Q9NS56 (TOPRS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase Topors
EC=6.3.2.-

Alternative name(s):
SUMO1-protein E3 ligase Topors
Topoisomerase I-binding RING finger protein
Topoisomerase I-binding arginine/serine-rich protein
Tumor suppressor p53-binding protein 3
Short name=p53-binding protein 3
Short name=p53BP3

Gene names

Name:	TOPORS
Synonyms:	LUN, TP53BPL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1045 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 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. Ref.8 Ref.11 Ref.12 Ref.14 Ref.16 Ref.18 Ref.20
Subunit structure	Interacts with PARK7/DJ-1 By similarity. Interacts with TOP1. Interacts with p53/TP53; can both ubiquitinate and sumoylate p53/TP53. Interacts with the SUMO1 conjugating enzyme UBE2I. Interacts with SUMO1. Interacts with NKX3-1; polyubiquitinates NKX3-1 and induces its proteasomal degradation. Interacts with SIN3A; sumoylates SIN3A. Interacts with IKBKE; induced by DNA damage. Ref.1 Ref.5 Ref.7 Ref.14 Ref.16 Ref.18 Ref.20
Subcellular location	Nucleus. Nucleus › PML body. Note: Localizes to discrete nuclear foci which partly overlap with PML nuclear bodies. Targeted to PML nuclear bodies upon DNA damage. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 Ref.16 Ref.18 Ref.20
Tissue specificity	Expressed at highest levels in testis and at lower levels in adrenal gland, bone marrow, brain, colon, heart, kidney, liver, muscle, ovary, pancreas, placenta, prostate, skeletal muscle, skin, small intestine, spleen, stomach, testis, thymus, thyroid and uterus. Expressed in the alveolar epithelium of the lung. Expression is commonly decreased in colon adenocarcinomas and lung cancers. Ref.2 Ref.5 Ref.10
Induction	By genotoxic agents such as cisplatin and camptothecin. Ref.12
Post-translational modification	Phosphorylation at Ser-98 regulates the E3 ubiquitin-protein ligase activity but not the SUMO1-protein ligase activity. Phosphorylation at Ser-718 increases the E3 ubiquitin-protein ligase activity versus the SUMO1-protein ligase activity resulting in increased p53/TP53 ubiquitination and degradation. Sumoylated. Ref.7 Ref.11
Involvement in disease	Retinitis pigmentosa 31 (RP31) [MIM:609923]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Contains 1 RING-type zinc finger.
Caution	Was originally (Ref.2) thought to bind to the palindromic consensus sequence 5'-TCCCAGCACTTTGGGA-3' and to regulate the transcription of numerous genes in the lung.
Sequence caution	The sequence AAC98530.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	DNA damage Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Retinitis pigmentosa
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intrinsic apoptotic signaling pathway in response to DNA damage Inferred from direct assay Ref.20. Source: UniProtKB maintenance of protein location in nucleus Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity PubMed 21159800. Source: BHF-UCL photoreceptor cell outer segment organization Inferred from sequence or structural similarity PubMed 21159800. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara positive regulation of ubiquitin-protein ligase activity Inferred from direct assay Ref.8. Source: BHF-UCL proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.16. Source: UniProtKB protein K48-linked ubiquitination Inferred from direct assay Ref.8. Source: BHF-UCL protein monoubiquitination Inferred from direct assay Ref.8. Source: BHF-UCL protein sumoylation Inferred from direct assay Ref.14. Source: UniProtKB regulation of cell proliferation Inferred from electronic annotation. Source: Compara retina layer formation Inferred from sequence or structural similarity PubMed 21159800. Source: BHF-UCL retinal cone cell development Inferred from sequence or structural similarity PubMed 21159800. Source: BHF-UCL retinal rod cell development Inferred from sequence or structural similarity PubMed 21159800. Source: BHF-UCL transcription, DNA-dependent Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	PML body Inferred from direct assay Ref.20. Source: UniProtKB centriole Inferred from direct assay PubMed 21159800. Source: BHF-UCL cilium basal body Inferred from direct assay PubMed 21159800. Source: BHF-UCL gamma-tubulin complex Inferred from direct assay PubMed 21159800. Source: BHF-UCL midbody Traceable author statement PubMed 21159800. Source: BHF-UCL nuclear speck Inferred from direct assay Ref.7. Source: UniProtKB photoreceptor connecting cilium Inferred from direct assay PubMed 21159800. Source: BHF-UCL spindle pole Inferred from direct assay PubMed 21159800. Source: BHF-UCL
Molecular_function	DNA binding Inferred from direct assay Ref.2. Source: UniProtKB SUMO ligase activity Inferred from direct assay Ref.14. Source: UniProtKB antigen binding Inferred from physical interaction Ref.5. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.16. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NS56-1)

Also known as: LUN-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NS56-2)

Also known as: LUN-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
     66-66: E → M

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1045	1045	E3 ubiquitin-protein ligase Topors		PRO_0000232626
Regions
	Zinc finger	103 – 142	40	RING-type
	Region	1 – 195	195	E3 ubiquitin-protein ligase activity
	Region	51 – 374	324	Required for DNA-binding
	Region	437 – 654	218	Interaction with SUMO1
	Region	437 – 574	138	Required for sumoylation and localization to discrete nuclear foci
	Region	456 – 882	427	Interaction with TOP1
	Region	456 – 731	276	Interaction with p53/TP53
	Region	854 – 917	64	Interaction with UBE2I
	Compositional bias	579 – 788	210	Arg-rich
	Compositional bias	854 – 895	42	Lys-rich
Amino acid modifications
	Modified residue	98	1	Phosphoserine Ref.15 Ref.17 Ref.19 Ref.21 Ref.22
	Modified residue	499	1	Phosphoserine Ref.15
	Modified residue	585	1	Phosphoserine Ref.15
	Modified residue	718	1	Phosphoserine; by PLK1 Ref.18
	Modified residue	864	1	Phosphoserine Ref.19 Ref.22
	Modified residue	866	1	Phosphoserine Ref.15 Ref.19 Ref.22
	Modified residue	914	1	Phosphoserine By similarity
	Cross-link	560		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Natural variations
	Alternative sequence	1 – 65	65	Missing in isoform 2.		VSP_017916
	Alternative sequence	66	1	E → M in isoform 2.		VSP_017917
	Natural variant	154	1	A → T. Ref.4 Corresponds to variant rs17855104 [ dbSNP | Ensembl ].		VAR_037629
	Natural variant	517	1	E → K. Ref.4 Corresponds to variant rs17855103 [ dbSNP | Ensembl ].		VAR_037630
	Natural variant	749	1	N → D. Ref.4 Corresponds to variant rs17857515 [ dbSNP | Ensembl ].		VAR_037631
	Natural variant	812	1	P → R. Corresponds to variant rs36034138 [ dbSNP | Ensembl ].		VAR_037632
Experimental info
	Mutagenesis	76	1	K → R: No effect on sumoylation. Ref.7
	Mutagenesis	98	1	S → A: Loss of phosphorylation but no effect on E3 ubiquitin-protein ligase activity. Ref.15
	Mutagenesis	98	1	S → D: Increase in E3 ubiquitin-protein ligase activity and increased binding to UBE2D1. No effect on SUMO1-protein ligase activity. Ref.15
	Mutagenesis	131	1	W → A: Abrogates E3 ubiquitin-protein ligase activity. Ref.8
	Mutagenesis	301	1	K → R: No effect on sumoylation. Ref.7
	Mutagenesis	485	1	K → R: No effect on sumoylation. Ref.7
	Mutagenesis	560	1	K → R: Strongly reduces sumoylation. Ref.7
	Mutagenesis	718	1	S → A: Loss of phosphorylation by PLK1 and increases in p53/TP53 stability. Ref.18
	Mutagenesis	921	1	K → R: No effect on sumoylation. Ref.7
	Sequence conflict	124 – 125	2	CF → K in AAC98530. Ref.5
	Sequence conflict	257	1	N → S in AAD23379. Ref.1
	Sequence conflict	308	1	F → S in AAD23379. Ref.1
	Sequence conflict	922	1	E → G in AAD23379. Ref.1
	Sequence conflict	1040	1	R → K in AAD23379. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (LUN-1) [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 3DA635FDB5C83B77	FASTA	1,045	119,198
	10 20 30 40 50 60 MGSQPPLGSP LSREEGEAPP PAPASEGRRR SRRVRLRGSC RHRPSFLGCR ELAASAPARP 70 80 90 100 110 120 APASSEIMAS AAKEFKMDNF SPKAGTSKLQ QTVPADASPD SKCPICLDRF DNVSYLDRCL 130 140 150 160 170 180 HKFCFRCVQE WSKNKAECPL CKQPFDSIFH SVRAEDDFKE YVLRPSYNGS FVTPDRRFRY 190 200 210 220 230 240 RTTLTRERNA SVYSPSGPVN RRTTTPPDSG VLFEGLGIST RPRDVEIPQF MRQIAVRRPT 250 260 270 280 290 300 TADERSLRKI QEQDIINFRR TLYRAGARVR NIEDGGRYRD ISAEFFRRNP ACLHRLVPWL 310 320 330 340 350 360 KRELTVLFGA HGSLVNIVQH IIMSNVTRYD LESQAFVSDL RPFLLNRTEH FIHEFISFAR 370 380 390 400 410 420 SPFNMAAFDQ HANYDCPAPS YEEGSHSDSS VITISPDEAE TQELDINVAT VSQAPWDDET 430 440 450 460 470 480 PGPSYSSSEQ VHVTMSSLLN TSDSSDEELV TGGATSQIQG VQTNDDLNND SDDSSDNCVI 490 500 510 520 530 540 VGFVKPLAER TPELVELSSD SEDLGSYEKM ETVKTQEQEQ SYSSGDSDVS RCSSPHSVLG 550 560 570 580 590 600 KDEQINKGHC DSSTRIKSKK EEKRSTSLSS PRNLNSSVRG DRVYSPYNHR HRKRGRSRSS 610 620 630 640 650 660 DSRSQSRSGH DQKNHRKHHG KKRMKSKRSR SRESSRPRGR RDKKRSRTRD SSWSRRSQTL 670 680 690 700 710 720 SLSSESTSRS RSRSSDHGKR RSRSRNRDRY YLRNNYGSRY KWEYTYYSRN KDRDGYESSY 730 740 750 760 770 780 RRRTLSRAHY SRQSSSPEFR VQSFSERTNA RKKNNHSERK YYYYERHRSR SLSSNRSRTA 790 800 810 820 830 840 STGTDRVRNE KPGGKRKYKT RHLEGTNEVA QPSREFASKA KDSHYQKSSS KLDGNYKNES 850 860 870 880 890 900 DTFSDSRSSD RETKHKRRKR KTRSLSVEIV YEGKATDTTK HHKKKKKKHK KKHKKHHGDN 910 920 930 940 950 960 ASRSPVVITI DSDSDKDSEV KEDTECDNSG PQDPLQNEFL APSLEPFETK DVVTIEAEFG 970 980 990 1000 1010 1020 VLDKECDIAT LSNNLNNANK TVDNIPPLAA SVEQTLDVRE ESTFVSDLEN QPSNIVSLQT 1030 1040 EPSRQLPSPR TSLMSVCLGR DCDMS
	Isoform 2 (LUN-2) [UniParc]. Checksum: 85E2A39A2978B20E	FASTA	980	112,344
	10 20 30 40 50 60 MIMASAAKEF KMDNFSPKAG TSKLQQTVPA DASPDSKCPI CLDRFDNVSY LDRCLHKFCF 70 80 90 100 110 120 RCVQEWSKNK AECPLCKQPF DSIFHSVRAE DDFKEYVLRP SYNGSFVTPD RRFRYRTTLT 130 140 150 160 170 180 RERNASVYSP SGPVNRRTTT PPDSGVLFEG LGISTRPRDV EIPQFMRQIA VRRPTTADER 190 200 210 220 230 240 SLRKIQEQDI INFRRTLYRA GARVRNIEDG GRYRDISAEF FRRNPACLHR LVPWLKRELT 250 260 270 280 290 300 VLFGAHGSLV NIVQHIIMSN VTRYDLESQA FVSDLRPFLL NRTEHFIHEF ISFARSPFNM 310 320 330 340 350 360 AAFDQHANYD CPAPSYEEGS HSDSSVITIS PDEAETQELD INVATVSQAP WDDETPGPSY 370 380 390 400 410 420 SSSEQVHVTM SSLLNTSDSS DEELVTGGAT SQIQGVQTND DLNNDSDDSS DNCVIVGFVK 430 440 450 460 470 480 PLAERTPELV ELSSDSEDLG SYEKMETVKT QEQEQSYSSG DSDVSRCSSP HSVLGKDEQI 490 500 510 520 530 540 NKGHCDSSTR IKSKKEEKRS TSLSSPRNLN SSVRGDRVYS PYNHRHRKRG RSRSSDSRSQ 550 560 570 580 590 600 SRSGHDQKNH RKHHGKKRMK SKRSRSRESS RPRGRRDKKR SRTRDSSWSR RSQTLSLSSE 610 620 630 640 650 660 STSRSRSRSS DHGKRRSRSR NRDRYYLRNN YGSRYKWEYT YYSRNKDRDG YESSYRRRTL 670 680 690 700 710 720 SRAHYSRQSS SPEFRVQSFS ERTNARKKNN HSERKYYYYE RHRSRSLSSN RSRTASTGTD 730 740 750 760 770 780 RVRNEKPGGK RKYKTRHLEG TNEVAQPSRE FASKAKDSHY QKSSSKLDGN YKNESDTFSD 790 800 810 820 830 840 SRSSDRETKH KRRKRKTRSL SVEIVYEGKA TDTTKHHKKK KKKHKKKHKK HHGDNASRSP 850 860 870 880 890 900 VVITIDSDSD KDSEVKEDTE CDNSGPQDPL QNEFLAPSLE PFETKDVVTI EAEFGVLDKE 910 920 930 940 950 960 CDIATLSNNL NNANKTVDNI PPLAASVEQT LDVREESTFV SDLENQPSNI VSLQTEPSRQ 970 980 LPSPRTSLMS VCLGRDCDMS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interaction between human topoisomerase I and a novel RING finger/arginine-serine protein." Haluska P. Jr., Saleem A., Rasheed Z., Ahmed F., Su E.W., Liu L.F., Rubin E.H. Nucleic Acids Res. 27:2538-2544(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TOP1, SUBCELLULAR LOCATION.
[2]	"Cloning and characterization of LUN, a novel RING-finger protein that is highly expressed in lung and specifically binds to a palindromic sequence." Chu D., Kakazu N., Gorrin-Rivas M.J., Lu H.P., Kawata M., Abe T., Ueda K., Adachi Y. J. Biol. Chem. 276:14004-14013(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PUTATIVE DNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Lung.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS THR-154; LYS-517 AND ASP-749. Tissue: Placenta.
[5]	"Identification of a novel gene encoding a p53-associated protein." Zhou R., Wen H., Ao S.-Z. Gene 235:93-101(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-1045 (ISOFORM 1), INTERACTION WITH TP53, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"The topoisomerase I-binding RING protein, topors, is associated with promyelocytic leukemia nuclear bodies." Rasheed Z.A., Saleem A., Ravee Y., Pandolfi P.P., Rubin E.H. Exp. Cell Res. 277:152-160(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"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. 290:13-27(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUMO1 AND UBE2I, SUBCELLULAR LOCATION, SUMOYLATION, MUTAGENESIS OF LYS-76; LYS-301; LYS-485; LYS-560 AND LYS-921.
[8]	"Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53." Rajendra R., Malegaonkar D., Pungaliya P., Marshall H., Rasheed Z., Brownell J., Liu L.F., Lutzker S., Saleem A., Rubin E.H. J. Biol. Chem. 279:36440-36444(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TRP-131.
[9]	"Expression of LUN gene that encodes a novel RING finger protein is correlated with development and progression of non-small cell lung cancer." Oyanagi H., Takenaka K., Ishikawa S., Kawano Y., Adachi Y., Ueda K., Wada H., Tanaka F. Lung Cancer 46:21-28(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REDUCED EXPRESSION IN LUNG CANCERS.
[10]	"The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor." Saleem A., Dutta J., Malegaonkar D., Rasheed F., Rasheed Z., Rajendra R., Marshall H., Luo M., Li H., Rubin E.H. Oncogene 23:5293-5300(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, REDUCED EXPRESSION IN COLON CANCERS.
[11]	"Topors acts as a SUMO-1 E3 ligase for p53 in vitro and in vivo." Weger S., Hammer E., Heilbronn R. FEBS Lett. 579:5007-5012(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUMOYLATION.
[12]	"Topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage." Lin L., Ozaki T., Takada Y., Kageyama H., Nakamura Y., Hata A., Zhang J.H., Simonds W.F., Nakagawara A., Koseki H. Oncogene 24:3385-3396(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
[13]	"Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular retinal pigment epithelium atrophy." Chakarova C.F., Papaioannou M.G., Khanna H., Lopez I., Waseem N., Shah A., Theis T., Friedman J., Maubaret C., Bujakowska K., Veraitch B., El-Aziz M.M.A., Prescott de Q., Parapuram S.K., Bickmore W.A., Munro P.M.G., Gal A., Hamel C.P. , Marigo V., Ponting C.P., Wissinger B., Zrenner E., Matter K., Swaroop A., Koenekoop R.K., Bhattacharya S.S. Am. J. Hum. Genet. 81:1098-1103(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN RP31.
[14]	"TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins." Pungaliya P., Kulkarni D., Park H.J., Marshall H., Zheng H., Lackland H., Saleem A., Rubin E.H. J. Proteome Res. 6:3918-3923(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIN3A.
[15]	"Identification of phosphorylation sites of TOPORS and a role for serine 98 in the regulation of ubiquitin but not SUMO E3 ligase activity." Park H.J., Zheng H., Kulkarni D., Kerrigan J., Pungaliya P., Saleem A., Rubin E.H. Biochemistry 47:13887-13896(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-98; SER-499; SER-585 AND SER-866, MASS SPECTROMETRY, MUTAGENESIS OF SER-98.
[16]	"Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1." Guan B., Pungaliya P., Li X., Uquillas C., Mutton L.N., Rubin E.H., Bieberich C.J. J. Biol. Chem. 283:4834-4840(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NKX3-1, SUBCELLULAR LOCATION.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Plk1-mediated phosphorylation of Topors regulates p53 stability." Yang X., Li H., Zhou Z., Wang W.H., Deng A., Andrisani O., Liu X. J. Biol. Chem. 284:18588-18592(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLK1, PHOSPHORYLATION AT SER-718 BY PLK1, MUTAGENESIS OF SER-718, SUBCELLULAR LOCATION.
[19]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-864 AND SER-866, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is essential for protection against DNA-damage-triggered cell death." Renner F., Moreno R., Schmitz M.L. Mol. Cell 37:503-515(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH IKBKE, SUBCELLULAR LOCATION.
[21]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-864 AND SER-866, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF098300 mRNA. Translation: AAD23379.1. AB045732 mRNA. Translation: BAB03714.1. AB045733 mRNA. Translation: BAB03715.1. AL353671 Genomic DNA. Translation: CAH71253.1. AL353671 Genomic DNA. Translation: CAH71254.1. BC060884 mRNA. Translation: AAH60884.1. U82939 mRNA. Translation: AAC98530.1. Different initiation.
IPI	IPI00396077. IPI00643426.
RefSeq	NP_001182551.1. NM_001195622.1. NP_005793.2. NM_005802.4.
UniGene	Hs.589962.
3D structure databases
ProteinModelPortal	Q9NS56.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NS56. 11 interactions.
MINT	MINT-94004.
STRING	9606.ENSP00000353735.
PTM databases
PhosphoSite	Q9NS56.
Polymorphism databases
DMDM	74752935.
Proteomic databases
PaxDb	Q9NS56.
PRIDE	Q9NS56.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360538; ENSP00000353735; ENSG00000197579. ENST00000379858; ENSP00000369187; ENSG00000197579.
GeneID	10210.
KEGG	hsa:10210.
UCSC	uc003zrb.3. human. uc003zrc.3. human.
Organism-specific databases
CTD	10210.
GeneCards	GC09M032496.
HGNC	HGNC:21653. TOPORS.
MIM	609507. gene. 609923. phenotype.
neXtProt	NX_Q9NS56.
Orphanet	791. Retinitis pigmentosa.
PharmGKB	PA134979531.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG244178.
HOGENOM	HOG000231723.
HOVERGEN	HBG080410.
InParanoid	Q9NS56.
KO	K10631.
OMA	DIINFRR.
OrthoDB	EOG47H5PC.
PhylomeDB	Q9NS56.
Gene expression databases
Bgee	Q9NS56.
CleanEx	HS_TOPORS.
Genevestigator	Q9NS56.
GermOnline	ENSG00000197579. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TOPORS. human.
GenomeRNAi	10210.
NextBio	38656.
SOURCE	Search...

Entry information

Entry name

TOPRS_HUMAN

Accession

Primary (citable) accession number: Q9NS56
Secondary accession number(s): O43273 , Q6P987, Q9NS55, Q9UNR9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2006
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.