ID UBA3_MOUSE Reviewed; 462 AA. AC Q8C878; O88598; Q3TG68; Q9D6B7; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 24-JAN-2024, entry version 163. DE RecName: Full=NEDD8-activating enzyme E1 catalytic subunit; DE EC=6.2.1.64 {ECO:0000250|UniProtKB:Q8TBC4}; DE AltName: Full=NEDD8-activating enzyme E1C; DE AltName: Full=Ubiquitin-activating enzyme E1C; DE AltName: Full=Ubiquitin-like modifier-activating enzyme 3; DE Short=Ubiquitin-activating enzyme 3; GN Name=Uba3; Synonyms=Ube1c; 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; TISSUE=Embryonic head, Kidney, and Placenta; 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 GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-462 (ISOFORM 1). 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-462 (ISOFORM 1). RC TISSUE=Liver; RX PubMed=10207026; DOI=10.1074/jbc.274.17.12036; RA Gong L., Yeh E.T.H.; RT "Identification of the activating and conjugating enzymes of the NEDD8 RT conjugation pathway."; RL J. Biol. Chem. 274:12036-12042(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-462 (ISOFORM 1), AND FUNCTION. RC STRAIN=C57BL/6J; RX PubMed=11696557; DOI=10.1083/jcb.200104035; RA Tateishi K., Omata M., Tanaka K., Chiba T.; RT "The NEDD8 system is essential for cell cycle progression and morphogenetic RT pathway in mice."; RL J. Cell Biol. 155:571-580(2001). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [7] RP INTERACTION WITH TBATA. RX PubMed=20937703; DOI=10.1084/jem.20092759; RA Flomerfelt F.A., El Kassar N., Gurunathan C., Chua K.S., League S.C., RA Schmitz S., Gershon T.R., Kapoor V., Yan X.Y., Schwartz R.H., Gress R.E.; RT "Tbata modulates thymic stromal cell proliferation and thymus function."; RL J. Exp. Med. 207:2521-2532(2010). CC -!- FUNCTION: Catalytic subunit of the dimeric UBA3-NAE1 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 UBE2M. Down- CC regulates steroid receptor activity. Necessary for cell cycle CC progression. {ECO:0000269|PubMed:11696557}. CC -!- CATALYTIC ACTIVITY: [NEDD8-activating enzyme E1 catalytic subunit]: 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 Evidence={ECO:0000250|UniProtKB:Q8TBC4}; CC -!- ACTIVITY REGULATION: Binding of TP53BP2 to the regulatory subunit NAE1 CC decreases activity. {ECO:0000250}. CC -!- PATHWAY: Protein modification; protein neddylation. CC -!- SUBUNIT: Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and CC UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By similarity). CC Interacts with TBATA. {ECO:0000250, ECO:0000269|PubMed:20937703}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8C878-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8C878-2; Sequence=VSP_010787; CC -!- DISEASE: Note=Defects in Uba3 are a cause of embryonic lethality. Mouse CC embryos deficient in Uba3 die at the preimplantation stage CC (PubMed:11696557). {ECO:0000269|PubMed:11696557}. CC -!- MISCELLANEOUS: Arg-211 acts as a selectivity gate, preventing CC misactivation of ubiquitin by this NEDD8-specific E1 complex. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA3 CC subfamily. {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; AK014433; BAB29346.1; -; mRNA. DR EMBL; AK032514; BAC27905.1; -; mRNA. DR EMBL; AK048148; BAC33258.1; -; mRNA. DR EMBL; AK159381; BAE35036.1; -; mRNA. DR EMBL; AK168859; BAE40680.1; -; mRNA. DR EMBL; CH466523; EDK99352.1; -; Genomic_DNA. DR EMBL; BC002002; AAH02002.1; -; mRNA. DR EMBL; AF077330; AAC27323.1; -; mRNA. DR EMBL; AY029181; AAK33015.1; -; mRNA. DR CCDS; CCDS51860.1; -. [Q8C878-1] DR RefSeq; NP_001104576.1; NM_001111106.2. DR RefSeq; NP_001288786.1; NM_001301857.1. DR RefSeq; NP_001288787.1; NM_001301858.1. DR RefSeq; NP_001288788.1; NM_001301859.1. [Q8C878-2] DR RefSeq; NP_035796.2; NM_011666.3. [Q8C878-1] DR RefSeq; XP_006505976.1; XM_006505913.3. DR RefSeq; XP_011239592.1; XM_011241290.2. DR AlphaFoldDB; Q8C878; -. DR BMRB; Q8C878; -. DR SMR; Q8C878; -. DR BioGRID; 204409; 16. DR STRING; 10090.ENSMUSP00000086701; -. DR GlyGen; Q8C878; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8C878; -. DR PhosphoSitePlus; Q8C878; -. DR SwissPalm; Q8C878; -. DR EPD; Q8C878; -. DR MaxQB; Q8C878; -. DR PaxDb; 10090-ENSMUSP00000086701; -. DR PeptideAtlas; Q8C878; -. DR ProteomicsDB; 298176; -. [Q8C878-1] DR ProteomicsDB; 298177; -. [Q8C878-2] DR Pumba; Q8C878; -. DR Antibodypedia; 31863; 223 antibodies from 30 providers. DR DNASU; 22200; -. DR Ensembl; ENSMUST00000089287.7; ENSMUSP00000086701.6; ENSMUSG00000030061.17. [Q8C878-1] DR GeneID; 22200; -. DR KEGG; mmu:22200; -. DR UCSC; uc009dam.3; mouse. [Q8C878-1] DR AGR; MGI:1341217; -. DR CTD; 9039; -. DR MGI; MGI:1341217; Uba3. DR VEuPathDB; HostDB:ENSMUSG00000030061; -. DR eggNOG; KOG2015; Eukaryota. DR GeneTree; ENSGT00550000074831; -. DR InParanoid; Q8C878; -. DR OMA; ATSCNPY; -. DR OrthoDB; 20494at2759; -. DR PhylomeDB; Q8C878; -. DR TreeFam; TF300499; -. DR Reactome; R-MMU-5607761; Dectin-1 mediated noncanonical NF-kB signaling. DR Reactome; R-MMU-5676590; NIK-->noncanonical NF-kB signaling. DR Reactome; R-MMU-8951664; Neddylation. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00885; -. DR BioGRID-ORCS; 22200; 22 hits in 77 CRISPR screens. DR PRO; PR:Q8C878; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q8C878; Protein. DR Bgee; ENSMUSG00000030061; Expressed in otic placode and 261 other cell types or tissues. DR ExpressionAtlas; Q8C878; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IDA:MGI. DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0007113; P:endomitotic cell cycle; IMP:MGI. DR GO; GO:0000278; P:mitotic cell cycle; IMP:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0045116; P:protein neddylation; ISO:MGI. DR GO; GO:0051726; P:regulation of cell cycle; IMP:MGI. DR CDD; cd01488; Uba3_RUB; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 1.10.10.520; Ubiquitin activating enzymes (Uba3). Chain: B, domain 2; 1. DR Gene3D; 3.10.290.20; Ubiquitin-like 2 activating enzyme e1b. Chain: B, domain 3; 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_N. DR InterPro; IPR035985; Ubiquitin-activating_enz. DR InterPro; IPR033127; UBQ-activ_enz_E1_Cys_AS. DR PANTHER; PTHR10953:SF6; NEDD8-ACTIVATING ENZYME E1 CATALYTIC SUBUNIT; 1. DR PANTHER; PTHR10953; UBIQUITIN-ACTIVATING ENZYME E1; 1. DR Pfam; PF08825; E2_bind; 1. DR Pfam; PF00899; ThiF; 1. DR SMART; SM01181; E2_bind; 1. DR SUPFAM; SSF69572; Activating enzymes of the ubiquitin-like proteins; 1. DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1. DR Genevisible; Q8C878; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Cell cycle; Ligase; KW Nucleotide-binding; Reference proteome; Ubl conjugation pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q8TBC4" FT CHAIN 2..462 FT /note="NEDD8-activating enzyme E1 catalytic subunit" FT /id="PRO_0000194942" FT REGION 53..70 FT /note="Interaction with UBE2M N-terminus" FT /evidence="ECO:0000250" FT REGION 157..161 FT /note="Interaction with UBE2M N-terminus" FT /evidence="ECO:0000250" FT REGION 192..217 FT /note="Interaction with UBE2M N-terminus" FT /evidence="ECO:0000250" FT REGION 227..229 FT /note="Interaction with NEDD8" FT /evidence="ECO:0000250" FT REGION 242..248 FT /note="Interaction with NAE1" FT /evidence="ECO:0000250" FT REGION 292..295 FT /note="Interaction with NAE1" FT /evidence="ECO:0000250" FT REGION 331..338 FT /note="Interaction with UBE2M N-terminus" FT /evidence="ECO:0000250" FT REGION 352..357 FT /note="Interaction with NEDD8" FT /evidence="ECO:0000250" FT REGION 368..462 FT /note="Interaction with UBE2M core domain" FT /evidence="ECO:0000250" FT ACT_SITE 237 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10132" FT BINDING 100..124 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 148..171 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT SITE 211 FT /note="Determines specificity for NEDD8" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q8TBC4" FT VAR_SEQ 396..462 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_010787" FT CONFLICT 147 FT /note="K -> E (in Ref. 1; BAB29346)" FT /evidence="ECO:0000305" FT CONFLICT 334 FT /note="S -> G (in Ref. 1; BAB29346)" FT /evidence="ECO:0000305" FT CONFLICT 397 FT /note="M -> I (in Ref. 1; BAC33258)" FT /evidence="ECO:0000305" SQ SEQUENCE 462 AA; 51737 MW; 4034CE39E6E9A14E CRC64; MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDV GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA SMPRLPEHCI EYVRMLQWPK EQPFGDGVPL DGDDPEHIQW IFQKSIERAS QYNIRGVTYR LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FT //