CUL3_CAEEL
ID CUL3_CAEEL Reviewed; 777 AA.
AC Q17391; Q95Y32;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Cullin-3;
DE Short=CUL-3;
GN Name=cul-3 {ECO:0000312|WormBase:Y108G3AL.1a};
GN ORFNames=Y108G3AL.1 {ECO:0000312|WormBase:Y108G3AL.1a};
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 [MRNA].
RC STRAIN=Bristol N2;
RX PubMed=8681378; DOI=10.1016/s0092-8674(00)81267-2;
RA Kipreos E.T., Lander L.E., Wing J.P., He W.W., Hedgecock E.M.;
RT "cul-1 is required for cell cycle exit in C. elegans and identifies a novel
RT gene family.";
RL Cell 85:829-839(1996).
RN [2]
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 [3]
RP FUNCTION, NEDDYLATION, AND DENEDDYLATION BY THE CSN COMPLEX.
RX PubMed=12781129; DOI=10.1016/s0960-9822(03)00336-1;
RA Pintard L., Kurz T., Glaser S., Willis J.H., Peter M., Bowerman B.;
RT "Neddylation and deneddylation of CUL-3 is required to target MEI-1/katanin
RT for degradation at the meiosis-to-mitosis transition in C. elegans.";
RL Curr. Biol. 13:911-921(2003).
RN [4]
RP FUNCTION, AND INTERACTION WITH MEL-26; BATH-15; BATH-40; BATH-41; BATH-42;
RP C17F4.8; TAG-303; D2045.8; F57C2.1; ZC239.15 AND B0281.5.
RX PubMed=13679922; DOI=10.1038/nature01985;
RA Xu L., Wei Y., Reboul J., Vaglio P., Shin T.H., Vidal M., Elledge S.J.,
RA Harper J.W.;
RT "BTB proteins are substrate-specific adaptors in an SCF-like modular
RT ubiquitin ligase containing CUL-3.";
RL Nature 425:316-321(2003).
RN [5]
RP INTERACTION WITH DCN-1.
RX PubMed=15988528; DOI=10.1038/nature03662;
RA Kurz T., Oezlue N., Rudolf F., O'Rourke S.M., Luke B., Hofmann K.,
RA Hyman A.A., Bowerman B., Peter M.;
RT "The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C.
RT elegans and S. cerevisiae.";
RL Nature 435:1257-1261(2005).
RN [6]
RP FUNCTION, INTERACTION WITH MEL-26, AND DISRUPTION PHENOTYPE.
RX PubMed=22621901; DOI=10.1091/mbc.e12-01-0055;
RA Wilson K.J., Qadota H., Mains P.E., Benian G.M.;
RT "UNC-89 (obscurin) binds to MEL-26, a BTB-domain protein, and affects the
RT function of MEI-1 (katanin) in striated muscle of Caenorhabditis elegans.";
RL Mol. Biol. Cell 23:2623-2634(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=34593637; DOI=10.1073/pnas.2104664118;
RA Snoznik C., Medvedeva V., Mojsilovic-Petrovic J., Rudich P., Oosten J.,
RA Kalb R.G., Lamitina T.;
RT "The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of
RT C9orf72 dipeptide toxicity.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: Probable core component of multiple cullin-RING-based BCB
CC (BTB-CUL3-BTB) E3 ubiquitin-protein ligase complexes which mediate the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins (PubMed:13679922). Probably acts as a scaffold protein which
CC may contribute to catalysis through positioning of the substrate and
CC the ubiquitin-conjugating enzyme (PubMed:13679922). Required to target
CC mei-3/katanin for degradation at the meiosis to mitosis transition via
CC its neddylation and deneddylation (PubMed:12781129). Functions in
CC ubiquitin-mediated degradation of CKIs to target cki-1 for degradation
CC (PubMed:12781129). Regulates microtubule stability in the early embryo
CC (PubMed:12781129). In body wall muscles, involved in the organization
CC of myosin thick filaments, likely by regulating the degradation of
CC microtubule severing protein mei-1 downstream of unc-89
CC (PubMed:22621901). Together with spop-1, may promote the ubiquitination
CC and proteasomal degradation of target bromodomain-containing proteins
CC such as bet-1 (PubMed:34593637). {ECO:0000269|PubMed:12781129,
CC ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:34593637,
CC ECO:0000305|PubMed:13679922}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Probable component of multiple cullin-RING-based BCB (BTB-
CC CUL3-BTB) E3 ubiquitin-protein ligase complexes formed by cul-3, rbx-1
CC and a variable BTB domain-containing protein acting as both, adapter to
CC cullin and substrate recognition component (PubMed:13679922). Interacts
CC with bath-15, bath-40, bath-41, bath-42, C17F4.8, tag-303, D2045.8,
CC F57C2.1, ZC239.15 and B0281.5 (PubMed:13679922). Interacts with mel-26
CC (via BTB domain) (PubMed:13679922, PubMed:22621901). Interacts with
CC dcn-1 (PubMed:13679922). {ECO:0000269|PubMed:13679922,
CC ECO:0000269|PubMed:15988528, ECO:0000269|PubMed:22621901}.
CC -!- INTERACTION:
CC Q17391; Q9NF14: bath-40; NbExp=2; IntAct=EBI-593075, EBI-313743;
CC Q17391; P41886: bath-41; NbExp=2; IntAct=EBI-593075, EBI-314147;
CC Q17391; P34371: bath-42; NbExp=3; IntAct=EBI-593075, EBI-315422;
CC Q17391; O16612: CELE_B0281.5; NbExp=2; IntAct=EBI-593075, EBI-326132;
CC Q17391; Q18986: CELE_D2045.8; NbExp=2; IntAct=EBI-593075, EBI-326795;
CC Q17391; Q18776: inso-1; NbExp=3; IntAct=EBI-593075, EBI-312114;
CC Q17391; Q94420: mel-26; NbExp=3; IntAct=EBI-593075, EBI-320790;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- DEVELOPMENTAL STAGE: Highest levels in embryos and lower levels in
CC larvae and adults.
CC -!- PTM: Neddylated. Deneddylated via its interaction with the COP9
CC signalosome (CSN) complex. {ECO:0000269|PubMed:12781129}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown at L1 larval stage
CC results in the disorganization of myosin thick filaments in adult body
CC wall muscles characterized by the formation of abnormal myosin heavy
CC chain myo-3 aggregates and V-shaped crossing of A-bands
CC (PubMed:22621901). RNAi-mediated knockdown suppresses the age-dependent
CC paralysis and growth arrest induced by exogenous dipeptide repeat
CC protein PR50 (PubMed:34593637). {ECO:0000269|PubMed:22621901,
CC ECO:0000269|PubMed:34593637}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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; U58085; AAC47122.1; -; mRNA.
DR EMBL; BX284605; CCD74336.1; -; Genomic_DNA.
DR RefSeq; NP_503151.1; NM_070750.5.
DR AlphaFoldDB; Q17391; -.
DR SMR; Q17391; -.
DR BioGRID; 43622; 23.
DR IntAct; Q17391; 16.
DR MINT; Q17391; -.
DR STRING; 6239.Y108G3AL.1.2; -.
DR EPD; Q17391; -.
DR PaxDb; Q17391; -.
DR PeptideAtlas; Q17391; -.
DR EnsemblMetazoa; Y108G3AL.1a.1; Y108G3AL.1a.1; WBGene00000838.
DR EnsemblMetazoa; Y108G3AL.1a.2; Y108G3AL.1a.2; WBGene00000838.
DR GeneID; 178547; -.
DR KEGG; cel:CELE_Y108G3AL.1; -.
DR UCSC; Y108G3AL.1.1; c. elegans.
DR CTD; 178547; -.
DR WormBase; Y108G3AL.1a; CE27593; WBGene00000838; cul-3.
DR eggNOG; KOG2166; Eukaryota.
DR GeneTree; ENSGT00940000155066; -.
DR HOGENOM; CLU_004747_7_1_1; -.
DR InParanoid; Q17391; -.
DR OMA; MFKDMTI; -.
DR OrthoDB; 1040292at2759; -.
DR PhylomeDB; Q17391; -.
DR Reactome; R-CEL-4641258; Degradation of DVL.
DR Reactome; R-CEL-5632684; Hedgehog 'on' state.
DR Reactome; R-CEL-8951664; Neddylation.
DR Reactome; R-CEL-9706019; RHOBTB3 ATPase cycle.
DR Reactome; R-CEL-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q17391; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000838; Expressed in adult organism and 4 other tissues.
DR ExpressionAtlas; Q17391; baseline and differential.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0031208; F:POZ domain binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0010623; P:programmed cell death involved in cell development; IMP:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; IMP:WormBase.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0071688; P:striated muscle myosin thick filament assembly; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR045093; Cullin.
DR InterPro; IPR016157; Cullin_CS.
DR InterPro; IPR016158; Cullin_homology.
DR InterPro; IPR036317; Cullin_homology_sf.
DR InterPro; IPR001373; Cullin_N.
DR InterPro; IPR019559; Cullin_neddylation_domain.
DR InterPro; IPR016159; Cullin_repeat-like_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11932; PTHR11932; 1.
DR Pfam; PF00888; Cullin; 1.
DR Pfam; PF10557; Cullin_Nedd8; 1.
DR SMART; SM00182; CULLIN; 1.
DR SMART; SM00884; Cullin_Nedd8; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF74788; SSF74788; 1.
DR SUPFAM; SSF75632; SSF75632; 1.
DR PROSITE; PS01256; CULLIN_1; 1.
DR PROSITE; PS50069; CULLIN_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Isopeptide bond; Nucleus; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..777
FT /note="Cullin-3"
FT /id="PRO_0000119782"
FT REGION 568..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 721
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
FT CONFLICT 586
FT /note="S -> G (in Ref. 1; AAC47122)"
FT /evidence="ECO:0000305"
FT CONFLICT 614
FT /note="F -> L (in Ref. 1; AAC47122)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="Q -> QHEQ (in Ref. 1; AAC47122)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 777 AA; 90236 MW; 3D90A41092E540A7 CRC64;
MSGRSGNGGQ QKMRIRPFMA TIDEQYVTQT WELLKRAIQE IQRKNNSGLS FEELYRNAYT
MVLHKHGERL YNGLKDVIQD HMASVRIRII ESMNSGSFLE TVAESWADHT VAMVMIRDIL
MYMDRIYVAQ NNHVLPVYNL GLDAYRTEIL RQNGIGDRIR DALLELIKLD RKSNQINWHG
IKNACDMLIS LGIDSRTVYE DEFERPLLKE TSDYYRDVCK NWLSGDNDAC FYLAQVEIAM
HDEASRASRY LDKMTEAKIL QVMDDVMVAE HIQTIVYMQN GGVKFMLEHK KIEDLTRIFR
IFKRIGDSVT VPGGGLKALL KAVSEYLNET GSNIVKNEDL LKNPVNFVNE LLQLKDYFSS
LLTTAFADDR DFKNRFQHDF ETFLNSNRQS PEFVALYMDD MLRSGLKCVS DAEMDNKLDN
VMILFRYLQE KDVFEKYFKQ YLAKRLLLDK SCSDDVEKAL LAKLKTECGC QFTQKLENMF
RDKELWLTLA TSFRDWREAQ PTKMSIDISL RVLTAGVWPT VQCNPVVLPQ ELSVAYEMFT
QYYTEKHTGR KLTINTLLGN ADVKATFYPP PKASMSNEEN GPGPSSSGES MKERKPEHKI
LQVNTHQMII LLQFNHHNRI SCQQLMDELK IPERELKRNL QSLALGKASQ RILVRKNKGK
DAIDMSDEFA VNDNFQSKLT RVKVQMVTGK VESEPEIRET RQKVEDDRKL EVEAAIVRIM
KARKKLNHNN LVAEVTQQLR HRFMPSPIII KQRIETLIER EYLARDEHDH RAYQYIA
