UBA3_PONAB
ID UBA3_PONAB Reviewed; 463 AA.
AC Q5R4A0; Q5R6V2; Q5R6X8; Q5RDU8;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 101.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:Q8TBC4}.
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 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5R4A0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5R4A0-2; Sequence=VSP_016392;
CC Name=3;
CC IsoId=Q5R4A0-3; Sequence=VSP_016392, VSP_016393;
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 -!- CAUTION: It is uncertain whether Met-1 or Met-22 is the initiator.
CC {ECO:0000305}.
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DR EMBL; CR857798; CAH90059.1; -; mRNA.
DR EMBL; CR859959; CAH92113.1; -; mRNA.
DR EMBL; CR860349; CAH92482.1; -; mRNA.
DR EMBL; CR860381; CAH92508.1; -; mRNA.
DR EMBL; CR861356; CAH93416.1; -; mRNA.
DR RefSeq; NP_001126234.1; NM_001132762.2. [Q5R4A0-1]
DR RefSeq; NP_001128861.1; NM_001135389.1. [Q5R4A0-2]
DR RefSeq; XP_009237088.1; XM_009238813.1. [Q5R4A0-3]
DR AlphaFoldDB; Q5R4A0; -.
DR BMRB; Q5R4A0; -.
DR SMR; Q5R4A0; -.
DR STRING; 9601.ENSPPYP00000015351; -.
DR Ensembl; ENSPPYT00000015964; ENSPPYP00000015351; ENSPPYG00000013729. [Q5R4A0-1]
DR Ensembl; ENSPPYT00000059435; ENSPPYP00000029247; ENSPPYG00000013729. [Q5R4A0-2]
DR GeneID; 100173204; -.
DR KEGG; pon:100173204; -.
DR CTD; 9039; -.
DR eggNOG; KOG2015; Eukaryota.
DR GeneTree; ENSGT00550000074831; -.
DR HOGENOM; CLU_013325_13_1_1; -.
DR InParanoid; Q5R4A0; -.
DR UniPathway; UPA00885; -.
DR Proteomes; UP000001595; Chromosome 3.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IEA:UniProtKB-EC.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0007113; P:endomitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045116; P:protein neddylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
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 2: Evidence at transcript 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..463
FT /note="NEDD8-activating enzyme E1 catalytic subunit"
FT /id="PRO_0000194943"
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..463
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 8..21
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_016392"
FT VAR_SEQ 62..88
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_016393"
FT CONFLICT 231
FT /note="Q -> E (in Ref. 1; CAH93416)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="H -> R (in Ref. 1; CAH93416)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 463 AA; 51822 MW; 1DEFB0C656566E13 CRC64;
MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST
ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDI
GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI
SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA
SMPRLPEHCI EYVRMLQWPK EQPFGEGVPL DGDDPEHIQW IFQKSLERAS QYNIRGVTYR
LTQGVVKRII PAVASTNAVV AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER
KENCPACSQL PQNIQFSPSA KLQEVLDFLT NSASLQMKSP AITATLEGKN RTLYLQSVTS
IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FTS
