SLX8_YEAST
ID SLX8_YEAST Reviewed; 274 AA.
AC P40072; D3DM22;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=E3 ubiquitin-protein ligase complex SLX5-SLX8 subunit SLX8;
DE EC=2.3.2.27 {ECO:0000269|PubMed:18032921};
DE AltName: Full=RING-type E3 ubiquitin transferase SLX8 {ECO:0000305};
DE AltName: Full=Synthetic lethal of unknown function protein 8;
GN Name=SLX8; OrderedLocusNames=YER116C;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [2]
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 [3]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, AND INTERACTION WITH SLX5.
RX PubMed=11139495; DOI=10.1093/genetics/157.1.103;
RA Mullen J.R., Kaliraman V., Ibrahim S.S., Brill S.J.;
RT "Requirement for three novel protein complexes in the absence of the Sgs1
RT DNA helicase in Saccharomyces cerevisiae.";
RL Genetics 157:103-118(2001).
RN [4]
RP FUNCTION IN STABILIZATION OF DNA DAMAGE.
RX PubMed=16325482; DOI=10.1016/j.dnarep.2005.10.010;
RA Zhang C., Roberts T.M., Yang J., Desai R., Brown G.W.;
RT "Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces
RT cerevisiae.";
RL DNA Repair 5:336-346(2006).
RN [5]
RP FUNCTION IN STABILIZATION OF DNA DAMAGE.
RX PubMed=16387868; DOI=10.1534/genetics.105.052811;
RA Wang Z., Jones G.M., Prelich G.;
RT "Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in
RT Saccharomyces cerevisiae.";
RL Genetics 172:1499-1509(2006).
RN [6]
RP UBIQUITIN-PROTEIN LIGASE ACTIVITY, FUNCTION IN STIMULATION OF UBIQUITIN
RP CONJUGASTING ENZYMES, AND INTERACTION WITH SLX5/HEX3.
RX PubMed=18032921; DOI=10.4161/cc.6.22.4882;
RA Ii T., Fung J., Mullen J.R., Brill S.J.;
RT "The yeast Slx5-Slx8 DNA integrity complex displays ubiquitin ligase
RT activity.";
RL Cell Cycle 6:2800-2809(2007).
RN [7]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, AND INTERACTION WITH
RP SLX5/HEX3.
RX PubMed=17669696; DOI=10.1016/j.dnarep.2007.06.004;
RA Ii T., Mullen J.R., Slagle C.E., Brill S.J.;
RT "Stimulation of in vitro sumoylation by Slx5-Slx8: evidence for a
RT functional interaction with the SUMO pathway.";
RL DNA Repair 6:1679-1691(2007).
RN [8]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, LIGASE ACTIVITY, AND
RP INTERACTION WITH SLX5.
RX PubMed=17728242; DOI=10.1074/jbc.m706505200;
RA Uzunova K., Goettsche K., Miteva M., Weisshaar S.R., Glanemann C.,
RA Schnellhardt M., Niessen M., Scheel H., Hofmann K., Johnson E.S.,
RA Praefcke G.J.K., Dohmen R.J.;
RT "Ubiquitin-dependent proteolytic control of SUMO conjugates.";
RL J. Biol. Chem. 282:34167-34175(2007).
RN [9]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, LIGASE ACTIVITY, AND
RP INTERACTION WITH SLX5.
RX PubMed=17848550; DOI=10.1074/jbc.m706025200;
RA Xie Y., Kerscher O., Kroetz M.B., McConchie H.F., Sung P., Hochstrasser M.;
RT "The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by
RT substrate sumoylation.";
RL J. Biol. Chem. 282:34176-34184(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; THR-66 AND SER-67, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [11]
RP FUNCTION IN NEGATIVE REGULATION OF RECOMBINATION, AND SUBCELLULAR LOCATION.
RX PubMed=17591698; DOI=10.1128/mcb.00787-07;
RA Burgess R.C., Rahman S., Lisby M., Rothstein R., Zhao X.;
RT "The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and
RT negatively regulates recombination.";
RL Mol. Cell. Biol. 27:6153-6162(2007).
RN [12]
RP DELETION ANALYSIS.
RX PubMed=18562670; DOI=10.1534/genetics.108.089250;
RA Andersen M.P., Nelson Z.W., Hetrick E.D., Gottschling D.E.;
RT "A genetic screen for increased loss of heterozygosity in Saccharomyces
RT cerevisiae.";
RL Genetics 179:1179-1195(2008).
RN [13]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS.
RX PubMed=18499666; DOI=10.1074/jbc.m802690200;
RA Mullen J.R., Brill S.J.;
RT "Activation of the Slx5-Slx8 ubiquitin ligase by poly-small ubiquitin-like
RT modifier conjugates.";
RL J. Biol. Chem. 283:19912-19921(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [15]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, INTERACTION WITH SLX5/HEX3,
RP AND SUBCELLULAR LOCATION.
RX PubMed=18948542; DOI=10.1126/science.1162790;
RA Nagai S., Dubrana K., Tsai-Pflugfelder M., Davidson M.B., Roberts T.M.,
RA Brown G.W., Varela E., Hediger F., Gasser S.M., Krogan N.J.;
RT "Functional targeting of DNA damage to a nuclear pore-associated SUMO-
RT dependent ubiquitin ligase.";
RL Science 322:597-602(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; THR-66 AND SER-67, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [17]
RP FUNCTION.
RX PubMed=23785440; DOI=10.1371/journal.pone.0065628;
RA van de Pasch L.A., Miles A.J., Nijenhuis W., Brabers N.A., van Leenen D.,
RA Lijnzaad P., Brown M.K., Ouellet J., Barral Y., Kops G.J., Holstege F.C.;
RT "Centromere binding and a conserved role in chromosome stability for SUMO-
RT dependent ubiquitin ligases.";
RL PLoS ONE 8:E65628-E65628(2013).
RN [18]
RP FUNCTION, INTERACTION WITH KAR9, AND SUBCELLULAR LOCATION.
RX PubMed=26906737; DOI=10.1016/j.devcel.2016.01.011;
RA Schweiggert J., Stevermann L., Panigada D., Kammerer D., Liakopoulos D.;
RT "Regulation of a spindle positioning factor at kinetochores by SUMO-
RT targeted ubiquitin ligases.";
RL Dev. Cell 36:415-427(2016).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26960795; DOI=10.1091/mbc.e15-12-0827;
RA Ohkuni K., Takahashi Y., Fulp A., Lawrimore J., Au W.C., Pasupala N.,
RA Levy-Myers R., Warren J., Strunnikov A., Baker R.E., Kerscher O., Bloom K.,
RA Basrai M.A.;
RT "SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of
RT centromeric histone H3 variant Cse4 and prevents its mislocalization to
RT euchromatin.";
RL Mol. Biol. Cell 0:0-0(2016).
RN [20]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30479332; DOI=10.1038/s41467-018-07364-x;
RA Talhaoui I., Bernal M., Mullen J.R., Dorison H., Palancade B., Brill S.J.,
RA Mazon G.;
RT "Slx5-Slx8 ubiquitin ligase targets active pools of the Yen1 nuclease to
RT limit crossover formation.";
RL Nat. Commun. 9:5016-5016(2018).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, DISRUPTION PHENOTYPE, AND
RP DOMAIN.
RX PubMed=31015336; DOI=10.15252/embj.2018100368;
RA Hoepfler M., Kern M.J., Straub T., Prytuliak R., Habermann B.H.,
RA Pfander B., Jentsch S.;
RT "Slx5/Slx8-dependent ubiquitin hotspots on chromatin contribute to stress
RT tolerance.";
RL EMBO J. 38:0-0(2019).
CC -!- FUNCTION: Component of the SUMO-targeted ubiquitin ligase (STUbL)
CC complex SLX5/SLX8 that mediates ubiquitination and subsequent
CC desumoylation of sumoylated proteins and proteins containing SUMO-like
CC domains for their degradation (PubMed:11139495, PubMed:16325482,
CC PubMed:18032921, PubMed:17669696, PubMed:17848550, PubMed:18499666,
CC PubMed:18948542, PubMed:31015336). The STUbL complex SLX5/SLX8
CC stimulates ubiquitin conjugating enzymes, including UBC1, UBC4, UBC5
CC and UBC13-MMS2, and mediates the proteolytic down-regulation of
CC sumoylated proteins (PubMed:18032921). The STUbL complex SLX5/SLX8 is
CC involved in ubiquitin-mediated degradation of histone variant CSE4,
CC preventing mislocalization to euchromatin (PubMed:26960795). The
CC complex plays an essential role in maintenance of chromosome stability
CC and links SUMO-dependent ubiquitination to a centromere-specific
CC function during mitosis (PubMed:23785440). The complex is involved in
CC proteolysis of spindle positioning protein KAR9 and ensures correct
CC spindle function by regulating levels of microtubule-associated
CC proteins (PubMed:26906737). During replication, the complex helps to
CC prevent DNA lesions via recombination and has a role in localizing the
CC DNA damage protein DCD2 (PubMed:16325482, PubMed:17591698). The complex
CC especially ubiquitinates the nuclease YEN1 and prevents persistent
CC accumulation of a fraction of YEN1 associated with sites of activity in
CC late G2/M and helps maintain the balance between pro- and anti-
CC crossover pathways during homologous recombination (PubMed:30479332).
CC It is also involved in ubiquitin-mediated degradation of DNA repair
CC proteins RAD52 and RAD57 (PubMed:18032921). Finally, the complex is
CC recruited to distinct genomic hotspots of non-H2B protein
CC ubiquitination (ub-hotspots) by the sumoylated transcription factor-
CC like protein EUC1 where it ubiquitinates EUC1 and presumably other
CC targets (PubMed:31015336). {ECO:0000269|PubMed:11139495,
CC ECO:0000269|PubMed:16325482, ECO:0000269|PubMed:17591698,
CC ECO:0000269|PubMed:17669696, ECO:0000269|PubMed:17848550,
CC ECO:0000269|PubMed:18032921, ECO:0000269|PubMed:18499666,
CC ECO:0000269|PubMed:18948542, ECO:0000269|PubMed:23785440,
CC ECO:0000269|PubMed:26906737, ECO:0000269|PubMed:26960795,
CC ECO:0000269|PubMed:30479332, ECO:0000269|PubMed:31015336}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:18032921};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the heterodimeric SUMO-targeted ubiquitin ligase
CC (STUbL) complex composed of SLX5 and SLX8.
CC {ECO:0000269|PubMed:11139495, ECO:0000269|PubMed:17669696,
CC ECO:0000269|PubMed:17728242, ECO:0000269|PubMed:17848550,
CC ECO:0000269|PubMed:18032921, ECO:0000269|PubMed:18948542}.
CC -!- INTERACTION:
CC P40072; P32828: SLX5; NbExp=2; IntAct=EBI-22661, EBI-8276;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17591698,
CC ECO:0000269|PubMed:18948542}. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:26906737}. Note=Localizes to few distinct genomic
CC hotspots of non-H2B protein ubiquitination (ub-hotspots).
CC {ECO:0000269|PubMed:31015336}.
CC -!- DISRUPTION PHENOTYPE: Leads to the persistence of YEN1 foci.
CC {ECO:0000269|PubMed:30479332}.
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DR EMBL; U18916; AAC03214.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07776.1; -; Genomic_DNA.
DR PIR; S50619; S50619.
DR RefSeq; NP_011041.3; NM_001179006.3.
DR AlphaFoldDB; P40072; -.
DR SMR; P40072; -.
DR BioGRID; 36861; 516.
DR ComplexPortal; CPX-3179; Slx5-Slx8 SUMO-targeted ubiquitin ligase (STUbL) complex.
DR DIP; DIP-1365N; -.
DR IntAct; P40072; 5.
DR MINT; P40072; -.
DR STRING; 4932.YER116C; -.
DR iPTMnet; P40072; -.
DR PaxDb; P40072; -.
DR PRIDE; P40072; -.
DR EnsemblFungi; YER116C_mRNA; YER116C; YER116C.
DR GeneID; 856852; -.
DR KEGG; sce:YER116C; -.
DR SGD; S000000918; SLX8.
DR VEuPathDB; FungiDB:YER116C; -.
DR eggNOG; KOG2164; Eukaryota.
DR HOGENOM; CLU_081643_0_0_1; -.
DR InParanoid; P40072; -.
DR OMA; XLENTSE; -.
DR BioCyc; YEAST:G3O-30280-MON; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:P40072; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P40072; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:InterPro.
DR GO; GO:0000776; C:kinetochore; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0033768; C:SUMO-targeted ubiquitin ligase complex; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:SGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016925; P:protein sumoylation; IMP:SGD.
DR GO; GO:0016567; P:protein ubiquitination; IDA:SGD.
DR GO; GO:0000723; P:telomere maintenance; IMP:SGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045103; RNF5/RNF185-like.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR12313; PTHR12313; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Centromere; Chromosome; DNA damage; DNA repair; Kinetochore; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..274
FT /note="E3 ubiquitin-protein ligase complex SLX5-SLX8
FT subunit SLX8"
FT /id="PRO_0000056336"
FT ZN_FING 206..250
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 72..108
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 66
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
SQ SEQUENCE 274 AA; 30764 MW; 358DB6D137155DC1 CRC64;
MARRPDNQNP EGENLRIKRV RLESVRQNDE EEENEVSRTQ NIVTDNRHDS PEAVVEIIGE
RALENTSEED GDDDLSLFRA LEEDPGSDHN TSNNDSGNHD RETMHTEEPE ASSGNNITLT
NNVEELHTMD VLSQTANTPS ASPMLDAAPP TTKPGTNSKE QTVDLTADAI DLDAEEQQVL
QISDDDFQEE TKEAPKEYGA AKDYRCPICF EPPETALMTL CGHVFCCPCL FQMVNSSRTC
RQFGHCALCR SKVYLKDVRL IILRKKQVKK KVKS
