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Identification
HMDB Protein ID HMDBP09258
Secondary Accession Numbers
  • 15086
Name E3 ubiquitin-protein ligase Topors
Synonyms
  1. SUMO1-protein E3 ligase Topors
  2. Topoisomerase I-binding RING finger protein
  3. Topoisomerase I-binding arginine/serine-rich protein
  4. Tumor suppressor p53-binding protein 3
  5. p53-binding protein 3
  6. p53BP3
Gene Name TOPORS
Protein Type Enzyme
Biological Properties
General Function Involved in protein binding
Specific Function Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA damage- induced cell death through IKBKE sumoylation
Pathways Not Available
Reactions Not Available
GO Classification
Function
ion binding
cation binding
metal ion binding
binding
transition metal ion binding
zinc ion binding
protein binding
Cellular Location
  1. Nucleus
  2. Nucleus
  3. PML body
Gene Properties
Chromosome Location Chromosome:9
Locus 9p21
SNPs TOPORS
Gene Sequence
>3138 bp
ATGGGGTCGCAGCCGCCGCTGGGGTCTCCGCTGTCTCGCGAGGAGGGTGAAGCGCCCCCG
CCTGCTCCCGCTTCGGAGGGTAGGCGGAGAAGTCGCCGGGTACGCCTTCGCGGATCCTGC
CGACACCGACCTAGCTTTCTGGGCTGCCGGGAGCTCGCGGCGAGCGCCCCAGCCAGGCCT
GCGCCGGCATCCTCCGAGATAATGGCATCAGCTGCTAAGGAATTTAAAATGGACAACTTT
TCACCTAAAGCTGGCACTAGCAAATTGCAACAGACAGTACCAGCTGATGCATCTCCTGAT
TCTAAGTGTCCTATATGCTTGGATAGATTTGATAATGTGTCTTACTTAGATCGCTGCTTA
CATAAGTTCTGTTTTCGCTGTGTACAGGAGTGGTCAAAAAACAAAGCTGAATGCCCACTA
TGTAAACAGCCCTTTGATTCTATTTTCCATTCTGTGAGGGCAGAAGATGACTTCAAGGAG
TATGTCCTAAGGCCTTCGTATAATGGTTCTTTTGTCACCCCTGATCGACGATTTCGCTAC
CGTACAACTCTGACAAGGGAACGAAACGCTTCTGTGTATTCACCTAGTGGTCCTGTGAAC
AGAAGAACAACAACTCCACCGGATAGTGGAGTACTGTTTGAAGGGTTAGGCATTTCAACA
AGACCTAGAGATGTTGAAATTCCTCAGTTTATGAGACAGATTGCAGTAAGGAGGCCAACT
ACGGCAGATGAAAGATCTTTGCGGAAAATTCAAGAACAAGATATTATTAATTTTAGACGA
ACTCTTTATCGTGCTGGTGCTCGAGTTAGAAATATTGAAGATGGTGGCCGCTACAGGGAT
ATTTCAGCTGAATTTTTCCGTAGAAATCCAGCTTGCCTTCACAGATTAGTCCCCTGGTTA
AAACGTGAACTTACAGTTCTTTTTGGAGCTCATGGATCTTTAGTGAATATTGTCCAGCAT
ATTATCATGAGTAATGTTACTCGCTATGACTTGGAGAGTCAGGCATTTGTGTCTGATTTA
AGACCATTTTTACTTAATCGAACTGAGCATTTTATACATGAATTTATCAGTTTTGCCCGA
TCTCCTTTTAACATGGCAGCCTTTGACCAGCATGCCAATTATGATTGCCCTGCTCCTTCA
TACGAAGAAGGCAGCCATTCTGATTCTTCAGTCATAACAATATCTCCAGATGAGGCTGAG
ACCCAAGAGCTGGATATTAATGTAGCCACTGTTAGTCAGGCACCATGGGATGATGAAACT
CCAGGACCATCTTACTCAAGCTCAGAGCAGGTACACGTTACTATGTCTTCTCTTTTAAAT
ACTTCTGACAGTTCAGATGAAGAACTTGTCACAGGAGGAGCCACGTCTCAGATACAAGGA
GTACAAACCAATGACGACCTAAATAATGACAGTGATGATTCTTCAGATAATTGTGTCATT
GTTGGGTTTGTTAAACCACTAGCTGAGAGGACCCCAGAACTTGTTGAACTGTCCTCTGAT
TCTGAGGACTTAGGTTCTTATGAGAAAATGGAGACAGTGAAGACACAAGAACAGGAGCAA
TCTTACAGTTCTGGTGATAGCGATGTTAGTAGATGCTCATCTCCACACTCTGTCCTTGGA
AAGGATGAACAAATAAATAAAGGTCATTGTGATTCTAGTACAAGAATCAAATCAAAGAAG
GAAGAGAAACGATCTACATCATTGTCATCTCCCAGAAACCTGAACTCATCTGTAAGAGGA
GACAGAGTATATTCTCCATATAACCATAGACACAGAAAGAGGGGAAGATCAAGAAGTTCA
GATTCACGTTCTCAGAGTAGAAGTGGGCATGATCAGAAGAATCATAGAAAGCATCATGGG
AAGAAAAGAATGAAAAGTAAACGATCCAGAAGCAGGGAAAGTAGCAGACCTAGAGGGAGA
AGAGACAAAAAGAGATCAAGAACTAGAGATAGCAGTTGGTCCAGAAGAAGCCAAACTCTG
TCTCTAAGTAGTGAAAGCACAAGCAGATCAAGGTCTCGTAGCAGTGATCATGGTAAAAGA
AGATCACGGAGCAGAAATAGAGATCGTTATTATTTAAGAAATAATTATGGAAGCAGATAC
AAATGGGAGTATACTTATTACAGTAGAAACAAGGACAGGGATGGGTACGAATCATCTTAC
AGGAGGAGGACTCTGTCCAGAGCTCATTATTCTAGACAGTCTTCAAGTCCAGAATTTAGA
GTTCAGTCCTTTTCTGAAAGAACAAATGCTAGGAAAAAAAATAATCACAGTGAGAGGAAG
TATTACTACTATGAAAGGCACAGATCAAGGAGCCTGTCTAGTAACAGATCAAGGACTGCA
TCTACCGGGACTGACCGGGTGAGAAATGAAAAGCCTGGAGGGAAACGAAAATACAAAACA
CGGCATTTGGAGGGTACTAACGAAGTGGCTCAGCCATCTCGTGAATTTGCTTCTAAAGCA
AAGGACAGTCATTACCAAAAATCTTCATCAAAATTGGATGGAAACTACAAAAATGAGAGT
GATACCTTTTCAGACAGCCGATCATCAGACAGAGAGACAAAACACAAAAGGAGAAAAAGG
AAGACCCGGAGCCTAAGTGTAGAGATAGTTTATGAAGGAAAAGCTACTGATACAACTAAA
CACCATAAAAAGAAAAAGAAGAAACATAAGAAGAAGCATAAGAAACACCATGGAGATAAT
GCTTCACGTTCCCCAGTTGTAATTACCATTGACAGTGACAGTGATAAGGATTCTGAAGTA
AAGGAGGATACAGAATGTGACAATAGTGGTCCTCAAGACCCTCTACAAAATGAGTTTTTG
GCTCCTTCCTTGGAACCATTTGAAACTAAAGATGTAGTTACAATAGAAGCTGAATTTGGT
GTGCTGGACAAGGAATGTGATATTGCCACACTTAGTAACAACTTGAATAATGCCAACAAA
ACTGTAGATAATATTCCACCTCTGGCAGCTTCAGTTGAACAAACTCTCGATGTAAGAGAA
GAGAGCACCTTTGTTTCTGATTTGGAGAACCAGCCCAGTAACATTGTGTCTCTTCAAACT
GAGCCATCAAGGCAATTGCCATCGCCACGGACATCATTAATGTCAGTATGTCTTGGTAGA
GACTGTGATATGTCTTAA
Protein Properties
Number of Residues 1045
Molecular Weight 119196.4
Theoretical pI 9.99
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>E3 ubiquitin-protein ligase Topors
MGSQPPLGSPLSREEGEAPPPAPASEGRRRSRRVRLRGSCRHRPSFLGCRELAASAPARP
APASSEIMASAAKEFKMDNFSPKAGTSKLQQTVPADASPDSKCPICLDRFDNVSYLDRCL
HKFCFRCVQEWSKNKAECPLCKQPFDSIFHSVRAEDDFKEYVLRPSYNGSFVTPDRRFRY
RTTLTRERNASVYSPSGPVNRRTTTPPDSGVLFEGLGISTRPRDVEIPQFMRQIAVRRPT
TADERSLRKIQEQDIINFRRTLYRAGARVRNIEDGGRYRDISAEFFRRNPACLHRLVPWL
KRELTVLFGAHGSLVNIVQHIIMSNVTRYDLESQAFVSDLRPFLLNRTEHFIHEFISFAR
SPFNMAAFDQHANYDCPAPSYEEGSHSDSSVITISPDEAETQELDINVATVSQAPWDDET
PGPSYSSSEQVHVTMSSLLNTSDSSDEELVTGGATSQIQGVQTNDDLNNDSDDSSDNCVI
VGFVKPLAERTPELVELSSDSEDLGSYEKMETVKTQEQEQSYSSGDSDVSRCSSPHSVLG
KDEQINKGHCDSSTRIKSKKEEKRSTSLSSPRNLNSSVRGDRVYSPYNHRHRKRGRSRSS
DSRSQSRSGHDQKNHRKHHGKKRMKSKRSRSRESSRPRGRRDKKRSRTRDSSWSRRSQTL
SLSSESTSRSRSRSSDHGKRRSRSRNRDRYYLRNNYGSRYKWEYTYYSRNKDRDGYESSY
RRRTLSRAHYSRQSSSPEFRVQSFSERTNARKKNNHSERKYYYYERHRSRSLSSNRSRTA
STGTDRVRNEKPGGKRKYKTRHLEGTNEVAQPSREFASKAKDSHYQKSSSKLDGNYKNES
DTFSDSRSSDRETKHKRRKRKTRSLSVEIVYEGKATDTTKHHKKKKKKHKKKHKKHHGDN
ASRSPVVITIDSDSDKDSEVKEDTECDNSGPQDPLQNEFLAPSLEPFETKDVVTIEAEFG
VLDKECDIATLSNNLNNANKTVDNIPPLAASVEQTLDVREESTFVSDLENQPSNIVSLQT
EPSRQLPSPRTSLMSVCLGRDCDMS
GenBank ID Protein 9664146
UniProtKB/Swiss-Prot ID Q9NS56
UniProtKB/Swiss-Prot Entry Name TOPRS_HUMAN
PDB IDs Not Available
GenBank Gene ID AB045732
GeneCard ID TOPORS
GenAtlas ID TOPORS
HGNC ID HGNC:21653
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  5. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP: Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9. [PubMed:15302935 ]
  6. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  7. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  8. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [PubMed:15164053 ]
  9. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  10. Rajendra R, Malegaonkar D, Pungaliya P, Marshall H, Rasheed Z, Brownell J, Liu LF, Lutzker S, Saleem A, Rubin EH: Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J Biol Chem. 2004 Aug 27;279(35):36440-4. Epub 2004 Jul 9. [PubMed:15247280 ]
  11. Yang X, Li H, Zhou Z, Wang WH, Deng A, Andrisani O, Liu X: Plk1-mediated phosphorylation of Topors regulates p53 stability. J Biol Chem. 2009 Jul 10;284(28):18588-92. doi: 10.1074/jbc.C109.001560. Epub 2009 May 27. [PubMed:19473992 ]
  12. Haluska P Jr, Saleem A, Rasheed Z, Ahmed F, Su EW, Liu LF, Rubin EH: Interaction between human topoisomerase I and a novel RING finger/arginine-serine protein. Nucleic Acids Res. 1999 Jun 15;27(12):2538-44. [PubMed:10352183 ]
  13. Chu D, Kakazu N, Gorrin-Rivas MJ, Lu HP, Kawata M, Abe T, Ueda K, Adachi Y: Cloning and characterization of LUN, a novel ring finger protein that is highly expressed in lung and specifically binds to a palindromic sequence. J Biol Chem. 2001 Apr 27;276(17):14004-13. Epub 2001 Jan 25. [PubMed:11278651 ]
  14. Zhou R, Wen H, Ao SZ: Identification of a novel gene encoding a p53-associated protein. Gene. 1999 Jul 22;235(1-2):93-101. [PubMed:10415337 ]
  15. Rasheed ZA, Saleem A, Ravee Y, Pandolfi PP, Rubin EH: The topoisomerase I-binding RING protein, topors, is associated with promyelocytic leukemia nuclear bodies. Exp Cell Res. 2002 Jul 15;277(2):152-60. [PubMed:12083797 ]
  16. Weger S, Hammer E, Engstler M: The DNA topoisomerase I binding protein topors as a novel cellular target for SUMO-1 modification: characterization of domains necessary for subcellular localization and sumolation. Exp Cell Res. 2003 Oct 15;290(1):13-27. [PubMed:14516784 ]
  17. Oyanagi H, Takenaka K, Ishikawa S, Kawano Y, Adachi Y, Ueda K, Wada H, Tanaka F: Expression of LUN gene that encodes a novel RING finger protein is correlated with development and progression of non-small cell lung cancer. Lung Cancer. 2004 Oct;46(1):21-8. [PubMed:15364129 ]
  18. Saleem A, Dutta J, Malegaonkar D, Rasheed F, Rasheed Z, Rajendra R, Marshall H, Luo M, Li H, Rubin EH: The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor. Oncogene. 2004 Jul 8;23(31):5293-300. [PubMed:15107820 ]
  19. Weger S, Hammer E, Heilbronn R: Topors acts as a SUMO-1 E3 ligase for p53 in vitro and in vivo. FEBS Lett. 2005 Sep 12;579(22):5007-12. [PubMed:16122737 ]
  20. Lin L, Ozaki T, Takada Y, Kageyama H, Nakamura Y, Hata A, Zhang JH, Simonds WF, Nakagawara A, Koseki H: topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage. Oncogene. 2005 May 12;24(21):3385-96. [PubMed:15735665 ]
  21. Chakarova CF, Papaioannou MG, Khanna H, Lopez I, Waseem N, Shah A, Theis T, Friedman J, Maubaret C, Bujakowska K, Veraitch B, Abd El-Aziz MM, Prescott de Q, Parapuram SK, Bickmore WA, Munro PM, Gal A, Hamel CP, Marigo V, Ponting CP, Wissinger B, Zrenner E, Matter K, Swaroop A, Koenekoop RK, Bhattacharya SS: Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular retinal pigment epithelium atrophy. Am J Hum Genet. 2007 Nov;81(5):1098-103. Epub 2007 Sep 26. [PubMed:17924349 ]
  22. Pungaliya P, Kulkarni D, Park HJ, Marshall H, Zheng H, Lackland H, Saleem A, Rubin EH: TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins. J Proteome Res. 2007 Oct;6(10):3918-23. Epub 2007 Sep 6. [PubMed:17803295 ]
  23. Park HJ, Zheng H, Kulkarni D, Kerrigan J, Pungaliya P, Saleem A, Rubin EH: Identification of phosphorylation sites of TOPORS and a role for serine 98 in the regulation of ubiquitin but not SUMO E3 ligase activity. Biochemistry. 2008 Dec 30;47(52):13887-96. doi: 10.1021/bi801904q. [PubMed:19053840 ]
  24. Guan B, Pungaliya P, Li X, Uquillas C, Mutton LN, Rubin EH, Bieberich CJ: Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1. J Biol Chem. 2008 Feb 22;283(8):4834-40. Epub 2007 Dec 12. [PubMed:18077445 ]
  25. Renner F, Moreno R, Schmitz ML: SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death. Mol Cell. 2010 Feb 26;37(4):503-15. doi: 10.1016/j.molcel.2010.01.018. [PubMed:20188669 ]