RNF41_MOUSE
ID RNF41_MOUSE Reviewed; 317 AA.
AC Q8BH75; Q8BGJ2; Q8BMC9; Q8VEA2; Q9CRK6; Q9D568;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=E3 ubiquitin-protein ligase NRDP1;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 41;
DE AltName: Full=RING-type E3 ubiquitin transferase NRDP1 {ECO:0000305};
GN Name=Rnf41; Synonyms=Flrf, Nrdp1;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Brain cortex, Embryo, Pituitary, Skin, Testis, and Wolffian duct;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary tumor;
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 INTERACTION WITH EPOR; IL3RA AND CSF2RB.
RX PubMed=18495327; DOI=10.1016/j.exphem.2008.04.001;
RA Jing X., Infante J., Nachtman R.G., Jurecic R.;
RT "E3 ligase FLRF (Rnf41) regulates differentiation of hematopoietic
RT progenitors by governing steady-state levels of cytokine and retinoic acid
RT receptors.";
RL Exp. Hematol. 36:1110-1120(2008).
RN [4]
RP FUNCTION, AND INTERACTION WITH MYD88 AND TBK1.
RX PubMed=19483718; DOI=10.1038/ni.1742;
RA Wang C., Chen T., Zhang J., Yang M., Li N., Xu X., Cao X.;
RT "The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated
RT production of type I interferon.";
RL Nat. Immunol. 10:744-752(2009).
RN [5]
RP FUNCTION IN MITOPHAGY, AND INTERACTION WITH CLEC16A.
RX PubMed=24949970; DOI=10.1016/j.cell.2014.05.016;
RA Soleimanpour S.A., Gupta A., Bakay M., Ferrari A.M., Groff D.N.,
RA Fadista J., Spruce L.A., Kushner J.A., Groop L., Seeholzer S.H.,
RA Kaufman B.A., Hakonarson H., Stoffers D.A.;
RT "The diabetes susceptibility gene Clec16a regulates mitophagy.";
RL Cell 157:1577-1590(2014).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 193-317, AND INTERACTION WITH
RP ERBB3.
RX PubMed=17384230; DOI=10.1110/ps.062700307;
RA Bouyain S., Leahy D.J.;
RT "Structure-based mutagenesis of the substrate-recognition domain of
RT Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase
RT ErbB3.";
RL Protein Sci. 16:654-661(2007).
CC -!- FUNCTION: Acts as E3 ubiquitin-protein ligase and regulates the
CC degradation of target proteins. Polyubiquitinates MYD88 (By
CC similarity). Negatively regulates MYD88-dependent production of pro-
CC inflammatory cytokines. Can promote TRIF-dependent production of type I
CC interferon and inhibits infection with vesicular stomatitis virus.
CC Promotes also activation of TBK1 and IRF3 (PubMed:19483718). Involved
CC in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3)
CC receptors. Thus, through maintaining basal levels of cytokine
CC receptors, RNF41 is involved in the control of hematopoietic progenitor
CC cell differentiation into myeloerythroid lineages (PubMed:18495327).
CC Contributes to the maintenance of steady-state ERBB3 levels by
CC mediating its growth factor-independent degradation. Involved in the
CC degradation of the inhibitor of apoptosis BIRC6 and thus is an
CC important regulator of cell death by promoting apoptosis. Acts also as
CC a PRKN modifier that accelerates its degradation, resulting in a
CC reduction of PRKN activity, influencing the balance of intracellular
CC redox state. The RNF41-PRKN pathway regulates autophagosome-lysosome
CC fusion during late mitophagy. Mitophagy is a selective form of
CC autophagy necessary for mitochondrial quality control
CC (PubMed:24949970). {ECO:0000250, ECO:0000269|PubMed:18495327,
CC ECO:0000269|PubMed:19483718, ECO:0000269|PubMed:24949970}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with USP8, ERBB3, PRKN and BIRC6 (By similarity).
CC Interacts with CSF2RB, EPOR, IL3RA, MYD88 and TBK1. Interacts with
CC Clec16a (PubMed:24949970). {ECO:0000250, ECO:0000269|PubMed:17384230,
CC ECO:0000269|PubMed:18495327, ECO:0000269|PubMed:19483718,
CC ECO:0000269|PubMed:24949970}.
CC -!- INTERACTION:
CC Q8BH75; Q80U30-2: Clec16a; NbExp=3; IntAct=EBI-7059583, EBI-9696757;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BH75-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BH75-2; Sequence=VSP_058649, VSP_058650;
CC -!- PTM: Autoubiquitinated. Autoubiquitination leads to proteasomal
CC degradation. Deubiquitinated by USP8 to get stabilized which induces
CC apoptosis. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH19415.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC27496.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=BAC31779.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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; AK015745; BAB29953.1; -; mRNA.
DR EMBL; AK020527; BAB32125.1; -; mRNA.
DR EMBL; AK028551; BAC26004.1; -; mRNA.
DR EMBL; AK030558; BAC27020.1; -; mRNA.
DR EMBL; AK031657; BAC27496.1; ALT_SEQ; mRNA.
DR EMBL; AK032848; BAC28054.1; -; mRNA.
DR EMBL; AK034551; BAC28750.1; -; mRNA.
DR EMBL; AK044103; BAC31779.1; ALT_SEQ; mRNA.
DR EMBL; AK077466; BAC36813.1; -; mRNA.
DR EMBL; BC019415; AAH19415.1; ALT_INIT; mRNA.
DR EMBL; BC049078; AAH49078.1; -; mRNA.
DR CCDS; CCDS24277.1; -. [Q8BH75-1]
DR RefSeq; NP_001157709.1; NM_001164237.1. [Q8BH75-1]
DR RefSeq; NP_080535.2; NM_026259.3. [Q8BH75-1]
DR PDB; 2OGB; X-ray; 1.95 A; A/B=193-317.
DR PDBsum; 2OGB; -.
DR AlphaFoldDB; Q8BH75; -.
DR SMR; Q8BH75; -.
DR BioGRID; 212296; 28.
DR IntAct; Q8BH75; 3.
DR MINT; Q8BH75; -.
DR STRING; 10090.ENSMUSP00000100869; -.
DR MoonDB; Q8BH75; Predicted.
DR iPTMnet; Q8BH75; -.
DR PhosphoSitePlus; Q8BH75; -.
DR EPD; Q8BH75; -.
DR MaxQB; Q8BH75; -.
DR PaxDb; Q8BH75; -.
DR PRIDE; Q8BH75; -.
DR ProteomicsDB; 300502; -. [Q8BH75-1]
DR Antibodypedia; 15762; 205 antibodies from 31 providers.
DR DNASU; 67588; -.
DR Ensembl; ENSMUST00000096386; ENSMUSP00000100869; ENSMUSG00000025373. [Q8BH75-1]
DR Ensembl; ENSMUST00000171342; ENSMUSP00000132751; ENSMUSG00000025373. [Q8BH75-1]
DR Ensembl; ENSMUST00000217826; ENSMUSP00000151260; ENSMUSG00000025373. [Q8BH75-2]
DR GeneID; 67588; -.
DR KEGG; mmu:67588; -.
DR UCSC; uc007hmr.2; mouse. [Q8BH75-1]
DR CTD; 10193; -.
DR MGI; MGI:1914838; Rnf41.
DR VEuPathDB; HostDB:ENSMUSG00000025373; -.
DR eggNOG; KOG0297; Eukaryota.
DR GeneTree; ENSGT00530000063647; -.
DR HOGENOM; CLU_076732_0_0_1; -.
DR InParanoid; Q8BH75; -.
DR OMA; EASSHNC; -.
DR OrthoDB; 918518at2759; -.
DR PhylomeDB; Q8BH75; -.
DR TreeFam; TF351947; -.
DR Reactome; R-MMU-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 67588; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Rnf41; mouse.
DR EvolutionaryTrace; Q8BH75; -.
DR PRO; PR:Q8BH75; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BH75; protein.
DR Bgee; ENSMUSG00000025373; Expressed in cortical plate and 242 other tissues.
DR ExpressionAtlas; Q8BH75; baseline and differential.
DR Genevisible; Q8BH75; MM.
DR GO; GO:0071782; C:endoplasmic reticulum tubular network; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005128; F:erythropoietin receptor binding; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005135; F:interleukin-3 receptor binding; IDA:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1901525; P:negative regulation of mitophagy; IGI:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0051865; P:protein autoubiquitination; ISO:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0045619; P:regulation of lymphocyte differentiation; IDA:MGI.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0045637; P:regulation of myeloid cell differentiation; IDA:MGI.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:MGI.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR015036; NRDP1.
DR InterPro; IPR037255; NRDP1_C.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR InterPro; IPR013010; Znf_SIAH.
DR Pfam; PF08941; USP8_interact; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF160088; SSF160088; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS51081; ZF_SIAH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Autophagy; Metal-binding;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..317
FT /note="E3 ubiquitin-protein ligase NRDP1"
FT /id="PRO_0000223955"
FT ZN_FING 18..57
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 78..138
FT /note="SIAH-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00455"
FT VAR_SEQ 31..36
FT /note="APHCEH -> PGDAQR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_058649"
FT VAR_SEQ 37..317
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_058650"
FT CONFLICT 7
FT /note="R -> H (in Ref. 1; BAC31779)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="S -> T (in Ref. 2; AAH19415)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="S -> R (in Ref. 2; AAH19415)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="R -> Q (in Ref. 1; BAC28054)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="K -> E (in Ref. 1; BAB29953)"
FT /evidence="ECO:0000305"
FT HELIX 196..205
FT /evidence="ECO:0007829|PDB:2OGB"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 223..235
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 240..248
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:2OGB"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 262..267
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:2OGB"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:2OGB"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:2OGB"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:2OGB"
FT STRAND 303..312
FT /evidence="ECO:0007829|PDB:2OGB"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:2OGB"
SQ SEQUENCE 317 AA; 35891 MW; 43FE844C06392802 CRC64;
MGYDVTRFQG DVDEDLICPI CSGVLEEPVQ APHCEHAFCN ACITQWFSQQ QTCPVDRSVV
TVAHLRPVPR IMRNMLSKLQ IACDNAVFGC SAVVRLDNLM SHLSDCEHNP KRPVTCEQGC
GLEMPKDELP NHNCIKHLRS VVQQQQSRIA ELEKTSAEHK HQLAEQKRDI QLLKAYMRAI
RSVNPNLQNL EETIEYNEIL EWVNSLQPAR VTRWGGMIST PDAVLQAVIK RSLVESGCPA
SIVNELIENA HERSWPQGLA TLETRQMNRR YYENYVAKRI PGKQAVVVMA CENQHMGDDM
VQEPGLVMIF AHGVEEI
