RN135_HUMAN
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 03-AUG-2022, entry version 159.
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 DDX58,
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 DDX58, 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 DDX58, 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 DDX58; 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 DDX58, 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 RIG-I/DDX58 coreceptor in the sensing of viral RNAs in cell cytoplasm
CC and the activation of the antiviral innate immune response
CC (PubMed:19017631, PubMed:19484123, PubMed:21147464, PubMed:23950712,
CC PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and
CC UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of
CC RIG-I/DDX58 oligomerized on viral RNAs, an essential step in the
CC activation of the RIG-I signaling pathway (PubMed:19017631,
CC PubMed:21147464, PubMed:28469175, PubMed:31006531). Through a
CC ubiquitin-independent parallel mechanism, which consists in bridging
CC RIG-I/DDX58 filaments forming on longer viral RNAs, further activates
CC the RIG-I signaling pathway (PubMed:31006531). This second mechanism
CC that synergizes with the ubiquitin-dependent one would thereby allow an
CC RNA length-dependent regulation of the RIG-I signaling pathway
CC (Probable). Associated with the E2 ligase UBE2N, also constitutively
CC synthesizes unanchored 'Lys-63'-linked polyubiquitin chains that may
CC also activate the RIG-I signaling pathway (PubMed:28469175,
CC 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 DDX58
CC (double-stranded RNA-bound oligomeric form); involved in both DDX58
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 DDX58 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 RIG-I/DDX58. {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 RIG-I/DDX58 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";
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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 PDBsum; 7JL1; -.
DR PDBsum; 7JL3; -.
DR AlphaFoldDB; Q8IUD6; -.
DR SMR; Q8IUD6; -.
DR BioGRID; 124009; 29.
DR IntAct; Q8IUD6; 18.
DR STRING; 9606.ENSP00000328340; -.
DR GlyGen; Q8IUD6; 1 site, 1 O-linked glycan (1 site).
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; Q8IUD6; -.
DR PeptideAtlas; Q8IUD6; -.
DR PRIDE; Q8IUD6; -.
DR ProteomicsDB; 24321; -.
DR ProteomicsDB; 70552; -. [Q8IUD6-1]
DR ProteomicsDB; 70553; -. [Q8IUD6-2]
DR Antibodypedia; 15187; 164 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 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 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; 751018at2759; -.
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; 9 hits in 1110 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 186 other tissues.
DR ExpressionAtlas; Q8IUD6; baseline and differential.
DR Genevisible; Q8IUD6; HS.
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; cd12902; SPRY_PRY_RNF135; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.40.10; -; 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 Pfam; PF00622; SPRY; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00589; PRY; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
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; unknown
FT pathological 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
