Msx2-interacting protein (SPEN homolog, SMART/HDAC1-associated repressor protein, SPEN, KIAA0929, MINT, SHARP)
Jump to navigation
Jump to search
Function
- corepressor protein
- regulates key pathways, including Notch pathway
- negative regulator of Notch pathway via its interaction with RBPSUH, which prevents association of NOTCH1 with RBPSUH, thius suppresses transactivation activity of Notch signaling
- blocks differentiation of precursor B-cells into marginal zone B-cells
- represses transcription via recruitment of large complexes containing histone deacetylase proteins.
- may bind both to DNA & RNA
- interacts with MSX2
- interacts with NCOR2, HDAC1, HDAC2, RBBP4, MBD3 & MTA1L1
- interacts with RBPSUH; interaction may prevent interaction of RBPSUH with NOTCH1
- interacts with nuclear receptors RAR & PPARD
- interacts with RAR in absence of ligand
- bind to steroid receptor RNA coactivator SRA
- phosphorylated upon DNA damage, probably by ATM or ATR
Structure
- belongs to the RRM Spen family
- contains 1 RID (receptor interacting) domain, mediates interaction with nuclear receptors
- contains 4 RRM domain (RNA recognition motif)
- contains 1 SPOC domain, mediates interaction with NCOR2, essential for repressive activity
Compartment
nucleus, associates with chromatin
Alternative splicing
named isoforms=1
Expression
- expressed in brain, testis, spleen, thymus > kidney, liver, mammary gland, skin
- induced by hormone 17-beta-estradiol (E2)