ID RN182_HUMAN Reviewed; 247 AA. AC Q8N6D2; B2RDG2; Q8NBG3; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 28-JAN-2026, entry version 155. DE RecName: Full=E3 ubiquitin-protein ligase RNF182 {ECO:0000303|PubMed:18298843}; DE EC=2.3.2.27 {ECO:0000269|PubMed:18298843}; DE AltName: Full=RING finger protein 182; DE AltName: Full=RING-type E3 ubiquitin transferase RNF182 {ECO:0000305}; GN Name=RNF182; 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]. RC TISSUE=Brain; 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=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Testis; 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 VARIANTS [LARGE SCALE ANALYSIS] ALA-43 AND LEU-58. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [6] RP FUNCTION, INTERACTION WITH ATP6V0C, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND CATALYTIC ACTIVITY. RX PubMed=18298843; DOI=10.1186/1750-1326-3-4; RA Liu Q.Y., Lei J.X., Sikorska M., Liu R.; RT "A novel brain-enriched E3 ubiquitin ligase RNF182 is up regulated in the RT brains of Alzheimer's patients and targets ATP6V0C for degradation."; RL Mol. Neurodegener. 3:4-4(2008). RN [7] RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=31432514; DOI=10.1002/1873-3468.13583; RA Cao Y., Sun Y., Chang H., Sun X., Yang S.; RT "The E3 ubiquitin ligase RNF182 inhibits TLR-triggered cytokine production RT through promoting p65 ubiquitination and degradation."; RL FEBS Lett. 593:3210-3219(2019). CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates the ubiquitination CC of ATP6V0C and targets it to degradation via the ubiquitin-proteasome CC pathway (PubMed:18298843). Also plays a role in the inhibition of TLR- CC triggered innate immune response by mediating 'Lys'-48-linked CC ubiquitination and subsequent degradation of NF-kappa-B component RELA CC (PubMed:31432514). {ECO:0000269|PubMed:18298843, CC ECO:0000269|PubMed:31432514}. 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:18298843}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:18298843}. CC -!- SUBUNIT: Interacts with ATP6V0C. {ECO:0000269|PubMed:18298843}. CC -!- INTERACTION: CC Q8N6D2; P51668: UBE2D1; NbExp=3; IntAct=EBI-2130099, EBI-743540; CC Q8N6D2; P61086: UBE2K; NbExp=3; IntAct=EBI-2130099, EBI-473850; CC Q8N6D2; P68036: UBE2L3; NbExp=3; IntAct=EBI-2130099, EBI-711173; CC Q8N6D2; P61088: UBE2N; NbExp=2; IntAct=EBI-2130099, EBI-1052908; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane CC protein {ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:18298843, CC ECO:0000269|PubMed:31432514}. CC -!- TISSUE SPECIFICITY: Up-regulated in neuronal cells subjected to cell CC death-inducing injuries, such as oxygen and glucose deprivation (at CC protein level). Could be up-regulated in Alzheimer disease brains CC (PubMed:18298843). Highly expressed in innate immune organs such as CC lymph nodes and spleen and in immune cells such as macrophages and CC dendritic cells (PubMed:31432514). {ECO:0000269|PubMed:18298843, CC ECO:0000269|PubMed:31432514}. CC -!- DOMAIN: The RING-type zinc finger domain is required for E3 ligase CC activity. {ECO:0000250}. 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; AK090576; BAC03481.1; -; mRNA. DR EMBL; AK315528; BAG37909.1; -; mRNA. DR EMBL; AL138718; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471087; EAW55349.1; -; Genomic_DNA. DR EMBL; BC030666; AAH30666.1; -; mRNA. DR EMBL; BC050030; AAH50030.1; -; mRNA. DR CCDS; CCDS4531.1; -. DR RefSeq; NP_001158504.1; NM_001165032.2. DR RefSeq; NP_001158505.1; NM_001165033.2. DR RefSeq; NP_001158506.1; NM_001165034.2. DR RefSeq; NP_689950.1; NM_152737.4. DR RefSeq; XP_016865939.1; XM_017010450.3. DR RefSeq; XP_047274326.1; XM_047418370.1. DR RefSeq; XP_047274327.1; XM_047418371.1. DR RefSeq; XP_054210605.1; XM_054354630.1. DR RefSeq; XP_054210606.1; XM_054354631.1. DR RefSeq; XP_054210607.1; XM_054354632.1. DR AlphaFoldDB; Q8N6D2; -. DR SMR; Q8N6D2; -. DR BioGRID; 128745; 12. DR FunCoup; Q8N6D2; 546. DR IntAct; Q8N6D2; 6. DR STRING; 9606.ENSP00000420465; -. DR iPTMnet; Q8N6D2; -. DR PhosphoSitePlus; Q8N6D2; -. DR BioMuta; RNF182; -. DR DMDM; 74751050; -. DR jPOST; Q8N6D2; -. DR MassIVE; Q8N6D2; -. DR PaxDb; 9606-ENSP00000420465; -. DR PeptideAtlas; Q8N6D2; -. DR ProteomicsDB; 72159; -. DR Pumba; Q8N6D2; -. DR Antibodypedia; 1547; 129 antibodies from 18 providers. DR DNASU; 221687; -. DR Ensembl; ENST00000488300.6; ENSP00000420465.1; ENSG00000180537.14. DR Ensembl; ENST00000537388.1; ENSP00000441271.1; ENSG00000180537.14. DR Ensembl; ENST00000537663.5; ENSP00000443228.1; ENSG00000180537.14. DR Ensembl; ENST00000544682.5; ENSP00000442021.1; ENSG00000180537.14. DR GeneID; 221687; -. DR KEGG; hsa:221687; -. DR MANE-Select; ENST00000488300.6; ENSP00000420465.1; NM_152737.4; NP_689950.1. DR UCSC; uc003nbe.4; human. DR AGR; HGNC:28522; -. DR ClinPGx; PA134975171; -. DR CTD; 221687; -. DR DisGeNET; 221687; -. DR GeneCards; RNF182; -. DR HGNC; HGNC:28522; RNF182. DR HPA; ENSG00000180537; Tissue enhanced (bone marrow, brain, retina). DR MIM; 621026; gene. DR OpenTargets; ENSG00000180537; -. DR VEuPathDB; HostDB:ENSG00000180537; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00730000111020; -. DR HOGENOM; CLU_100624_0_0_1; -. DR InParanoid; Q8N6D2; -. DR OMA; SWTVWNC; -. DR OrthoDB; 8936585at2759; -. DR PAN-GO; Q8N6D2; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q8N6D2; -. DR PathwayCommons; Q8N6D2; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q8N6D2; -. DR SIGNOR; Q8N6D2; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000180537; -. DR BioGRID-ORCS; 221687; 17 hits in 1190 CRISPR screens. DR ChiTaRS; RNF182; human. DR GenomeRNAi; 221687; -. DR Pharos; Q8N6D2; Tdark. DR PRO; PR:Q8N6D2; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q8N6D2; protein. DR Bgee; ENSG00000180537; Expressed in endothelial cell and 138 other cell types or tissues. DR ExpressionAtlas; Q8N6D2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:UniProtKB-EC. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR CDD; cd16555; RING-HC_RNF182; 1. DR FunFam; 3.30.40.10:FF:000319; E3 ubiquitin-protein ligase RNF182; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR042285; RNF182. DR InterPro; IPR047986; RNF182_RING-HC. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR46675; E3 UBIQUITIN-PROTEIN LIGASE RNF182; 1. DR PANTHER; PTHR46675:SF2; E3 UBIQUITIN-PROTEIN LIGASE RNF182; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW Cytoplasm; Membrane; Metal-binding; Proteomics identification; KW Reference proteome; Transferase; Transmembrane; Transmembrane helix; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..247 FT /note="E3 ubiquitin-protein ligase RNF182" FT /id="PRO_0000261620" FT TRANSMEM 184..204 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 211..231 FT /note="Helical" FT /evidence="ECO:0000255" FT ZN_FING 20..68 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT VARIANT 43 FT /note="V -> A (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035959" FT VARIANT 58 FT /note="P -> L (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035960" FT CONFLICT 108 FT /note="L -> P (in Ref. 1; BAC03481)" FT /evidence="ECO:0000305" FT CONFLICT 139 FT /note="E -> K (in Ref. 1; BAC03481)" FT /evidence="ECO:0000305" SQ SEQUENCE 247 AA; 27402 MW; 0012F055C7F2A233 CRC64; MASQPPEDTA ESQASDELEC KICYNRYNLK QRKPKVLECC HRVCAKCLYK IIDFGDSPQG VIVCPFCRFE TCLPDDEVSS LPDDNNILVN LTCGGKGKKC LPENPTELLL TPKRLASLVS PSHTSSNCLV ITIMEVQRES SPSLSSTPVV EFYRPASFDS VTTVSHNWTV WNCTSLLFQT SIRVLVWLLG LLYFSSLPLG IYLLVSKKVT LGVVFVSLVP SSLVILMVYG FCQCVCHEFL DCMAPPS //