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FLASH GENE

Symbol

TOPORS

contributors: mct - updated : 15-03-2011

HGNC name	topoisomerase I binding, arginine/serine-rich
HGNC id	21653

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	RP31 retinitis pigmentosa 31
Location	9p21.1      Physical location : 32.540.542 - 32.552.622
Synonym name	topoisomerase I binding protein
	ring finger protein
	E3 ubiquitin-protein ligase Topors
	tumor suppressor p53-binding protein 3
Synonym symbol(s)	TP53BPL, LUN, RP31, P53BP3, TP53BPL
EC.number	6.3.2.-

DNA

TYPE	functioning gene
STRUCTURE	12.08 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005802 3 - 4184 119 1045 - 2001 11278651 NM_001195622 - - 3988 - 980 - 2001 11278651

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Digestive liver       moderately Endocrine neuroendocrine pituitary     highly   parathyroid       highly Lymphoid/Immune thymus       highly Nervous brain       moderately Respiratory lung       highly Visual eye retina     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Respiratory epithelial cell Visual cone photoreceptor Homo sapiens Visual rod photoreceptor Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal RING-type zinc-finger domain (amino acids 103
	141)
	five stretches enriched in proline, glutamic acid, serine, and threonine (PEST) residues
	a bipartite nuclear localization signal
	a region rich in Arg-Ser
	coiled-coil structure and leucine zipper
	two putative SUMO-1 conjugation sites

HOMOLOGY

interspecies

homolog to murine Topors (87.4pc)

Homologene

FAMILY

ring finger protein family

CATEGORY

tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text	cilia-centrosomal protein

basic FUNCTION	trans-acting transcriptional regulator of E-cadherin and talin gene in the alveolar epithelial cell during lung development, differentiation, tumorigenesis
	E3 ubiquitin ligase with specific E2 enzymes, and it can ubiquitinate TP53
	can function as both an ubiquitin and SUMO-1 E3 ligase for TP53
	enhancing the formation of high molecular weight SUMO-1 conjugates of TOP1
	potential binary switch function for TOPORS in protein ubiquitination versus sumoylation
	ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide ligase (SUMO E3) ligase
	involved in normal mitotic progression, since its depletion delays mitotic entry and affects mitotic progression
	has both ubiquitin and SUMO E3 ligase activity
	unique role in the maintenance of genomic stability and pericentric heterochromatin, as well as in cellular sensitivity to histone deacetylase inhibitors
	may play a key role in regulating primary cilia-dependent photoreceptor development and function
	promotes proteasomal degradation of NKX3.1 through direct interaction, predisposing cells to oncogenic transformation by providing an irreversible growth advantage as the first steps in prostate carcinogenesis

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

component of the photoreceptor sensory cilium, which is a modified primary cilium involved with polarized trafficking of proteins

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	ions Zn2+

protein	potentially binding to the palindromic sequence in the 5'UTR of E-cadherin and in two intervening regions of TALIN
	negative regulator of NKX3.1 (implicate TOPORS in prostate cancer progression)
	binding partner of p53 and TOP1
	PLK1 target (PLK1 phosphorylates TOPORS on Ser(718))

cell & other

REGULATION

Other

PLK1 phosphorylation is involved in its degradation

ASSOCIATED DISORDERS

corresponding disease(s)

RP31

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   leads to NKX3.1 proteasomal degradation in prostate cancer cells tumoral         lung carcinoma constitutional somatic mutation insertion     causing autosomal dominant retinitis pigmentosa constitutional somatic mutation deletion     causing autosomal dominant retinitis pigmentosa

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Somatic-gene-therapy rescue has been achieved in several animal models of retinal degeneration, including the rds mouse, and may also prove to be a successful approach for this type of adRP