RN182_HUMAN
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 03-AUG-2022, entry version 140.
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}.
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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_001165032.1.
DR RefSeq; NP_001158505.1; NM_001165033.1.
DR RefSeq; NP_001158506.1; NM_001165034.1.
DR RefSeq; NP_689950.1; NM_152737.3.
DR RefSeq; XP_016865937.1; XM_017010448.1.
DR RefSeq; XP_016865938.1; XM_017010449.1.
DR RefSeq; XP_016865939.1; XM_017010450.1.
DR AlphaFoldDB; Q8N6D2; -.
DR SMR; Q8N6D2; -.
DR BioGRID; 128745; 9.
DR IntAct; Q8N6D2; 6.
DR STRING; 9606.ENSP00000420465; -.
DR iPTMnet; Q8N6D2; -.
DR PhosphoSitePlus; Q8N6D2; -.
DR BioMuta; RNF182; -.
DR DMDM; 74751050; -.
DR EPD; Q8N6D2; -.
DR jPOST; Q8N6D2; -.
DR MassIVE; Q8N6D2; -.
DR PaxDb; Q8N6D2; -.
DR PeptideAtlas; Q8N6D2; -.
DR PRIDE; Q8N6D2; -.
DR ProteomicsDB; 72159; -.
DR Antibodypedia; 1547; 133 antibodies from 19 providers.
DR DNASU; 221687; -.
DR Ensembl; ENST00000488300.6; ENSP00000420465.1; ENSG00000180537.13.
DR Ensembl; ENST00000537388.1; ENSP00000441271.1; ENSG00000180537.13.
DR Ensembl; ENST00000537663.5; ENSP00000443228.1; ENSG00000180537.13.
DR Ensembl; ENST00000544682.5; ENSP00000442021.1; ENSG00000180537.13.
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 CTD; 221687; -.
DR DisGeNET; 221687; -.
DR GeneCards; RNF182; -.
DR HGNC; HGNC:28522; RNF182.
DR HPA; ENSG00000180537; Tissue enhanced (brain, choroid plexus).
DR neXtProt; NX_Q8N6D2; -.
DR OpenTargets; ENSG00000180537; -.
DR PharmGKB; PA134975171; -.
DR VEuPathDB; HostDB:ENSG00000180537; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00730000111020; -.
DR HOGENOM; CLU_100624_0_0_1; -.
DR InParanoid; Q8N6D2; -.
DR OMA; FLDCMAL; -.
DR OrthoDB; 1216224at2759; -.
DR PhylomeDB; Q8N6D2; -.
DR TreeFam; TF331690; -.
DR PathwayCommons; Q8N6D2; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8N6D2; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 221687; 14 hits in 1112 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 136 other tissues.
DR ExpressionAtlas; Q8N6D2; baseline and differential.
DR Genevisible; Q8N6D2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR042285; RNF182.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR46675; PTHR46675; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 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; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation pathway; Zinc;
KW 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
