RN111_HUMAN
ID RN111_HUMAN Reviewed; 994 AA.
AC Q6ZNA4; C9JUS4; H0YN55; Q6P9A4; Q6ZMU2; Q7L428; Q7Z346; Q8N1P9; Q8WUA3;
AC Q9NSR1;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=E3 ubiquitin-protein ligase Arkadia {ECO:0000305|PubMed:14657019};
DE EC=2.3.2.27 {ECO:0000269|PubMed:23751493};
DE AltName: Full=RING finger protein 111 {ECO:0000312|HGNC:HGNC:17384};
DE Short=hRNF111 {ECO:0000303|PubMed:23751493};
DE AltName: Full=RING-type E3 ubiquitin transferase Arkadia {ECO:0000305};
GN Name=RNF111 {ECO:0000312|HGNC:HGNC:17384};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP LYS-9.
RC TISSUE=Thymus, 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), AND VARIANT
RP LYS-9.
RC TISSUE=Amygdala, and Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 553-994 (ISOFORM 1), AND VARIANT LYS-9.
RC TISSUE=Brain, Colon, and 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 [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14657019; DOI=10.1093/emboj/cdg632;
RA Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A.,
RA Ebina M., Nukiwa T., Miyazawa K., Imamura T., Miyazono K.;
RT "Arkadia amplifies TGF-beta superfamily signaling through degradation of
RT Smad7.";
RL EMBO J. 22:6458-6470(2003).
RN [7]
RP INTERACTION WITH AXIN1 AND AXIN2, IDENTIFICATION IN COMPLEX WITH AXIN1 AND
RP SMAD7, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16601693; DOI=10.1038/sj.emboj.7601057;
RA Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S.,
RA Chan S.C., Chen Y.-G., Han J., Lin S.-C.;
RT "Axin is a scaffold protein in TGF-beta signaling that promotes degradation
RT of Smad7 by Arkadia.";
RL EMBO J. 25:1646-1658(2006).
RN [8]
RP INTERACTION WITH SKIL, AND FUNCTION.
RX PubMed=17591695; DOI=10.1128/mcb.00664-07;
RA Levy L., Howell M., Das D., Harkin S., Episkopou V., Hill C.S.;
RT "Arkadia activates Smad3/Smad4-dependent transcription by triggering
RT signal-induced SnoN degradation.";
RL Mol. Cell. Biol. 27:6068-6083(2007).
RN [9]
RP IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, DOMAIN, INTERACTION WITH
RP SUMO1 AND SUMO2, AND MUTAGENESIS OF VAL-382; VAL-383; ASP-384; LEU-385 AND
RP THR-386.
RX PubMed=23086935; DOI=10.1074/jbc.m112.410985;
RA Sun H., Hunter T.;
RT "PolySUMO-binding proteins identified through a string search.";
RL J. Biol. Chem. 287:42071-42083(2012).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF
RP 300-VAL--ILE-303; 326-VAL--VAL-329 AND 382-VAL--LEU-385.
RX PubMed=23751493; DOI=10.1083/jcb.201212075;
RA Poulsen S.L., Hansen R.K., Wagner S.A., van Cuijk L., van Belle G.J.,
RA Streicher W., Wikstroem M., Choudhary C., Houtsmuller A.B., Marteijn J.A.,
RA Bekker-Jensen S., Mailand N.;
RT "RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the
RT DNA damage response.";
RL J. Cell Biol. 201:797-807(2013).
RN [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-19, AND IDENTIFICATION BY MASS
RP 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 [12]
RP FUNCTION, SUBUNIT, AND DOMAIN.
RX PubMed=26656854; DOI=10.1038/nsmb.3142;
RA Wright J.D., Mace P.D., Day C.L.;
RT "Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase
RT activity.";
RL Nat. Struct. Mol. Biol. 23:45-52(2016).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-19; LYS-28; LYS-34; LYS-47;
RP LYS-59; LYS-73; LYS-87; LYS-96; LYS-110; LYS-173; LYS-198; LYS-218; LYS-923
RP AND LYS-927, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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).
RN [14]
RP STRUCTURE BY NMR OF 927-994, AND FUNCTION.
RX PubMed=22411132; DOI=10.1002/prot.24048;
RA Chasapis C.T., Kandias N.G., Episkopou V., Bentrop D., Spyroulias G.A.;
RT "NMR-based insights into the conformational and interaction properties of
RT Arkadia RING-H2 E3 Ub ligase.";
RL Proteins 80:1484-1489(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase (PubMed:26656854). Required for
CC mesoderm patterning during embryonic development (By similarity). Acts
CC as an enhancer of the transcriptional responses of the SMAD2/SMAD3
CC effectors, which are activated downstream of BMP (PubMed:14657019,
CC PubMed:16601693). Acts by mediating ubiquitination and degradation of
CC SMAD inhibitors such as SMAD7, inducing their proteasomal degradation
CC and thereby enhancing the transcriptional activity of TGF-beta and BMP
CC (PubMed:14657019, PubMed:16601693). In addition to enhance
CC transcription of SMAD2/SMAD3 effectors, also regulates their turnover
CC by mediating their ubiquitination and subsequent degradation, coupling
CC their activation with degradation, thereby ensuring that only effectors
CC 'in use' are degraded (By similarity). Activates SMAD3/SMAD4-dependent
CC transcription by triggering signal-induced degradation of SNON isoform
CC of SKIL (PubMed:17591695). Associates with UBE2D2 as an E2 enzyme
CC (PubMed:22411132). Specifically binds polysumoylated chains via SUMO
CC interaction motifs (SIMs) and mediates ubiquitination of sumoylated
CC substrates (PubMed:23751493). Catalyzes 'Lys-63'-linked ubiquitination
CC of sumoylated XPC in response to UV irradiation, promoting nucleotide
CC excision repair (PubMed:23751493). Mediates ubiquitination and
CC degradation of sumoylated PML (By similarity). The regulation of the
CC BMP-SMAD signaling is however independent of sumoylation and is not
CC dependent of SUMO interaction motifs (SIMs) (By similarity).
CC {ECO:0000250|UniProtKB:Q99ML9, ECO:0000269|PubMed:14657019,
CC ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17591695,
CC ECO:0000269|PubMed:22411132, ECO:0000269|PubMed:23751493,
CC ECO:0000269|PubMed:26656854}.
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:23751493};
CC -!- ACTIVITY REGULATION: Binds free ubiquitin non-covalently via its RING-
CC type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-
CC protein ligase activity by stabilizing the ubiquitin-conjugating enzyme
CC E2 (donor ubiquitin) in the 'closed' conformation and activating
CC ubiquitin transfer. {ECO:0000250|UniProtKB:Q6ZSG1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:14657019, ECO:0000269|PubMed:16601693,
CC ECO:0000269|PubMed:17591695, ECO:0000269|PubMed:22411132,
CC ECO:0000269|PubMed:23751493, ECO:0000269|PubMed:26656854}.
CC -!- SUBUNIT: Monomer (PubMed:26656854). Interacts with SMAD6, SMAD7, AXIN1,
CC AXIN2 and SKIL isoform SNON (PubMed:16601693, PubMed:17591695).
CC Interacts with (phosphorylated) SMAD2 and SMAD3 (By similarity). Part
CC of a complex containing RNF111, AXIN1 and SMAD7 (PubMed:16601693).
CC Interacts (via SIM domains) with SUMO1 and SUMO2 (PubMed:23086935).
CC {ECO:0000250|UniProtKB:Q99ML9, ECO:0000269|PubMed:16601693,
CC ECO:0000269|PubMed:17591695, ECO:0000269|PubMed:23086935,
CC ECO:0000269|PubMed:26656854}.
CC -!- INTERACTION:
CC Q6ZNA4; O15169: AXIN1; NbExp=2; IntAct=EBI-2129175, EBI-710484;
CC Q6ZNA4; P68400: CSNK2A1; NbExp=6; IntAct=EBI-2129175, EBI-347804;
CC Q6ZNA4; Q8WWZ3: EDARADD; NbExp=3; IntAct=EBI-2129175, EBI-2949647;
CC Q6ZNA4; P26371: KRTAP5-9; NbExp=5; IntAct=EBI-2129175, EBI-3958099;
CC Q6ZNA4; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-2129175, EBI-10246358;
CC Q6ZNA4; P51668: UBE2D1; NbExp=5; IntAct=EBI-2129175, EBI-743540;
CC Q6ZNA4; P61077: UBE2D3; NbExp=5; IntAct=EBI-2129175, EBI-348268;
CC Q6ZNA4; P63279: UBE2I; NbExp=5; IntAct=EBI-2129175, EBI-80168;
CC Q6ZNA4; Q13404: UBE2V1; NbExp=2; IntAct=EBI-2129175, EBI-1050671;
CC Q6ZNA4; B2R8Y4; NbExp=3; IntAct=EBI-2129175, EBI-10175581;
CC Q6ZNA4-2; P02649: APOE; NbExp=3; IntAct=EBI-21535400, EBI-1222467;
CC Q6ZNA4-2; P05067: APP; NbExp=3; IntAct=EBI-21535400, EBI-77613;
CC Q6ZNA4-2; P05067-2: APP; NbExp=3; IntAct=EBI-21535400, EBI-17264467;
CC Q6ZNA4-2; P54253: ATXN1; NbExp=6; IntAct=EBI-21535400, EBI-930964;
CC Q6ZNA4-2; P54252: ATXN3; NbExp=6; IntAct=EBI-21535400, EBI-946046;
CC Q6ZNA4-2; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-21535400, EBI-21603100;
CC Q6ZNA4-2; P42858: HTT; NbExp=18; IntAct=EBI-21535400, EBI-466029;
CC Q6ZNA4-2; Q92597: NDRG1; NbExp=3; IntAct=EBI-21535400, EBI-716486;
CC Q6ZNA4-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-21535400, EBI-748974;
CC Q6ZNA4-2; Q99497: PARK7; NbExp=3; IntAct=EBI-21535400, EBI-1164361;
CC Q6ZNA4-2; O60260-5: PRKN; NbExp=6; IntAct=EBI-21535400, EBI-21251460;
CC Q6ZNA4-2; P49768-2: PSEN1; NbExp=6; IntAct=EBI-21535400, EBI-11047108;
CC Q6ZNA4-2; P37840: SNCA; NbExp=3; IntAct=EBI-21535400, EBI-985879;
CC Q6ZNA4-2; P00441: SOD1; NbExp=3; IntAct=EBI-21535400, EBI-990792;
CC Q6ZNA4-2; Q9NUW8: TDP1; NbExp=3; IntAct=EBI-21535400, EBI-2902553;
CC Q6ZNA4-2; P61086: UBE2K; NbExp=3; IntAct=EBI-21535400, EBI-473850;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16601693,
CC ECO:0000269|PubMed:23751493}. Cytoplasm {ECO:0000269|PubMed:16601693}.
CC Nucleus, PML body {ECO:0000250|UniProtKB:Q99ML9}. Note=Upon TGF-beta
CC treatment, translocates from nucleus to cytosol.
CC {ECO:0000269|PubMed:16601693}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6ZNA4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZNA4-2; Sequence=VSP_023841;
CC Name=3;
CC IsoId=Q6ZNA4-3; Sequence=VSP_023840;
CC Name=4;
CC IsoId=Q6ZNA4-4; Sequence=VSP_023840, VSP_023841;
CC -!- TISSUE SPECIFICITY: Broadly expressed. {ECO:0000269|PubMed:14657019}.
CC -!- DOMAIN: The SUMO interaction motifs (SIMs) mediates the binding to
CC polysumoylated substrate. {ECO:0000269|PubMed:23086935,
CC ECO:0000269|PubMed:23751493}.
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity and binds directly to free ubiquitin (PubMed:26656854).
CC Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating
CC enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates
CC ubiquitin transfer (By similarity). {ECO:0000250|UniProtKB:Q6ZSG1,
CC ECO:0000305|PubMed:26656854}.
CC -!- SIMILARITY: Belongs to the Arkadia family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH10369.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC04531.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD18633.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK095327; BAC04531.1; ALT_INIT; mRNA.
DR EMBL; AK131304; BAD18471.1; -; mRNA.
DR EMBL; AK131488; BAD18633.1; ALT_INIT; mRNA.
DR EMBL; AL157474; CAB75669.2; -; mRNA.
DR EMBL; BX538130; CAD98031.1; -; mRNA.
DR EMBL; BX647259; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC025918; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090515; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092757; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77561.1; -; Genomic_DNA.
DR EMBL; BC010369; AAH10369.1; ALT_INIT; mRNA.
DR EMBL; BC020984; AAH20984.1; -; mRNA.
DR EMBL; BC060862; AAH60862.1; -; mRNA.
DR CCDS; CCDS10169.1; -. [Q6ZNA4-2]
DR CCDS; CCDS58365.1; -. [Q6ZNA4-4]
DR CCDS; CCDS58366.1; -. [Q6ZNA4-1]
DR CCDS; CCDS81888.1; -. [Q6ZNA4-3]
DR PIR; T46904; T46904.
DR RefSeq; NP_001257457.1; NM_001270528.1. [Q6ZNA4-4]
DR RefSeq; NP_001257458.1; NM_001270529.1.
DR RefSeq; NP_001257459.1; NM_001270530.1. [Q6ZNA4-1]
DR RefSeq; NP_001317260.1; NM_001330331.1. [Q6ZNA4-3]
DR RefSeq; NP_060080.6; NM_017610.7. [Q6ZNA4-2]
DR RefSeq; XP_006720642.1; XM_006720579.3. [Q6ZNA4-3]
DR RefSeq; XP_016877827.1; XM_017022338.1. [Q6ZNA4-1]
DR PDB; 2KIZ; NMR; -; A=927-994.
DR PDB; 5LG0; NMR; -; A=927-994.
DR PDB; 5LG7; NMR; -; A=927-994.
DR PDB; 7P2K; NMR; -; A=927-994.
DR PDBsum; 2KIZ; -.
DR PDBsum; 5LG0; -.
DR PDBsum; 5LG7; -.
DR PDBsum; 7P2K; -.
DR AlphaFoldDB; Q6ZNA4; -.
DR BMRB; Q6ZNA4; -.
DR SMR; Q6ZNA4; -.
DR BioGRID; 120146; 93.
DR IntAct; Q6ZNA4; 68.
DR MINT; Q6ZNA4; -.
DR STRING; 9606.ENSP00000453872; -.
DR MoonDB; Q6ZNA4; Predicted.
DR iPTMnet; Q6ZNA4; -.
DR PhosphoSitePlus; Q6ZNA4; -.
DR BioMuta; RNF111; -.
DR DMDM; 308153555; -.
DR EPD; Q6ZNA4; -.
DR jPOST; Q6ZNA4; -.
DR MassIVE; Q6ZNA4; -.
DR MaxQB; Q6ZNA4; -.
DR PaxDb; Q6ZNA4; -.
DR PeptideAtlas; Q6ZNA4; -.
DR PRIDE; Q6ZNA4; -.
DR ProteomicsDB; 40461; -.
DR ProteomicsDB; 68002; -. [Q6ZNA4-1]
DR ProteomicsDB; 68003; -. [Q6ZNA4-2]
DR ProteomicsDB; 68004; -. [Q6ZNA4-3]
DR Antibodypedia; 25360; 132 antibodies from 26 providers.
DR DNASU; 54778; -.
DR Ensembl; ENST00000348370.9; ENSP00000288199.5; ENSG00000157450.16. [Q6ZNA4-2]
DR Ensembl; ENST00000557998.5; ENSP00000452732.1; ENSG00000157450.16. [Q6ZNA4-1]
DR Ensembl; ENST00000559209.5; ENSP00000453872.1; ENSG00000157450.16. [Q6ZNA4-4]
DR Ensembl; ENST00000561186.5; ENSP00000453015.1; ENSG00000157450.16. [Q6ZNA4-3]
DR GeneID; 54778; -.
DR KEGG; hsa:54778; -.
DR MANE-Select; ENST00000348370.9; ENSP00000288199.5; NM_017610.8; NP_060080.6. [Q6ZNA4-2]
DR UCSC; uc002afs.5; human. [Q6ZNA4-1]
DR CTD; 54778; -.
DR DisGeNET; 54778; -.
DR GeneCards; RNF111; -.
DR HGNC; HGNC:17384; RNF111.
DR HPA; ENSG00000157450; Low tissue specificity.
DR MIM; 605840; gene.
DR neXtProt; NX_Q6ZNA4; -.
DR OpenTargets; ENSG00000157450; -.
DR PharmGKB; PA134868772; -.
DR VEuPathDB; HostDB:ENSG00000157450; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000157691; -.
DR HOGENOM; CLU_309031_0_0_1; -.
DR InParanoid; Q6ZNA4; -.
DR OMA; EPGPPAM; -.
DR OrthoDB; 1098052at2759; -.
DR PhylomeDB; Q6ZNA4; -.
DR TreeFam; TF331862; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q6ZNA4; -.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q6ZNA4; -.
DR SIGNOR; Q6ZNA4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54778; 17 hits in 1127 CRISPR screens.
DR ChiTaRS; RNF111; human.
DR GeneWiki; RNF111; -.
DR GenomeRNAi; 54778; -.
DR Pharos; Q6ZNA4; Tbio.
DR PRO; PR:Q6ZNA4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q6ZNA4; protein.
DR Bgee; ENSG00000157450; Expressed in secondary oocyte and 199 other tissues.
DR ExpressionAtlas; Q6ZNA4; baseline and differential.
DR Genevisible; Q6ZNA4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046332; F:SMAD binding; IBA:GO_Central.
DR GO; GO:0032184; F:SUMO polymer binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:BHF-UCL.
DR GO; GO:0070911; P:global genome nucleotide-excision repair; TAS:Reactome.
DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IMP:BHF-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR029306; RNF111_N.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF15303; RNF111_N; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW DNA damage; DNA repair; Isopeptide bond; Metal-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..994
FT /note="E3 ubiquitin-protein ligase Arkadia"
FT /id="PRO_0000280690"
FT ZN_FING 942..983
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 66..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 120..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 212..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..404
FT /note="Interaction with AXIN1"
FT /evidence="ECO:0000269|PubMed:16601693"
FT REGION 337..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 388..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..684
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 696..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 907..909
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT REGION 957..961
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT MOTIF 300..304
FT /note="SUMO interaction motif 1 (SIM)"
FT /evidence="ECO:0000269|PubMed:23086935,
FT ECO:0000269|PubMed:23751493"
FT MOTIF 325..331
FT /note="SUMO interaction motif 2 (SIM)"
FT /evidence="ECO:0000269|PubMed:23086935,
FT ECO:0000269|PubMed:23751493"
FT MOTIF 382..386
FT /note="SUMO interaction motif 3 (SIM)"
FT /evidence="ECO:0000269|PubMed:23086935,
FT ECO:0000269|PubMed:23751493"
FT COMPBIAS 66..93
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..277
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..523
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..642
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..684
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 942
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 945
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 965
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT BINDING 968
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q6ZSG1"
FT CROSSLNK 19
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 28
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 34
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 47
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
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 87
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 110
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 173
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 198
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 218
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 923
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 927
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 766
FT /note="T -> TGLFVFCVSR (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_023840"
FT VAR_SEQ 914..921
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_023841"
FT VARIANT 9
FT /note="N -> K (in dbSNP:rs2899642)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_031185"
FT VARIANT 718
FT /note="A -> T (in dbSNP:rs34086812)"
FT /id="VAR_057216"
FT MUTAGEN 300..303
FT /note="VVVI->AAAA,AVAA: Abolishes binding to sumoylated
FT proteins and ubiquitination and degradation of XPC; when
FT associated with 326-A--A-329 and 382-A--A-385."
FT /evidence="ECO:0000269|PubMed:23751493"
FT MUTAGEN 326..329
FT /note="VEIV->AAAA,AEAA: Abolishes binding to sumoylated
FT proteins and ubiquitination and degradation of XPC; when
FT associated with 300-A--A-303 and 382-A--A-385."
FT /evidence="ECO:0000269|PubMed:23751493"
FT MUTAGEN 382..385
FT /note="VVDL->AAAA,AADA: Abolishes binding to sumoylated
FT proteins and ubiquitination and degradation of XPC; when
FT associated with 300-A--A-303 and 326-A--A-329."
FT /evidence="ECO:0000269|PubMed:23751493"
FT MUTAGEN 382
FT /note="V->A: Abolishes SUMO binding."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 382
FT /note="V->L: Loss of affinity to SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 382
FT /note="V->Y: No loss of affinity toward SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 383
FT /note="V->A: Abolishes SUMO binding."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 383
FT /note="V->I: No loss of affinity toward SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 384
FT /note="D->A: Abolishes SUMO binding."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 384
FT /note="D->E: Loss of affinity to SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 384
FT /note="D->N: Loss of affinity to SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 385
FT /note="L->A: Abolishes SUMO binding."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 385
FT /note="L->I: Loss of affinity to SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 386
FT /note="T->A: Abolishes SUMO binding."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 386
FT /note="T->S: Loss of affinity to SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT MUTAGEN 386
FT /note="T->V: Loss of affinity to SUMO1 and SUMO2."
FT /evidence="ECO:0000269|PubMed:23086935"
FT CONFLICT 165
FT /note="H -> R (in Ref. 2; BX647259)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="A -> E (in Ref. 2; CAD98031)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="Missing (in Ref. 3; AAH60862/AAH20984)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="M -> T (in Ref. 2; BX647259)"
FT /evidence="ECO:0000305"
FT CONFLICT 738
FT /note="T -> I (in Ref. 2; BX647259)"
FT /evidence="ECO:0000305"
FT CONFLICT 809
FT /note="E -> G (in Ref. 2; CAD98031)"
FT /evidence="ECO:0000305"
FT CONFLICT 931
FT /note="E -> G (in Ref. 2; CAD98031)"
FT /evidence="ECO:0000305"
FT CONFLICT 938
FT /note="T -> A (in Ref. 2; BX647259)"
FT /evidence="ECO:0000305"
FT CONFLICT 974
FT /note="I -> V (in Ref. 1; BAD18471)"
FT /evidence="ECO:0000305"
FT STRAND 938..942
FT /evidence="ECO:0007829|PDB:5LG0"
FT TURN 943..946
FT /evidence="ECO:0007829|PDB:2KIZ"
FT STRAND 951..953
FT /evidence="ECO:0007829|PDB:2KIZ"
FT STRAND 955..957
FT /evidence="ECO:0007829|PDB:2KIZ"
FT TURN 959..961
FT /evidence="ECO:0007829|PDB:5LG0"
FT STRAND 963..965
FT /evidence="ECO:0007829|PDB:2KIZ"
FT HELIX 966..975
FT /evidence="ECO:0007829|PDB:2KIZ"
FT TURN 980..982
FT /evidence="ECO:0007829|PDB:2KIZ"
FT STRAND 984..986
FT /evidence="ECO:0007829|PDB:2KIZ"
SQ SEQUENCE 994 AA; 108862 MW; 7E387321E5F61FAB CRC64;
MSQWTPEYNE LYTLKVDMKS EIPSDAPKTQ ESLKGILLHP EPIGAAKSFP AGVEMINSKV
GNEFSHLCDD SQKQEKEMNG NQQEQEKSLV VRKKRKSQQA GPSYVQNCVK ENQGILGLRQ
HLGTPSDEDN DSSFSDCLSS PSSSLHFGDS DTVTSDEDKE VSVRHSQTIL NAKSRSHSAR
SHKWPRTETE SVSGLLMKRP CLHGSSLRRL PCRKRFVKNN SSQRTQKQKE RILMQRKKRE
VLARRKYALL PSSSSSSEND LSSESSSSSS TEGEEDLFVS ASENHQNNPA VPSGSIDEDV
VVIEASSTPQ VTANEEINVT STDSEVEIVT VGESYRSRST LGHSRSHWSQ GSSSHASRPQ
EPRNRSRIST VIQPLRQNAA EVVDLTVDED EPTVVPTTSA RMESQATSAS INNSNPSTSE
QASDTASAVT SSQPSTVSET SATLTSNSTT GTSIGDDSRR TTSSAVTETG PPAMPRLPSC
CPQHSPCGGS SQNHHALGHP HTSCFQQHGH HFQHHHHHHH TPHPAVPVSP SFSDPACPVE
RPPQVQAPCG ANSSSGTSYH EQQALPVDLS NSGIRSHGSG SFHGASAFDP CCPVSSSRAA
IFGHQAAAAA PSQPLSSIDG YGSSMVAQPQ PQPPPQPSLS SCRHYMPPPY ASLTRPLHHQ
ASACPHSHGN PPPQTQPPPQ VDYVIPHPVH AFHSQISSHA TSHPVAPPPP THLASTAAPI
PQHLPPTHQP ISHHIPATAP PAQRLHPHEV MQRMEVQRRR MMQHPTRAHE RPPPHPHRMH
PNYGHGHHIH VPQTMSSHPR QAPERSAWEL GIEAGVTAAT YTPGALHPHL AHYHAPPRLH
HLQLGALPLM VPDMAGYPHI RYISSGLDGT SFRGPFRGNF EELIHLEERL GNVNRGASQG
TIERCTYPHK YKKVTTDWFS QRKLHCKQDG EEGTEEDTEE KCTICLSILE EGEDVRRLPC
MHLFHQVCVD QWLITNKKCP ICRVDIEAQL PSES
