ID RN166_HUMAN Reviewed; 237 AA. AC Q96A37; B3KQ03; D3DX75; H3BTU8; Q96DM0; DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 24-JAN-2024, entry version 163. DE RecName: Full=E3 ubiquitin-protein ligase RNF166 {ECO:0000303|PubMed:27880896}; DE EC=2.3.2.27 {ECO:0000269|PubMed:27880896}; DE AltName: Full=RING finger protein 166; DE AltName: Full=RING-type E3 ubiquitin transferase RNF166 {ECO:0000305}; GN Name=RNF166; 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] (ISOFORM 2). RC TISSUE=Small intestine, and Synovial cell; 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 GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, Eye, and Leukocyte; 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 [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26456228; DOI=10.1038/srep14770; RA Chen H.W., Yang Y.K., Xu H., Yang W.W., Zhai Z.H., Chen D.Y.; RT "Ring finger protein 166 potentiates RNA virus-induced interferon-beta RT production via enhancing the ubiquitination of TRAF3 and TRAF6."; RL Sci. Rep. 5:14770-14770(2015). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-33 AND CYS-36, AND RP PATHWAY. RX PubMed=27880896; DOI=10.1016/j.celrep.2016.11.005; RA Heath R.J., Goel G., Baxt L.A., Rush J.S., Mohanan V., Paulus G.L.C., RA Jani V., Lassen K.G., Xavier R.J.; RT "RNF166 Determines Recruitment of Adaptor Proteins during Antibacterial RT Autophagy."; RL Cell Rep. 17:2183-2194(2016). CC -!- FUNCTION: E3 ubiquitin-protein ligase that promotes the ubiquitination CC of different substrates (PubMed:27880896). In turn, participates in CC different biological processes including interferon production or CC autophagy (PubMed:26456228, PubMed:27880896). Plays a role in the CC activation of RNA virus-induced interferon-beta production by promoting CC the ubiquitination of TRAF3 and TRAF6 (PubMed:26456228). Also plays a CC role in the early recruitment of autophagy adapters to bacteria CC (PubMed:27880896). Mediates 'Lys-29' and 'Lys-33'-linked ubiquitination CC of SQSTM1 leading to xenophagic targeting of bacteria and inhibition of CC their replication (PubMed:27880896). {ECO:0000269|PubMed:26456228, CC ECO:0000269|PubMed:27880896}. 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:27880896}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:27880896}. CC -!- INTERACTION: CC Q96A37; O60260-5: PRKN; NbExp=3; IntAct=EBI-2130320, EBI-21251460; CC Q96A37; Q13148: TARDBP; NbExp=3; IntAct=EBI-2130320, EBI-372899; CC Q96A37; Q9Y2X8: UBE2D4; NbExp=4; IntAct=EBI-2130320, EBI-745527; CC Q96A37; P61086: UBE2K; NbExp=3; IntAct=EBI-2130320, EBI-473850; CC Q96A37; Q6GPH4: XAF1; NbExp=3; IntAct=EBI-2130320, EBI-2815120; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26456228}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96A37-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96A37-2; Sequence=VSP_019750; CC Name=3; CC IsoId=Q96A37-3; Sequence=VSP_046147; 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; AK057106; BAG51865.1; -; mRNA. DR EMBL; AK057201; BAB71380.1; -; mRNA. DR EMBL; AC138028; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471184; EAW66784.1; -; Genomic_DNA. DR EMBL; CH471184; EAW66781.1; -; Genomic_DNA. DR EMBL; CH471184; EAW66785.1; -; Genomic_DNA. DR EMBL; BC013948; AAH13948.1; -; mRNA. DR EMBL; BC017226; AAH17226.1; -; mRNA. DR EMBL; BI911983; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS10969.1; -. [Q96A37-1] DR CCDS; CCDS54056.1; -. [Q96A37-2] DR CCDS; CCDS54057.1; -. [Q96A37-3] DR RefSeq; NP_001165286.1; NM_001171815.1. [Q96A37-3] DR RefSeq; NP_001165287.1; NM_001171816.1. [Q96A37-2] DR RefSeq; NP_849163.1; NM_178841.3. [Q96A37-1] DR RefSeq; XP_016878402.1; XM_017022913.1. DR AlphaFoldDB; Q96A37; -. DR SMR; Q96A37; -. DR BioGRID; 125465; 95. DR IntAct; Q96A37; 53. DR STRING; 9606.ENSP00000326095; -. DR iPTMnet; Q96A37; -. DR PhosphoSitePlus; Q96A37; -. DR BioMuta; RNF166; -. DR DMDM; 74762644; -. DR EPD; Q96A37; -. DR jPOST; Q96A37; -. DR MassIVE; Q96A37; -. DR MaxQB; Q96A37; -. DR PaxDb; 9606-ENSP00000326095; -. DR PeptideAtlas; Q96A37; -. DR ProteomicsDB; 42744; -. DR ProteomicsDB; 75905; -. [Q96A37-1] DR ProteomicsDB; 75906; -. [Q96A37-2] DR Pumba; Q96A37; -. DR Antibodypedia; 30751; 153 antibodies from 20 providers. DR DNASU; 115992; -. DR Ensembl; ENST00000312838.9; ENSP00000326095.4; ENSG00000158717.11. [Q96A37-1] DR Ensembl; ENST00000537718.6; ENSP00000446301.2; ENSG00000158717.11. [Q96A37-2] DR Ensembl; ENST00000541206.6; ENSP00000440454.2; ENSG00000158717.11. [Q96A37-2] DR Ensembl; ENST00000567844.1; ENSP00000457336.1; ENSG00000158717.11. [Q96A37-3] DR GeneID; 115992; -. DR KEGG; hsa:115992; -. DR MANE-Select; ENST00000312838.9; ENSP00000326095.4; NM_178841.4; NP_849163.1. DR UCSC; uc002flk.3; human. [Q96A37-1] DR AGR; HGNC:28856; -. DR CTD; 115992; -. DR DisGeNET; 115992; -. DR GeneCards; RNF166; -. DR HGNC; HGNC:28856; RNF166. DR HPA; ENSG00000158717; Tissue enhanced (bone marrow, lymphoid tissue). DR neXtProt; NX_Q96A37; -. DR OpenTargets; ENSG00000158717; -. DR PharmGKB; PA134915234; -. DR VEuPathDB; HostDB:ENSG00000158717; -. DR eggNOG; ENOG502RB47; Eukaryota. DR GeneTree; ENSGT00950000182909; -. DR HOGENOM; CLU_092448_1_0_1; -. DR InParanoid; Q96A37; -. DR OMA; PCLQVAS; -. DR OrthoDB; 26661at2759; -. DR PhylomeDB; Q96A37; -. DR TreeFam; TF331012; -. DR PathwayCommons; Q96A37; -. DR SignaLink; Q96A37; -. DR SIGNOR; Q96A37; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 115992; 11 hits in 1193 CRISPR screens. DR ChiTaRS; RNF166; human. DR GenomeRNAi; 115992; -. DR Pharos; Q96A37; Tdark. DR PRO; PR:Q96A37; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q96A37; Protein. DR Bgee; ENSG00000158717; Expressed in granulocyte and 137 other cell types or tissues. DR ExpressionAtlas; Q96A37; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR CDD; cd16549; RING-HC_RNF166; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR008598; Di19_Zn-bd. DR InterPro; IPR034734; ZF_C2HC_RNF. DR InterPro; IPR027370; Znf-RING_euk. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR46016:SF4; E3 UBIQUITIN-PROTEIN LIGASE RNF166; 1. DR PANTHER; PTHR46016; ZINC FINGER, RING/FYVE/PHD-TYPE; 1. DR Pfam; PF05605; zf-Di19; 1. DR Pfam; PF13445; zf-RING_UBOX; 1. DR Pfam; PF18574; zf_C2HC_14; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS51803; ZF_C2HC_RNF; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q96A37; HS. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Cytoplasm; Immunity; Innate immunity; KW Metal-binding; Reference proteome; Transferase; Ubl conjugation pathway; KW Zinc; Zinc-finger. FT CHAIN 1..237 FT /note="E3 ubiquitin-protein ligase RNF166" FT /id="PRO_0000245588" FT DOMAIN 221..237 FT /note="UIM" FT /evidence="ECO:0000305" FT ZN_FING 33..73 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 98..117 FT /note="C2HC RNF-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 98 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 101 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 113 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT BINDING 117 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144" FT VAR_SEQ 1..109 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019750" FT VAR_SEQ 39..119 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_046147" FT MUTAGEN 33 FT /note="C->A: Complete loss of SQSTM1 ubiquitination; in FT association with A-36." FT /evidence="ECO:0000269|PubMed:27880896" FT MUTAGEN 36 FT /note="C->A: Complete loss of SQSTM1 ubiquitination; in FT association with A-33." FT /evidence="ECO:0000269|PubMed:27880896" FT CONFLICT 11 FT /note="A -> V (in Ref. 4; BI911983)" FT /evidence="ECO:0000305" FT CONFLICT 38 FT /note="E -> K (in Ref. 4; BI911983)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="S -> G (in Ref. 1; BAB71380)" FT /evidence="ECO:0000305" SQ SEQUENCE 237 AA; 26122 MW; 2802E758F4681716 CRC64; MAMFRSLVAS AQQRQPPAGP AGGDSGLEAQ YTCPICLEVY HRPVAIGSCG HTFCGECLQP CLQVPSPLCP LCRLPFDPKK VDKATHVEKQ LSSYKAPCRG CNKKVTLAKM RVHISSCLKV QEQMANCPKF VPVVPTSQPI PSNIPNRSTF ACPYCGARNL DQQELVKHCV ESHRSDPNRV VCPICSAMPW GDPSYKSANF LQHLLHRHKF SYDTFVDYSI DEEAAFQAAL ALSLSEN //