ID RN135_HUMAN Reviewed; 432 AA. AC Q8IUD6; A0AVM5; B2R7G9; B6ZLM5; F5GX60; Q9BSE9; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 2. DT 27-MAR-2024, entry version 168. DE RecName: Full=E3 ubiquitin-protein ligase RNF135 {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:31006531}; DE AltName: Full=RIG-I E3 ubiquitin ligase {ECO:0000303|PubMed:19484123}; DE Short=REUL {ECO:0000303|PubMed:19484123}; DE AltName: Full=RING finger protein 135; DE AltName: Full=RING finger protein leading to RIG-I activation {ECO:0000303|PubMed:19017631}; DE Short=Riplet {ECO:0000303|PubMed:19017631}; DE AltName: Full=RING-type E3 ubiquitin transferase RNF135 {ECO:0000305}; GN Name=RNF135 {ECO:0000312|HGNC:HGNC:21158}; ORFNames=L13; 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). RX PubMed=12696059; DOI=10.1002/gcc.10206; RA Jenne D.E., Tinschert S., Dorschner M.O., Hameister H., Stephens K., RA Kehrer-Sawatzki H.; RT "Complete physical map and gene content of the human NF1 tumor suppressor RT region in human and mouse."; RL Genes Chromosomes Cancer 37:111-120(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=15334068; DOI=10.1038/sj.onc.1207921; RA Petroziello J., Yamane A., Westendorf L., Thompson M., McDonagh C., RA Cerveny C., Law C.-L., Wahl A., Carter P.; RT "Suppression subtractive hybridization and expression profiling identifies RT a unique set of genes overexpressed in non-small-cell lung cancer."; RL Oncogene 23:7734-7745(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH RIGI, RP AND TISSUE SPECIFICITY. RX PubMed=19017631; DOI=10.1074/jbc.m804259200; RA Oshiumi H., Matsumoto M., Hatakeyama S., Seya T.; RT "Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote RT interferon-beta induction during the early phase of viral infection."; RL J. Biol. Chem. 284:807-817(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Mammary gland, and Urinary bladder; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Brain, Lung carcinoma, 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 [8] RP INTERACTION WITH PCBP2. RX PubMed=19881509; DOI=10.1038/ni.1815; RA You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.; RT "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin RT ligase AIP4."; RL Nat. Immunol. 10:1300-1308(2009). RN [9] RP FUNCTION, INTERACTION WITH RIGI, AND SUBCELLULAR LOCATION. RX PubMed=19484123; DOI=10.1371/journal.pone.0005760; RA Gao D., Yang Y.K., Wang R.P., Zhou X., Diao F.C., Li M.D., Zhai Z.H., RA Jiang Z.F., Chen D.Y.; RT "REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid- RT inducible gene-I."; RL PLoS ONE 4:E5760-E5760(2009). RN [10] RP FUNCTION. RX PubMed=21147464; DOI=10.1016/j.chom.2010.11.008; RA Oshiumi H., Miyashita M., Inoue N., Okabe M., Matsumoto M., Seya T.; RT "The ubiquitin ligase Riplet is essential for RIG-I-dependent innate immune RT responses to RNA virus infection."; RL Cell Host Microbe 8:496-509(2010). RN [11] RP FUNCTION, INTERACTION WITH RIGI, SUBCELLULAR LOCATION, CLEAVAGE BY RP HEPATITIS C VIRUS NS3/NS4A (MICROBIAL INFECTION), AND MUTAGENESIS OF RP 16-GLU--ASP-18. RX PubMed=23950712; DOI=10.1371/journal.ppat.1003533; RA Oshiumi H., Miyashita M., Matsumoto M., Seya T.; RT "A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RT RIG-I repressor domain in human antiviral innate immune responses."; RL PLoS Pathog. 9:E1003533-E1003533(2013). RN [12] RP FUNCTION, INTERACTION WITH RIGI; UBE2D3 AND UBE2N, DOMAIN, AND MUTAGENESIS RP OF CYS-21 AND CYS-24. RX PubMed=28469175; DOI=10.1038/ncomms15138; RA Shi Y., Yuan B., Zhu W., Zhang R., Li L., Hao X., Chen S., Hou F.; RT "Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in RT antiviral innate immunity."; RL Nat. Commun. 8:15138-15138(2017). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, INTERACTION WITH RIGI, AND RP DOMAIN. RX PubMed=31006531; DOI=10.1016/j.cell.2019.03.017; RA Cadena C., Ahmad S., Xavier A., Willemsen J., Park S., Park J.W., Oh S.W., RA Fujita T., Hou F., Binder M., Hur S.; RT "Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate RT Immunity."; RL Cell 177:1187-1200(2019). RN [14] RP VARIANT HIS-286. RX PubMed=17632510; DOI=10.1038/ng2083; RA Douglas J., Cilliers D., Coleman K., Tatton-Brown K., Barker K., RA Bernhard B., Burn J., Huson S., Josifova D., Lacombe D., Malik M., RA Mansour S., Reid E., Cormier-Daire V., Cole T., Rahman N.; RT "Mutations in RNF135, a gene within the NF1 microdeletion region, cause RT phenotypic abnormalities including overgrowth."; RL Nat. Genet. 39:963-965(2007). RN [15] RP VARIANTS GLN-71; PRO-108; LYS-115 AND CYS-415. RX PubMed=19291764; DOI=10.1002/ajmg.a.32694; RA Visser R., Koelma N., Vijfhuizen L., van der Wielen M.J., Kant S.G., RA Breuning M.H., Wit J.M., Losekoot M.; RT "RNF135 mutations are not present in patients with Sotos syndrome-like RT features."; RL Am. J. Med. Genet. A 149:806-808(2009). CC -!- FUNCTION: E2-dependent E3 ubiquitin-protein ligase that functions as a CC RIGI coreceptor in the sensing of viral RNAs in cell cytoplasm and the CC activation of the antiviral innate immune response (PubMed:19017631, CC PubMed:19484123, PubMed:21147464, PubMed:23950712, PubMed:28469175, CC PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, CC catalyzes the 'Lys-63'-linked polyubiquitination of RIGI oligomerized CC on viral RNAs, an essential step in the activation of the RIG-I CC signaling pathway (PubMed:19017631, PubMed:21147464, PubMed:28469175, CC PubMed:31006531). Through a ubiquitin-independent parallel mechanism, CC which consists in bridging RIGI filaments forming on longer viral RNAs, CC further activates the RIG-I signaling pathway (PubMed:31006531). This CC second mechanism that synergizes with the ubiquitin-dependent one would CC thereby allow an RNA length-dependent regulation of the RIG-I signaling CC pathway (Probable). Associated with the E2 ligase UBE2N, also CC constitutively synthesizes unanchored 'Lys-63'-linked polyubiquitin CC chains that may also activate the RIG-I signaling pathway CC (PubMed:28469175, PubMed:31006531). {ECO:0000269|PubMed:19017631, CC ECO:0000269|PubMed:19484123, ECO:0000269|PubMed:21147464, CC ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:28469175, CC ECO:0000269|PubMed:31006531, ECO:0000305|PubMed:31006531}. 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:31006531}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:31006531}. CC -!- SUBUNIT: Homodimer (PubMed:31006531). Interacts (homodimer) with RIGI CC (double-stranded RNA-bound oligomeric form); involved in both RIGI CC ubiquitination, oligomerization into filaments associated with viral CC RNAs and the bridging of these filaments (PubMed:19017631, CC PubMed:19484123, PubMed:23950712, PubMed:28469175, PubMed:31006531). CC Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in CC RNF135-mediated ubiquitination of RIGI and activation of the RIG-I CC signaling pathway (PubMed:28469175). Interacts with PCBP2 CC (PubMed:19881509). {ECO:0000269|PubMed:19017631, CC ECO:0000269|PubMed:19484123, ECO:0000269|PubMed:19881509, CC ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:28469175, CC ECO:0000269|PubMed:31006531}. CC -!- INTERACTION: CC Q8IUD6; P56545-3: CTBP2; NbExp=3; IntAct=EBI-9916363, EBI-10171902; CC Q8IUD6; Q9UBT7: CTNNAL1; NbExp=6; IntAct=EBI-9916363, EBI-514206; CC Q8IUD6; Q08379: GOLGA2; NbExp=6; IntAct=EBI-9916363, EBI-618309; CC Q8IUD6; O75031: HSF2BP; NbExp=3; IntAct=EBI-9916363, EBI-7116203; CC Q8IUD6; Q8IUD6: RNF135; NbExp=4; IntAct=EBI-9916363, EBI-9916363; CC Q8IUD6; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-9916363, EBI-11139477; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19484123, CC ECO:0000269|PubMed:23950712}. Cytoplasm, Stress granule CC {ECO:0000269|PubMed:23950712}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8IUD6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IUD6-2; Sequence=VSP_023785, VSP_023786; CC Name=3; CC IsoId=Q8IUD6-3; Sequence=VSP_045359, VSP_045360; CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, spleen, kidney, CC placenta, prostate, stomach, thyroid and tongue. Also weakly expressed CC in heart, thymus, liver and lung. {ECO:0000269|PubMed:19017631}. CC -!- DOMAIN: The B30.2/SPRY domain mediates the interaction with the CC substrate RIGI. {ECO:0000269|PubMed:28469175, CC ECO:0000269|PubMed:31006531}. CC -!- DOMAIN: The coiled-coil domains mediate homodimerization and the CC bridging of viral RNA-associated RIGI filaments. CC {ECO:0000269|PubMed:31006531}. CC -!- PTM: (Microbial infection) Cleaved and inactivated by hepatitis C virus CC NS3/NS4A. {ECO:0000269|PubMed:23950712}. CC -!- WEB RESOURCE: Name=Leiden Open Variation Database; Note=Ring finger CC protein 135 (RNF135); CC URL="https://databases.lovd.nl/shared/variants/RNF135/unique"; 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; AJ496729; CAD43140.1; -; mRNA. DR EMBL; AY598332; AAT06743.1; -; mRNA. DR EMBL; AB470605; BAG84604.1; -; mRNA. DR EMBL; AK122646; BAG53638.1; -; mRNA. DR EMBL; AK312979; BAG35816.1; -; mRNA. DR EMBL; AC138207; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471147; EAW80286.1; -; Genomic_DNA. DR EMBL; BC005084; AAH05084.1; -; mRNA. DR EMBL; BC082262; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC126420; AAI26421.1; -; mRNA. DR EMBL; BC126422; AAI26423.1; -; mRNA. DR CCDS; CCDS11262.1; -. [Q8IUD6-1] DR CCDS; CCDS11263.1; -. [Q8IUD6-2] DR CCDS; CCDS54104.1; -. [Q8IUD6-3] DR RefSeq; NP_001171921.1; NM_001184992.1. [Q8IUD6-3] DR RefSeq; NP_115698.3; NM_032322.3. [Q8IUD6-1] DR RefSeq; NP_922921.1; NM_197939.1. [Q8IUD6-2] DR PDB; 7JL1; EM; 3.90 A; B=249-432. DR PDB; 7JL3; EM; 4.20 A; B/D/F=249-432. DR PDB; 8G7T; EM; 3.20 A; B/D=1-432. DR PDB; 8G7U; EM; 4.00 A; B/D=1-432. DR PDB; 8G7V; EM; 3.90 A; B/D=1-432. DR PDBsum; 7JL1; -. DR PDBsum; 7JL3; -. DR PDBsum; 8G7T; -. DR PDBsum; 8G7U; -. DR PDBsum; 8G7V; -. DR AlphaFoldDB; Q8IUD6; -. DR EMDB; EMD-22369; -. DR EMDB; EMD-22371; -. DR EMDB; EMD-29823; -. DR EMDB; EMD-29824; -. DR EMDB; EMD-29825; -. DR SMR; Q8IUD6; -. DR BioGRID; 124009; 32. DR IntAct; Q8IUD6; 17. DR STRING; 9606.ENSP00000328340; -. DR GlyCosmos; Q8IUD6; 1 site, 1 glycan. DR GlyGen; Q8IUD6; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q8IUD6; -. DR PhosphoSitePlus; Q8IUD6; -. DR BioMuta; RNF135; -. DR DMDM; 269849639; -. DR EPD; Q8IUD6; -. DR jPOST; Q8IUD6; -. DR MassIVE; Q8IUD6; -. DR MaxQB; Q8IUD6; -. DR PaxDb; 9606-ENSP00000328340; -. DR PeptideAtlas; Q8IUD6; -. DR ProteomicsDB; 24321; -. DR ProteomicsDB; 70552; -. [Q8IUD6-1] DR ProteomicsDB; 70553; -. [Q8IUD6-2] DR Pumba; Q8IUD6; -. DR Antibodypedia; 15187; 172 antibodies from 24 providers. DR DNASU; 84282; -. DR Ensembl; ENST00000324689.8; ENSP00000323693.4; ENSG00000181481.14. [Q8IUD6-2] DR Ensembl; ENST00000328381.10; ENSP00000328340.5; ENSG00000181481.14. [Q8IUD6-1] DR Ensembl; ENST00000535306.6; ENSP00000440470.2; ENSG00000181481.14. [Q8IUD6-3] DR Ensembl; ENST00000708425.1; ENSP00000517220.1; ENSG00000291712.1. [Q8IUD6-2] DR Ensembl; ENST00000708426.1; ENSP00000517221.1; ENSG00000291712.1. [Q8IUD6-1] DR Ensembl; ENST00000708427.1; ENSP00000517222.1; ENSG00000291712.1. [Q8IUD6-3] DR GeneID; 84282; -. DR KEGG; hsa:84282; -. DR MANE-Select; ENST00000328381.10; ENSP00000328340.5; NM_032322.4; NP_115698.3. DR UCSC; uc002hfz.4; human. [Q8IUD6-1] DR AGR; HGNC:21158; -. DR CTD; 84282; -. DR DisGeNET; 84282; -. DR GeneCards; RNF135; -. DR HGNC; HGNC:21158; RNF135. DR HPA; ENSG00000181481; Low tissue specificity. DR MalaCards; RNF135; -. DR MIM; 611358; gene. DR neXtProt; NX_Q8IUD6; -. DR OpenTargets; ENSG00000181481; -. DR Orphanet; 137634; Overgrowth-macrocephaly-facial dysmorphism syndrome. DR PharmGKB; PA134978537; -. DR VEuPathDB; HostDB:ENSG00000181481; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00830000128449; -. DR HOGENOM; CLU_032372_2_0_1; -. DR InParanoid; Q8IUD6; -. DR OMA; DCLKGLW; -. DR OrthoDB; 5355412at2759; -. DR PhylomeDB; Q8IUD6; -. DR TreeFam; TF351089; -. DR PathwayCommons; Q8IUD6; -. DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation. DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10. DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; Q8IUD6; -. DR SIGNOR; Q8IUD6; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 84282; 10 hits in 1188 CRISPR screens. DR ChiTaRS; RNF135; human. DR GeneWiki; RNF135; -. DR GenomeRNAi; 84282; -. DR Pharos; Q8IUD6; Tbio. DR PRO; PR:Q8IUD6; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q8IUD6; Protein. DR Bgee; ENSG00000181481; Expressed in pancreatic ductal cell and 188 other cell types or tissues. DR ExpressionAtlas; Q8IUD6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:UniProtKB. DR GO; GO:0039552; F:RIG-I binding; IPI:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0140374; P:antiviral innate immune response; IMP:UniProtKB. DR GO; GO:0010994; P:free ubiquitin chain polymerization; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0045088; P:regulation of innate immune response; IMP:UniProtKB. DR GO; GO:0039529; P:RIG-I signaling pathway; IDA:UniProtKB. DR CDD; cd16604; RING-HC_TRIM47-like_C-IV; 1. DR CDD; cd12902; SPRY_PRY_RNF135; 1. DR Gene3D; 2.60.120.920; -; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR043136; B30.2/SPRY_sf. DR InterPro; IPR003879; Butyrophylin_SPRY. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR006574; PRY. DR InterPro; IPR042723; RNF135_SPRY_PRY_dom. DR InterPro; IPR003877; SPRY_dom. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR25465; B-BOX DOMAIN CONTAINING; 1. DR PANTHER; PTHR25465:SF41; E3 UBIQUITIN-PROTEIN LIGASE RNF135; 1. DR Pfam; PF00622; SPRY; 1. DR Pfam; PF15227; zf-C3HC4_4; 1. DR PRINTS; PR01407; BUTYPHLNCDUF. DR SMART; SM00589; PRY; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00449; SPRY; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50188; B302_SPRY; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q8IUD6; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; KW Disease variant; Immunity; Innate immunity; Metal-binding; KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc; KW Zinc-finger. FT CHAIN 1..432 FT /note="E3 ubiquitin-protein ligase RNF135" FT /id="PRO_0000280557" FT DOMAIN 241..432 FT /note="B30.2/SPRY" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT ZN_FING 21..63 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 95..121 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 121..156 FT /evidence="ECO:0000255" FT COILED 191..216 FT /evidence="ECO:0000255" FT VAR_SEQ 173..210 FT /note="AFSSGVDLSMASPKLVTSDTAAGKIRDILHDLEEIQEK -> ENSWKPRLPP FT HAHCLTRATLHSGELLGLLSGPSIQPLT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_023785" FT VAR_SEQ 211..432 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_023786" FT VAR_SEQ 228..286 FT /note="ELLEAPSSSSCPLPDQSHPALRRASRFAQWAIHPTFNLKSLSCSLEVSKDSR FT TVTVSHR -> SLLPRLECSGTITAASISQAQENSWKPRLPPHAHCLTRATLHSGELLG FT LLSGPSIQPLT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045359" FT VAR_SEQ 287..432 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045360" FT VARIANT 71 FT /note="H -> Q (in dbSNP:rs7225888)" FT /evidence="ECO:0000269|PubMed:19291764" FT /id="VAR_031165" FT VARIANT 108 FT /note="S -> P (in dbSNP:rs7211440)" FT /evidence="ECO:0000269|PubMed:19291764" FT /id="VAR_031166" FT VARIANT 115 FT /note="R -> K (in dbSNP:rs111902263)" FT /evidence="ECO:0000269|PubMed:19291764" FT /id="VAR_063495" FT VARIANT 286 FT /note="R -> H (found in an individual with overgrowth, FT learning disability and dysmorphic features; uncertain FT significance; dbSNP:rs121918162)" FT /evidence="ECO:0000269|PubMed:17632510" FT /id="VAR_037652" FT VARIANT 415 FT /note="W -> C (in dbSNP:rs61749868)" FT /evidence="ECO:0000269|PubMed:19291764" FT /id="VAR_063496" FT MUTAGEN 16..18 FT /note="EDD->AAA: Prevents degradation by hepatitis C virus FT NS3/NS4A." FT /evidence="ECO:0000269|PubMed:23950712" FT MUTAGEN 21 FT /note="C->A: Loss of function in RIG-I signaling pathway; FT when associated with A-24." FT /evidence="ECO:0000269|PubMed:28469175" FT MUTAGEN 24 FT /note="C->A: Loss of function in RIG-I signaling pathway; FT when associated with A-21." FT /evidence="ECO:0000269|PubMed:28469175" FT CONFLICT 274 FT /note="V -> G (in Ref. 1; CAD43140 and 2; AAT06743)" FT /evidence="ECO:0000305" FT CONFLICT 293 FT /note="S -> N (in Ref. 1; CAD43140 and 2; AAT06743)" FT /evidence="ECO:0000305" SQ SEQUENCE 432 AA; 47888 MW; 488F05406996311D CRC64; MAGLGLGSAV PVWLAEDDLG CIICQGLLDW PATLPCGHSF CRHCLEALWG ARDARRWACP TCRQGAAQQP HLRKNTLLQD LADKYRRAAR EIQAGSDPAH CPCPGSSSLS SAAARPRRRP ELQRVAVEKS ITEVAQELTE LVEHLVDIVR SLQNQRPLSE SGPDNELSIL GKAFSSGVDL SMASPKLVTS DTAAGKIRDI LHDLEEIQEK LQESVTWKEA PEAQMQGELL EAPSSSSCPL PDQSHPALRR ASRFAQWAIH PTFNLKSLSC SLEVSKDSRT VTVSHRPQPY RWSCERFSTS QVLCSQALSS GKHYWEVDTR NCSHWAVGVA SWEMSRDQVL GRTMDSCCVE WKGTSQLSAW HMVKETVLGS DRPGVVGIWL NLEEGKLAFY SVDNQEKLLY ECTISASSPL YPAFWLYGLH PGNYLIIKQV KV //