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FLASH GENE

Symbol

TOP1

contributors: mct - updated : 30-11-2015

HGNC name	topoisomerase (DNA) I
HGNC id	11986

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	20q12      Physical location : 39.657.461 - 39.753.124
Synonym symbol(s)	TOPI
EC.number	5.99.1.2

DNA

TYPE	functioning gene
STRUCTURE	95.67 kb     21 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003286 21 - 3734 NP_003277 90.6 765 - -

EXPRESSION

Type	ubiquitous

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 Digestive esophagus       highly   mouth tongue     highly Lymphoid/Immune lymph node       moderately Nervous brain hindbrain cerebellum   highly Reproductive female system placenta     moderately Respiratory respiratory tract trachea     highly Urinary kidney       moderately

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an unstructured N-terminal domain of 200 amino acids, poorly conserved N-terminal domain
	a coiled-coil linker domain of variable length
	a structured functional domain of 565 AAS that binds and relaxes supercoiled DNA
	the highly conserved core and C-terminal domains involved in catalysis

conjugated

Other

mono polymer

monomer

HOMOLOGY

interspecies	homolog to rattus Top1 (97.3 pc)
	homolog to murine Top1 (97.3 pc)

Homologene

FAMILY

eukaryotic type I topoisomerase family

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,nucleolus
text	perikaryon
	very high levels of topoisomerase 1 (TOP1) in the nucleus, and specifically the nucleolus, of human Purkinje neurons (Gorodetsky 2007)

basic FUNCTION	DNA topoisomerase I, relaxing negatively supercoiled DNA and releasing torsion stress created by DNA transcription
	catalyzing the ATP independent breakage and rejoining of single strand of DNA
	involved in DNA repair
	aborting in cells treated by antitumor drugs with the production of topoisomerase-DNA damage, finally distroyed by ubiquitin after conjugation with SUMO1 (UBL1)
	function of TOP1 in regulating senescence
	involvement of TOP1, TDP1 , and single-strand break repair (SSBR) in modulating transcription-dependent CAG repeat contractions
	is involved in transcription-associated mutation at dinucleotide repeats in yeast and in triplet-repeat contraction in mammals
	initiates an independent form of repair to remove ribonucleotides from genomic DNA
	TOP1, TOP2A are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
	controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission
	during processes such as DNA replication and transcription, DNA topoisomerase I (TOP1) catalyzes the relaxation of DNA supercoils
	complex interplay between replication and transcription in regulating TOP1-dependent genetic instability

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, replication
	nucleotide, recombination

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding to single stand

RNA

small molecule

protein	CCR7 was found to interact directly with TOPI
	TOP2A, TOP1 are involved in initiating aphidicolin-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
	RECQL5 helicase promotes TOP1 SUMOylation by facilitating the interaction between PIAS1, SRSF1 and TOP1

cell & other

REGULATION

activated by

phosphorylation (stimulates its DNA relaxation activity)

inhibited by

camptothecin (specifically)

Other

sumoylation playing a role in partitioning TOP1 between nucleoli and nucleoplasm (Lys-117 being the main site of sumoylation)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       fused with NUP98 in t(11;20)(p15;q11) in therapy related myelodysplastic syndrome tumoral   amplification     is associated with advanced tumours and poor prognosis in melanoma

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS