110259, PubMed:20225202). Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864).
Involvement in disease
Charcot-Marie-Tooth disease, axonal, 2Z
CMT2Z
An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy
DIGFAN
An autosomal dominant disease characterized by developmental delay, intellectual disability, hypotonia, poor growth, short stature, microcephaly, and variable craniofacial dysmorphism. Patients often present weakness, hyporeflexia, and electrophysiologic abnormalities consistent with an axonal sensorimotor peripheral neuropathy. Additional features may include hearing loss, pigmentary retinopathy, and abnormalities on brain imaging, including cerebral or cerebellar atrophy, hypomyelination, and lesions in the basal ganglia or brainstem. Disease severity is highly variable.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated by PAK1 at Ser-739 upon DNA damage. Phosphorylation is required for ATPase activity and recruitment to damaged chromatin.
Tissue Specificity
Highly expressed in smooth muscle, pancreas and testis.
Cellular localization
- Nucleus
- Cytoplasm
- Cytosol
- Chromosome
- Nucleus matrix
- Mainly located in the nucleus (PubMed:20225202). Upon phosphorylation at Ser-739, recruited to damaged chromatin (PubMed:23260667).
Alternative names
KIAA0852, ZCWCC1, MORC2, ATPase MORC2, MORC family CW-type zinc finger protein 2, Zinc finger CW-type coiled-coil domain protein 1