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E3 ubiquitin-protein ligase Topors; SUMO1-protein E3 ligase Topors; Topoisomerase I-binding RING finger protein; Topoisomerase I-binding arginine/serine-rich protein; tumor suppressor p53-binding protein 3; p53-binding protein 3; p53BP3 (TOPORS, LUN, TP53BPL)
Function:
1) ubiquitin-protein E3 ligase
2) E3 SUMO1-protein ligase
3) ubiquitinates & sumoylates p53
4) regulates p53/TP53 stability through ubiquitin-dependent degradation.
5) probable tumor suppressor involved in cell growth, cell proliferation & apoptosis
6) may regulate chromatin modification through sumoylation of several chromatin modification-associated proteins
7) may be involved in DNA damage-induced cell death through IKBKE sumoylation
8) phosphorylation at Ser-98
a) regulates E3 ubiquitin-protein ligase activity
b) does not regulate SUMO1-protein ligase activity
9) phosphorylation at Ser-718
a) increases E3 ubiquitin-protein ligase activity versus the SUMO1-protein ligase activity
b) results in increased p53/TP53 ubiquitination & degradation
10) polyubiquitinates NKX3-1 & induces its proteasomal degradation
11) sumoylates SIN3A
12) interacts with PARK7, TOP1, p53, UBE2I, NKX3-1, SIN3A, IKBKE, SUMO1
13) sumoylated
Structure: contains 1 RING-type Zn+2 finger
Compartment:
- nucleus
- localizes to discrete nuclear foci, partly overlap with PML nuclear bodies
Alternative splicing: named isoforms=2
Expression:
- expressed in testis > adrenal gland, bone marrow, brain, colon, heart, kidney, liver, muscle, ovary, pancreas, placenta, prostate, skeletal muscle, skin, small intestine, spleen, stomach, testis, thymus, thyroid, uterus, alveolar epithelium of the lung
- induction by genotoxic agents such as cisplatin & camptothecin
Pathology:
- defects in TOPORS are the cause of retinitis pigmentosa type 31
- expression is commonly decreased in:
a) colon adenocarcinomas
b) lung cancers
General
nuclear protein
phosphoprotein
ring finger protein
E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein
Properties
SIZE: entity length = 1045 aa
MW = 119 kD
COMPARTMENT: cell nucleus
MOTIF: E3 ubiquitin-protein ligase activity {1-195}
domain {51-374}
MOTIF: Ser phosphorylation site {S98}
RING-finger {103-142}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
Ser phosphorylation site {S194}
SUMO1 interaction {437-654}
MOTIF: sumoylation {437-574}
TOP1 interaction {456-882}
MOTIF: p53/TP53 interaction {456-731}
Ser phosphorylation site {S499}
arginine-rich region {579-788}
MOTIF: arginine residue (SEVERAL)
Ser phosphorylation site {S585}
Ser phosphorylation site {S718}
UBE2I interaction {854-917}
MOTIF: lysine-rich region {854-895}
MOTIF: lysine residue (SEVERAL)
Ser phosphorylation site {S864}
Ser phosphorylation site {S866}
Ser phosphorylation site {S902}
Ser phosphorylation site {S912}
Ser phosphorylation site {S914}
Database Correlations
OMIM correlations
UniProt Q9NS56
Pfam PF00097
Entrez Gene 10210
Kegg hsa:10210
ENZYME 6.3.2.-
References
UniProt :accession Q9NS56