TOPRS_HUMAN
ID TOPRS_HUMAN Reviewed; 1045 AA.
AC Q9NS56; O43273; Q6P987; Q9NS55; Q9UNR9;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=E3 ubiquitin-protein ligase Topors;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase Topors {ECO:0000305};
DE AltName: Full=SUMO1-protein E3 ligase Topors;
DE AltName: Full=Topoisomerase I-binding RING finger protein;
DE AltName: Full=Topoisomerase I-binding arginine/serine-rich protein;
DE AltName: Full=Tumor suppressor p53-binding protein 3;
DE Short=p53-binding protein 3;
DE Short=p53BP3;
GN Name=TOPORS; Synonyms=LUN, TP53BPL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TOP1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10352183; DOI=10.1093/nar/27.12.2538;
RA Haluska P. Jr., Saleem A., Rasheed Z., Ahmed F., Su E.W., Liu L.F.,
RA Rubin E.H.;
RT "Interaction between human topoisomerase I and a novel RING
RT finger/arginine-serine protein.";
RL Nucleic Acids Res. 27:2538-2544(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PUTATIVE DNA-BINDING,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=11278651; DOI=10.1074/jbc.m010262200;
RA Chu D., Kakazu N., Gorrin-Rivas M.J., Lu H.P., Kawata M., Abe T., Ueda K.,
RA Adachi Y.;
RT "Cloning and characterization of LUN, a novel RING-finger protein that is
RT highly expressed in lung and specifically binds to a palindromic
RT sequence.";
RL J. Biol. Chem. 276:14004-14013(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS THR-154;
RP LYS-517 AND ASP-749.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-1045 (ISOFORM 1), INTERACTION WITH TP53,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10415337; DOI=10.1016/s0378-1119(99)00203-6;
RA Zhou R., Wen H., Ao S.-Z.;
RT "Identification of a novel gene encoding a p53-associated protein.";
RL Gene 235:93-101(1999).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=12083797; DOI=10.1006/excr.2002.5550;
RA Rasheed Z.A., Saleem A., Ravee Y., Pandolfi P.P., Rubin E.H.;
RT "The topoisomerase I-binding RING protein, topors, is associated with
RT promyelocytic leukemia nuclear bodies.";
RL Exp. Cell Res. 277:152-160(2002).
RN [7]
RP INTERACTION WITH SUMO1 AND UBE2I, SUBCELLULAR LOCATION, SUMOYLATION, AND
RP MUTAGENESIS OF LYS-76; LYS-301; LYS-485; LYS-560 AND LYS-921.
RX PubMed=14516784; DOI=10.1016/s0014-4827(03)00292-1;
RA Weger S., Hammer E., Engstler M.;
RT "The DNA topoisomerase I binding protein topors as a novel cellular target
RT for SUMO-1 modification: characterization of domains necessary for
RT subcellular localization and sumolation.";
RL Exp. Cell Res. 290:13-27(2003).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF TRP-131.
RX PubMed=15247280; DOI=10.1074/jbc.c400300200;
RA Rajendra R., Malegaonkar D., Pungaliya P., Marshall H., Rasheed Z.,
RA Brownell J., Liu L.F., Lutzker S., Saleem A., Rubin E.H.;
RT "Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and
RT ubiquitinates p53.";
RL J. Biol. Chem. 279:36440-36444(2004).
RN [9]
RP REDUCED EXPRESSION IN LUNG CANCERS.
RX PubMed=15364129; DOI=10.1016/j.lungcan.2004.03.009;
RA Oyanagi H., Takenaka K., Ishikawa S., Kawano Y., Adachi Y., Ueda K.,
RA Wada H., Tanaka F.;
RT "Expression of LUN gene that encodes a novel RING finger protein is
RT correlated with development and progression of non-small cell lung
RT cancer.";
RL Lung Cancer 46:21-28(2004).
RN [10]
RP TISSUE SPECIFICITY, AND REDUCED EXPRESSION IN COLON CANCERS.
RX PubMed=15107820; DOI=10.1038/sj.onc.1207700;
RA Saleem A., Dutta J., Malegaonkar D., Rasheed F., Rasheed Z., Rajendra R.,
RA Marshall H., Luo M., Li H., Rubin E.H.;
RT "The topoisomerase I- and p53-binding protein topors is differentially
RT expressed in normal and malignant human tissues and may function as a tumor
RT suppressor.";
RL Oncogene 23:5293-5300(2004).
RN [11]
RP FUNCTION, AND SUMOYLATION.
RX PubMed=16122737; DOI=10.1016/j.febslet.2005.07.088;
RA Weger S., Hammer E., Heilbronn R.;
RT "Topors acts as a SUMO-1 E3 ligase for p53 in vitro and in vivo.";
RL FEBS Lett. 579:5007-5012(2005).
RN [12]
RP FUNCTION, AND INDUCTION.
RX PubMed=15735665; DOI=10.1038/sj.onc.1208554;
RA Lin L., Ozaki T., Takada Y., Kageyama H., Nakamura Y., Hata A., Zhang J.H.,
RA Simonds W.F., Nakagawara A., Koseki H.;
RT "Topors, a p53 and topoisomerase I-binding RING finger protein, is a
RT coactivator of p53 in growth suppression induced by DNA damage.";
RL Oncogene 24:3385-3396(2005).
RN [13]
RP INVOLVEMENT IN RP31.
RX PubMed=17924349; DOI=10.1086/521953;
RA Chakarova C.F., Papaioannou M.G., Khanna H., Lopez I., Waseem N., Shah A.,
RA Theis T., Friedman J., Maubaret C., Bujakowska K., Veraitch B.,
RA El-Aziz M.M.A., Prescott de Q., Parapuram S.K., Bickmore W.A.,
RA Munro P.M.G., Gal A., Hamel C.P., Marigo V., Ponting C.P., Wissinger B.,
RA Zrenner E., Matter K., Swaroop A., Koenekoop R.K., Bhattacharya S.S.;
RT "Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with
RT perivascular retinal pigment epithelium atrophy.";
RL Am. J. Hum. Genet. 81:1098-1103(2007).
RN [14]
RP FUNCTION, AND INTERACTION WITH SIN3A.
RX PubMed=17803295; DOI=10.1021/pr0703674;
RA Pungaliya P., Kulkarni D., Park H.J., Marshall H., Zheng H., Lackland H.,
RA Saleem A., Rubin E.H.;
RT "TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins.";
RL J. Proteome Res. 6:3918-3923(2007).
RN [15]
RP PHOSPHORYLATION AT SER-98; SER-499; SER-585 AND SER-866, MUTAGENESIS OF
RP SER-98, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19053840; DOI=10.1021/bi801904q;
RA Park H.J., Zheng H., Kulkarni D., Kerrigan J., Pungaliya P., Saleem A.,
RA Rubin E.H.;
RT "Identification of phosphorylation sites of TOPORS and a role for serine 98
RT in the regulation of ubiquitin but not SUMO E3 ligase activity.";
RL Biochemistry 47:13887-13896(2008).
RN [16]
RP FUNCTION, INTERACTION WITH NKX3-1, AND SUBCELLULAR LOCATION.
RX PubMed=18077445; DOI=10.1074/jbc.m708630200;
RA Guan B., Pungaliya P., Li X., Uquillas C., Mutton L.N., Rubin E.H.,
RA Bieberich C.J.;
RT "Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1.";
RL J. Biol. Chem. 283:4834-4840(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP FUNCTION, INTERACTION WITH PLK1, PHOSPHORYLATION AT SER-718 BY PLK1,
RP MUTAGENESIS OF SER-718, AND SUBCELLULAR LOCATION.
RX PubMed=19473992; DOI=10.1074/jbc.c109.001560;
RA Yang X., Li H., Zhou Z., Wang W.H., Deng A., Andrisani O., Liu X.;
RT "Plk1-mediated phosphorylation of Topors regulates p53 stability.";
RL J. Biol. Chem. 284:18588-18592(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-864 AND SER-866, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP FUNCTION, INTERACTION WITH IKBKE, AND SUBCELLULAR LOCATION.
RX PubMed=20188669; DOI=10.1016/j.molcel.2010.01.018;
RA Renner F., Moreno R., Schmitz M.L.;
RT "SUMOylation-dependent localization of IKKepsilon in PML nuclear bodies is
RT essential for protection against DNA-damage-triggered cell death.";
RL Mol. Cell 37:503-515(2010).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-864 AND SER-866, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-194; SER-585 AND
RP SER-734, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-76; LYS-83; LYS-249 AND LYS-701,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-76 AND LYS-701, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-76 AND LYS-701, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-73; LYS-76; LYS-83; LYS-88;
RP LYS-159; LYS-249; LYS-701; LYS-819 AND LYS-837, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Functions as an E3 ubiquitin-protein ligase and as an E3
CC SUMO1-protein ligase. Probable tumor suppressor involved in cell
CC growth, cell proliferation and apoptosis that regulates p53/TP53
CC stability through ubiquitin-dependent degradation. May regulate
CC chromatin modification through sumoylation of several chromatin
CC modification-associated proteins. May be involved in DNA damage-induced
CC cell death through IKBKE sumoylation. {ECO:0000269|PubMed:15247280,
CC ECO:0000269|PubMed:15735665, ECO:0000269|PubMed:16122737,
CC ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:18077445,
CC ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:20188669}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- SUBUNIT: Interacts with PARK7/DJ-1 (By similarity). Interacts with
CC TOP1. Interacts with p53/TP53; can both ubiquitinate and sumoylate
CC p53/TP53. Interacts with the SUMO1 conjugating enzyme UBE2I. Interacts
CC with SUMO1. Interacts with NKX3-1; polyubiquitinates NKX3-1 and induces
CC its proteasomal degradation. Interacts with SIN3A; sumoylates SIN3A.
CC Interacts with IKBKE; induced by DNA damage.
CC {ECO:0000250|UniProtKB:Q80Z37, ECO:0000269|PubMed:10352183,
CC ECO:0000269|PubMed:10415337, ECO:0000269|PubMed:14516784,
CC ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:18077445,
CC ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:20188669}.
CC -!- INTERACTION:
CC Q9NS56; P03132: Rep68; Xeno; NbExp=3; IntAct=EBI-1996473, EBI-7387242;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, PML body. Note=Localizes to
CC discrete nuclear foci which partly overlap with PML nuclear bodies.
CC Targeted to PML nuclear bodies upon DNA damage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LUN-1;
CC IsoId=Q9NS56-1; Sequence=Displayed;
CC Name=2; Synonyms=LUN-2;
CC IsoId=Q9NS56-2; Sequence=VSP_017916, VSP_017917;
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in testis and at lower
CC levels in adrenal gland, bone marrow, brain, colon, heart, kidney,
CC liver, muscle, ovary, pancreas, placenta, prostate, skeletal muscle,
CC skin, small intestine, spleen, stomach, testis, thymus, thyroid and
CC uterus. Expressed in the alveolar epithelium of the lung. Expression is
CC commonly decreased in colon adenocarcinomas and lung cancers.
CC {ECO:0000269|PubMed:10415337, ECO:0000269|PubMed:11278651,
CC ECO:0000269|PubMed:15107820}.
CC -!- INDUCTION: By genotoxic agents such as cisplatin and camptothecin.
CC {ECO:0000269|PubMed:15735665}.
CC -!- PTM: Phosphorylation at Ser-98 regulates the E3 ubiquitin-protein
CC ligase activity but not the SUMO1-protein ligase activity.
CC Phosphorylation at Ser-718 increases the E3 ubiquitin-protein ligase
CC activity versus the SUMO1-protein ligase activity resulting in
CC increased p53/TP53 ubiquitination and degradation.
CC {ECO:0000269|PubMed:19053840, ECO:0000269|PubMed:19473992}.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:14516784,
CC ECO:0000269|PubMed:16122737}.
CC -!- DISEASE: Retinitis pigmentosa 31 (RP31) [MIM:609923]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:17924349}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- CAUTION: Was originally thought to bind to the palindromic consensus
CC sequence 5'-TCCCAGCACTTTGGGA-3' and to regulate the transcription of
CC numerous genes in the lung. {ECO:0000305|PubMed:11278651}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC98530.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TOPORSID42663ch9p21.html";
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DR EMBL; AF098300; AAD23379.1; -; mRNA.
DR EMBL; AB045732; BAB03714.1; -; mRNA.
DR EMBL; AB045733; BAB03715.1; -; mRNA.
DR EMBL; AL353671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC060884; AAH60884.1; -; mRNA.
DR EMBL; U82939; AAC98530.1; ALT_INIT; mRNA.
DR CCDS; CCDS56566.1; -. [Q9NS56-2]
DR CCDS; CCDS6527.1; -. [Q9NS56-1]
DR RefSeq; NP_001182551.1; NM_001195622.1. [Q9NS56-2]
DR RefSeq; NP_005793.2; NM_005802.4. [Q9NS56-1]
DR AlphaFoldDB; Q9NS56; -.
DR SMR; Q9NS56; -.
DR BioGRID; 115505; 88.
DR IntAct; Q9NS56; 35.
DR MINT; Q9NS56; -.
DR STRING; 9606.ENSP00000353735; -.
DR GlyGen; Q9NS56; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NS56; -.
DR PhosphoSitePlus; Q9NS56; -.
DR BioMuta; TOPORS; -.
DR DMDM; 74752935; -.
DR EPD; Q9NS56; -.
DR jPOST; Q9NS56; -.
DR MassIVE; Q9NS56; -.
DR MaxQB; Q9NS56; -.
DR PaxDb; Q9NS56; -.
DR PeptideAtlas; Q9NS56; -.
DR PRIDE; Q9NS56; -.
DR ProteomicsDB; 82481; -. [Q9NS56-1]
DR ProteomicsDB; 82482; -. [Q9NS56-2]
DR Antibodypedia; 25068; 216 antibodies from 25 providers.
DR DNASU; 10210; -.
DR Ensembl; ENST00000360538.7; ENSP00000353735.2; ENSG00000197579.8. [Q9NS56-1]
DR Ensembl; ENST00000379858.1; ENSP00000369187.1; ENSG00000197579.8. [Q9NS56-2]
DR GeneID; 10210; -.
DR KEGG; hsa:10210; -.
DR MANE-Select; ENST00000360538.7; ENSP00000353735.2; NM_005802.5; NP_005793.2.
DR UCSC; uc003zrb.4; human. [Q9NS56-1]
DR CTD; 10210; -.
DR DisGeNET; 10210; -.
DR GeneCards; TOPORS; -.
DR GeneReviews; TOPORS; -.
DR HGNC; HGNC:21653; TOPORS.
DR HPA; ENSG00000197579; Low tissue specificity.
DR MalaCards; TOPORS; -.
DR MIM; 609507; gene.
DR MIM; 609923; phenotype.
DR neXtProt; NX_Q9NS56; -.
DR OpenTargets; ENSG00000197579; -.
DR Orphanet; 2754; Orofaciodigital syndrome type 6.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA134979531; -.
DR VEuPathDB; HostDB:ENSG00000197579; -.
DR eggNOG; KOG4430; Eukaryota.
DR GeneTree; ENSGT00530000064170; -.
DR HOGENOM; CLU_012046_0_0_1; -.
DR InParanoid; Q9NS56; -.
DR OMA; ERHYYCY; -.
DR OrthoDB; 528095at2759; -.
DR PhylomeDB; Q9NS56; -.
DR TreeFam; TF339497; -.
DR PathwayCommons; Q9NS56; -.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-4085377; SUMOylation of SUMOylation proteins.
DR Reactome; R-HSA-4755510; SUMOylation of immune response proteins.
DR SignaLink; Q9NS56; -.
DR SIGNOR; Q9NS56; -.
DR BioGRID-ORCS; 10210; 12 hits in 1123 CRISPR screens.
DR ChiTaRS; TOPORS; human.
DR GeneWiki; TOPORS; -.
DR GenomeRNAi; 10210; -.
DR Pharos; Q9NS56; Tbio.
DR PRO; PR:Q9NS56; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9NS56; protein.
DR Bgee; ENSG00000197579; Expressed in secondary oocyte and 205 other tissues.
DR Genevisible; Q9NS56; HS.
DR GO; GO:0005814; C:centriole; IDA:BHF-UCL.
DR GO; GO:0036064; C:ciliary basal body; IDA:BHF-UCL.
DR GO; GO:0000930; C:gamma-tubulin complex; IDA:BHF-UCL.
DR GO; GO:0030496; C:midbody; TAS:BHF-UCL.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:BHF-UCL.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:BHF-UCL.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:BHF-UCL.
DR GO; GO:0003823; F:antigen binding; IPI:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0044547; F:DNA topoisomerase binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019789; F:SUMO transferase activity; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:BHF-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; ISS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IDA:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:BHF-UCL.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:BHF-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:BHF-UCL.
DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010842; P:retina layer formation; ISS:BHF-UCL.
DR GO; GO:0046549; P:retinal cone cell development; ISS:BHF-UCL.
DR GO; GO:0046548; P:retinal rod cell development; ISS:BHF-UCL.
DR GO; GO:0006351; P:transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA damage; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Retinitis pigmentosa; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1045
FT /note="E3 ubiquitin-protein ligase Topors"
FT /id="PRO_0000232626"
FT ZN_FING 103..142
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..195
FT /note="E3 ubiquitin-protein ligase activity"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..374
FT /note="Required for DNA-binding"
FT REGION 437..654
FT /note="Interaction with SUMO1"
FT /evidence="ECO:0000269|PubMed:14516784"
FT REGION 437..574
FT /note="Required for sumoylation and localization to
FT discrete nuclear foci"
FT REGION 442..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 456..882
FT /note="Interaction with TOP1"
FT /evidence="ECO:0000269|PubMed:10352183"
FT REGION 456..731
FT /note="Interaction with p53/TP53"
FT /evidence="ECO:0000269|PubMed:10415337"
FT REGION 511..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..936
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 854..917
FT /note="Interaction with UBE2I"
FT /evidence="ECO:0000269|PubMed:14516784"
FT COMPBIAS 516..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..567
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 568..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..645
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..669
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 729..744
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 745..772
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 783..804
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 838..852
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 879..899
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 910..928
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19053840,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19053840"
FT MOD_RES 585
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19053840,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 718
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000269|PubMed:19473992"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 866
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19053840,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT MOD_RES 912
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z37"
FT MOD_RES 914
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z37"
FT MOD_RES 1028
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z37"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 76
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 83
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 88
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 560
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT CROSSLNK 701
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 819
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 837
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..65
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11278651"
FT /id="VSP_017916"
FT VAR_SEQ 66
FT /note="E -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11278651"
FT /id="VSP_017917"
FT VARIANT 154
FT /note="A -> T (in dbSNP:rs17855104)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037629"
FT VARIANT 517
FT /note="E -> K (in dbSNP:rs17855103)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037630"
FT VARIANT 749
FT /note="N -> D (in dbSNP:rs17857515)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037631"
FT VARIANT 812
FT /note="P -> R (in dbSNP:rs36034138)"
FT /id="VAR_037632"
FT MUTAGEN 76
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:14516784"
FT MUTAGEN 98
FT /note="S->A: Loss of phosphorylation but no effect on E3
FT ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:19053840"
FT MUTAGEN 98
FT /note="S->D: Increase in E3 ubiquitin-protein ligase
FT activity and increased binding to UBE2D1. No effect on
FT SUMO1-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:19053840"
FT MUTAGEN 131
FT /note="W->A: Abrogates E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:15247280"
FT MUTAGEN 301
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:14516784"
FT MUTAGEN 485
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:14516784"
FT MUTAGEN 560
FT /note="K->R: Strongly reduces sumoylation."
FT /evidence="ECO:0000269|PubMed:14516784"
FT MUTAGEN 718
FT /note="S->A: Loss of phosphorylation by PLK1 and increases
FT in p53/TP53 stability."
FT /evidence="ECO:0000269|PubMed:19473992"
FT MUTAGEN 921
FT /note="K->R: No effect on sumoylation."
FT /evidence="ECO:0000269|PubMed:14516784"
FT CONFLICT 124..125
FT /note="CF -> K (in Ref. 5; AAC98530)"
FT /evidence="ECO:0000305"
FT CONFLICT 257
FT /note="N -> S (in Ref. 1; AAD23379)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="F -> S (in Ref. 1; AAD23379)"
FT /evidence="ECO:0000305"
FT CONFLICT 922
FT /note="E -> G (in Ref. 1; AAD23379)"
FT /evidence="ECO:0000305"
FT CONFLICT 1040
FT /note="R -> K (in Ref. 1; AAD23379)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1045 AA; 119198 MW; 3DA635FDB5C83B77 CRC64;
MGSQPPLGSP LSREEGEAPP PAPASEGRRR SRRVRLRGSC RHRPSFLGCR ELAASAPARP
APASSEIMAS AAKEFKMDNF SPKAGTSKLQ QTVPADASPD SKCPICLDRF DNVSYLDRCL
HKFCFRCVQE WSKNKAECPL CKQPFDSIFH SVRAEDDFKE YVLRPSYNGS FVTPDRRFRY
RTTLTRERNA SVYSPSGPVN RRTTTPPDSG VLFEGLGIST RPRDVEIPQF MRQIAVRRPT
TADERSLRKI QEQDIINFRR TLYRAGARVR NIEDGGRYRD ISAEFFRRNP ACLHRLVPWL
KRELTVLFGA HGSLVNIVQH IIMSNVTRYD LESQAFVSDL RPFLLNRTEH FIHEFISFAR
SPFNMAAFDQ HANYDCPAPS YEEGSHSDSS VITISPDEAE TQELDINVAT VSQAPWDDET
PGPSYSSSEQ VHVTMSSLLN TSDSSDEELV TGGATSQIQG VQTNDDLNND SDDSSDNCVI
VGFVKPLAER TPELVELSSD SEDLGSYEKM ETVKTQEQEQ SYSSGDSDVS RCSSPHSVLG
KDEQINKGHC DSSTRIKSKK EEKRSTSLSS PRNLNSSVRG DRVYSPYNHR HRKRGRSRSS
DSRSQSRSGH DQKNHRKHHG KKRMKSKRSR SRESSRPRGR RDKKRSRTRD SSWSRRSQTL
SLSSESTSRS RSRSSDHGKR RSRSRNRDRY YLRNNYGSRY KWEYTYYSRN KDRDGYESSY
RRRTLSRAHY SRQSSSPEFR VQSFSERTNA RKKNNHSERK YYYYERHRSR SLSSNRSRTA
STGTDRVRNE KPGGKRKYKT RHLEGTNEVA QPSREFASKA KDSHYQKSSS KLDGNYKNES
DTFSDSRSSD RETKHKRRKR KTRSLSVEIV YEGKATDTTK HHKKKKKKHK KKHKKHHGDN
ASRSPVVITI DSDSDKDSEV KEDTECDNSG PQDPLQNEFL APSLEPFETK DVVTIEAEFG
VLDKECDIAT LSNNLNNANK TVDNIPPLAA SVEQTLDVRE ESTFVSDLEN QPSNIVSLQT
EPSRQLPSPR TSLMSVCLGR DCDMS
