UBC2M_DROME
ID UBC2M_DROME Reviewed; 181 AA.
AC Q9VSF3;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Nedd8-conjugating enzyme UbcE2M {ECO:0000312|FlyBase:FBgn0035853};
DE EC=2.3.2.34;
DE AltName: Full=Nedd8 carrier protein;
GN Name=UbcE2M {ECO:0000312|FlyBase:FBgn0035853};
GN Synonyms=Ubc12 {ECO:0000303|PubMed:21931660};
GN ORFNames=CG7375 {ECO:0000312|FlyBase:FBgn0035853};
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; 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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF 2-ILE--LYS-23.
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: Accepts the ubiquitin-like protein Nedd8 from the Uba3-APP-
CC BP1 E1 complex and catalyzes its covalent attachment to other proteins.
CC Required for Cul1 and Cul3 neddylation. Negatively regulates full-
CC length ci stability and hedgehog signaling.
CC {ECO:0000269|PubMed:21931660}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine +
CC [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating
CC enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-
CC yl-L-cysteine.; EC=2.3.2.34;
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Interacts with Uba3. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the wing disk.
CC {ECO:0000269|PubMed:21931660}.
CC -!- DOMAIN: Both the N-terminal docking peptide and the catalytic core
CC domain must bind the Uba3-Ula1 complex simultaneously for optimal
CC transfer of Nedd8. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. UBC12
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; AE014296; AAF50468.1; -; Genomic_DNA.
DR EMBL; AY118545; AAM49914.1; -; mRNA.
DR RefSeq; NP_001261567.1; NM_001274638.1.
DR RefSeq; NP_001261568.1; NM_001274639.1.
DR RefSeq; NP_648187.1; NM_139930.2.
DR AlphaFoldDB; Q9VSF3; -.
DR SMR; Q9VSF3; -.
DR BioGRID; 64336; 17.
DR IntAct; Q9VSF3; 5.
DR STRING; 7227.FBpp0304449; -.
DR PaxDb; Q9VSF3; -.
DR PRIDE; Q9VSF3; -.
DR DNASU; 38916; -.
DR EnsemblMetazoa; FBtr0076722; FBpp0076445; FBgn0035853.
DR EnsemblMetazoa; FBtr0332138; FBpp0304448; FBgn0035853.
DR EnsemblMetazoa; FBtr0332139; FBpp0304449; FBgn0035853.
DR GeneID; 38916; -.
DR KEGG; dme:Dmel_CG7375; -.
DR UCSC; CG7375-RA; d. melanogaster.
DR CTD; 38916; -.
DR FlyBase; FBgn0035853; UbcE2M.
DR VEuPathDB; VectorBase:FBgn0035853; -.
DR eggNOG; KOG0420; Eukaryota.
DR GeneTree; ENSGT00940000163935; -.
DR HOGENOM; CLU_030988_6_0_1; -.
DR InParanoid; Q9VSF3; -.
DR OMA; GYPHDAP; -.
DR OrthoDB; 1302735at2759; -.
DR PhylomeDB; Q9VSF3; -.
DR Reactome; R-DME-8951664; Neddylation.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9VSF3; -.
DR UniPathway; UPA00885; -.
DR BioGRID-ORCS; 38916; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 38916; -.
DR PRO; PR:Q9VSF3; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035853; Expressed in saliva-secreting gland and 22 other tissues.
DR ExpressionAtlas; Q9VSF3; baseline and differential.
DR Genevisible; Q9VSF3; DM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061654; F:NEDD8 conjugating enzyme activity; IDA:FlyBase.
DR GO; GO:0019788; F:NEDD8 transferase activity; ISS:UniProtKB.
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:0036211; P:protein modification process; ISS:UniProtKB.
DR GO; GO:0045116; P:protein neddylation; IDA:FlyBase.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Nucleotide-binding; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..181
FT /note="Nedd8-conjugating enzyme UbcE2M"
FT /id="PRO_0000082492"
FT DOMAIN 26..170
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 4..7
FT /note="Interaction with Uba3"
FT /evidence="ECO:0000250"
FT REGION 24..54
FT /note="Interaction with Uba3"
FT /evidence="ECO:0000250"
FT ACT_SITE 108
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT MUTAGEN 2..23
FT /note="Missing: Abolishes neddylation E2 activity."
FT /evidence="ECO:0000269|PubMed:21931660"
SQ SEQUENCE 181 AA; 20738 MW; B8580A25E1E7543D CRC64;
MIKLFTLKQQ KKDGEQKGSQ QKKASAAQLR IQKDINELNL PNTCATDFPD PNDLLNFKLI
ISPDEGFYRD GRFVFNFRVG SNYPHEPPKV KCATQVYHPN IDLDGNVCLN ILREDWNPVL
NINSIVYGLQ FLFLEPNPED PLNKEAADVL QTNRRQFENN VKKAMRGGCV GETYFECCLL
K
