TOP1
DNA topoisomerase 1
Also known as: TOP1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P11387
- Gene
- TOP1
- Ensembl
- ENSG00000198900
- Chromosome
- 20
- Canonical length
- 765 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nucleoli fibrillar center
OverviewNCBI Gene
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
765 residues, UniProt reviewed canonical sequence.
>P11387|TOP1
1 MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK
61 HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP
121 EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD
181 KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF
241 YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC
301 DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL
361 FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI
421 QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY
481 FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK
541 VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ
601 QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD
661 ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK
721 LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TOP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.4
- Highest tissue expression
- 71 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 71 nTPM
- tonsil: 57 nTPM
- lymph node: 56 nTPM
- thymus: 55 nTPM
- placenta: 47 nTPM
- appendix: 47 nTPM
Single-cell type
- syncytiotrophoblasts: 1,442 nCPM
- alveolar cells type 2: 1,250 nCPM
- neutrophils: 1,184 nCPM
- transitional alveolar cells: 883 nCPM
- ocular epithelial cells: 736 nCPM
- esophageal apical cells: 694 nCPM
Immune cell
- neutrophil: 19 nTPM
- plasmacytoid DC: 19 nTPM
- eosinophil: 17 nTPM
- non-classical monocyte: 13 nTPM
- basophil: 13 nTPM
- memory B-cell: 11 nTPM
Brain region
- choroid plexus: 39 nTPM
- cerebellum: 31 nTPM
- cerebral cortex: 28 nTPM
- thalamus: 26 nTPM
- hypothalamus: 25 nTPM
- white matter: 25 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TOP1.
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 78 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- DNA topoisomerase I, camptothecin-resistant
Disease | ImmuneIEDB
Conditions an epitope on TOP1 was assayed in.
- systemic scleroderma B and T cell
- Behcet's disease T cell
- sarcoidosis T cell
- Vogt-Koyanagi-Harada disease T cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against TOP1 are reported. Each links to that disease's full target list.
- Scleroderma, Systemic 358
- Lupus Erythematosus, Systemic 48
- Lung Diseases, Interstitial 35
- Raynaud Disease 31
- Scleroderma, Localized 20
- Pulmonary Fibrosis 18
- Hypertension, Pulmonary 15
- Arthritis, Rheumatoid 13
- Sjogren's Syndrome 11
- Mixed Connective Tissue Disease 9
- Collagen Diseases 8
- Calcinosis 7
- Dermatomyositis 6
- Lung Neoplasms 6
- Myositis 6
- Breast Neoplasms 3
- Liver Cirrhosis, Biliary 3
- Muscle Weakness 3
- Ovarian Neoplasms 3
- Polymyositis 3
Showing 20 of 27 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for TOP1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
485 publications
- Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database.
2007 · Ann Rheum Dis · RCR 20.9 · 693 citations - Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome.
1980 · Arthritis Rheum · RCR 19 · 583 citations - Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers.
2023 · Clin Rev Allergy Immunol · RCR 14.5 · 101 citations - Predictors of progression in systemic sclerosis patients with interstitial lung disease.
2020 · Eur Respir J · RCR 11.5 · 183 citations - High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population.
1987 · Clin Exp Immunol · RCR 10.8 · 346 citations
Show 20 more of 485 total
- Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement.
2003 · Arthritis Rheum · RCR 10.5 · 369 citations - Association of antinuclear and antinucleolar antibodies in progressive systemic sclerosis.
1982 · Clin Exp Immunol · RCR 8.8 · 214 citations - High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients.
1986 · Science · RCR 8.6 · 321 citations - Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature.
2019 · Arthritis Res Ther · RCR 8.1 · 148 citations - Different antibody patterns and different prognoses in patients with scleroderma with various extent of skin sclerosis.
1986 · J Rheumatol · RCR 7.8 · 188 citations - Brief Report: Pulmonary Function Tests: High Rate of False-Negative Results in the Early Detection and Screening of Scleroderma-Related Interstitial Lung Disease.
2015 · Arthritis Rheumatol · RCR 7.3 · 164 citations - Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.
2004 · Rheumatology (Oxford) · RCR 6.8 · 208 citations - Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis.
2014 · Ann Rheum Dis · RCR 6.4 · 151 citations - The clinical relevance of autoantibodies in scleroderma.
2003 · Arthritis Res Ther · RCR 6.1 · 243 citations - Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma.
2014 · Arthritis Res Ther · RCR 6 · 156 citations - Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers.
2002 · Arthritis Res · RCR 5.9 · 239 citations - Autoantibody reactive with RNA polymerase III in systemic sclerosis.
1993 · Ann Intern Med · RCR 5.8 · 185 citations - Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants.
2001 · Semin Arthritis Rheum · RCR 5.7 · 216 citations - Prognostic Value of Lung Ultrasound B-Lines in Systemic Sclerosis.
2020 · Chest · RCR 5.5 · 71 citations - Biomarkers in the Pathogenesis, Diagnosis, and Treatment of Systemic Sclerosis.
2023 · J Inflamm Res · RCR 5.3 · 36 citations - Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies.
2010 · Arthritis Rheum · RCR 4.9 · 175 citations - Increased prevalence of systemic sclerosis in a Native American tribe in Oklahoma. Association with an Amerindian HLA haplotype.
1996 · Arthritis Rheum · RCR 4.8 · 169 citations - Lung ultrasound B-lines in systemic sclerosis: cut-off values and methodological indications for interstitial lung disease screening.
2022 · Rheumatology (Oxford) · RCR 4.4 · 37 citations - Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis.
2010 · J Dermatol · RCR 4.4 · 146 citations - Prognostic significance of anticentromere antibodies and anti-topoisomerase I antibodies in Raynaud's disease. A prospective study.
1991 · Arthritis Rheum · RCR 4.4 · 142 citations
Reference: B cellIEDB
2 publications
- Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis.
1989 · Proc Natl Acad Sci U S A · RCR 3.9 · 145 citations - Computational analysis of high-density peptide microarray data with application from systemic sclerosis to multiple sclerosis.
2012 · Autoimmun Rev · RCR 1 · 35 citations
Reference: T cellIEDB
5 publications
- Mapping of the immunodominant T cell epitopes of the protein topoisomerase I.
2004 · Ann Rheum Dis · RCR 0.5 · 21 citations - T cell lines from systemic sclerosis patients and healthy controls recognize multiple epitopes on DNA topoisomerase I.
2006 · J Autoimmun · RCR 0.5 · 18 citations - Evaluation of topoisomerase-1-specific CD8+ T-cell response in systemic sclerosis.
2005 · Ann N Y Acad Sci · RCR 0.2 · 12 citations - Determination of T Cell Responses in Thai Systemic Sclerosis Patients.
2022 · J Immunol Res · RCR 0.1 · 1 citations - Lymphocyte proliferation induced by high-affinity peptides for HLA-B*51:01 in Behçet's uveitis.
2019 · PLoS One · RCR 0.1 · 2 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.06
- gnomAD pLI
- 1
- gnomAD missense Z
- 4.47
- DepMap mean gene effect
- -1
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- animal organ regeneration
- cellular response to luteinizing hormone stimulus
- chromatin remodeling
- chromosome segregation
- circadian regulation of gene expression
- circadian rhythm
- DNA replication
- DNA topological change
- embryonic cleavage
- programmed cell death
- response to cAMP
- response to gamma radiation
- response to temperature stimulus
- response to xenobiotic stimulus
- rRNA transcription
Molecular functions
- ATP binding
- chromatin binding
- chromatin DNA binding
- DNA binding
- DNA binding, bending
- DNA topoisomerase type I (single strand cut, ATP-independent) activity
- double-stranded DNA binding
- molecular condensate scaffold activity
- protein domain specific binding
- protein serine/threonine kinase activity
- protein-containing complex binding
- RNA binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- single-stranded DNA binding
- supercoiled DNA binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- DNA topoisomerase I
- DNA topoisomerase I, DNA binding, eukaryotic-type
- DNA breaking-rejoining enzyme, catalytic core
- DNA topoisomerase I, DNA binding, N-terminal domain 2
- DNA topoisomerase I, DNA binding, N-terminal domain 1
- DNA topoisomerase I, eukaryotic-type
- DNA topoisomerase I, catalytic core, eukaryotic-type
- DNA topoisomerase I, catalytic core, alpha-helical subdomain, eukaryotic-type
- DNA topoisomerase I, catalytic core, alpha/beta subdomain
- DNA topoisomerase IB, active site
- Topoisomerase I C-terminal domain
- DNA topoisomerase I, DNA binding, eukaryotic-type, N-terminal domain superfamily
- DNA topoisomerase I, DNA-binding domain
- DNA topoisomerase IB
- Eukaryotic DNA topoisomerase I, catalytic core
- Eukaryotic DNA topoisomerase I, DNA binding fragment
- C-terminal topoisomerase domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TOP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TOP1 as an antibody target. Whether an autoantibody or antibody against TOP1 could matter depends on whether native TOP1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TOP1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label TOP1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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