RN183_HUMAN
ID RN183_HUMAN Reviewed; 192 AA.
AC Q96D59;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=E3 ubiquitin-protein ligase RNF183;
DE EC=2.3.2.27 {ECO:0000269|PubMed:29507230};
GN Name=RNF183;
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 GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-82 AND ARG-114.
RC TISSUE=Lung;
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 [3]
RP FUNCTION, INTERACTION WITH FATE1, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP CYS-13 AND CYS-59, AND UBIQUITINATION.
RX PubMed=26567849; DOI=10.1038/ncomms9840;
RA Maxfield K.E., Taus P.J., Corcoran K., Wooten J., Macion J., Zhou Y.,
RA Borromeo M., Kollipara R.K., Yan J., Xie Y., Xie X.J., Whitehurst A.W.;
RT "Comprehensive functional characterization of cancer-testis antigens
RT defines obligate participation in multiple hallmarks of cancer.";
RL Nat. Commun. 6:8840-8840(2015).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=29300766; DOI=10.1371/journal.pone.0190407;
RA Wu Y., Guo X.P., Kanemoto S., Maeoka Y., Saito A., Asada R., Matsuhisa K.,
RA Ohtake Y., Imaizumi K., Kaneko M.;
RT "Sec16A, a key protein in COPII vesicle formation, regulates the stability
RT and localization of the novel ubiquitin ligase RNF183.";
RL PLoS ONE 13:E0190407-E0190407(2018).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY, INDUCTION,
RP INTERACTION WITH BCL2L1, AND MUTAGENESIS OF CYS-13; CYS-16; LYS-28; LYS-101
RP AND LYS-105.
RX PubMed=29507230; DOI=10.1073/pnas.1716439115;
RA Wu Y., Li X., Jia J., Zhang Y., Li J., Zhu Z., Wang H., Tang J., Hu J.;
RT "Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by
RT degrading Bcl-xL.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E2762-E2771(2018).
CC -!- FUNCTION: Acts as a E3 ubiquitin ligase catalyzing the covalent
CC attachment of ubiquitin moieties onto substrate proteins
CC (PubMed:29507230). Triggers apoptosis in response to prolonged ER
CC stress by mediating the polyubiquitination and subsequent proteasomal
CC degradation of BCL2L1 (PubMed:29507230). May collaborate with FATE1 to
CC restrain BIK protein levels thus regulating apoptotic signaling
CC (PubMed:26567849). {ECO:0000269|PubMed:29507230,
CC ECO:0000305|PubMed:26567849}.
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:29507230};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:29507230}.
CC -!- SUBUNIT: Interacts with FATE1 (PubMed:26567849). Interacts with SEC16A
CC (By similarity). Interacts with BCL2L1 (PubMed:29507230).
CC {ECO:0000250|UniProtKB:Q8QZS5, ECO:0000269|PubMed:26567849,
CC ECO:0000269|PubMed:29507230}.
CC -!- INTERACTION:
CC Q96D59; P01023: A2M; NbExp=3; IntAct=EBI-743938, EBI-640741;
CC Q96D59; Q92870-2: APBB2; NbExp=3; IntAct=EBI-743938, EBI-21535880;
CC Q96D59; P54253: ATXN1; NbExp=6; IntAct=EBI-743938, EBI-930964;
CC Q96D59; P09172: DBH; NbExp=3; IntAct=EBI-743938, EBI-8589586;
CC Q96D59; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-743938, EBI-25840379;
CC Q96D59; P50570-2: DNM2; NbExp=3; IntAct=EBI-743938, EBI-10968534;
CC Q96D59; Q01658: DR1; NbExp=3; IntAct=EBI-743938, EBI-750300;
CC Q96D59; Q13216-2: ERCC8; NbExp=3; IntAct=EBI-743938, EBI-16466949;
CC Q96D59; Q969F0: FATE1; NbExp=4; IntAct=EBI-743938, EBI-743099;
CC Q96D59; Q16595: FXN; NbExp=3; IntAct=EBI-743938, EBI-949340;
CC Q96D59; Q53GS7: GLE1; NbExp=3; IntAct=EBI-743938, EBI-1955541;
CC Q96D59; Q9HD26: GOPC; NbExp=3; IntAct=EBI-743938, EBI-349832;
CC Q96D59; Q9HD26-2: GOPC; NbExp=3; IntAct=EBI-743938, EBI-11102276;
CC Q96D59; Q00403: GTF2B; NbExp=3; IntAct=EBI-743938, EBI-389564;
CC Q96D59; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-743938, EBI-1054873;
CC Q96D59; P07686: HEXB; NbExp=3; IntAct=EBI-743938, EBI-7133736;
CC Q96D59; P28358: HOXD10; NbExp=3; IntAct=EBI-743938, EBI-12690664;
CC Q96D59; P04792: HSPB1; NbExp=3; IntAct=EBI-743938, EBI-352682;
CC Q96D59; O43464: HTRA2; NbExp=3; IntAct=EBI-743938, EBI-517086;
CC Q96D59; P42858: HTT; NbExp=3; IntAct=EBI-743938, EBI-466029;
CC Q96D59; O60333-2: KIF1B; NbExp=3; IntAct=EBI-743938, EBI-10975473;
CC Q96D59; Q99732: LITAF; NbExp=3; IntAct=EBI-743938, EBI-725647;
CC Q96D59; P51608: MECP2; NbExp=3; IntAct=EBI-743938, EBI-1189067;
CC Q96D59; P19404: NDUFV2; NbExp=3; IntAct=EBI-743938, EBI-713665;
CC Q96D59; P35240-4: NF2; NbExp=3; IntAct=EBI-743938, EBI-1014514;
CC Q96D59; P29474: NOS3; NbExp=3; IntAct=EBI-743938, EBI-1391623;
CC Q96D59; D3DTS7: PMP22; NbExp=3; IntAct=EBI-743938, EBI-25882629;
CC Q96D59; O60260-5: PRKN; NbExp=3; IntAct=EBI-743938, EBI-21251460;
CC Q96D59; P41219: PRPH; NbExp=3; IntAct=EBI-743938, EBI-752074;
CC Q96D59; P60891: PRPS1; NbExp=3; IntAct=EBI-743938, EBI-749195;
CC Q96D59; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-743938, EBI-396669;
CC Q96D59; P37840: SNCA; NbExp=3; IntAct=EBI-743938, EBI-985879;
CC Q96D59; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-743938, EBI-5235340;
CC Q96D59; Q13148: TARDBP; NbExp=3; IntAct=EBI-743938, EBI-372899;
CC Q96D59; O14907: TAX1BP3; NbExp=3; IntAct=EBI-743938, EBI-723259;
CC Q96D59; O14773: TPP1; NbExp=3; IntAct=EBI-743938, EBI-2800203;
CC Q96D59; Q86WV8: TSC1; NbExp=3; IntAct=EBI-743938, EBI-12806590;
CC Q96D59; P02766: TTR; NbExp=3; IntAct=EBI-743938, EBI-711909;
CC Q96D59; P61086: UBE2K; NbExp=3; IntAct=EBI-743938, EBI-473850;
CC Q96D59; Q96FI0: UBE2W; NbExp=3; IntAct=EBI-743938, EBI-10285774;
CC Q96D59; O76024: WFS1; NbExp=3; IntAct=EBI-743938, EBI-720609;
CC Q96D59; Q9P1N4; NbExp=3; IntAct=EBI-743938, EBI-25878161;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29507230}; Single-pass type IV membrane protein
CC {ECO:0000305|PubMed:29507230}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:26567849}. Golgi apparatus, cis-Golgi network
CC membrane {ECO:0000250|UniProtKB:Q8QZS5}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q8QZS5}.
CC -!- TISSUE SPECIFICITY: Kidney and testis. {ECO:0000269|PubMed:29300766}.
CC -!- INDUCTION: Up-regulated by ER stress in an ERN1-dependent manner.
CC {ECO:0000269|PubMed:29507230}.
CC -!- PTM: Autoubiquitinated (in vitro). {ECO:0000269|PubMed:26567849,
CC ECO:0000269|PubMed:29507230}.
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DR EMBL; AL449305; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013036; AAH13036.1; -; mRNA.
DR CCDS; CCDS43866.1; -.
DR RefSeq; NP_659488.2; NM_145051.3.
DR RefSeq; XP_006717015.1; XM_006716952.2.
DR RefSeq; XP_011516520.1; XM_011518218.1.
DR RefSeq; XP_011516521.1; XM_011518219.1.
DR RefSeq; XP_011516522.1; XM_011518220.1.
DR RefSeq; XP_016869757.1; XM_017014268.1.
DR AlphaFoldDB; Q96D59; -.
DR SMR; Q96D59; -.
DR BioGRID; 126500; 21.
DR IntAct; Q96D59; 45.
DR STRING; 9606.ENSP00000419454; -.
DR BioMuta; RNF183; -.
DR DMDM; 74760778; -.
DR PaxDb; Q96D59; -.
DR PeptideAtlas; Q96D59; -.
DR PRIDE; Q96D59; -.
DR Antibodypedia; 54188; 104 antibodies from 19 providers.
DR DNASU; 138065; -.
DR Ensembl; ENST00000297894.5; ENSP00000417943.1; ENSG00000165188.14.
DR Ensembl; ENST00000416588.2; ENSP00000420740.1; ENSG00000165188.14.
DR Ensembl; ENST00000441031.3; ENSP00000417176.1; ENSG00000165188.14.
DR Ensembl; ENST00000478815.1; ENSP00000419454.1; ENSG00000165188.14.
DR Ensembl; ENST00000489339.2; ENSP00000508293.1; ENSG00000165188.14.
DR GeneID; 138065; -.
DR KEGG; hsa:138065; -.
DR MANE-Select; ENST00000489339.2; ENSP00000508293.1; NM_001371237.1; NP_001358166.1.
DR UCSC; uc004bgz.4; human.
DR CTD; 138065; -.
DR DisGeNET; 138065; -.
DR GeneCards; RNF183; -.
DR HGNC; HGNC:28721; RNF183.
DR HPA; ENSG00000165188; Tissue enhanced (epididymis, kidney).
DR neXtProt; NX_Q96D59; -.
DR OpenTargets; ENSG00000165188; -.
DR PharmGKB; PA142671055; -.
DR VEuPathDB; HostDB:ENSG00000165188; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000162965; -.
DR HOGENOM; CLU_122905_0_0_1; -.
DR InParanoid; Q96D59; -.
DR OMA; QTGPPQD; -.
DR OrthoDB; 1337075at2759; -.
DR PhylomeDB; Q96D59; -.
DR TreeFam; TF337102; -.
DR PathwayCommons; Q96D59; -.
DR SignaLink; Q96D59; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 138065; 10 hits in 1106 CRISPR screens.
DR ChiTaRS; RNF183; human.
DR GenomeRNAi; 138065; -.
DR Pharos; Q96D59; Tbio.
DR PRO; PR:Q96D59; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q96D59; protein.
DR Bgee; ENSG00000165188; Expressed in pancreatic ductal cell and 108 other tissues.
DR ExpressionAtlas; Q96D59; baseline and differential.
DR Genevisible; Q96D59; HS.
DR GO; GO:0033106; C:cis-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
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 Apoptosis; Endoplasmic reticulum; Golgi apparatus; Lysosome; Membrane;
KW Metal-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..192
FT /note="E3 ubiquitin-protein ligase RNF183"
FT /id="PRO_0000247358"
FT TOPO_DOM 1..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:29507230"
FT TRANSMEM 162..182
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..192
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:29507230"
FT ZN_FING 13..60
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT VARIANT 82
FT /note="A -> T (in dbSNP:rs3750533)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027095"
FT VARIANT 114
FT /note="Q -> R (in dbSNP:rs3750534)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027096"
FT MUTAGEN 13
FT /note="C->A: Abolishes autoubiquitination; when associated
FT with A-59."
FT /evidence="ECO:0000269|PubMed:26567849"
FT MUTAGEN 13
FT /note="C->S: Loss of autoubiquitination and reduced
FT ubiquitination of BCL2L1; when associated with S-16."
FT /evidence="ECO:0000269|PubMed:29507230"
FT MUTAGEN 16
FT /note="C->S: Loss of autoubiquitination and reduced
FT ubiquitination of BCL2L1; when associated with S-13."
FT /evidence="ECO:0000269|PubMed:29507230"
FT MUTAGEN 28
FT /note="K->R: Loss of autoubiquitination but no effect on
FT ubiquitination of BCL2L1; when associated with R-101 and R-
FT 105."
FT /evidence="ECO:0000269|PubMed:29507230"
FT MUTAGEN 59
FT /note="C->A: Abolishes autoubiquitination; when associated
FT with A-13."
FT /evidence="ECO:0000269|PubMed:26567849"
FT MUTAGEN 101
FT /note="K->R: Loss of autoubiquitination but no effect on
FT ubiquitination of BCL2L1; when associated with R-28 and R-
FT 105."
FT /evidence="ECO:0000269|PubMed:29507230"
FT MUTAGEN 105
FT /note="K->R: Loss of autoubiquitination but no effect on
FT ubiquitination of BCL2L1; when associated with R-28 and R-
FT 101."
FT /evidence="ECO:0000269|PubMed:29507230"
SQ SEQUENCE 192 AA; 21617 MW; 51D5B5272DFC9540 CRC64;
MAEQQGRELE AECPVCWNPF NNTFHTPKML DCCHSFCVEC LAHLSLVTPA RRRLLCPLCR
QPTVLASGQP VTDLPTDTAM LALLRLEPHH VILEGHQLCL KDQPKSRYFL RQPQVYTLDL
GPQPGGQTGP PPDTASATVS TPILIPSHHS LRECFRNPQF RIFAYLMAVI LSVTLLLIFS
IFWTKQFLWG VG
