CUL2_CAEEL
ID CUL2_CAEEL Reviewed; 791 AA.
AC Q17390; O46021; Q8I4A7; Q8WQ96; Q9NA22;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 4.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Cullin-2;
DE Short=CUL-2;
GN Name=cul-2 {ECO:0000312|WormBase:ZK520.4c};
GN Synonyms=ccd-3 {ECO:0000312|WormBase:ZK520.4c},
GN div-3 {ECO:0000312|WormBase:ZK520.4c};
GN ORFNames=ZK520.4 {ECO:0000312|WormBase:ZK520.4c};
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] (ISOFORM D).
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=10587644; DOI=10.1038/70272;
RA Feng H., Zhong W., Punkosdy G., Gu S., Zhou L., Seabolt E.K., Kipreos E.T.;
RT "CUL-2 is required for the G1-to-S-phase transition and mitotic chromosome
RT condensation in Caenorhabditis elegans.";
RL Nat. Cell Biol. 1:486-492(1999).
RN [4]
RP INTERACTION WITH SKR-10.
RX PubMed=11864566; DOI=10.1016/s0960-9822(02)00657-7;
RA Yamanaka A., Yada M., Imaki H., Koga M., Ohshima Y., Nakayama K.;
RT "Multiple Skp1-related proteins in Caenorhabditis elegans: diverse patterns
RT of interaction with Cullins and F-box proteins.";
RL Curr. Biol. 12:267-275(2002).
RN [5]
RP FUNCTION, AND IDENTIFICATION IN THE CBC(ZYF-1) COMPLEX.
RX PubMed=12894212; DOI=10.1038/nature01887.;
RA DeRenzo C., Reese K.J., Seydoux G.;
RT "Exclusion of germ plasm proteins from somatic lineages by cullin-dependent
RT degradation.";
RL Nature 424:685-689(2003).
RN [6]
RP FUNCTION, IDENTIFICATION IN THE CBC(FEM-1) COMPLEX, AND INTERACTION WITH
RP TRA-1 AND FEM-1.
RX PubMed=17609115; DOI=10.1016/j.devcel.2007.05.008;
RA Starostina N.G., Lim J.M., Schvarzstein M., Wells L., Spence A.M.,
RA Kipreos E.T.;
RT "A CUL-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to
RT regulate C. elegans sex determination.";
RL Dev. Cell 13:127-139(2007).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN COMPLEX WITH ZYG-11 AND ELC-1.
RX PubMed=17304241; DOI=10.1038/sj.embor.7400895;
RA Vasudevan S., Starostina N.G., Kipreos E.T.;
RT "The Caenorhabditis elegans cell-cycle regulator ZYG-11 defines a conserved
RT family of CUL-2 complex components.";
RL EMBO Rep. 8:279-286(2007).
RN [8]
RP FUNCTION, IDENTIFICATION IN THE CBC(LRR-1) COMPLEX, INTERACTION WITH
RP REPLISOME COMPLEX, AND DISRUPTION PHENOTYPE.
RX PubMed=28368371; DOI=10.1038/ncb3500;
RA Sonneville R., Moreno S.P., Knebel A., Johnson C., Hastie C.J., Gartner A.,
RA Gambus A., Labib K.;
RT "CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication
RT termination and mitosis.";
RL Nat. Cell Biol. 19:468-479(2017).
CC -!- FUNCTION: Core component of multiple cullin-RING-based CBC (Cul2-
CC ElonginB-ElonginC) E3 ubiquitin-protein ligase complexes which mediate
CC the ubiquitination and subsequent proteasomal degradation of target
CC proteins. As a scaffold protein may contribute to catalysis through
CC positioning of the substrate and the ubiquitin-conjugating enzyme. The
CC functional specificity of the CBC complex depends on the variable
CC substrate recognition component (By similarity). May function in
CC ubiquitin-mediated degradation of CKIs to target cki-1 for degradation.
CC CBC(zif-1) may ensure germline precursor cell asymmetry by targeting
CC germline proteins for destruction if expressed in non-germline cells
CC (PubMed:12894212). As part of the CBC(fem-1) complex directs
CC ubiquitination of tra-1 (PubMed:17609115). As part of the CBC(lrr-1)
CC complex, required for the ubiquitination and dissasembly of the CMG
CC helicase complex from chromatin at the end of DNA replication
CC (PubMed:28368371). Positive cell-cycle regulator that is required at
CC two distinct points in the cell cycle; the G1-to-S-phase transition and
CC mitosis (PubMed:10587644). Also required for proper cytoskeletal
CC movement and mitotic chromosome condensation (PubMed:10587644).
CC {ECO:0000250|UniProtKB:Q13617, ECO:0000269|PubMed:10587644,
CC ECO:0000269|PubMed:12894212, ECO:0000269|PubMed:17304241,
CC ECO:0000269|PubMed:17609115, ECO:0000269|PubMed:28368371}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of multiple CBC (Cul2-ElonginB-ElonginC) E3
CC ubiquitin-protein ligase complexes formed of cul-2, elb-1, elc-1, rbx-1
CC and a variable substrate recognition component (By similarity).
CC Component of the CBC(fem-1) E3 ubiquitin-protein ligase complex with
CC fem-1, fem-2 and fem-3 (PubMed:17609115). The CBC(fem-1) complex
CC interacts with tra-1 and promotes tra-1 degradation (PubMed:17609115).
CC Probable component of the CBC(lrr-1) E3 ubiquitin-protein ligase
CC complex incuding cul-2, elb-1, elc-1, rbx-1 and lrr-1
CC (PubMed:28368371). The CBC(lrr-1) complex interacts with the DNA
CC replisome complex at the end of S phase; the interaction promotes the
CC release of components of the CMG helicase complex (a component of the
CC replisome) from chromatin (PubMed:28368371). Probable component of an
CC CBC(zif-1) E3 ubiquitin-protein ligase including cul-2, elc-1, rbx-1
CC and zif-1 (PubMed:12894212). Part of an E3 ubiquitin-protein ligase
CC complex including cul-2, elc-1 and zyg-11 (PubMed:17304241). Interacts
CC with Skp1-related protein skr-10 (PubMed:11864566).
CC {ECO:0000250|UniProtKB:Q13617, ECO:0000269|PubMed:11864566,
CC ECO:0000269|PubMed:17304241, ECO:0000269|PubMed:17609115,
CC ECO:0000269|PubMed:28368371, ECO:0000305|PubMed:12894212}.
CC -!- INTERACTION:
CC Q17390; Q9BKS1: elc-1; NbExp=2; IntAct=EBI-1811231, EBI-300574;
CC Q17390; Q2WF59: zer-1; NbExp=2; IntAct=EBI-1811231, EBI-1811352;
CC Q17390; P21541: zyg-11; NbExp=3; IntAct=EBI-1811231, EBI-314647;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10587644}. Nucleus
CC {ECO:0000269|PubMed:10587644}. Note=Nuclear in oocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=c {ECO:0000312|WormBase:ZK520.4c};
CC IsoId=Q17390-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:ZK520.4b};
CC IsoId=Q17390-2; Sequence=VSP_060362;
CC Name=d {ECO:0000312|WormBase:ZK520.4d};
CC IsoId=Q17390-3; Sequence=VSP_060362, VSP_060363, VSP_060364;
CC -!- TISSUE SPECIFICITY: In adults, highly expressed in meiotic cells and
CC oocytes. In larvae, expressed in many proliferating cell types: P cells
CC during the L1 stage; seam cells when they divide at every molt; vulval
CC and somatic gonad cells in late L3 and L4 stages; and intestinal cells
CC throughout larval development. {ECO:0000269|PubMed:10587644}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Highest
CC levels in embryos and lower levels in larvae and adults.
CC {ECO:0000269|PubMed:10587644}.
CC -!- PTM: Neddylated; which enhances the ubiquitination activity of CBC
CC (Cul2-ElonginB-ElonginC) E3 ubiquitin-protein ligase complexes.
CC {ECO:0000250|UniProtKB:Q13617, ECO:0000250|UniProtKB:Q9D4H8}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown prevents the release of
CC sld-5 and psf-1 from chromatin prior to prophase in early embryos.
CC {ECO:0000269|PubMed:28368371}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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DR EMBL; U58084; AAC47121.1; -; mRNA.
DR EMBL; BX284603; CAB07302.3; -; Genomic_DNA.
DR EMBL; BX284603; CAD18893.2; -; Genomic_DNA.
DR EMBL; BX284603; CAD45612.3; -; Genomic_DNA.
DR PIR; C88618; C88618.
DR PIR; T27884; T27884.
DR RefSeq; NP_001023007.1; NM_001027836.2. [Q17390-2]
DR RefSeq; NP_001023008.1; NM_001027837.1. [Q17390-1]
DR RefSeq; NP_001023009.1; NM_001027838.2.
DR AlphaFoldDB; Q17390; -.
DR SMR; Q17390; -.
DR BioGRID; 41972; 14.
DR ComplexPortal; CPX-3383; CBC-fem-1 Ubiquitin Ligase complex.
DR IntAct; Q17390; 9.
DR MINT; Q17390; -.
DR STRING; 6239.ZK520.4a; -.
DR EPD; Q17390; -.
DR PaxDb; Q17390; -.
DR PeptideAtlas; Q17390; -.
DR EnsemblMetazoa; ZK520.4b.1; ZK520.4b.1; WBGene00000837. [Q17390-2]
DR EnsemblMetazoa; ZK520.4b.2; ZK520.4b.2; WBGene00000837. [Q17390-2]
DR EnsemblMetazoa; ZK520.4c.1; ZK520.4c.1; WBGene00000837. [Q17390-1]
DR EnsemblMetazoa; ZK520.4d.1; ZK520.4d.1; WBGene00000837. [Q17390-3]
DR GeneID; 176806; -.
DR KEGG; cel:CELE_ZK520.4; -.
DR UCSC; ZK520.4a; c. elegans.
DR CTD; 176806; -.
DR WormBase; ZK520.4b; CE32775; WBGene00000837; cul-2. [Q17390-2]
DR WormBase; ZK520.4c; CE32776; WBGene00000837; cul-2. [Q17390-1]
DR WormBase; ZK520.4d; CE36259; WBGene00000837; cul-2. [Q17390-3]
DR eggNOG; KOG2284; Eukaryota.
DR GeneTree; ENSGT00940000154926; -.
DR InParanoid; Q17390; -.
DR OrthoDB; 1040292at2759; -.
DR PhylomeDB; Q17390; -.
DR Reactome; R-CEL-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-CEL-8951664; Neddylation.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q17390; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q17390; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000837; Expressed in embryo and 6 other tissues.
DR GO; GO:0031462; C:Cul2-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; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent catabolic process; IMP:WormBase.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IMP:WormBase.
DR GO; GO:0030261; P:chromosome condensation; IEA:UniProtKB-KW.
DR GO; GO:0042078; P:germ-line stem cell division; IMP:WormBase.
DR GO; GO:0019100; P:male germ-line sex determination; IMP:WormBase.
DR GO; GO:0030238; P:male sex determination; IMP:ComplexPortal.
DR GO; GO:0019102; P:male somatic sex determination; IMP:WormBase.
DR GO; GO:0051232; P:meiotic spindle elongation; IMP:WormBase.
DR GO; GO:1902104; P:positive regulation of metaphase/anaphase transition of meiotic cell cycle; IMP:WormBase.
DR GO; GO:0008104; P:protein localization; IMP:WormBase.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0051759; P:sister chromosome movement towards spindle pole involved in meiotic sister chromatid segregation; IMP:WormBase.
DR GO; GO:0036369; P:transcription factor catabolic process; IMP:WormBase.
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 Alternative splicing; Cell cycle; Cell division; Cytoplasm;
KW Developmental protein; DNA condensation; Isopeptide bond; Mitosis; Nucleus;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..791
FT /note="Cullin-2"
FT /id="PRO_0000119781"
FT CROSSLNK 736
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000250|UniProtKB:Q13616"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform b and isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060362"
FT VAR_SEQ 547..579
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060363"
FT VAR_SEQ 718
FT /note="T -> TFQ (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_060364"
FT CONFLICT 72
FT /note="S -> I (in Ref. 1; AAC47121)"
FT /evidence="ECO:0000305"
FT CONFLICT 420..421
FT /note="KA -> NG (in Ref. 1; AAC47121)"
FT /evidence="ECO:0000305"
FT CONFLICT 621
FT /note="Y -> H (in Ref. 1; AAC47121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 791 AA; 91343 MW; 8993DF21905F0738 CRC64;
MASSTKVSLR RPPRPQVMYS LKPKVVEFDK VWVQLRPSII DIINLRPITN VQWHHKFSDV
YDICVSIPTP LSERLYNEVK ACIQEHVRQK RQDIVDVDPD LLLQEYHKMW RVFHEGAIFI
HRLFGYLNKQ FVKQKRCTDL DNFAQYAAFL QIPDVKEIGC LALEIWKEDL VKTILPQLVK
LLLIAIDNDR KGNFPHIANE VSGVINSFVK MEETDFDVVP AEGARYKARE STTAFYQESF
EKPLLTDTEQ YYSALAQKML TDLSCSEYME QVIVLLEQEE MRAKKYLHES SVEKVITLCQ
KVMIKAHKDK LHAVCHDLIT NEENKDLRNM YRLLKPIQAG LSVMVKEFEE YVKKKGLEAV
SRLTGENVPQ QFVENVLRVY NKFNDMKTAV FMDDGEFSSG LDKALQGVVN SKEPGQSVPK
ASERLARYTD GLLKKSTKGL SETDLEAKLD SAIVIFRYIE DKDIFQKFYS KMLANRLIAS
TSISMDAEEL MINKLKQACG YEFTSKLSRM FTDIGLSQEL SNNFDKHIAD IKTVQPDVKF
VPTQTMILQA GSWPLNAPQL STNSNNQTAQ DVANFHLPRI LQPVIQEFEK FYTGKHNGRK
LTWLFNMSQG DVRLTYLDKQ YVAQMYVYQM AALLCFERRD AILVKDIGEE IGVSGDYLLK
TIRTILDVTL LTCDDQNLTA DSLVRLNMSM TSKRMKFRLQ APQVNKAVEK EQEAVANTVS
QDRKYYMECA IVRIMKTRKV LKHNALVTEI MDQTKGRFSP DVPFIKKSIE DLIEKMYIQR
TDQNDEYQYL A
