RN186_MOUSE
ID RN186_MOUSE Reviewed; 226 AA.
AC Q9D241; Q78R58;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 3.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=E3 ubiquitin-protein ligase RNF186 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9NXI6};
DE AltName: Full=RING finger protein 186 {ECO:0000312|MGI:MGI:1914075};
GN Name=Rnf186 {ECO:0000312|MGI:MGI:1914075};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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, AND DISRUPTION PHENOTYPE.
RX PubMed=33280498; DOI=10.1080/15548627.2020.1851496;
RA Zhang H., Cui Z., Cheng D., Du Y., Guo X., Gao R., Chen J., Sun W., He R.,
RA Ma X., Peng Q., Martin B.N., Yan W., Rong Y., Wang C.;
RT "RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic
RT epithelial cells for the maintenance of intestinal homeostasis.";
RL Autophagy 17:3030-3047(2021).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=34623328; DOI=10.1172/jci145472;
RA Ranjan K., Hedl M., Sinha S., Zhang X., Abraham C.;
RT "Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate
RT receptor-induced unfolded protein response.";
RL J. Clin. Invest. 131:0-0(2021).
CC -!- FUNCTION: E3 ubiquitin protein ligase that is part of an apoptotic
CC signaling pathway activated by endoplasmic reticulum stress. Stimulates
CC the expression of proteins specific of the unfolded protein response
CC (UPR), ubiquitinates BNIP1 and regulates its localization to the
CC mitochondrion and induces calcium release from the endoplasmic
CC reticulum that ultimately leads to cell apoptosis. Plays a role in the
CC maintenance of intestinal homeostasis and clearance of enteric
CC pathogens (PubMed:34623328). Upon NOD2 stimulation, ubiquitinates the
CC ER stress sensor activating transcription factor 6/ATF6 and promotes
CC the unfolded protein response UPR. Participates in basal level of
CC autophagy maintenance by regulating the ubiquitination of EPHB2. Upon
CC stimulation by ligand EFNB1, ubiquitinates EPHB2 and further recruits
CC MAP1LC3B for autophagy induction (PubMed:33280498). Controls nutrient
CC sensing by ubiquitinating Sestrin-2/SESN2, which is an intracellular
CC sensor of cytosolic leucine and inhibitor of mTORC1 activity.
CC {ECO:0000250|UniProtKB:Q9NXI6, ECO:0000269|PubMed:33280498,
CC ECO:0000269|PubMed:34623328}.
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:0000250|UniProtKB:Q9NXI6};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9NXI6}.
CC -!- SUBUNIT: Interacts with BNIP1. {ECO:0000250|UniProtKB:Q9NXI6}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9NXI6}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: The RING-type domain is required for ubiquitination.
CC {ECO:0000250|UniProtKB:Q9NXI6}.
CC -!- PTM: Polyubiquitinated. 'Lys-29'-linked autoubiquitination leads to
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q9NXI6}.
CC -!- DISRUPTION PHENOTYPE: Mutant deletion mice demonstrate an increased
CC bacterial burden in the mesenteric lymph nodes and spleen compared with
CC WT mice (PubMed:34623328). They have also a more severe phenotype in
CC the dextran sodium sulfate-induced colitis model, which is due to a
CC defect in autophagy in colon epithelial cells (PubMed:33280498).
CC {ECO:0000269|PubMed:33280498, ECO:0000269|PubMed:34623328}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB32149.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK020617; BAB32149.2; ALT_INIT; mRNA.
DR EMBL; AK078919; BAC37459.1; -; mRNA.
DR EMBL; BC011492; AAH11492.3; -; mRNA.
DR CCDS; CCDS51338.1; -.
DR RefSeq; NP_080062.4; NM_025786.3.
DR AlphaFoldDB; Q9D241; -.
DR SMR; Q9D241; -.
DR STRING; 10090.ENSMUSP00000111780; -.
DR iPTMnet; Q9D241; -.
DR PhosphoSitePlus; Q9D241; -.
DR PaxDb; Q9D241; -.
DR PRIDE; Q9D241; -.
DR ProteomicsDB; 300493; -.
DR Antibodypedia; 29735; 107 antibodies from 22 providers.
DR DNASU; 66825; -.
DR Ensembl; ENSMUST00000116094; ENSMUSP00000111780; ENSMUSG00000070661.
DR GeneID; 66825; -.
DR KEGG; mmu:66825; -.
DR CTD; 54546; -.
DR MGI; MGI:1914075; Rnf186.
DR VEuPathDB; HostDB:ENSMUSG00000070661; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00510000049175; -.
DR InParanoid; Q9D241; -.
DR OrthoDB; 1446732at2759; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 66825; 4 hits in 73 CRISPR screens.
DR PRO; PR:Q9D241; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9D241; protein.
DR Bgee; ENSMUSG00000070661; Expressed in small intestine Peyer's patch and 59 other tissues.
DR ExpressionAtlas; Q9D241; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS: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:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0035519; P:protein K29-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038878; RNF186.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR22791:SF21; PTHR22791:SF21; 1.
DR Pfam; PF14634; zf-RING_5; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Membrane; Metal-binding; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..226
FT /note="E3 ubiquitin-protein ligase RNF186"
FT /id="PRO_0000261625"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 39..85
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
SQ SEQUENCE 226 AA; 24704 MW; 0031DAAC29F86AB2 CRC64;
MSCTEAPQPI PAGTTTTSTI IALGPTGRLS ISVEGDLECL VCREPYNCAR SPKLLSCQHT
FCAVCLKLLL YVQEDTWSIP CPLCRKVTAV PGGLICSLRD QEAMVGRLAL PCPEVRLCPQ
RLVGSAASAT RPANWTGEEE QDTVSVNRVA ARRLAVHLLL LALVIVLILP FIYPGVIRWV
LAFVIALALL MSTLFCCHPQ SQNSNWLCPR TLFCREQKQT QITSIA
