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Msx2-interacting protein (SPEN homolog, SMART/HDAC1-associated repressor protein, SPEN, KIAA0929, MINT, SHARP)
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)
General
phosphoprotein
transcriptional silencer (transcriptional repressor)
Properties
SIZE: MW = 402 kD
entity length = 3664 aa
COMPARTMENT: cell nucleus
MOTIF: DNA-binding motif
SITE: 1-573
MOTIF: RNP motif
NAME: RNP motif
SITE: 6-81
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
arginine-rich region {125-277}
MOTIF: arginine residue (SEVERAL)
serine-rich region {240-325}
MOTIF: serine residue (SEVERAL)
Ser phosphorylation site {S260}
Ser phosphorylation site {S263}
Thr phosphorylation site {T266}
RNP motif
NAME: RNP motif
SITE: 335-415
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
RNP motif
NAME: RNP motif
SITE: 438-513
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
RNP motif
NAME: RNP motif
SITE: 517-589
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
arginine-rich region {616-810}
MOTIF: arginine residue (SEVERAL)
coiled coil {688-715}
Ser phosphorylation site {S725}
Ser phosphorylation site {S727}
Ser phosphorylation site {S736}
Ser phosphorylation site {S740}
coiled coil {977-1004}
coiled coil {1170-1191}
Ser phosphorylation site {S1261}
Ser phosphorylation site {S1268}
Ser phosphorylation site {S1278}
Ser phosphorylation site {S1283}
Ser phosphorylation site {S1380}
Ser phosphorylation site {S1382}
coiled coil {1408-1428}
coiled coil {1496-1529}
coiled coil {1592-1612}
Ser phosphorylation site {S1797}
Ser phosphorylation site {S1857}
coiled coil {1928-1944}
Ser phosphorylation site {S2101}
Ser phosphorylation site {S2120}
MSX2 interaction {2130-2464}
RID {2201-2707}
MOTIF: Thr phosphorylation site {T2393}
proline-rich region
SITE: 2428-2520
MOTIF: proline residue (SEVERAL)
RBPSUH interaction {2709-2870}
proline-rich region
SITE: 3220-3482
MOTIF: proline residue (SEVERAL)
SPOC {3498-3664}
Database Correlations
UniProt Q96T58
PFAM correlations
References
UniProt :accession Q96T58