SLX4_YEAST
ID SLX4_YEAST Reviewed; 748 AA.
AC Q12098; D6VYD0;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Structure-specific endonuclease subunit SLX4 {ECO:0000255|HAMAP-Rule:MF_03110};
DE AltName: Full=Synthetic lethal of unknown function protein 4;
GN Name=SLX4 {ECO:0000255|HAMAP-Rule:MF_03110}; OrderedLocusNames=YLR135W;
GN ORFNames=L3140;
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=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP FUNCTION, AND INTERACTION WITH SLX1.
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 [5]
RP FUNCTION.
RX PubMed=12228808; DOI=10.1007/s00294-002-0319-6;
RA Kaliraman V., Brill S.J.;
RT "Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces
RT cerevisiae.";
RL Curr. Genet. 41:389-400(2002).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12832395; DOI=10.1101/gad.1105203;
RA Fricke W.M., Brill S.J.;
RT "Slx1-Slx4 is a second structure-specific endonuclease functionally
RT redundant with Sgs1-Top3.";
RL Genes Dev. 17:1768-1778(2003).
RN [7]
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 [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP FUNCTION, AND PHOSPHORYLATION BY MEC1 AND TEL1.
RX PubMed=15975089; DOI=10.1042/bj20050768;
RA Flott S., Rouse J.;
RT "Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent
RT manner and is required for repair of DNA alkylation damage.";
RL Biochem. J. 391:325-333(2005).
RN [10]
RP FUNCTION.
RX PubMed=15834151; DOI=10.1534/genetics.104.028795;
RA Deng C., Brown J.A., You D., Brown J.M.;
RT "Multiple endonucleases function to repair covalent topoisomerase I
RT complexes in Saccharomyces cerevisiae.";
RL Genetics 170:591-600(2005).
RN [11]
RP INTERACTION WITH RTT107.
RX PubMed=17094803; DOI=10.1186/1471-2199-7-40;
RA Zappulla D.C., Maharaj A.S.R., Connelly J.J., Jockusch R.A., Sternglanz R.;
RT "Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different
RT BRCT motifs.";
RL BMC Mol. Biol. 7:40-40(2006).
RN [12]
RP FUNCTION, AND INTERACTION WITH RTT107.
RX PubMed=16267268; DOI=10.1091/mbc.e05-08-0785;
RA Roberts T.M., Kobor M.S., Bastin-Shanower S.A., Ii M., Horte S.A.,
RA Gin J.W., Emili A., Rine J., Brill S.J., Brown G.W.;
RT "Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT
RT domain protein Rtt107/Esc4.";
RL Mol. Biol. Cell 17:539-548(2006).
RN [13]
RP FUNCTION, INTERACTION WITH RAD1 AND SLX1, AND PHOSPHORYLATION AT THR-72;
RP SER-289 AND SER-329 BY MEC1 AND TEL1.
RX PubMed=17636031; DOI=10.1128/mcb.00135-07;
RA Flott S., Alabert C., Toh G.W., Toth R., Sugawara N., Campbell D.G.,
RA Haber J.E., Pasero P., Rouse J.;
RT "Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand
RT annealing mode of DNA repair in budding yeast.";
RL Mol. Cell. Biol. 27:6433-6445(2007).
RN [14]
RP FUNCTION.
RX PubMed=18579504; DOI=10.1534/genetics.108.090654;
RA Lyndaker A.M., Goldfarb T., Alani E.;
RT "Mutants defective in Rad1-Rad10-Slx4 exhibit a unique pattern of viability
RT during mating-type switching in Saccharomyces cerevisiae.";
RL Genetics 179:1807-1821(2008).
RN [15]
RP FUNCTION, AND INTERACTION WITH RAD1.
RX PubMed=18471978; DOI=10.1016/j.molcel.2008.02.028;
RA Li F., Dong J., Pan X., Oum J.-H., Boeke J.D., Lee S.E.;
RT "Microarray-based genetic screen defines SAW1, a gene required for
RT Rad1/Rad10-dependent processing of recombination intermediates.";
RL Mol. Cell 30:325-335(2008).
RN [16]
RP IDENTIFICATION BY 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).
CC -!- FUNCTION: Regulatory subunit that interacts with and increases the
CC activity of different structure-specific endonucleases. Has several
CC distinct roles in protecting genome stability by resolving diverse
CC forms of deleterious DNA structures. Component of the SLX1-SLX4
CC structure-specific endonuclease that resolves DNA secondary structures
CC generated during DNA repair and recombination. Has endonuclease
CC activity towards branched DNA substrates, introducing single-strand
CC cuts in duplex DNA close to junctions with ss-DNA. Has a preference for
CC simple Y, 5'-flap and replication fork-like structures. It cleaves the
CC strand bearing the 5'-non-homologous arm at the branch site junction
CC and generates ligatable, nicked products from the 5'-flap or
CC replication fork substrates. Plays a critical role in maintaining the
CC integrity of the ribosomal DNA (rDNA) loci, where it has a role in re-
CC starting stalled replication forks. Has Holliday junction resolvase
CC activity in vitro. Interacts with the structure-specific RAD1-RAD10
CC endonuclease and promotes RAD1-RAD10-dependent 3'-non-homologous tail
CC removal (NHTR) during repair of double-strand breaks by single-strand
CC annealing. SLX4 also promotes recovery from DNA-alkylation-induced
CC replisome stalling during DNA replication by facilitating the error-
CC free mode of lesion bypass. This does not require SLX1 or RAD1-RAD10,
CC but probably RTT107. {ECO:0000255|HAMAP-Rule:MF_03110,
CC ECO:0000269|PubMed:11139495, ECO:0000269|PubMed:12228808,
CC ECO:0000269|PubMed:12832395, ECO:0000269|PubMed:15834151,
CC ECO:0000269|PubMed:15975089, ECO:0000269|PubMed:16267268,
CC ECO:0000269|PubMed:17636031, ECO:0000269|PubMed:18471978,
CC ECO:0000269|PubMed:18579504}.
CC -!- SUBUNIT: Forms a heterodimer with SLX1. Interacts with RAD1; catalytic
CC subunit of the RAD1-RAD10 endonuclease. Interacts with RTT107.
CC {ECO:0000255|HAMAP-Rule:MF_03110, ECO:0000269|PubMed:11139495,
CC ECO:0000269|PubMed:16267268, ECO:0000269|PubMed:17094803,
CC ECO:0000269|PubMed:17636031, ECO:0000269|PubMed:18471978}.
CC -!- INTERACTION:
CC Q12098; P47027: DPB11; NbExp=2; IntAct=EBI-37788, EBI-25984;
CC Q12098; P06777: RAD1; NbExp=3; IntAct=EBI-37788, EBI-14752;
CC Q12098; P38850: RTT107; NbExp=6; IntAct=EBI-37788, EBI-24788;
CC Q12098; P38324: SLX1; NbExp=6; IntAct=EBI-37788, EBI-21016;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- PTM: Phosphorylated by ATR (MEC1) and ATM (TEL1) upon DNA damage. This
CC appears to be required for the function with the RAD1-RAD10
CC endonuclease. {ECO:0000255|HAMAP-Rule:MF_03110,
CC ECO:0000269|PubMed:15975089, ECO:0000269|PubMed:17636031}.
CC -!- MISCELLANEOUS: Present with 274 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the SLX4 family. {ECO:0000255|HAMAP-
CC Rule:MF_03110}.
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DR EMBL; Z73307; CAA97706.1; -; Genomic_DNA.
DR EMBL; U53881; AAB82394.1; -; Genomic_DNA.
DR EMBL; X91258; CAA62650.1; -; Genomic_DNA.
DR EMBL; AY692839; AAT92858.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09446.1; -; Genomic_DNA.
DR PIR; S59327; S59327.
DR RefSeq; NP_013236.1; NM_001182022.1.
DR PDB; 6J0Y; X-ray; 1.80 A; C/D=535-587.
DR PDB; 7CQ2; X-ray; 2.50 A; C/D=610-747.
DR PDB; 7CQ3; X-ray; 1.45 A; B=675-748.
DR PDB; 7CQ4; X-ray; 3.29 A; B=610-748.
DR PDBsum; 6J0Y; -.
DR PDBsum; 7CQ2; -.
DR PDBsum; 7CQ3; -.
DR PDBsum; 7CQ4; -.
DR AlphaFoldDB; Q12098; -.
DR SMR; Q12098; -.
DR BioGRID; 31404; 290.
DR ComplexPortal; CPX-1355; RTT107-SLX4-SLX1 complex.
DR ComplexPortal; CPX-1362; SLX4-RAD1-RAD10 endonuclease complex.
DR ComplexPortal; CPX-3159; Slx1-Slx4 complex.
DR DIP; DIP-1771N; -.
DR IntAct; Q12098; 7.
DR MINT; Q12098; -.
DR STRING; 4932.YLR135W; -.
DR iPTMnet; Q12098; -.
DR MaxQB; Q12098; -.
DR PaxDb; Q12098; -.
DR PRIDE; Q12098; -.
DR EnsemblFungi; YLR135W_mRNA; YLR135W; YLR135W.
DR GeneID; 850826; -.
DR KEGG; sce:YLR135W; -.
DR SGD; S000004125; SLX4.
DR VEuPathDB; FungiDB:YLR135W; -.
DR eggNOG; ENOG502RYEW; Eukaryota.
DR HOGENOM; CLU_022388_0_0_1; -.
DR InParanoid; Q12098; -.
DR OMA; FMNTQIQ; -.
DR BioCyc; YEAST:G3O-32275-MON; -.
DR PRO; PR:Q12098; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q12098; protein.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1905348; C:endonuclease complex; IPI:ComplexPortal.
DR GO; GO:0000228; C:nuclear chromosome; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IMP:SGD.
DR GO; GO:0033557; C:Slx1-Slx4 complex; IPI:SGD.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:SGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IGI:SGD.
DR GO; GO:0006260; P:DNA replication; IMP:SGD.
DR GO; GO:0006261; P:DNA-templated DNA replication; IGI:SGD.
DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IGI:SGD.
DR GO; GO:0000736; P:double-strand break repair via single-strand annealing, removal of nonhomologous ends; IMP:SGD.
DR GO; GO:0036297; P:interstrand cross-link repair; IGI:SGD.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:SGD.
DR GO; GO:1903775; P:regulation of DNA double-strand break processing; IMP:SGD.
DR GO; GO:1905261; P:regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination; IMP:SGD.
DR GO; GO:1902681; P:regulation of replication fork arrest at rDNA repeats; IC:ComplexPortal.
DR HAMAP; MF_03110; Endonuc_su_Slx4; 1.
DR InterPro; IPR027784; Slx4_ascomycetes.
DR InterPro; IPR018574; Structure-sp_endonuc_su_Slx4.
DR Pfam; PF09494; Slx4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA damage; DNA recombination; DNA repair;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..748
FT /note="Structure-specific endonuclease subunit SLX4"
FT /id="PRO_0000270574"
FT REGION 62..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 591..610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..297
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphothreonine; by ATR and ATM"
FT /evidence="ECO:0000269|PubMed:17636031"
FT MOD_RES 113
FT /note="Phosphothreonine; by ATR and ATM"
FT /evidence="ECO:0000255"
FT MOD_RES 289
FT /note="Phosphoserine; by ATR and ATM"
FT /evidence="ECO:0000269|PubMed:17636031"
FT MOD_RES 319
FT /note="Phosphothreonine; by ATR and ATM"
FT /evidence="ECO:0000255"
FT MOD_RES 329
FT /note="Phosphoserine; by ATR and ATM"
FT /evidence="ECO:0000269|PubMed:17636031"
FT MOD_RES 355
FT /note="Phosphoserine; by ATR and ATM"
FT /evidence="ECO:0000255"
FT STRAND 537..543
FT /evidence="ECO:0007829|PDB:6J0Y"
FT HELIX 544..549
FT /evidence="ECO:0007829|PDB:6J0Y"
FT STRAND 556..561
FT /evidence="ECO:0007829|PDB:6J0Y"
FT STRAND 578..584
FT /evidence="ECO:0007829|PDB:6J0Y"
FT TURN 624..627
FT /evidence="ECO:0007829|PDB:7CQ4"
FT HELIX 630..640
FT /evidence="ECO:0007829|PDB:7CQ4"
FT HELIX 648..664
FT /evidence="ECO:0007829|PDB:7CQ4"
FT HELIX 676..678
FT /evidence="ECO:0007829|PDB:7CQ3"
FT HELIX 681..692
FT /evidence="ECO:0007829|PDB:7CQ3"
FT HELIX 696..703
FT /evidence="ECO:0007829|PDB:7CQ3"
FT HELIX 710..720
FT /evidence="ECO:0007829|PDB:7CQ3"
FT HELIX 722..726
FT /evidence="ECO:0007829|PDB:7CQ3"
FT HELIX 729..739
FT /evidence="ECO:0007829|PDB:7CQ3"
SQ SEQUENCE 748 AA; 84362 MW; 52C0FD889C8C5835 CRC64;
MELQRAQRNL KFLQNEDYVN VTDQTNLNGE SQNAYSLGME TQVPEMQFSL SSDDDSIGTQ
VKSVTAQKSP MTQETTKNDT ERNKDVDKSC NPVSTSHPDL GGSNIEENIF INTQIQSRLD
DAEEETNLKL KLEKFKYSFK SSNADDTHSN ANVTAKRRPA IRKANSKLKT KPKTKRDPKI
IKNITDFNIN NYERSRTASL LKQLSGKHKK VLDIIKTQNE GNSDKPPRAR NNKGEKATFD
TYSEQEWKDI MKLLLQKFPQ SEETDLNEVQ KFLYGSEKSS NSLDNQESSQ QRLWTASQLP
PELPDEAIQP EQEERIRDTQ SAVNFLSLSQ VMDDKSEIMK DEESIIISRG DSTSSQEYGN
GLEPQQPVGN VVGEDIELAV GTRINAFSLT DYKACKPMSV EVSRRCENST DNDYDNISIV
SDTTDETSTL FPLDQYRYVF IENDERPPLA TDTIGSTQFF TPNTSPLDGI IDLTQESFKA
VRSLISPLKV ENNKTGVTSQ ASNQVQVPAT RTPTIIPQKN LTTTLKTEEE KNNIGSSIRV
KLLQESVVKL NPKLVKHNFY RVEANDSEEE ETEFDDQFCI ADIQLVDSSK ISTKDSTQNP
TTSNDIIDTS AASSIASPEK FCEIMMSQSM KELRQSLKTV GLKPMRTKVE IIQSLQTASQ
ILSTANPDNK GEHGGVANFS KIEIFDHLTE LIEAFPDFLE RIYTFEPIPL NELIEKLFSA
EPFVSQIDEM TIREWADVQG ICLRNDKK
