UBA3_CAEEL
ID UBA3_CAEEL Reviewed; 430 AA.
AC Q19360;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=NEDD8-activating enzyme E1 catalytic subunit;
DE EC=6.2.1.64;
DE AltName: Full=Ectopic membrane ruffles in embryo protein 1;
DE AltName: Full=Ubiquitin-activating enzyme 3 homolog;
GN Name=rfl-1 {ECO:0000303|PubMed:11847342};
GN Synonyms=uba-3 {ECO:0000303|PubMed:10993680}; ORFNames=F11H8.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP IDENTIFICATION, NOMENCLATURE, AND DEVELOPMENTAL STAGE.
RX PubMed=10993680; DOI=10.1006/dbio.2000.9847;
RA Jones D., Candido E.P.M.;
RT "The NED-8 conjugating system in Caenorhabditis elegans is required for
RT embryogenesis and terminal differentiation of the hypodermis.";
RL Dev. Biol. 226:152-165(2000).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11847342; DOI=10.1126/science.1067765;
RA Kurz T., Pintard L., Willis J.H., Hamill D.R., Goenczy P., Peter M.,
RA Bowerman B.;
RT "Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification
RT pathway.";
RL Science 295:1294-1298(2002).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF ALA-262.
RX PubMed=19528325; DOI=10.1534/genetics.109.104885;
RA Dorfman M., Gomes J.E., O'Rourke S., Bowerman B.;
RT "Using RNA interference to identify specific modifiers of a temperature-
RT sensitive, embryonic-lethal mutation in the Caenorhabditis elegans
RT ubiquitin-like Nedd8 protein modification pathway E1-activating gene rfl-
RT 1.";
RL Genetics 182:1035-1049(2009).
CC -!- FUNCTION: Catalytic subunit of the dimeric rfl-1 (uba-3)-ula-1 E1
CC enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine
CC residue with ATP, thereafter linking this residue to the side chain of
CC the catalytic cysteine, yielding a NEDD8-uba-3 thioester and free AMP.
CC E1 finally transfers NEDD8 to the catalytic cysteine of ubc-12 (By
CC similarity). Required for cytokinesis and mitotic spindle orientation
CC during early embryogenesis (PubMed:11847342, PubMed:19528325).
CC {ECO:0000250|UniProtKB:Q8TBC4, ECO:0000269|PubMed:11847342,
CC ECO:0000269|PubMed:19528325}.
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 -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of uba-3 and ula-1. Interacts with NEDD8 and ubc-
CC 12 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19528325}. Cytoplasm
CC {ECO:0000269|PubMed:19528325}. Note=Predominantly localizes in the
CC nucleus in the 1- and 2-cell embryos. {ECO:0000269|PubMed:19528325}.
CC -!- TISSUE SPECIFICITY: Expressed in intestine, vulva epithelium and head
CC and tail neurons. {ECO:0000269|PubMed:19528325}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development.
CC {ECO:0000269|PubMed:10993680, ECO:0000269|PubMed:19528325}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in temperature-
CC sensitive embryonic lethality. {ECO:0000269|PubMed:11847342}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA3
CC subfamily. {ECO:0000305}.
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DR EMBL; FO080391; CCD63395.1; -; Genomic_DNA.
DR PIR; T16037; T16037.
DR RefSeq; NP_498534.2; NM_066133.5.
DR AlphaFoldDB; Q19360; -.
DR SMR; Q19360; -.
DR BioGRID; 41194; 7.
DR DIP; DIP-25942N; -.
DR IntAct; Q19360; 1.
DR STRING; 6239.F11H8.1.2; -.
DR EPD; Q19360; -.
DR PaxDb; Q19360; -.
DR PeptideAtlas; Q19360; -.
DR EnsemblMetazoa; F11H8.1.1; F11H8.1.1; WBGene00004341.
DR EnsemblMetazoa; F11H8.1.2; F11H8.1.2; WBGene00004341.
DR GeneID; 175982; -.
DR KEGG; cel:CELE_F11H8.1; -.
DR UCSC; F11H8.1.1; c. elegans.
DR CTD; 175982; -.
DR WormBase; F11H8.1; CE34538; WBGene00004341; rfl-1.
DR eggNOG; KOG2015; Eukaryota.
DR GeneTree; ENSGT00550000074831; -.
DR HOGENOM; CLU_013325_13_1_1; -.
DR InParanoid; Q19360; -.
DR OMA; LENYMMY; -.
DR OrthoDB; 686413at2759; -.
DR PhylomeDB; Q19360; -.
DR Reactome; R-CEL-8951664; Neddylation.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00885; -.
DR PRO; PR:Q19360; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00004341; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IBA:GO_Central.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; IMP:WormBase.
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 ATP-binding; Cytoplasm; Developmental protein; Ligase; Nucleotide-binding;
KW Nucleus; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..430
FT /note="NEDD8-activating enzyme E1 catalytic subunit"
FT /id="PRO_0000194947"
FT ACT_SITE 211
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10132"
FT BINDING 52..76
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MUTAGEN 262
FT /note="A->V: In or198; at 25 degrees Celsius, embryonic
FT lethal due to incomplete cytokinesis with ectopic furrow
FT formation and mis-orientation of mitotic spindle. Reduced
FT cul-3 neddylation."
FT /evidence="ECO:0000269|PubMed:19528325"
SQ SEQUENCE 430 AA; 48024 MW; C711152290204C0F CRC64;
MVSVDPLATE RWRSIRRLTD RDSAYKVPWF VPGPENFEAL QNTKILVIGA GGLGCELLKN
LALSGFRTIE VIDMDTIDVS NLNRQFLFRE SDVGKSKAEV AAAFVQQRVV GCQVTAHNCR
IEDKGQEFYR KFSIIICGLD SIPARRWING MLCDLVLEMA DGKPDENTII PMIDGGTEGF
KGNARVIYPK FTACIDCTLD LYPPQVNFPL CTIAHTPRLP EHCIEYIKVV VWPEEKPFEG
VSLDADDPIH VEWVLERASL RAEKYNIRGV DRRLTSGVLK RIIPAVASTN AVIAASCALE
ALKLATNIAK PIDNYLNFTQ IHGAYTSVVS MMKDDNCLTC SGGRLPFEVS PSSTLESLII
RLSERFHLKH PTLATSTRKL YCISSFMPQF EQESKENLHT SMKDLVSDGE EILVSDEALS
RALTLRIQLI
