RN135_MOUSE
ID RN135_MOUSE Reviewed; 417 AA.
AC Q9CWS1; Q3UBK5; Q8R161; Q9DCH3;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=E3 ubiquitin-protein ligase RNF135 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8IUD6};
DE AltName: Full=RING finger protein 135;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF135 {ECO:0000305};
GN Name=Rnf135 {ECO:0000312|MGI:MGI:1919206};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C3H/He, and FVB/N; TISSUE=Mammary tumor, and Mesenchymal stem cell;
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 [4]
RP FUNCTION, PATHWAY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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 [5]
RP FUNCTION.
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION.
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).
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:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531).
CC Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the
CC 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 oligomerized on viral
CC RNAs, an essential step in the activation of the RIG-I signaling
CC pathway (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 (PubMed:31006531). 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 (By
CC similarity). It is not involved in the innate immune response against
CC DNA viruses (PubMed:21147464). {ECO:0000250|UniProtKB:Q8IUD6,
CC ECO:0000269|PubMed:21147464, ECO:0000269|PubMed:23950712,
CC ECO:0000269|PubMed:28469175, ECO:0000269|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:0000250|UniProtKB:Q8IUD6};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:21147464}.
CC -!- SUBUNIT: Homodimer. Interacts (homodimer) with DDX58 (double-stranded
CC RNA-bound oligomeric form); involved in both DDX58 ubiquitination,
CC oligomerization into filaments associated with viral RNAs and the
CC bridging of these filaments. Interacts with UBE2D3 and UBE2N; E2
CC ubiquitin ligases involved in RNF135-mediated ubiquitination of DDX58
CC and activation of the RIG-I signaling pathway. Interacts with PCBP2.
CC {ECO:0000250|UniProtKB:Q8IUD6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28469175}.
CC Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q8IUD6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CWS1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CWS1-2; Sequence=VSP_023787;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:21147464}.
CC -!- DOMAIN: The B30.2/SPRY domain mediates the interaction with the
CC substrate RIG-I/DDX58. {ECO:0000250|UniProtKB:Q8IUD6}.
CC -!- DOMAIN: The coiled-coil domains mediate homodimerization and the
CC bridging of viral RNA-associated RIG-I/DDX58 filaments.
CC {ECO:0000250|UniProtKB:Q8IUD6}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Rnf135 develop and breed normally
CC (PubMed:21147464). They are susceptible to RNA viruses infection
CC (PubMed:21147464). {ECO:0000269|PubMed:21147464}.
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DR EMBL; AK002781; BAB22354.1; -; mRNA.
DR EMBL; AK010429; BAB26931.1; -; mRNA.
DR EMBL; AK150921; BAE29959.1; -; mRNA.
DR EMBL; AK152096; BAE30944.1; -; mRNA.
DR EMBL; AL591426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025209; AAH25209.1; -; mRNA.
DR EMBL; BC096385; AAH96385.1; -; mRNA.
DR EMBL; BC132307; AAI32308.1; -; mRNA.
DR CCDS; CCDS25129.1; -. [Q9CWS1-1]
DR RefSeq; NP_082295.1; NM_028019.3. [Q9CWS1-1]
DR AlphaFoldDB; Q9CWS1; -.
DR SMR; Q9CWS1; -.
DR IntAct; Q9CWS1; 1.
DR MINT; Q9CWS1; -.
DR STRING; 10090.ENSMUSP00000017839; -.
DR iPTMnet; Q9CWS1; -.
DR PhosphoSitePlus; Q9CWS1; -.
DR EPD; Q9CWS1; -.
DR MaxQB; Q9CWS1; -.
DR PaxDb; Q9CWS1; -.
DR PeptideAtlas; Q9CWS1; -.
DR PRIDE; Q9CWS1; -.
DR ProteomicsDB; 299916; -. [Q9CWS1-1]
DR ProteomicsDB; 299917; -. [Q9CWS1-2]
DR DNASU; 71956; -.
DR Ensembl; ENSMUST00000017839; ENSMUSP00000017839; ENSMUSG00000020707. [Q9CWS1-1]
DR GeneID; 71956; -.
DR KEGG; mmu:71956; -.
DR UCSC; uc007kln.1; mouse. [Q9CWS1-1]
DR CTD; 84282; -.
DR MGI; MGI:1919206; Rnf135.
DR VEuPathDB; HostDB:ENSMUSG00000020707; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000164538; -.
DR HOGENOM; CLU_032372_2_0_1; -.
DR InParanoid; Q9CWS1; -.
DR OMA; DCLKGLW; -.
DR PhylomeDB; Q9CWS1; -.
DR TreeFam; TF351089; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 71956; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Rnf135; mouse.
DR PRO; PR:Q9CWS1; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9CWS1; protein.
DR Bgee; ENSMUSG00000020707; Expressed in proximal tubule and 237 other tissues.
DR ExpressionAtlas; Q9CWS1; baseline and differential.
DR Genevisible; Q9CWS1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; ISS:UniProtKB.
DR GO; GO:0039552; F:RIG-I binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; IMP:UniProtKB.
DR GO; GO:0010994; P:free ubiquitin chain polymerization; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IGI:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0039529; P:RIG-I signaling pathway; IMP: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; 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; 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 2: Evidence at transcript level;
KW Alternative splicing; Coiled coil; Cytoplasm; Immunity; Innate immunity;
KW Metal-binding; Receptor; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..417
FT /note="E3 ubiquitin-protein ligase RNF135"
FT /id="PRO_0000280558"
FT DOMAIN 225..417
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 21..67
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 95..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 121..145
FT /evidence="ECO:0000255"
FT COILED 180..204
FT /evidence="ECO:0000255"
FT VAR_SEQ 78..346
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023787"
SQ SEQUENCE 417 AA; 46462 MW; C79AD6FA1D2CF683 CRC64;
MAAVCSGNAV PVWLSEDDLS CIICQGLLDQ PTTLPCGHSF CLRCLHDLWV SKRGAVDGCP
WACPICRKGP LTKPKLHKNP LLQDLVDKYL QAAREVEAGS EPEPAPAPRS APQVTVQKST
TNVIQELTDM VRQLVDDVKS LQTQRPNLGS GQDNAQGTPP TDSSSEGEHS LDSPKLVTFS
ISQKKIQEIL HNLEEIQEKL QGSVPGRAPP RERVQEMTSS LCLLPDQRRP APRKASHLSL
WAISPTFDLR TLSYNLEVSN NSRRVTVSRG DLHTYHWSPQ RFSISQVFCS QALSSGQKYW
EVDTRNCSHW AIGVASWGMK RDGMLGRTMD SWCIEWRGPG QFSAWAKMKK TDLQSDLPEV
VGVWLDLESG ELAFYAVADH ERLLYECEVS SSSPLHPAFW LYGLSPGNYL EIKQLNT
