UniProt Accession

 TOPRS_HUMAN; Q9NS56; O43273; Q6P987; Q9NS55; Q9UNR9 

Genbank Protein ID

 AF098300; AB045732; AB045733; AL353671; AL353671; BC060884; U82939 

Genbank Nucleotide ID

 AAD23379.1; BAB03714.1; BAB03715.1; CAH71253.1; CAH71254.1; AAH60884.1; AAC98530.1 

Protein Name

 E3 ubiquitin-protein ligase Topors 

Protein Synonyms/Alias

 SUMO1-protein E3 ligase Topors; Topoisomerase I-binding RING finger protein; Topoisomerase I-binding arginine/serine-rich protein; Tumor suppressor p53-binding protein 3; p53-binding protein 3; p53BP3 

Gene Name

 TOPORS 

Gene Synonyms/Alias

 LUN; TP53BPL 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
73	EIMASAAKEFKMDNF	ubiquitination	[1, 2, 3, 4, 5, 6]
76	ASAAKEFKMDNFSPK	ubiquitination	[4, 6]
83	KMDNFSPKAGTSKLQ	ubiquitination	[2, 4, 6, 7, 8]
88	SPKAGTSKLQQTVPA	ubiquitination	[2, 4, 7]
102	ADASPDSKCPICLDR	ubiquitination	[4]
122	YLDRCLHKFCFRCVQ	ubiquitination	[4]
133	RCVQEWSKNKAECPL	ubiquitination	[4]
135	VQEWSKNKAECPLCK	ubiquitination	[4, 6]
249	ADERSLRKIQEQDII	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9, 10]
560	STRIKSKKEEKRSTS	sumoylation	[11]
711	YTYYSRNKDRDGYES	ubiquitination	[3, 4, 6]
760	KNNHSERKYYYYERH	ubiquitination	[4, 6]
819	PSREFASKAKDSHYQ	ubiquitination	[2, 4, 8]
831	HYQKSSSKLDGNYKN	ubiquitination	[3]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [9] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [10] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [11] 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.
 Weger S, Hammer E, Engstler M.
 Exp Cell Res. 2003 Oct 15;290(1):13-27. [PMID: 14516784] 

Functional Description

 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 p53/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. 

Sequence Annotation

 ZN_FING 103 142 RING-type.
 REGION 1 195 E3 ubiquitin-protein ligase activity.
 REGION 51 374 Required for DNA-binding.
 REGION 437 654 Interaction with SUMO1.
 REGION 437 574 Required for sumoylation and localization
 REGION 456 882 Interaction with TOP1.
 REGION 456 731 Interaction with p53/TP53.
 REGION 854 917 Interaction with UBE2I.
 MOD_RES 98 98 Phosphoserine.
 MOD_RES 499 499 Phosphoserine.
 MOD_RES 585 585 Phosphoserine.
 MOD_RES 718 718 Phosphoserine; by PLK1.
 MOD_RES 864 864 Phosphoserine.
 MOD_RES 866 866 Phosphoserine.
 MOD_RES 914 914 Phosphoserine (By similarity).
 CROSSLNK 560 560 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 Alternative splicing; Complete proteome; DNA damage; Isopeptide bond; Ligase; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Retinitis pigmentosa; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1045 AA 

Protein Sequence

Gene Ontology

 GO:0005814; C:centriole; IDA:BHF-UCL.
 GO:0036064; C:cilium basal body; IDA:BHF-UCL.
 GO:0000930; C:gamma-tubulin complex; IDA:BHF-UCL.
 GO:0030496; C:midbody; TAS:BHF-UCL.
 GO:0016607; C:nuclear speck; IDA:UniProtKB.
 GO:0032391; C:photoreceptor connecting cilium; IDA:BHF-UCL.
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0000922; C:spindle pole; IDA:BHF-UCL.
 GO:0003823; F:antigen binding; IPI:UniProtKB.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0019789; F:SUMO ligase activity; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
 GO:0051457; P:maintenance of protein location in nucleus; IDA:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
 GO:0035845; P:photoreceptor cell outer segment organization; ISS:BHF-UCL.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0051443; P:positive regulation of ubiquitin-protein ligase activity; IDA:BHF-UCL.
 GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
 GO:0070936; P:protein K48-linked ubiquitination; IDA:BHF-UCL.
 GO:0006513; P:protein monoubiquitination; IDA:BHF-UCL.
 GO:0016925; P:protein sumoylation; IDA:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; IEA:Compara.
 GO:0010842; P:retina layer formation; ISS:BHF-UCL.
 GO:0046549; P:retinal cone cell development; ISS:BHF-UCL.
 GO:0046548; P:retinal rod cell development; ISS:BHF-UCL.
 GO:0006351; P:transcription, DNA-dependent; NAS:UniProtKB. 

Interpro

 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 

Pfam

  

SMART

 SM00184; RING 

PROSITE

 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS