RN166_HUMAN
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 03-AUG-2022, entry version 155.
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. [Q96A37-2]
DR AlphaFoldDB; Q96A37; -.
DR SMR; Q96A37; -.
DR BioGRID; 125465; 94.
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; Q96A37; -.
DR PeptideAtlas; Q96A37; -.
DR PRIDE; Q96A37; -.
DR ProteomicsDB; 42744; -.
DR ProteomicsDB; 75905; -. [Q96A37-1]
DR ProteomicsDB; 75906; -. [Q96A37-2]
DR Antibodypedia; 30751; 126 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 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; FCGDCLQ; -.
DR PhylomeDB; Q96A37; -.
DR TreeFam; TF331012; -.
DR PathwayCommons; Q96A37; -.
DR SignaLink; Q96A37; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 115992; 11 hits in 1115 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 136 other tissues.
DR ExpressionAtlas; Q96A37; baseline and differential.
DR Genevisible; Q96A37; HS.
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 Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR008598; Di19_Zn-bd.
DR InterPro; IPR034734; ZF_C2HC_RNF.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF05605; zf-Di19; 1.
DR Pfam; PF18574; zf_C2HC_14; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS51803; ZF_C2HC_RNF; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
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
