IRU_DROME
ID IRU_DROME Reviewed; 380 AA.
AC Q9VHI7;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=E3 ubiquitin-protein ligase Iruka {ECO:0000303|PubMed:30503771, ECO:0000312|FlyBase:FBgn0037653};
DE EC=2.3.2.27 {ECO:0000269|PubMed:30503771};
GN Name=Iru {ECO:0000303|PubMed:30503771, ECO:0000312|FlyBase:FBgn0037653};
GN ORFNames=CG11982 {ECO:0000312|FlyBase:FBgn0037653};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|FlyBase:FBgn0037653}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|FlyBase:FBgn0037653};
RC TISSUE=Embryo {ECO:0000312|FlyBase:FBgn0037653};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH CG7546, AND
RP MUTAGENESIS OF 15-LYS--PRO-47; CYS-253 AND CYS-256.
RX PubMed=30503771; DOI=10.1016/j.molcel.2018.10.033;
RA Kobayashi H., Shoji K., Kiyokawa K., Negishi L., Tomari Y.;
RT "Iruka Eliminates Dysfunctional Argonaute by Selective Ubiquitination of
RT Its Empty State.";
RL Mol. Cell 73:119.E5-129.E5(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates E2-dependent, 'Lys-
CC 48'- and/or 'Lys-63'-linked polyubiquitination of substrates
CC (PubMed:30503771). Recognizes miRNA-empty Ago1 and triggers its
CC degradation via polyubiquitination independently of the Bag6 complex
CC (PubMed:30503771). By targeting miRNA-empty Ago1, eliminates
CC dysfunctional Ago1 not able to bind miRNA and thereby plays a role in
CC the quality control of miRNA-mediated silencing (PubMed:30503771).
CC {ECO:0000269|PubMed:30503771}.
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:30503771};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:30503771}.
CC -!- SUBUNIT: Interacts (via N-terminus) with CG7546 (via Ubl domain).
CC {ECO:0000269|PubMed:30503771}.
CC -!- MISCELLANEOUS: 'Iruka' means dolphin in Japanese. The name was chosen
CC because dolphin preys on the Argonauta octopus, similar to Iruka
CC 'preying' on the protein Argonaute. {ECO:0000305|PubMed:30503771}.
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DR EMBL; AE014297; AAF54321.1; -; Genomic_DNA.
DR EMBL; AY052007; AAK93431.1; -; mRNA.
DR RefSeq; NP_649859.1; NM_141602.4.
DR AlphaFoldDB; Q9VHI7; -.
DR SMR; Q9VHI7; -.
DR IntAct; Q9VHI7; 7.
DR STRING; 7227.FBpp0081445; -.
DR PaxDb; Q9VHI7; -.
DR PRIDE; Q9VHI7; -.
DR DNASU; 41080; -.
DR EnsemblMetazoa; FBtr0081965; FBpp0081445; FBgn0037653.
DR GeneID; 41080; -.
DR KEGG; dme:Dmel_CG11982; -.
DR UCSC; CG11982-RA; d. melanogaster.
DR CTD; 41080; -.
DR FlyBase; FBgn0037653; Iru.
DR VEuPathDB; VectorBase:FBgn0037653; -.
DR eggNOG; KOG0800; Eukaryota.
DR GeneTree; ENSGT00940000168353; -.
DR HOGENOM; CLU_034892_0_1_1; -.
DR InParanoid; Q9VHI7; -.
DR OMA; QDNRTNE; -.
DR OrthoDB; 1249953at2759; -.
DR PhylomeDB; Q9VHI7; -.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 41080; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41080; -.
DR PRO; PR:Q9VHI7; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037653; Expressed in testis and 24 other tissues.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:FlyBase.
DR GO; GO:0000209; P:protein polyubiquitination; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR039525; RNF126-like_zinc-ribbon.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR Pfam; PF14369; zinc_ribbon_9; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Reference proteome; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..380
FT /note="E3 ubiquitin-protein ligase Iruka"
FT /id="PRO_0000447647"
FT ZN_FING 253..294
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 50..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..92
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..350
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 15..47
FT /note="Missing: Loss of interaction with CG7546. Retains
FT ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:30503771"
FT MUTAGEN 253
FT /note="C->A: Loss of ubiquitination activity; when
FT associated with A-256."
FT /evidence="ECO:0000269|PubMed:30503771"
FT MUTAGEN 256
FT /note="C->A: Loss of ubiquitination activity; when
FT associated with A-253."
FT /evidence="ECO:0000269|PubMed:30503771"
SQ SEQUENCE 380 AA; 40319 MW; CF3F8F2F6477BFFE CRC64;
MAEAMVVEDR PAEAKRFFCH MCNVEINIPN SDFTCPLCAN GFVEELPANA PEMDSSTAGA
SGSARSGSSG SGSSGSHDTL SRGSSSSGSQ VNVESLRNDI VSLLNMRNVP NLEITIEPNR
RHSNVLHLGG FGGPSGSDSA RGLTAGGRVR PANLDRLDNV LFDFLQSLPL AGATAEIVTG
PGGGGVGGGG NSHMFFMGNP GDYAWGREGL DTIVTQMLNQ METSGPPPLS AQRINEIPNV
QINAEEVNRK IQCSICWDDF KIDETVRKLP CSHLYHENCI VPWLNLHSTC PICRKSLADD
GNDADDEFVM LDAFGPEMAA DGSNSERRSA STATGTDNPS PANNPSQAAA EGGRTRPDAN
PAQAARNNIF TFDDDNMFLD
