AFG2A
Domain
The first ATP-binding region binds ATP with low affinity whereas the second ATP-binding region binds ATP with high affinity.
Function
ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity (PubMed:38554706). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024, PubMed:38554706). May be involved in morphological and functional mitochondrial transformations during spermatogenesis (By similarity).
Involvement in disease
Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities
NEDHSB
An autosomal recessive disorder characterized by intellectual disability, intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the AAA ATPase family. AFG2 subfamily.
Cellular localization
- Cytoplasm
- Mitochondrion
- Cytoplasm
- Cytoskeleton
- Spindle
Alternative names
SPAF, SPATA5, AFG2A, ATPase family gene 2 protein homolog A, AFG2 AAA ATPase homolog A, Ribosome biogenesis protein SPATA5, Spermatogenesis-associated factor protein, Spermatogenesis-associated protein 5