RNF4_HUMAN
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 03-AUG-2022, entry version 191.
DE RecName: Full=E3 ubiquitin-protein ligase RNF4;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 4;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF4 {ECO:0000305};
DE AltName: Full=Small nuclear ring finger protein;
DE Short=Protein SNURF;
GN Name=RNF4; Synonyms=SNURF; 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 INTERACTION WITH PARP1.
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 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. Regulates
CC the degradation of several proteins including PML and the
CC transcriptional activator PEA3. Involved in chromosome alignment and
CC spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK
CC complex by targeting polysumoylated CENPI to proteasomal degradation.
CC Regulates the cellular responses to hypoxia and heat shock through
CC degradation of respectively EPAS1 and PARP1. Alternatively, it may also
CC bind DNA/nucleosomes and have a more direct role in the regulation of
CC transcription for instance enhancing basal transcription and steroid
CC receptor-mediated transcriptional activation.
CC {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:18408734,
CC ECO:0000269|PubMed:19307308, ECO:0000269|PubMed:20026589,
CC ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20943951}.
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 -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer (via RING-type zinc finger domain). Interacts with
CC GSC2 (By similarity). Interacts with AR/the androgen receptor and TBP
CC (By similarity). Interacts with TCF20 (By similarity). Interacts with
CC PATZ1. Interacts with TRPS1; negatively regulates TRPS1 transcriptional
CC repressor activity. Interacts with PML; SUMO1-dependent. Interacts with
CC PML; SUMO2-dependent. Interacts with PARP1. Interacts with PML (isoform
CC PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and
CC isoform PML-6). Interacts with PRDM1/Blimp-1 (PubMed:28842558).
CC {ECO:0000250, ECO:0000269|PubMed:10713105, ECO:0000269|PubMed:12885770,
CC ECO:0000269|PubMed:15707587, ECO:0000269|PubMed:19779455,
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; 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; Q96B23: C18orf25; NbExp=3; IntAct=EBI-2340927, EBI-742108;
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=4; 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. Nucleus. Nucleus, PML body. Nucleus,
CC nucleoplasm.
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}.
CC -!- PTM: Autoubiquitinated. {ECO:0000250}.
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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; 1411.
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; P78317; -.
DR PeptideAtlas; P78317; -.
DR PRIDE; P78317; -.
DR ProteomicsDB; 57562; -. [P78317-1]
DR Antibodypedia; 22369; 139 antibodies from 24 providers.
DR DNASU; 6047; -.
DR Ensembl; ENST00000314289.13; ENSP00000315212.8; ENSG00000063978.16. [P78317-1]
DR Ensembl; ENST00000506706.5; ENSP00000424076.1; ENSG00000063978.16. [P78317-1]
DR Ensembl; ENST00000511600.5; ENSP00000426503.1; ENSG00000063978.16. [P78317-1]
DR Ensembl; ENST00000511859.5; ENSP00000426615.1; ENSG00000063978.16. [P78317-2]
DR Ensembl; ENST00000541204.5; ENSP00000446369.2; ENSG00000063978.16. [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 CTD; 6047; -.
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; LRNANSC; -.
DR OrthoDB; 1431236at2759; -.
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; 508 hits in 1120 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 202 other tissues.
DR ExpressionAtlas; P78317; baseline and differential.
DR Genevisible; P78317; HS.
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; ISS: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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS: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; -; 1.
DR InterPro; IPR043295; RING-HC_RNF4.
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 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"
FT REGION 4..61
FT /note="Mediates interaction with TRPS1"
FT /evidence="ECO:0000250"
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 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 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
