CUL8_YEAST
ID CUL8_YEAST Reviewed; 842 AA.
AC P47050; D6VWD7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Cullin-8;
DE AltName: Full=Cullin-C;
DE AltName: Full=Regulator of Ty1 transposition protein 101;
GN Name=RTT101; Synonyms=CUL8; OrderedLocusNames=YJL047C; ORFNames=J1166;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INTERACTION WITH HRT1,
RP MUTAGENESIS OF 680-VAL--GLU-686 AND LYS-791, AND DISRUPTION PHENOTYPE.
RX PubMed=12676951; DOI=10.1074/jbc.m210358200;
RA Michel J.J., McCarville J.F., Xiong Y.;
RT "A role for Saccharomyces cerevisiae Cul8 ubiquitin ligase in proper
RT anaphase progression.";
RL J. Biol. Chem. 278:22828-22837(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=11779788; DOI=10.1093/genetics/159.4.1449;
RA Scholes D.T., Banerjee M., Bowen B., Curcio M.J.;
RT "Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae have
RT conserved roles in genome maintenance.";
RL Genetics 159:1449-1465(2001).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [6]
RP NEDDYLATION AT LYS-791, AND MUTAGENESIS OF LYS-791.
RX PubMed=14519104; DOI=10.1042/bj20030755;
RA Laplaza J.M., Bostick M., Scholes D.T., Curcio M.J., Callis J.;
RT "Saccharomyces cerevisiae ubiquitin-like protein Rub1 conjugates to cullin
RT proteins Rtt101 and Cul3 in vivo.";
RL Biochem. J. 377:459-467(2004).
RN [7]
RP FUNCTION.
RX PubMed=16631586; DOI=10.1016/j.cub.2006.02.071;
RA Luke B., Versini G., Jaquenoud M., Zaidi I.W., Kurz T., Pintard L.,
RA Pasero P., Peter M.;
RT "The cullin Rtt101p promotes replication fork progression through damaged
RT DNA and natural pause sites.";
RL Curr. Biol. 16:786-792(2006).
RN [8]
RP FUNCTION.
RX PubMed=18321796; DOI=10.1016/j.dnarep.2008.01.007;
RA Duro E., Vaisica J.A., Brown G.W., Rouse J.;
RT "Budding yeast Mms22 and Mms1 regulate homologous recombination induced by
RT replisome blockage.";
RL DNA Repair 7:811-818(2008).
RN [9]
RP FUNCTION, INTERACTION WITH MMS1, AND IDENTIFICATION IN COMPLEXES WITH MMS22
RP AND CRT10.
RX PubMed=18704118; DOI=10.1038/embor.2008.155;
RA Zaidi I.W., Rabut G., Poveda A., Scheel H., Malmstrom J., Ulrich H.,
RA Hofmann K., Pasero P., Peter M., Luke B.;
RT "Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase
RT that promotes replication through damaged DNA.";
RL EMBO Rep. 9:1034-1040(2008).
RN [10]
RP FUNCTION, AND INTERACTION WITH RTT107.
RX PubMed=17978089; DOI=10.1091/mbc.e07-09-0961;
RA Roberts T.M., Zaidi I.W., Vaisica J.A., Peter M., Brown G.W.;
RT "Regulation of rtt107 recruitment to stalled DNA replication forks by the
RT cullin rtt101 and the rtt109 acetyltransferase.";
RL Mol. Biol. Cell 19:171-180(2008).
RN [11]
RP FUNCTION.
RX PubMed=19390089; DOI=10.1101/gad.1775609;
RA Fujii K., Kitabatake M., Sakata T., Miyata A., Ohno M.;
RT "A role for ubiquitin in the clearance of nonfunctional rRNAs.";
RL Genes Dev. 23:963-974(2009).
RN [12]
RP INTERACTION WITH MMS1, AND IDENTIFICATION IN COMPLEXES WITH MMS22; RTT107;
RP CTF4; ESC2 AND ORC5.
RX PubMed=20139071; DOI=10.1074/jbc.m109.082107;
RA Mimura S., Yamaguchi T., Ishii S., Noro E., Katsura T., Obuse C.,
RA Kamura T.;
RT "Cul8/Rtt101 forms a variety of protein complexes that regulate DNA damage
RT response and transcriptional silencing.";
RL J. Biol. Chem. 285:9858-9867(2010).
RN [13]
RP FUNCTION.
RX PubMed=20634314; DOI=10.1101/gad.1887310;
RA Han J., Li Q., McCullough L., Kettelkamp C., Formosa T., Zhang Z.;
RT "Ubiquitylation of FACT by the cullin-E3 ligase Rtt101 connects FACT to DNA
RT replication.";
RL Genes Dev. 24:1485-1490(2010).
RN [14]
RP FUNCTION.
RX PubMed=21593207; DOI=10.1091/mbc.e10-10-0848;
RA Vaisica J.A., Baryshnikova A., Costanzo M., Boone C., Brown G.W.;
RT "Mms1 and Mms22 stabilize the replisome during replication stress.";
RL Mol. Biol. Cell 22:2396-2408(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP FUNCTION IN UBIQUITINATION OF H3.
RX PubMed=24209620; DOI=10.1016/j.cell.2013.10.014;
RA Han J., Zhang H., Zhang H., Wang Z., Zhou H., Zhang Z.;
RT "A Cul4 E3 ubiquitin ligase regulates histone hand-off during nucleosome
RT assembly.";
RL Cell 155:817-829(2013).
CC -!- FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-
CC protein ligase complexes (CRLs), which mediate the ubiquitination of
CC target proteins. As a scaffold protein may contribute to catalysis
CC through positioning of the substrate and the ubiquitin-conjugating
CC enzyme. The CRL associates with CDC34 as the E2 ubiquitin-conjugating
CC enzyme. The functional specificity of the CRL depends on the type of
CC the associated substrate receptor protein. RTT101(MMS1-MMS22) promotes
CC fork progression through damaged DNA or natural pause sites by
CC stabilizing replication proteins like the replication fork-pausing
CC complex (FPC) and leading-strand polymerase at stalled replication
CC forks. RTT101(MMS1-MMS22) ubiquitinates the acetylated histones
CC H3K56ac-H4 at lysine residues H3K121, H3K122 and H3K125. Ubiquitination
CC is required for efficient histone deposition during replication-coupled
CC nucleosome assembly, probably by facilitating the transfer of H3-H4
CC from ASF1 to other chaperones involved in histone deposition.
CC RTT101(MMS1-CRT10) may regulate nucleotide synthesis through
CC transcriptional regulation of ribonucleotide reductase. RTT101(MMS1) is
CC also involved in the non-functional rRNA decay (NRD) of 25S rRNA
CC through the selective, ubiquitination-dependent degradation of
CC nonfunctional ribosomal particles. Ubiquitinates the FACT (facilitates
CC chromatin transcription) complex subunit SPT16 in an MMS1-independent
CC manner. Involved in regulation of Ty1 transposition and protects the
CC genome from Ty1 integration upstream of tRNA genes.
CC {ECO:0000269|PubMed:11779788, ECO:0000269|PubMed:12676951,
CC ECO:0000269|PubMed:16631586, ECO:0000269|PubMed:17978089,
CC ECO:0000269|PubMed:18321796, ECO:0000269|PubMed:18704118,
CC ECO:0000269|PubMed:19390089, ECO:0000269|PubMed:20634314,
CC ECO:0000269|PubMed:21593207, ECO:0000269|PubMed:24209620}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of multiple cullin-RING ligases (CRLs) composed of 4
CC subunits: the RING protein HRT1, the cullin RTT101, a linker protein
CC MMS1, and one of many alternative substrate receptors belonging to a
CC protein family described as DCAF (DDB1- and CUL4-associated factor).
CC Component of a RTT101(MMS1-MMS22) complex with the substrate receptor
CC MMS22. This complex further interacts with RTT107 and CTF4 to form
CC RTT101-MMS1-MMS22-RTT107 and RTT101-MMS1-MMS22-CTF4 complexes
CC respectively. Component of a RTT101(MSS1-CRT10) complex with the
CC substrate receptor CRT10. Component of a RTT101(MSS1-ESC2) complex with
CC the potential substrate receptor ESC2. Component of a RTT101(MSS1-ORC5)
CC complex with the potential substrate receptor ORC5. Interacts (via C-
CC ter) with HRT1; required for ubiquitin-ligase activity. Interacts (via
CC N-ter) with MMS1. {ECO:0000269|PubMed:12676951,
CC ECO:0000269|PubMed:17978089, ECO:0000269|PubMed:18704118,
CC ECO:0000269|PubMed:20139071}.
CC -!- INTERACTION:
CC P47050; Q06340: ESC2; NbExp=4; IntAct=EBI-25861, EBI-33799;
CC P47050; Q08273: HRT1; NbExp=3; IntAct=EBI-25861, EBI-31686;
CC P47050; Q06211: MMS1; NbExp=12; IntAct=EBI-25861, EBI-38894;
CC P47050; Q06164: MMS22; NbExp=11; IntAct=EBI-25861, EBI-31156;
CC P47050; P50874: ORC5; NbExp=3; IntAct=EBI-25861, EBI-12584;
CC P47050; P38850: RTT107; NbExp=5; IntAct=EBI-25861, EBI-24788;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus
CC {ECO:0000269|PubMed:14562095}. Note=Recruited to chromatin in response
CC to replication fork stalling.
CC -!- PTM: Neddylated. HRT1-binding is necessary for RUB1/NEDD8 modification
CC of RTT101. The modification enhances ubiquitin-ligase activity.
CC {ECO:0000269|PubMed:14519104}.
CC -!- DISRUPTION PHENOTYPE: Delays anaphase progression.
CC {ECO:0000269|PubMed:12676951}.
CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00330}.
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DR EMBL; AY387707; AAQ91376.1; -; Genomic_DNA.
DR EMBL; Z49322; CAA89338.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08753.1; -; Genomic_DNA.
DR PIR; S56819; S56819.
DR RefSeq; NP_012488.3; NM_001181480.3.
DR AlphaFoldDB; P47050; -.
DR BioGRID; 33708; 276.
DR ComplexPortal; CPX-1157; CUL8-MMS1-MMS22-ESC4 E3 ubiquitin ligase complex.
DR ComplexPortal; CPX-1165; CUL8-MMS1-MMS22-CTF4 E3 ubiquitin ligase complex.
DR ComplexPortal; CPX-1166; CUL8-MMS1-ESC2 E3 ubiquitin ligase complex.
DR ComplexPortal; CPX-1167; CUL8-MMS1-ORC5 E3 ubiquitin ligase complex.
DR DIP; DIP-2887N; -.
DR IntAct; P47050; 18.
DR MINT; P47050; -.
DR STRING; 4932.YJL047C; -.
DR iPTMnet; P47050; -.
DR MaxQB; P47050; -.
DR PaxDb; P47050; -.
DR PRIDE; P47050; -.
DR EnsemblFungi; YJL047C_mRNA; YJL047C; YJL047C.
DR GeneID; 853400; -.
DR KEGG; sce:YJL047C; -.
DR SGD; S000003583; RTT101.
DR VEuPathDB; FungiDB:YJL047C; -.
DR eggNOG; KOG2166; Eukaryota.
DR HOGENOM; CLU_337750_0_0_1; -.
DR InParanoid; P47050; -.
DR OMA; LFQTCVL; -.
DR BioCyc; YEAST:G3O-31511-MON; -.
DR Reactome; R-SCE-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-SCE-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-SCE-6782135; Dual incision in TC-NER.
DR Reactome; R-SCE-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR UniPathway; UPA00143; -.
DR PRO; PR:P47050; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P47050; protein.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0035361; C:Cul8-RING ubiquitin ligase complex; IDA:SGD.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:SGD.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0010526; P:negative regulation of transposition, RNA-mediated; IMP:SGD.
DR GO; GO:0070651; P:nonfunctional rRNA decay; IMP:SGD.
DR GO; GO:0006334; P:nucleosome assembly; IC:ComplexPortal.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006275; P:regulation of DNA replication; IC:ComplexPortal.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IMP:SGD.
DR GO; GO:0031297; P:replication fork processing; IMP:SGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IC:SGD.
DR InterPro; IPR045093; Cullin.
DR InterPro; IPR016158; Cullin_homology.
DR InterPro; IPR036317; Cullin_homology_sf.
DR InterPro; IPR019559; Cullin_neddylation_domain.
DR PANTHER; PTHR11932; PTHR11932; 1.
DR SMART; SM00884; Cullin_Nedd8; 1.
DR SUPFAM; SSF75632; SSF75632; 1.
DR PROSITE; PS50069; CULLIN_2; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; DNA damage; DNA repair;
KW Isopeptide bond; Nucleus; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..842
FT /note="Cullin-8"
FT /id="PRO_0000119807"
FT REGION 1..50
FT /note="Required for interaction with MMS1"
FT REGION 755..775
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 791
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in NEDD8)"
FT /evidence="ECO:0000269|PubMed:14519104"
FT MUTAGEN 680..686
FT /note="Missing: Disrupts interaction with HRT1 and prevents
FT RUB1/NEDD8 modification."
FT /evidence="ECO:0000269|PubMed:12676951"
FT MUTAGEN 791
FT /note="K->A,R: Prevents RUB1/NEDD8 modification."
FT /evidence="ECO:0000269|PubMed:12676951,
FT ECO:0000269|PubMed:14519104"
SQ SEQUENCE 842 AA; 99326 MW; A86A48F6DC6AF163 CRC64;
MINESVSKRE GFHESISRET SASNALGLYN KFNDERNPRY RTMIAELHEF FHLTLAETIT
ETDVKELECN KEKAAKFRKL MPKMLNNCRE LTQRKSYIPY NSEFNGNDEK QKKFQLLHQH
QIVLSFQEFC DELAKLIIDA HVLSFLTRCD YSYEIIPKNW TSFYKLFQYV MGAVGPIISY
VPVNYPMIRK ELGFETLTIF QYYDSKLFEC MKSHFGREFS TLVSATIHHY IHMFPITNTM
LEKEVPMLRI MSNCNFSIEG LSPKDFYMKT LRQYYCEESN LRPRLETFKN FKVLLTRNAL
LASLFSPEWV SDANDLFISH LLLNKKSISE YIEIGKDTYD EEKERYFKTE THFSLLMFRN
AFEAKNMLSK FKEFCDDAVS EKLKAAYGSN HDTERLFDEV VQLANVDHLK IYSDSIEYHL
CNLLGSTSKA IEQYVKYFES HLFIIVRKIK TTKKDLPRDM KIKYLNENLP ILRLKFVNLP
TFPNFFERSI FRKTILQSDQ NSSFIKDILP VYKDSLMELF KQRIITNVSQ EDEMRYRDQY
QPYLSQFFQP VEVMADLRIK YASFLSFYEN IEAAVKFGKT YNENNSKSFF PLIFDRERIP
KVFQQSNEVK KNFVLPQEMD DTWNQFLRNY HEQNKVEDSD ASKKELYPMW NLHHCEVESP
YIIQDGTNLI FELTLFQTCV LTLFNESDHL TLQVISEQTK LAYKDLALVL KSFCNYKILT
RDIDNTYSIN ESFKPDMKKV KNGKLRVVLP RTASLQSSNT GGERTSSAHH EGSNSQWTQE
LLKACITRSV KSERNGLDYD HLFETVKQQI KGFSVGEFKD ALAKLLRDKF ITRDESTATY
KY
