UBA3_RAT
ID UBA3_RAT Reviewed; 462 AA.
AC Q99MI7;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ESR1 AND ESR2, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Uterus;
RX PubMed=11818503; DOI=10.1210/mend.16.2.0778;
RA Fan M., Long X., Bailey J.A., Reed C.A., Osborne E., Gize E.A., Kirk E.A.,
RA Bigsby R.M., Nephew K.P.;
RT "The activating enzyme of NEDD8 inhibits steroid receptor function.";
RL Mol. Endocrinol. 16:315-330(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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).
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:11818503}.
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 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 (By similarity). Binds ESR1 and ESR2 with bound steroid ligand.
CC Interacts with TBATA (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11818503}.
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}.
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DR EMBL; AF336829; AAK21298.1; -; mRNA.
DR EMBL; BC081743; AAH81743.1; -; mRNA.
DR RefSeq; NP_476553.1; NM_057205.2.
DR AlphaFoldDB; Q99MI7; -.
DR BMRB; Q99MI7; -.
DR SMR; Q99MI7; -.
DR BioGRID; 250766; 2.
DR STRING; 10116.ENSRNOP00000008893; -.
DR iPTMnet; Q99MI7; -.
DR PhosphoSitePlus; Q99MI7; -.
DR jPOST; Q99MI7; -.
DR PaxDb; Q99MI7; -.
DR PRIDE; Q99MI7; -.
DR GeneID; 117553; -.
DR KEGG; rno:117553; -.
DR UCSC; RGD:621084; rat.
DR CTD; 9039; -.
DR RGD; 621084; Uba3.
DR VEuPathDB; HostDB:ENSRNOG00000006221; -.
DR eggNOG; KOG2015; Eukaryota.
DR HOGENOM; CLU_013325_13_1_1; -.
DR InParanoid; Q99MI7; -.
DR OMA; LENYMMY; -.
DR OrthoDB; 686413at2759; -.
DR PhylomeDB; Q99MI7; -.
DR TreeFam; TF300499; -.
DR Reactome; R-RNO-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-RNO-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-RNO-8951664; Neddylation.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00885; -.
DR PRO; PR:Q99MI7; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000006221; Expressed in duodenum and 20 other tissues.
DR Genevisible; Q99MI7; RN.
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; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IDA:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IMP:RGD.
DR GO; GO:0007113; P:endomitotic cell cycle; ISO:RGD.
DR GO; GO:0000278; P:mitotic cell cycle; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
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; ATP-binding; Cell cycle; Ligase; Nucleotide-binding;
KW 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_0000194944"
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"
SQ SEQUENCE 462 AA; 51723 MW; 183FAB8C44486645 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 IFQKSVERAS QYNIRGVTYR
LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER
KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS
IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FT
