UBA3_DROME
ID UBA3_DROME Reviewed; 450 AA.
AC Q9V6U8; Q4QPQ3; Q960K2;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Nedd8-activating enzyme E1 catalytic subunit;
DE EC=6.2.1.64;
DE AltName: Full=Ubiquitin-activating enzyme 3 homolog;
GN Name=Uba3; ORFNames=CG13343;
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 MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-450.
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, INTERACTION WITH APP-BP1, AND TISSUE SPECIFICITY.
RX PubMed=21931660; DOI=10.1371/journal.pone.0024168;
RA Du J., Zhang J., Su Y., Liu M., Ospina J.K., Yang S., Zhu A.J.;
RT "In vivo RNAi screen reveals neddylation genes as novel regulators of
RT Hedgehog signaling.";
RL PLoS ONE 6:E24168-E24168(2011).
CC -!- FUNCTION: Catalytic subunit of the dimeric Uba3-APP-BP1 E1 enzyme. E1
CC activates Nedd8 by first adenylating its C-terminal glycine residue
CC with ATP, thereafter linking this residue to the side chain of the
CC catalytic cysteine, yielding a Nedd8-Uba3 thioester and free AMP. E1
CC finally transfers Nedd8 to the catalytic cysteine of UbcE2M. Required
CC for Cul1 and Cul3 neddylation. Negatively regulates full-length ci
CC stability and hedgehog signaling. {ECO:0000269|PubMed:21931660}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-
CC cysteine = AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8
CC protein]-yl-L-cysteine.; EC=6.2.1.64;
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of Uba3 and APP-BP1. Interacts with Nedd8 and
CC UbcE2M. {ECO:0000269|PubMed:21931660}.
CC -!- TISSUE SPECIFICITY: Expressed in the wing disk.
CC {ECO:0000269|PubMed:21931660}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA3
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK93440.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAY85113.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF58323.1; -; Genomic_DNA.
DR EMBL; BT023713; AAY85113.1; ALT_INIT; mRNA.
DR EMBL; AY052016; AAK93440.1; ALT_INIT; mRNA.
DR RefSeq; NP_610913.1; NM_137069.4.
DR AlphaFoldDB; Q9V6U8; -.
DR SMR; Q9V6U8; -.
DR BioGRID; 62293; 5.
DR IntAct; Q9V6U8; 3.
DR STRING; 7227.FBpp0086711; -.
DR PaxDb; Q9V6U8; -.
DR PRIDE; Q9V6U8; -.
DR DNASU; 36539; -.
DR EnsemblMetazoa; FBtr0087585; FBpp0086711; FBgn0263697.
DR GeneID; 36539; -.
DR KEGG; dme:Dmel_CG13343; -.
DR UCSC; CG13343-RA; d. melanogaster.
DR CTD; 9039; -.
DR FlyBase; FBgn0263697; Uba3.
DR VEuPathDB; VectorBase:FBgn0263697; -.
DR eggNOG; KOG2015; Eukaryota.
DR GeneTree; ENSGT00550000074831; -.
DR HOGENOM; CLU_013325_13_1_1; -.
DR InParanoid; Q9V6U8; -.
DR OMA; LENYMMY; -.
DR OrthoDB; 686413at2759; -.
DR PhylomeDB; Q9V6U8; -.
DR Reactome; R-DME-8951664; Neddylation.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9V6U8; -.
DR UniPathway; UPA00885; -.
DR BioGRID-ORCS; 36539; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 36539; -.
DR PRO; PR:Q9V6U8; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0263697; Expressed in egg chamber and 24 other tissues.
DR Genevisible; Q9V6U8; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IPI:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IEA:UniProtKB-EC.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; IDA:FlyBase.
DR Gene3D; 1.10.10.520; -; 1.
DR InterPro; IPR014929; E2-binding.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR023318; Ub_act_enz_dom_a_sf.
DR InterPro; IPR030468; Uba3.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR InterPro; IPR033127; UBQ-activ_enz_E1_Cys_AS.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR PANTHER; PTHR10953:SF6; PTHR10953:SF6; 1.
DR Pfam; PF08825; E2_bind; 1.
DR Pfam; PF00899; ThiF; 1.
DR SMART; SM01181; E2_bind; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Nucleotide-binding; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..450
FT /note="Nedd8-activating enzyme E1 catalytic subunit"
FT /id="PRO_0000194946"
FT ACT_SITE 217
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10132"
FT BINDING 58..82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 450 AA; 50032 MW; 9CFC49B3ECE081EE CRC64;
MSVHSPNPGL ILQSKRFNGL RNILEREGPF CKDGFAASSE NLEFLQTKCQ VLIIGAGGLG
CELLKDLALM GFGNLHVIDM DTIELSNLNR QFLFRRTDIG ASKAECAARF INARVPTCRV
TPHFKKIQDF DESFYQQFHL VVCGLDSIVA RRWINGMLLS MLRYEEDGTI DTSSIVPMID
GGTEGFKGNA RVILPGFTAC IECTLDLFPP QVNYPLCTIA NTPRLPEHCI EYVKIIQWEK
QNPFGVPLDG DDPQHIGWIY ERALERSNEF NITGVTYRLV QGVVKHIIPA VASTNAAIAA
ACALEVFKLA TSCYDSMANY LNFNDLDGIY TYTYEAEKSE NCLACSNTPQ PLPIEDPNTT
TLEDVIKLLC DSPRFQLKSP ALTTVMKDGK RRTLYMSGVK SIEEATRKNL TQSLGELGLH
DGQQLTVTDA TSPSAMTLQL KYQSNEVEMV
