SMARCA5
Description
The SMARCA5 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5) is a protein-coding gene located on chromosome 4.
SMARCA5 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5), also known as Sucrose nonfermenting protein 2 homolog, is a protein that in humans is encoded by the SMARCA5 gene. This protein is a member of the ISWI family, possessing helicase and ATPase activities, which are thought to regulate gene transcription by altering chromatin structure. SMARCA5 is a component of the chromatin remodeling and spacing factor RSF, facilitating the transcription of class II genes by RNA polymerase II. Its sequence is similar to the Drosophila ISWI chromatin remodeling protein.
SMARCA5 is a helicase with intrinsic ATP-dependent nucleosome-remodeling activity. It is the catalytic subunit of ISWI chromatin-remodeling complexes, which organize nucleosomes on chromatin and facilitate DNA access during replication, transcription, and repair, potentially requiring intact histone H4 tails. These complexes can slide histone octamers, with the specific movement and activity regulated by complex components. Notably, complexes containing BAZ1A/ACF1, BAZ1B/WSTF, BAZ2A/TIP5, and BAZ2B can slide mononucleosomes to the center of a DNA template in an ATP-dependent manner. In contrast, CECR2- and RSF1-containing complexes lack this capability. SMARCA5, together with RSF1, binds to core histones and contributes to the assembly of regular nucleosome arrays by the RSF-5 complex. It is involved in DNA replication, specifically aiding in pericentric heterochromatin replication in S-phase alongside BAZ1A/ACF1. SMARCA5 potentially represses RNA polymerase I transcription of the rDNA locus by recruiting the SIN3/HDAC1 corepressor complex to the promoter. It is an essential component of the WICH-5 (WICH) complex, which restructures irregular chromatin into a regular nucleosomal array. This complex regulates gene transcription and participates in RNA polymerase I transcription. Within the B-WICH complex, SMARCA5 plays a role in RNA polymerase III transcription. It mediates histone H2AX phosphorylation at 'Tyr-142' and contributes to maintaining chromatin structure during DNA replication. SMARCA5 is an essential component of the NoRC-5 (NoRC) complex, which silences a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing.
SMARCA5 is also known as ISWI, SNF2H, WCRF135, hISWI, hSNF2H.
