9lgo

Structural highlights

Disease

AFG2A_HUMAN Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

AFG2A_HUMAN 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).[UniProtKB:Q3UMC0]^{[1] [2]}

References

1. ↑ Ni C, Schmitz DA, Lee J, Pawłowski K, Wu J, Buszczak M. Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly. Cell Rep. 2022 Mar 29;38(13):110597. PMID:35354024 doi:10.1016/j.celrep.2022.110597
2. ↑ Krishnamoorthy V, Foglizzo M, Dilley RL, Wu A, Datta A, Dutta P, Campbell LJ, Degtjarik O, Musgrove LJ, Calabrese AN, Zeqiraj E, Greenberg RA. The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity. Cell. 2024 Apr 25;187(9):2250-2268.e31. PMID:38554706 doi:10.1016/j.cell.2024.03.002