UBA3_MOUSE
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 03-AUG-2022, entry version 155.
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, Spleen,
RC 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 iPTMnet; Q8C878; -.
DR PhosphoSitePlus; Q8C878; -.
DR SwissPalm; Q8C878; -.
DR EPD; Q8C878; -.
DR MaxQB; Q8C878; -.
DR PaxDb; Q8C878; -.
DR PeptideAtlas; Q8C878; -.
DR PRIDE; Q8C878; -.
DR ProteomicsDB; 298176; -. [Q8C878-1]
DR ProteomicsDB; 298177; -. [Q8C878-2]
DR Antibodypedia; 31863; 186 antibodies from 29 providers.
DR DNASU; 22200; -.
DR Ensembl; ENSMUST00000089287; ENSMUSP00000086701; ENSMUSG00000030061. [Q8C878-1]
DR GeneID; 22200; -.
DR KEGG; mmu:22200; -.
DR UCSC; uc009dam.3; mouse. [Q8C878-1]
DR CTD; 9039; -.
DR MGI; MGI:1341217; Uba3.
DR VEuPathDB; HostDB:ENSMUSG00000030061; -.
DR eggNOG; KOG2015; Eukaryota.
DR GeneTree; ENSGT00550000074831; -.
DR InParanoid; Q8C878; -.
DR OMA; LENYMMY; -.
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 72 CRISPR screens.
DR PRO; PR:Q8C878; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8C878; protein.
DR Bgee; ENSMUSG00000030061; Expressed in otic placode and 257 other tissues.
DR ExpressionAtlas; Q8C878; baseline and differential.
DR Genevisible; Q8C878; MM.
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 transcription, DNA-templated; ISO:MGI.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:MGI.
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 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
