ID RNF4_HUMAN Reviewed; 190 AA. AC P78317; B2R6D6; D6RF58; Q49AR8; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 200. DE RecName: Full=E3 ubiquitin-protein ligase RNF4 {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:35013556}; DE AltName: Full=RING finger protein 4 {ECO:0000305}; DE AltName: Full=Small nuclear ring finger protein {ECO:0000303|PubMed:15707587}; DE Short=Protein SNURF {ECO:0000303|PubMed:15707587}; GN Name=RNF4 {ECO:0000303|PubMed:15815621, ECO:0000312|HGNC:HGNC:10067}; GN Synonyms=SNURF {ECO:0000303|PubMed:15707587}; ORFNames=RES4-26; 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). RC TISSUE=Brain; RX PubMed=9734812; DOI=10.1093/dnares/5.3.177; RA Hadano S., Ishida Y., Ikeda J.-E.; RT "The primary structure and genomic organization of five novel transcripts RT located close to the Huntington's disease gene on human chromosome RT 4p16.3."; RL DNA Res. 5:177-186(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=9479498; DOI=10.1006/geno.1997.5105; RA Chiariotti L., Benvenuto G., Fedele M., Santoro M., Simeone A., Fusco A., RA Bruni C.B.; RT "Identification and characterization of a novel RING-finger gene (RNF4) RT mapping at 4p16.3."; RL Genomics 47:258-265(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hair follicle dermal papilla, Testis, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [6] RP INTERACTION WITH PATZ1. RX PubMed=10713105; DOI=10.1074/jbc.275.11.7894; RA Fedele M., Benvenuto G., Pero R., Majello B., Battista S., Lembo F., RA Vollono E., Day P.M., Santoro M., Lania L., Bruni C.B., Fusco A., RA Chiatiotti L.; RT "A novel member of the BTB/POZ family, PATZ, associates with the RNF4 RING RT finger protein and acts as a transcriptional repressor."; RL J. Biol. Chem. 275:7894-7901(2000). RN [7] RP FUNCTION, INTERACTION WITH TRPS1, AND SUBCELLULAR LOCATION. RX PubMed=12885770; DOI=10.1074/jbc.m306259200; RA Kaiser F.J., Moeroey T., Chang G.T., Horsthemke B., Luedecke H.J.; RT "The RING finger protein RNF4, a co-regulator of transcription, interacts RT with the TRPS1 transcription factor."; RL J. Biol. Chem. 278:38780-38785(2003). RN [8] RP INTERACTION WITH PML, AND SUBCELLULAR LOCATION. RX PubMed=15707587; DOI=10.1016/j.yexcr.2004.10.029; RA Haekli M., Karvonen U., Jaenne O.A., Palvimo J.J.; RT "SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies."; RL Exp. Cell Res. 304:224-233(2005). RN [9] RP FUNCTION, AND DOMAIN. RX PubMed=18408734; DOI=10.1038/ncb1716; RA Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N., RA Jaffray E.G., Palvimo J.J., Hay R.T.; RT "RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic- RT induced PML degradation."; RL Nat. Cell Biol. 10:538-546(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94 AND SER-95, AND RP IDENTIFICATION BY 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 [11] RP FUNCTION. RX PubMed=19779455; DOI=10.1038/emboj.2009.279; RA Martin N., Schwamborn K., Schreiber V., Werner A., Guillier C., Zhang X.D., RA Bischof O., Seeler J.S., Dejean A.; RT "PARP-1 transcriptional activity is regulated by sumoylation upon heat RT shock."; RL EMBO J. 28:3534-3548(2009). RN [12] RP FUNCTION. RX PubMed=19307308; DOI=10.1128/mcb.01128-08; RA Guo B., Sharrocks A.D.; RT "Extracellular signal-regulated kinase mitogen-activated protein kinase RT signaling initiates a dynamic interplay between sumoylation and RT ubiquitination to regulate the activity of the transcriptional activator RT PEA3."; RL Mol. Cell. Biol. 29:3204-3218(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94 AND SER-95, 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 [14] RP FUNCTION. RX PubMed=20212317; DOI=10.1083/jcb.200909008; RA Mukhopadhyay D., Arnaoutov A., Dasso M.; RT "The SUMO protease SENP6 is essential for inner kinetochore assembly."; RL J. Cell Biol. 188:681-692(2010). RN [15] RP FUNCTION, INTERACTION WITH SUMOYLATED PML, AND SUBCELLULAR LOCATION. RX PubMed=20943951; DOI=10.1091/mbc.e10-05-0449; RA Geoffroy M.C., Jaffray E.G., Walker K.J., Hay R.T.; RT "Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear RT bodies."; RL Mol. Biol. Cell 21:4227-4239(2010). RN [16] RP FUNCTION. RX PubMed=20026589; DOI=10.1093/nar/gkp1157; RA van Hagen M., Overmeer R.M., Abolvardi S.S., Vertegaal A.C.; RT "RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated RT Hypoxia-Inducible Factor-2alpha."; RL Nucleic Acids Res. 38:1922-1931(2010). RN [17] RP INTERACTION WITH PML. RX PubMed=23028697; DOI=10.1371/journal.pone.0044949; RA Maroui M.A., Kheddache-Atmane S., El Asmi F., Dianoux L., Aubry M., RA Chelbi-Alix M.K.; RT "Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide- RT induced degradation of nuclear PML isoforms."; RL PLoS ONE 7:E44949-E44949(2012). RN [18] RP INTERACTION WITH PRDM1. RX PubMed=28842558; DOI=10.1038/s41467-017-00476-w; RA Wang W.F., Yan L., Liu Z., Liu L.X., Lin J., Liu Z.Y., Chen X.P., Zhang W., RA Xu Z.Z., Shi T., Li J.M., Zhao Y.L., Meng G., Xia Y., Li J.Y., Zhu J.; RT "HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal RT misfolded Blimp-1s in lymphoma cells."; RL Nat. Commun. 8:363-363(2017). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF MET-136; HIS-156 RP AND ARG-177. RX PubMed=35013556; DOI=10.1038/s41556-021-00807-6; RA Krastev D.B., Li S., Sun Y., Wicks A.J., Hoslett G., Weekes D., RA Badder L.M., Knight E.G., Marlow R., Pardo M.C., Yu L., Talele T.T., RA Bartek J., Choudhary J.S., Pommier Y., Pettitt S.J., Tutt A.N.J., RA Ramadan K., Lord C.J.; RT "The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from RT chromatin."; RL Nat. Cell Biol. 24:62-73(2022). RN [20] RP STRUCTURE BY NMR OF 122-183. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the RING domain of the human RING finger protein RT 4."; RL Submitted (JUL-2007) to the PDB data bank. CC -!- FUNCTION: E3 ubiquitin-protein ligase which binds polysumoylated chains CC covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys- CC 48'- and 'Lys-63'-linked polyubiquitination of those substrates and CC their subsequent targeting to the proteasome for degradation CC (PubMed:18408734, PubMed:19307308, PubMed:35013556). Regulates the CC degradation of several proteins including PML and the transcriptional CC activator PEA3 (PubMed:18408734, PubMed:19307308, PubMed:20943951). CC Involved in chromosome alignment and spindle assembly, it regulates the CC kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI CC to proteasomal degradation (PubMed:20212317). Regulates the cellular CC responses to hypoxia and heat shock through degradation of respectively CC EPAS1 and PARP1 (PubMed:19779455, PubMed:20026589). Alternatively, it CC may also bind DNA/nucleosomes and have a more direct role in the CC regulation of transcription for instance enhancing basal transcription CC and steroid receptor-mediated transcriptional activation CC (PubMed:12885770). Catalyzes ubiquitination of sumoylated PARP1 in CC response to PARP1 trapping to chromatin, leading to PARP1 removal from CC chromatin by VCP/p97 (PubMed:35013556). {ECO:0000269|PubMed:12885770, CC ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:19307308, CC ECO:0000269|PubMed:19779455, ECO:0000269|PubMed:20026589, CC ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20943951, CC ECO:0000269|PubMed:35013556}. 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; Evidence={ECO:0000269|PubMed:35013556}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:35013556}. CC -!- SUBUNIT: Homodimer (via RING-type zinc finger domain) (By similarity). CC Interacts with GSC2 (By similarity). Interacts with AR/the androgen CC receptor and TBP (By similarity). Interacts with TCF20 (By similarity). CC Interacts with PATZ1 (PubMed:10713105). Interacts with TRPS1; CC negatively regulates TRPS1 transcriptional repressor activity CC (PubMed:12885770). Interacts with PML (isoform PML-1, isoform PML-2, CC isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6) CC (PubMed:15707587, PubMed:20943951, PubMed:23028697). Interacts with CC PRDM1/Blimp-1 (PubMed:28842558). {ECO:0000250|UniProtKB:O88846, CC ECO:0000250|UniProtKB:Q9QZS2, ECO:0000269|PubMed:10713105, CC ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:15707587, CC ECO:0000269|PubMed:20943951, ECO:0000269|PubMed:23028697, CC ECO:0000269|PubMed:28842558}. CC -!- INTERACTION: CC P78317; P60709: ACTB; NbExp=3; IntAct=EBI-2340927, EBI-353944; CC P78317; Q02040: AKAP17A; NbExp=5; IntAct=EBI-2340927, EBI-1042725; CC P78317; A6NKF2: ARID3C; NbExp=3; IntAct=EBI-2340927, EBI-12805486; CC P78317; Q96B23: ARK2N; NbExp=3; IntAct=EBI-2340927, EBI-742108; CC P78317; P15336: ATF2; NbExp=3; IntAct=EBI-2340927, EBI-1170906; CC P78317; Q07817: BCL2L1; NbExp=3; IntAct=EBI-2340927, EBI-78035; CC P78317; Q9H0C5: BTBD1; NbExp=3; IntAct=EBI-2340927, EBI-935503; CC P78317; Q9Y2F9: BTBD3; NbExp=3; IntAct=EBI-2340927, EBI-311155; CC P78317; Q9NWQ9: C14orf119; NbExp=3; IntAct=EBI-2340927, EBI-725606; CC P78317; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-2340927, EBI-11523526; CC P78317; Q13557-8: CAMK2D; NbExp=3; IntAct=EBI-2340927, EBI-11534483; CC P78317; P13500: CCL2; NbExp=3; IntAct=EBI-2340927, EBI-1034732; CC P78317; Q9Y281: CFL2; NbExp=3; IntAct=EBI-2340927, EBI-351218; CC P78317; P16220: CREB1; NbExp=3; IntAct=EBI-2340927, EBI-711855; CC P78317; Q9UER7: DAXX; NbExp=3; IntAct=EBI-2340927, EBI-77321; CC P78317; O00148: DDX39A; NbExp=3; IntAct=EBI-2340927, EBI-348253; CC P78317; Q13838: DDX39B; NbExp=3; IntAct=EBI-2340927, EBI-348622; CC P78317; P17661: DES; NbExp=3; IntAct=EBI-2340927, EBI-1055572; CC P78317; Q6ICB0: DESI1; NbExp=3; IntAct=EBI-2340927, EBI-2806959; CC P78317; Q08426: EHHADH; NbExp=3; IntAct=EBI-2340927, EBI-2339219; CC P78317; P11474: ESRRA; NbExp=3; IntAct=EBI-2340927, EBI-372412; CC P78317; Q13158: FADD; NbExp=5; IntAct=EBI-2340927, EBI-494804; CC P78317; Q9NWS6: FAM118A; NbExp=3; IntAct=EBI-2340927, EBI-8638992; CC P78317; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-2340927, EBI-8468186; CC P78317; O75344: FKBP6; NbExp=3; IntAct=EBI-2340927, EBI-744771; CC P78317; Q96IK5: GMCL1; NbExp=5; IntAct=EBI-2340927, EBI-2548508; CC P78317; O14964: HGS; NbExp=3; IntAct=EBI-2340927, EBI-740220; CC P78317; P07910: HNRNPC; NbExp=3; IntAct=EBI-2340927, EBI-357966; CC P78317; O60812: HNRNPCL1; NbExp=3; IntAct=EBI-2340927, EBI-1046507; CC P78317; B2RXH8: HNRNPCL2; NbExp=3; IntAct=EBI-2340927, EBI-9512317; CC P78317; P31943: HNRNPH1; NbExp=3; IntAct=EBI-2340927, EBI-351590; CC P78317; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-2340927, EBI-7060731; CC P78317; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-2340927, EBI-11522367; CC P78317; P20839-3: IMPDH1; NbExp=3; IntAct=EBI-2340927, EBI-12188657; CC P78317; Q53G59: KLHL12; NbExp=3; IntAct=EBI-2340927, EBI-740929; CC P78317; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-2340927, EBI-10245913; CC P78317; Q5T752: LCE1D; NbExp=3; IntAct=EBI-2340927, EBI-11741311; CC P78317; Q5T753: LCE1E; NbExp=3; IntAct=EBI-2340927, EBI-11955335; CC P78317; Q5T754: LCE1F; NbExp=3; IntAct=EBI-2340927, EBI-11958008; CC P78317; O14633: LCE2B; NbExp=3; IntAct=EBI-2340927, EBI-11478468; CC P78317; Q5TA81: LCE2C; NbExp=5; IntAct=EBI-2340927, EBI-11973993; CC P78317; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-2340927, EBI-10246750; CC P78317; Q5TA77: LCE3B; NbExp=3; IntAct=EBI-2340927, EBI-11974495; CC P78317; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-2340927, EBI-11955689; CC P78317; Q9BS40: LXN; NbExp=3; IntAct=EBI-2340927, EBI-1044504; CC P78317; Q99836: MYD88; NbExp=3; IntAct=EBI-2340927, EBI-447677; CC P78317; Q99801: NKX3-1; NbExp=3; IntAct=EBI-2340927, EBI-1385894; CC P78317; Q9HAN9: NMNAT1; NbExp=3; IntAct=EBI-2340927, EBI-3917542; CC P78317; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-2340927, EBI-741158; CC P78317; O15381-5: NVL; NbExp=3; IntAct=EBI-2340927, EBI-18577082; CC P78317; P22234: PAICS; NbExp=3; IntAct=EBI-2340927, EBI-712261; CC P78317; P57721-2: PCBP3; NbExp=3; IntAct=EBI-2340927, EBI-11983983; CC P78317; P78364: PHC1; NbExp=5; IntAct=EBI-2340927, EBI-725403; CC P78317; O75360: PROP1; NbExp=3; IntAct=EBI-2340927, EBI-9027467; CC P78317; P86480: PRR20D; NbExp=3; IntAct=EBI-2340927, EBI-12754095; CC P78317; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-2340927, EBI-372094; CC P78317; P78317: RNF4; NbExp=2; IntAct=EBI-2340927, EBI-2340927; CC P78317; Q06455-2: RUNX1T1; NbExp=3; IntAct=EBI-2340927, EBI-11984663; CC P78317; Q9UQR0: SCML2; NbExp=3; IntAct=EBI-2340927, EBI-2513111; CC P78317; Q9UH03: SEPTIN3; NbExp=3; IntAct=EBI-2340927, EBI-727037; CC P78317; O75971-2: SNAPC5; NbExp=3; IntAct=EBI-2340927, EBI-12004298; CC P78317; P35711-4: SOX5; NbExp=3; IntAct=EBI-2340927, EBI-11954419; CC P78317; O43805: SSNA1; NbExp=3; IntAct=EBI-2340927, EBI-2515299; CC P78317; Q16623: STX1A; NbExp=3; IntAct=EBI-2340927, EBI-712466; CC P78317; P32856-2: STX2; NbExp=3; IntAct=EBI-2340927, EBI-11956649; CC P78317; Q12846: STX4; NbExp=3; IntAct=EBI-2340927, EBI-744942; CC P78317; P63165: SUMO1; NbExp=3; IntAct=EBI-2340927, EBI-80140; CC P78317; Q92734: TFG; NbExp=5; IntAct=EBI-2340927, EBI-357061; CC P78317; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-2340927, EBI-741515; CC P78317; Q12933: TRAF2; NbExp=3; IntAct=EBI-2340927, EBI-355744; CC P78317; Q13114: TRAF3; NbExp=3; IntAct=EBI-2340927, EBI-357631; CC P78317; Q9BUZ4: TRAF4; NbExp=5; IntAct=EBI-2340927, EBI-3650647; CC P78317; O00463: TRAF5; NbExp=5; IntAct=EBI-2340927, EBI-523498; CC P78317; O00635: TRIM38; NbExp=3; IntAct=EBI-2340927, EBI-2130415; CC P78317; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-2340927, EBI-2130429; CC P78317; Q15645: TRIP13; NbExp=3; IntAct=EBI-2340927, EBI-358993; CC P78317; Q9UHF7: TRPS1; NbExp=2; IntAct=EBI-2340927, EBI-2556151; CC P78317; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-2340927, EBI-10180829; CC P78317; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-2340927, EBI-741480; CC P78317; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-2340927, EBI-947187; CC P78317; Q8WUN7: UBTD2; NbExp=3; IntAct=EBI-2340927, EBI-12867288; CC P78317; O95231: VENTX; NbExp=3; IntAct=EBI-2340927, EBI-10191303; CC P78317; Q9HCK0: ZBTB26; NbExp=3; IntAct=EBI-2340927, EBI-3918996; CC P78317; Q8NCN2: ZBTB34; NbExp=3; IntAct=EBI-2340927, EBI-11317716; CC P78317; Q15916: ZBTB6; NbExp=3; IntAct=EBI-2340927, EBI-7227791; CC P78317; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-2340927, EBI-742550; CC P78317; Q9NP64: ZCCHC17; NbExp=3; IntAct=EBI-2340927, EBI-746345; CC P78317; Q96MM3: ZFP42; NbExp=3; IntAct=EBI-2340927, EBI-12151755; CC P78317; Q9NSD4: ZNF275; NbExp=3; IntAct=EBI-2340927, EBI-17263125; CC P78317; Q9P2F9: ZNF319; NbExp=5; IntAct=EBI-2340927, EBI-11993110; CC P78317; Q9H7X3: ZNF696; NbExp=5; IntAct=EBI-2340927, EBI-11090299; CC P78317; Q3KQV3: ZNF792; NbExp=3; IntAct=EBI-2340927, EBI-10240849; CC P78317; O60232: ZNRD2; NbExp=3; IntAct=EBI-2340927, EBI-741415; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12885770}. Nucleus CC {ECO:0000269|PubMed:12885770}. Nucleus, PML body CC {ECO:0000269|PubMed:15707587, ECO:0000269|PubMed:20943951}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P78317-1; Sequence=Displayed; CC Name=2; CC IsoId=P78317-2; Sequence=VSP_045789, VSP_045790; CC -!- TISSUE SPECIFICITY: Widely expressed at low levels in many tissues; CC highly expressed in testis. {ECO:0000269|PubMed:9479498}. CC -!- DOMAIN: The SUMO interaction motifs (SIMs) mediates the binding to CC polysumoylated substrate. {ECO:0000269|PubMed:18408734}. CC -!- DOMAIN: The RING-type zinc finger domain is required for the CC ubiquitination of polysumoylated substrates. CC {ECO:0000250|UniProtKB:O88846}. CC -!- PTM: Sumoylated; conjugated by one or two SUMO1 moieties. CC {ECO:0000250|UniProtKB:O88846}. CC -!- PTM: Autoubiquitinated. {ECO:0000250|UniProtKB:O88846}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB000468; BAA19122.1; -; mRNA. DR EMBL; U95140; AAC52022.1; -; mRNA. DR EMBL; AK128038; BAG54620.1; -; mRNA. DR EMBL; AK309509; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK312534; BAG35433.1; -; mRNA. DR EMBL; AL110117; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL645924; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX322586; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR450722; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR545473; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC031935; AAH31935.1; -; mRNA. DR CCDS; CCDS47001.1; -. [P78317-1] DR CCDS; CCDS54713.1; -. [P78317-2] DR RefSeq; NP_001171938.1; NM_001185009.2. [P78317-1] DR RefSeq; NP_001171939.1; NM_001185010.2. [P78317-2] DR RefSeq; NP_002929.1; NM_002938.4. [P78317-1] DR PDB; 2EA6; NMR; -; A=122-183. DR PDB; 2XEU; X-ray; 1.50 A; A=130-190. DR PDB; 4PPE; X-ray; 2.00 A; A/B=120-190. DR PDBsum; 2EA6; -. DR PDBsum; 2XEU; -. DR PDBsum; 4PPE; -. DR AlphaFoldDB; P78317; -. DR BMRB; P78317; -. DR SMR; P78317; -. DR BioGRID; 111974; 1414. DR IntAct; P78317; 116. DR MINT; P78317; -. DR STRING; 9606.ENSP00000426503; -. DR iPTMnet; P78317; -. DR PhosphoSitePlus; P78317; -. DR BioMuta; RNF4; -. DR DMDM; 18202358; -. DR EPD; P78317; -. DR jPOST; P78317; -. DR MassIVE; P78317; -. DR MaxQB; P78317; -. DR PaxDb; 9606-ENSP00000426503; -. DR PeptideAtlas; P78317; -. DR ProteomicsDB; 57562; -. [P78317-1] DR Pumba; P78317; -. DR Antibodypedia; 22369; 163 antibodies from 24 providers. DR DNASU; 6047; -. DR Ensembl; ENST00000314289.13; ENSP00000315212.8; ENSG00000063978.17. [P78317-1] DR Ensembl; ENST00000506706.5; ENSP00000424076.1; ENSG00000063978.17. [P78317-1] DR Ensembl; ENST00000511600.5; ENSP00000426503.1; ENSG00000063978.17. [P78317-1] DR Ensembl; ENST00000511859.5; ENSP00000426615.1; ENSG00000063978.17. [P78317-2] DR Ensembl; ENST00000541204.5; ENSP00000446369.2; ENSG00000063978.17. [P78317-2] DR GeneID; 6047; -. DR KEGG; hsa:6047; -. DR MANE-Select; ENST00000314289.13; ENSP00000315212.8; NM_002938.5; NP_002929.1. DR UCSC; uc003gfb.4; human. [P78317-1] DR AGR; HGNC:10067; -. DR DisGeNET; 6047; -. DR GeneCards; RNF4; -. DR HGNC; HGNC:10067; RNF4. DR HPA; ENSG00000063978; Low tissue specificity. DR MIM; 602850; gene. DR neXtProt; NX_P78317; -. DR OpenTargets; ENSG00000063978; -. DR PharmGKB; PA34439; -. DR VEuPathDB; HostDB:ENSG00000063978; -. DR eggNOG; KOG0320; Eukaryota. DR GeneTree; ENSGT00390000010318; -. DR HOGENOM; CLU_106856_0_0_1; -. DR InParanoid; P78317; -. DR OMA; ICMDVYS; -. DR OrthoDB; 2919802at2759; -. DR PhylomeDB; P78317; -. DR TreeFam; TF328387; -. DR PathwayCommons; P78317; -. DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; P78317; -. DR SIGNOR; P78317; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 6047; 528 hits in 1204 CRISPR screens. DR ChiTaRS; RNF4; human. DR EvolutionaryTrace; P78317; -. DR GeneWiki; RNF4; -. DR GenomeRNAi; 6047; -. DR Pharos; P78317; Tbio. DR PRO; PR:P78317; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P78317; Protein. DR Bgee; ENSG00000063978; Expressed in thymus and 204 other cell types or tissues. DR ExpressionAtlas; P78317; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:1990752; C:microtubule end; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030374; F:nuclear receptor coactivator activity; TAS:UniProtKB. DR GO; GO:0031491; F:nucleosome binding; ISS:UniProtKB. DR GO; GO:0032184; F:SUMO polymer binding; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0120186; P:negative regulation of protein localization to chromatin; IDA:UniProt. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB. DR GO; GO:0070979; P:protein K11-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0090234; P:regulation of kinetochore assembly; IMP:UniProtKB. DR GO; GO:0090169; P:regulation of spindle assembly; IMP:UniProtKB. DR GO; GO:0046685; P:response to arsenic-containing substance; IDA:UniProtKB. DR CDD; cd16533; RING-HC_RNF4; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR043295; RING-HC_RNF4. DR InterPro; IPR047134; RNF4. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR23041:SF78; E3 UBIQUITIN-PROTEIN LIGASE RNF4; 1. DR PANTHER; PTHR23041; RING FINGER DOMAIN-CONTAINING; 1. DR Pfam; PF13639; zf-RING_2; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; P78317; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cytoplasm; DNA-binding; KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..190 FT /note="E3 ubiquitin-protein ligase RNF4" FT /id="PRO_0000056043" FT ZN_FING 132..177 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 1..29 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1..16 FT /note="Required for ubiquitination activity" FT /evidence="ECO:0000250|UniProtKB:Q9QZS2" FT REGION 4..61 FT /note="Mediates interaction with TRPS1" FT /evidence="ECO:0000250|UniProtKB:Q9QZS2" FT MOTIF 36..39 FT /note="SUMO interaction motif 1" FT /evidence="ECO:0000269|PubMed:18408734" FT MOTIF 46..49 FT /note="SUMO interaction motif 2" FT /evidence="ECO:0000269|PubMed:18408734" FT MOTIF 57..59 FT /note="SUMO interaction motif 3" FT /evidence="ECO:0000269|PubMed:18408734" FT MOTIF 67..70 FT /note="SUMO interaction motif 4" FT /evidence="ECO:0000269|PubMed:18408734" FT COMPBIAS 1..27 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 132 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 135 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 154 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 156 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 159 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 162 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 173 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O88846" FT BINDING 176 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O88846" FT MOD_RES 94 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 95 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT VAR_SEQ 72..113 FT /note="ERRRPRRNARRLPQDHADSCVVSSDDEELSRDRDVYVTTHTP -> GPQVLS FT VVPSAWTDTQRSCRMDVSSFPQNAAMSSVASASVIP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045789" FT VAR_SEQ 114..190 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045790" FT MUTAGEN 136 FT /note="M->S: Dominant-negative E2-binding mutant, leads to FT increased trapping of PARP1 to chromatin; when associated FT with A-177." FT /evidence="ECO:0000269|PubMed:35013556" FT MUTAGEN 156 FT /note="H->A: Abolished E3 ubiquitin-protein ligase FT activity." FT /evidence="ECO:0000269|PubMed:35013556" FT MUTAGEN 177 FT /note="R->A: Dominant-negative E2-binding mutant, leads to FT increased trapping of PARP1 to chromatin; when associated FT with S-136." FT /evidence="ECO:0000269|PubMed:35013556" FT TURN 133..135 FT /evidence="ECO:0007829|PDB:2XEU" FT HELIX 139..144 FT /evidence="ECO:0007829|PDB:2XEU" FT STRAND 149..152 FT /evidence="ECO:0007829|PDB:2XEU" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:2EA6" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:2XEU" FT HELIX 160..169 FT /evidence="ECO:0007829|PDB:2XEU" FT TURN 174..176 FT /evidence="ECO:0007829|PDB:2XEU" FT TURN 181..183 FT /evidence="ECO:0007829|PDB:2XEU" FT STRAND 185..187 FT /evidence="ECO:0007829|PDB:2XEU" SQ SEQUENCE 190 AA; 21319 MW; E5E3AE4A9B28CF9D CRC64; MSTRKRRGGA INSRQAQKRT REATSTPEIS LEAEPIELVE TAGDEIVDLT CESLEPVVVD LTHNDSVVIV DERRRPRRNA RRLPQDHADS CVVSSDDEEL SRDRDVYVTT HTPRNARDEG ATGLRPSGTV SCPICMDGYS EIVQNGRLIV STECGHVFCS QCLRDSLKNA NTCPTCRKKI NHKRYHPIYI //