ID RBX1A_DROME Reviewed; 108 AA.
AC Q9W5E1; O77429;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 27-MAR-2024, entry version 178.
DE RecName: Full=RING-box protein 1A;
DE AltName: Full=Regulator of cullins 1a;
DE AltName: Full=dRbx1;
GN Name=Roc1a; ORFNames=CG16982;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Oregon-R;
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP ASN-59 AND CYS-68.
RX PubMed=12062088; DOI=10.1016/s1534-5807(02)00164-8;
RA Noureddine M.A., Donaldson T.D., Thacker S.A., Duronio R.J.;
RT "Drosophila Roc1a encodes a RING-H2 protein with a unique function in
RT processing the Hh signal transducer Ci by the SCF E3 ubiquitin ligase.";
RL Dev. Cell 2:757-770(2002).
RN [6]
RP INTERACTION WITH CUL1 AND SLMB.
RX PubMed=11500045; DOI=10.1006/bbrc.2001.5394;
RA Bocca S.N., Muzzopappa M., Silberstein S., Wappner P.;
RT "Occurrence of a putative SCF ubiquitin ligase complex in Drosophila.";
RL Biochem. Biophys. Res. Commun. 286:357-364(2001).
RN [7]
RP REVIEW ON E3 UBIQUITIN LIGASE COMPLEXES.
RX PubMed=12850443; DOI=10.1016/s0168-9525(03)00146-x;
RA Ou C.-Y., Pi H., Chien C.-T.;
RT "Control of protein degradation by E3 ubiquitin ligases in Drosophila eye
RT development.";
RL Trends Genet. 19:382-389(2003).
RN [8]
RP FUNCTION, IDENTIFICATION IN SCF COMPLEX, AND DISRUPTION PHENOTYPE.
RX PubMed=24068890; DOI=10.1371/journal.pbio.1001657;
RA Wong J.J., Li S., Lim E.K., Wang Y., Wang C., Zhang H., Kirilly D., Wu C.,
RA Liou Y.C., Wang H., Yu F.;
RT "A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway
RT to regulate neuronal pruning.";
RL PLoS Biol. 11:E1001657-E1001657(2013).
RN [9]
RP FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=24413555; DOI=10.1002/embr.201337966;
RA Li S., Wang C., Sandanaraj E., Aw S.S., Koe C.T., Wong J.J., Yu F.,
RA Ang B.T., Tang C., Wang H.;
RT "The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit
RT neuroblast overgrowth.";
RL EMBO Rep. 15:165-174(2014).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=27331610; DOI=10.7554/elife.15258;
RA Li T., Giagtzoglou N., Eberl D.F., Jaiswal S.N., Cai T., Godt D.,
RA Groves A.K., Bellen H.J.;
RT "The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in
RT the auditory organs of Drosophila and mammals.";
RL Elife 5:E15258-E15258(2016).
CC -!- FUNCTION: Core component of multiple SCF (SKP1-CUL1-F-box protein) E3
CC ubiquitin-protein ligase complexes which mediate the ubiquitination of
CC proteins involved in cell cycle progression, signal transduction and
CC transcription. Through the RING-type zinc finger, seems to recruit the
CC E2 ubiquitination enzyme to the complex and brings it into close
CC proximity to the substrate. Required for the specific SCF-dependent
CC proteolysis of CI, but not that of ARM, suggesting that it also
CC participates in the selection of substrates inside the SCF complex
CC (PubMed:12062088). During early metamorphosis, part of the SCF-slmb
CC complex that negatively regulates the InR/PI3K/TOR pathway to activate
CC the pruning of unnecessary larval ddaC dendrites and mushroom body
CC axons (PubMed:24068890). The SCF-slmb complex also regulates
CC asymmetrical division of neuroblasts and inhibits ectopic neuroblast
CC formation partly through SAK and Akt1 (PubMed:24413555). Also part of
CC an SCF complex required for caspase activation during sperm
CC differentiation (Probable). {ECO:0000269|PubMed:12062088,
CC ECO:0000269|PubMed:24068890, ECO:0000269|PubMed:24413555, ECO:0000305}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of SCF E3 ubiquitin-protein ligase complexes
CC consisting of Skpa, Cul1, Roc1a and an F-box protein. In larvae
CC neuroblast self renewal and asymmetric division, as well as ddaC
CC dendrite and mushroom body axon pruning, the complex contains the F-box
CC protein slmb (SCF-slmb) (PubMed:24068890, PubMed:24413555). Interacts
CC directly with Cul1 and Slmb (PubMed:11500045). In caspase activation
CC during sperm differentiation, the complex contains the F-box protein
CC ntc (Probable). {ECO:0000269|PubMed:11500045,
CC ECO:0000269|PubMed:24068890, ECO:0000269|PubMed:24413555, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in embryonic, larval
CC and adult tissues. {ECO:0000269|PubMed:12062088}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:12062088}.
CC -!- DOMAIN: The RING-type zinc finger domain is essential for ubiquitin
CC ligase activity. It coordinates an additional third zinc ion (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Severe pruning defect in ddaC neurons
CC (PubMed:24068890). Also shows defects in ddaD and ddaE neuron pruning
CC and in ddaF apoptosis (PubMed:24068890). RNAi-mediated knockdown
CC results in apical detachment of scolopidial cells in Johnston's organ
CC (PubMed:27331610). {ECO:0000269|PubMed:24068890,
CC ECO:0000269|PubMed:27331610}.
CC -!- SIMILARITY: Belongs to the RING-box family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA20888.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF45536.1; -; Genomic_DNA.
DR EMBL; AL031581; CAA20888.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AY119265; AAM51125.1; -; mRNA.
DR PIR; T13388; T13388.
DR RefSeq; NP_001138143.2; NM_001144671.3.
DR RefSeq; NP_001284754.1; NM_001297825.1.
DR RefSeq; NP_569852.1; NM_130496.4.
DR AlphaFoldDB; Q9W5E1; -.
DR SMR; Q9W5E1; -.
DR BioGRID; 57582; 10.
DR ComplexPortal; CPX-2561; VHL-Elongin C-Elongin B E3 ubiquitin ligase complex.
DR ComplexPortal; CPX-2646; SCF-SLMB E3 ubiquitin ligase complex.
DR DIP; DIP-60717N; -.
DR IntAct; Q9W5E1; 2.
DR STRING; 7227.FBpp0300874; -.
DR DNASU; 31014; -.
DR EnsemblMetazoa; FBtr0070122; FBpp0070117; FBgn0025638.
DR EnsemblMetazoa; FBtr0343564; FBpp0310165; FBgn0025638.
DR GeneID; 31014; -.
DR KEGG; dme:Dmel_CG16982; -.
DR UCSC; CG16982-RA; d. melanogaster.
DR AGR; FB:FBgn0025638; -.
DR CTD; 31014; -.
DR FlyBase; FBgn0025638; Roc1a.
DR VEuPathDB; VectorBase:FBgn0025638; -.
DR HOGENOM; CLU_115512_2_1_1; -.
DR InParanoid; Q9W5E1; -.
DR OrthoDB; 3546417at2759; -.
DR PhylomeDB; Q9W5E1; -.
DR Reactome; R-DME-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-DME-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-DME-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-DME-209360; Ubiquitination and proteolysis of phosphorylated CI.
DR Reactome; R-DME-209461; Ubiquitination and degradation of phosphorylated ARM.
DR Reactome; R-DME-4641258; Degradation of DVL.
DR Reactome; R-DME-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-DME-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-DME-5632684; Hedgehog 'on' state.
DR Reactome; R-DME-5696394; DNA Damage Recognition in GG-NER.
DR Reactome; R-DME-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-DME-5696400; Dual Incision in GG-NER.
DR Reactome; R-DME-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-DME-6782135; Dual incision in TC-NER.
DR Reactome; R-DME-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-DME-68949; Orc1 removal from chromatin.
DR Reactome; R-DME-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-DME-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-DME-8951664; Neddylation.
DR Reactome; R-DME-9020702; Interleukin-1 signaling.
DR Reactome; R-DME-9708530; Regulation of BACH1 activity.
DR Reactome; R-DME-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-DME-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9W5E1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 31014; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 31014; -.
DR PRO; PR:Q9W5E1; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0025638; Expressed in saliva-secreting gland and 27 other cell types or tissues.
DR ExpressionAtlas; Q9W5E1; baseline and differential.
DR Genevisible; Q9W5E1; DM.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:FlyBase.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:FlyBase.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IDA:FlyBase.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0097602; F:cullin family protein binding; IPI:FlyBase.
DR GO; GO:0061663; F:NEDD8 ligase activity; ISS:FlyBase.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0008283; P:cell population proliferation; IMP:FlyBase.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IPI:FlyBase.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:1904801; P:positive regulation of neuron remodeling; IMP:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:FlyBase.
DR GO; GO:0045116; P:protein neddylation; ISS:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IMP:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0016032; P:viral process; IC:FlyBase.
DR CDD; cd16485; mRING-H2-C3H2C2D_RBX1; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR024766; Znf_RING_H2.
DR PANTHER; PTHR11210:SF2; E3 UBIQUITIN-PROTEIN LIGASE RBX1; 1.
DR PANTHER; PTHR11210; RING BOX; 1.
DR Pfam; PF12678; zf-rbx1; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; Metal-binding; Nucleus;
KW Reference proteome; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..108
FT /note="RING-box protein 1A"
FT /id="PRO_0000056017"
FT ZN_FING 53..98
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 45
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 56
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P62878"
FT MUTAGEN 59
FT /note="N->C: Loss of function; when associated with R-68."
FT /evidence="ECO:0000269|PubMed:12062088"
FT MUTAGEN 68
FT /note="C->R: Loss of function; when associated with C-59."
FT /evidence="ECO:0000269|PubMed:12062088"
SQ SEQUENCE 108 AA; 12538 MW; 15784198281BCD13 CRC64;
MEVDEDGYEV PSSSSKGDKK RFEVKKWNAV ALWAWDIVVD NCAICRNHIM DLCIECQANQ
ASATSEECTV AWGVCNHAFH FHCISRWLKT RQVCPLDNRE WDFQKYGH
//
