TOPORS topoisomerase I binding, arginine/serine-rich, E3 ubiquitin protein ligase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: TOPORSprovided by HGNC
Official Full Name: topoisomerase I binding, arginine/serine-rich, E3 ubiquitin protein ligaseprovided by HGNC
Primary source: HGNC:21653
Locus tag: RP11-205M20.5
See related: Ensembl:ENSG00000197579; HPRD:11642; MIM:609507; Vega:OTTHUMG00000019743
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LUN; RP31; P53BP3; TP53BPL
Summary: This gene encodes a nuclear protein which is serine and arginine rich, and contains a RING-type zinc finger domain. It is highly expressed in the testis, and functions as an ubiquitin-protein E3 ligase. Mutations in this gene are associated with retinitis pigmentosa type 31. Alternatively spliced transcript variants, encoding different isoforms, have been observed for this locus. [provided by RefSeq, Sep 2010]

Genomic context

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Location :: 9p21

Sequence :: Chromosome: 9; NC_000009.11 (32540542..32552626, complement)

See TOPORS in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data suggest that TOPORS plays key role in turnover of H2AX (H2A histone family, member X protein) depending on the type of oxidative stress/DNA damage; TOPORS may act as an E3 ubiquitin ligase for histones.
Title: TOPORS modulates H2AX discriminating genotoxic stresses.
Disturbed flow induces peroxynitrite production and binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy).
Title: Disturbed flow: p53 SUMOylation in the turnover of endothelial cells.
In photoreceptors, TOPORS localizes primarily to the basal bodies of connecting cilium and in the centrosomes.
Title: TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein.
Polo-like kinase 1 (Plk1)-associated phosphorylation of Topors at S718 is essential for nocodazole-induced degradation of Topors.
Title: Plk1 phosphorylation of Topors is involved in its degradation.
We present a novel mutation in the TOPORS gene co-segregating with a distinct phenotype of adPRD in a large Norwegian family.
Title: Autosomal dominant pericentral retinal dystrophy caused by a novel missense mutation in the TOPORS gene.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Plk1 modulates Topors activity in suppressing p53 function
Title: Plk1-mediated phosphorylation of Topors regulates p53 stability.
Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).
Title: Mutations in TOPORS: a rare cause of autosomal dominant retinitis pigmentosa in continental Europe?
Observational study of gene-disease association. (HuGE Navigator)
Title: Mutations in TOPORS: a rare cause of autosomal dominant retinitis pigmentosa in continental Europe?
Point mutations and small insertions or deletions in TOPORS cause approximately 1% of autosomal dominant retinitis pigmentosa.
Title: Mutations in the TOPORS gene cause 1% of autosomal dominant retinitis pigmentosa.

Submit: New GeneRIF Correction See all (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Retinitis pigmentosa (RP) is a group of inherited disorders in which abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina lead to progressive visual loss. Affected individuals first experience defective dark adaptation or "night blindness," followed by constriction of peripheral visual fields and, eventually, loss of central vision late in the course of the disease.

Diagnosis Testing

The diagnosis of RP relies on documentation of progressive loss in photoreceptor function by electroretinography (ERG) and visual field testing. Mutations in more than 50 different genes or loci are known to cause nonsyndromic RP. Molecular genetic testing is available on a clinical basis for many RP- related genes. For all other genes, molecular genetic testing is available on a research basis only.

Genetic Counseling

The mode of inheritance of RP is determined by family history and, in some instances, by molecular genetic testing. RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Females with an X-linked RP mutation may be unaffected or may show clinical symptoms. Such affected females are usually (but not always) less severely affected than males of the same age. Some digenic and mitochondrial forms have also been described. Genetic counseling depends on an accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing.

References

PMID: 20301590

NHGRI GWAS Catalog

Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005793.2	NP_000537.2	TP53	BIND	PubMed	Topors interacts with p53. This interaction was modelled on a demonstrated interaction between human Topors and mouse p53.
NP_005793.2	AAC03774.1		BIND	PubMed	Topors interacts with adeno-associated virus (AAV-2) Rep68.
NP_005793.2	AAC03775.1		BIND	PubMed	Topors interacts with adeno-associated virus (AAV-2) Rep78
Q9NS56	Q14790	CASP8	HPRD	PubMed
Q9NS56	Q5JVS0	HABP4	HPRD	PubMed
Q9NS56	SERPINE1 mRNA binding protein 1	SERBP1	HPRD	PubMed
Q9NS56	Q8TAD8	SNIP1	HPRD	PubMed
Q9NS56	P63165	SUMO1	HPRD	PubMed
Q9NS56	P11387	TOP1	HPRD	PubMed
Q9NS56	Q9NS56	TOPORS	HPRD	PubMed
Q9NS56	P04637	TP53	HPRD	PubMed
Q9NS56	P63279	UBE2I	HPRD	PubMed
BioGRID:115505	BioGRID:107291	CASP8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:115505	BioGRID:108010	DDB2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:108029	DHX15	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:108237	EEF1A1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:109224	GTF2I	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:109268	H2AFX	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:115505	BioGRID:116587	HABP4	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:109420	HNRNPA1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:109432	HNRNPL	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:110751	HNRNPM	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:115000	IKBKE	BioGRID	PubMed	Affinity Capture-Western; Co-localization
BioGRID:115505	BioGRID:110888	NKX3-1	BioGRID	PubMed	Biochemical Activity; Reconstituted Complex
BioGRID:115505	BioGRID:110904	NONO	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:106652	PARP1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:111362	PLK1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:115505	BioGRID:111384	PML	BioGRID	PubMed	Co-localization
BioGRID:115505	BioGRID:111840	RANGAP1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:111863	RBBP4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:111866	RBBP7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:112188	S100A9	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:115022	SAFB2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:112211	SATB1	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:117571	SERBP1	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:117017	SF3B1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:112319	SFPQ	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:117439	SIN3A	BioGRID	PubMed	Affinity Capture-MS; Biochemical Activity
BioGRID:115505	BioGRID:112485	SMARCC2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:113188	SUMO1	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:113003	TOP1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Two-hybrid
BioGRID:115505	BioGRID:113010	TP53	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex; Two-hybrid
BioGRID:115505	BioGRID:115457	TRIM28	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:204323	Trp53	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:113169	UBE2D1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:115505	BioGRID:113170	UBE2D2	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:113171	UBE2D3	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:115505	BioGRID:119641	UBE2D4	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:113172	UBE2E1	BioGRID	PubMed	Reconstituted Complex
BioGRID:115505	BioGRID:113177	UBE2I	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:119555	UBE2J1	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:114672	UBE2L6	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:113182	UBE2N	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:120572	UBE2W	BioGRID	PubMed	Two-hybrid
BioGRID:115505	BioGRID:117507	UBXN7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:115505	BioGRID:122397	UPF3A	BioGRID	PubMed	Affinity Capture-MS

General gene information

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Markers

STS-H04756 (e-PCR)
- UniSTS:57886

RH98974 (e-PCR)
- UniSTS:91240

RH93565 (e-PCR)
- UniSTS:88465

RH68036 (e-PCR)
- UniSTS:10650

G30177 (e-PCR)
- UniSTS:62369

RH81057 (e-PCR)
- UniSTS:87749

Genotypes

See TOPORS SNP Geneview Report
See TOPORS SNP Genotype Report
See TOPORS SNP Variation Viewer Report

Related pseudogene(s)

1 found Review record(s) in Gene

Potential readthrough

Included gene: DDX58

Homology

Homologs of the TOPORS gene: The TOPORS gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA topoisomerase binding	IPI Inferred from Physical Interaction more info	PubMed
SUMO ligase activity	IDA Inferred from Direct Assay more info	PubMed
SUMO ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed
antigen binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin-protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
ubiquitin-protein ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
intrinsic apoptotic signaling pathway in response to DNA damage	IDA Inferred from Direct Assay more info
maintenance of protein location in nucleus	IDA Inferred from Direct Assay more info	PubMed
negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
photoreceptor cell outer segment organization	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info
positive regulation of ubiquitin-protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
protein K48-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein localization to nucleus	IMP Inferred from Mutant Phenotype more info
protein monoubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein sumoylation	IDA Inferred from Direct Assay more info	PubMed
protein sumoylation	IMP Inferred from Mutant Phenotype more info
regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
response to DNA damage stimulus	IDA Inferred from Direct Assay more info	PubMed
retina layer formation	ISS Inferred from Sequence or Structural Similarity more info
retinal cone cell development	ISS Inferred from Sequence or Structural Similarity more info
retinal rod cell development	ISS Inferred from Sequence or Structural Similarity more info
transcription, DNA-dependent	NAS Non-traceable Author Statement more info	PubMed
ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
PML body	IDA Inferred from Direct Assay more info
colocalizes_with PML body	IDA Inferred from Direct Assay more info
centriole	IDA Inferred from Direct Assay more info
cilium basal body	IDA Inferred from Direct Assay more info
colocalizes_with cytoplasmic dynein complex	TAS Traceable Author Statement more info
gamma-tubulin complex	IDA Inferred from Direct Assay more info
midbody	TAS Traceable Author Statement more info
nuclear speck	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
photoreceptor connecting cilium	IDA Inferred from Direct Assay more info
spindle pole	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: E3 ubiquitin-protein ligase Topors

Names: E3 ubiquitin-protein ligase Topors; SUMO1-protein E3 ligase Topors; tumor suppressor p53-binding protein 3; topoisomerase I-binding RING finger protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_017050.1 RefSeqGene

Range

4997..17081

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001195622.1 → NP_001182551.1 E3 ubiquitin-protein ligase Topors isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AB045733, BC060884, BJ993131, BQ007035, BU674865, DA238762, U82939

Consensus CDS

CCDS56566.1

UniProtKB/Swiss-Prot

Q9NS56

Related

ENSP00000369187, OTTHUMP00000021183, ENST00000379858, OTTHUMT00000052008

Conserved Domains (2) summary

cd00162
Location:37 – 80
Blast Score: 149

RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...

pfam13923
Location:34 – 78
Blast Score: 147

zf-C3HC4_2; Zinc finger, C3HC4 type (RING finger)
NM_005802.4 → NP_005793.2 E3 ubiquitin-protein ligase Topors isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BC060884, BJ993131, BQ007035, BU674865, DA238762, U82939

Consensus CDS

CCDS6527.1

UniProtKB/Swiss-Prot

Q9NS56

Related

ENSP00000353735, OTTHUMP00000021182, ENST00000360538, OTTHUMT00000052007

Conserved Domains (2) summary

cd00162
Location:102 – 145
Blast Score: 148

RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...

pfam13923
Location:99 – 143
Blast Score: 146

zf-C3HC4_2; Zinc finger, C3HC4 type (RING finger)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000009.11 Reference GRCh37.p10 Primary Assembly

Range

32540542..32552626, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

32496996..32509408, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018920.1 Alternate CHM1_1.0

Range

32511131..32523216, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01065079.1 (89845..94904)	None
genomic	ABBA01065080.1 (7049..14381)	None
genomic	AF241192.1	AAK12843.1
genomic	AL353671.6 (78497..90581)	None
genomic	AMYH01019320.1 (81791..93876)	None
genomic	CH471071.2	EAW58546.1
mRNA	AB045732.1	BAB03714.1
mRNA	AB045733.1	BAB03715.1
mRNA	AF098300.1	AAD23379.1
mRNA	AI934577.1	None
mRNA	AU280552.1	None
mRNA	AV712580.1	None
mRNA	BC060884.1	AAH60884.1
mRNA	BJ993131.1	None
mRNA	BQ007035.1	None
mRNA	BU674865.1	None
mRNA	DA238762.1	None
mRNA	U82939.1	AAC98530.1