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E3 SUMO-protein ligase PIAS4; PIASy; protein inhibitor of activated STAT protein 4; protein inhibitor of activated STAT protein gamma; PIAS-gamma (PIAS4, PIASG)
Function:
- E3-type small ubiquitin-like modifier (SUMO) ligase
- stabilizes interaction between UBE2I & substrate
- SUMO-tethering factor
- role in transcriptional coregulation in cellular pathways
a) STAT pathway
b) p53 pathway
c) Wnt pathway
d) steroid hormone signaling pathway
- role in gene silencing
- promotes PARK7 sumoylation
- in Wnt signaling
a) represses LEF1
b) enhances TCF4 transcriptional activities through promoting their sumoylations
- protein modification; protein sumoylation
- sumoylated
- Lys-35 is the main site of sumoylation
- sumoylation is required for TCF4 sumoylation & transcriptional activation
- represses LEF1 transcriptional activity
- SUMO1 is the preferred conjugate
- interacts with AR, AXIN1, GATA2, LEF1, TP53 & STAT1 (IFNG-induced)
- preferentially binds AT-rich DNA sequences, known as matrix attachment regions or scaffold attachment regions (putative)
- interacts with TICAM1
- interacts with KLF8; the interaction results in SUMO ligation & repression of KLF8 transcriptional activity & of its cell cycle progression into G1 phase
Structure:
- the LXXLL motif is a coregulator signature essential for transcriptional corepression
- belongs to the PIAS family
- contains 1 PINIT domain
- contains 1 SAP domain
- contains 1 SP-RING-type Zn+2 finger
Compartment:
- nucleus, PML body
- colocalizes with SUMO1 & TCF7L2/TCF4 & LEF1 in a subset of PML (promyelocytic leukemia) nuclear bodies
Expression:
- highly expressed in testis
- lower expression in spleen, prostate, ovary, colon & peripheral blood leukocytes
Related
protein inhibitor of activated STAT (PIAS)
General
nuclear protein
ring finger protein
Properties
SIZE: entity length = 510 aa
MW = 57 kD
COMPARTMENT: cell nucleus
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
SAP {12-46}
MOTIF: LXXLL {20-24}
PINIT {119-279}
RING-finger {311-388}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
acidic region {464-492}
MOTIF: acidic residue (SEVERAL)
Database Correlations
OMIM 605989
UniProt Q8N2W9
Pfam PF02891
Entrez Gene 51588
Kegg hsa:51588
References
UniProt :accession Q8N2W9