SRCAP (Snf2-related CREBBP activator protein), also known as EAF1, SWR1, or DOMO1, is a 3,230 amino acid protein that belongs to a family of helicases and contains one HSA domain, one helicase SLCterminal domain, one helicase ATP-binding domain and three A.T hook DNA-binding domains. Localized to the nucleus, SRCAP functions as a catalytic component of the SRCAP complex, a multi-protein structure that mediates the ATP-dependent exchange of histone dimers for nucleosomal histones, an event that regulates the transcription of select genes via chromatin remodeling. Additionally, the SRCAP complex acts as a coactivator for steroid receptor-mediated transcription, Notch-mediated transcription and CREB-mediated transcription. SRCAP is expressed as multiple alternatively spliced isoforms and is subject to DNA damage-dependent phosphorylation by ATM or ATR.
Function:
Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription (from SwissProt).
Subunit:
Interacts with CREBBP and EP300. May be part of a complex containing SRCAP, CREBBP, CARM1 and GRIP1. Component of the chromatin-remodeling SRCAP complex composed of at least SRCAP, DMAP1, RUVBL1, RUVBL2, ACTL6A, YEATS4, VPS72, ACTR6 and ZNHIT1. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Interacts with hepatitis C virus (HCV) NS5A and human adenovirus 2 DBP.
Subcellular Location:
Nuclear
Post-translational modifications:
Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE:
Defects in SRCAP are the cause of Floating-Harbor syndrome (FLHS) [MIM:136140]. A rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips.
Similarity:
Belongs to the SNF2/RAD54 helicase family. SWR1 subfamily.
Contains 3 A.T hook DNA-binding domains.
Contains 1 helicase ATP-binding domain.
Contains 1 helicase SLCterminal domain.
Contains 1 HSA domain.
SWISS:
Q6ZRS2
Gene ID:
10847
Database links:
Entrez Gene: 10847 Human
Entrez Gene: 100043597 Mouse
Entrez Gene: 361652 Rat
Omim: 611421 Human
SwissProt: Q6ZRS2 Human
Unigene: 620916 Human
Unigene: 428042 Mouse
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