Q12098 (SLX4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Structure-specific endonuclease subunit SLX4

Alternative name(s):
Synthetic lethal of unknown function protein 4

Gene names

Name:	SLX4
Ordered Locus Names:	YLR135W
ORF Names:	L3140

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	748 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for simple Y, 5'-flap and replication fork-like structures. It cleaves the strand bearing the 5'-non-homologous arm at the branch site junction and generates ligatable, nicked products from the 5'-flap or replication fork substrates. Plays a critical role in maintaining the integrity of the ribosomal DNA (rDNA) loci, where it has a role in re-starting stalled replication forks. Has Holliday junction resolvase activity in vitro. Interacts with the structure-specific RAD1-RAD10 endonuclease and promotes RAD1-RAD10-dependent 3'-non-homologous tail removal (NHTR) during repair of double-strand breaks by single-strand annealing. SLX4 also promotes recovery from DNA-alkylation-induced replisome stalling during DNA replication by facilitating the error-free mode of lesion bypass. This does not require SLX1 or RAD1-RAD10, but probably RTT107. Ref.4 Ref.5 Ref.6 Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16
Subunit structure	Forms a heterodimer with SLX1. Interacts with RAD1; catalytic subunit of the RAD1-RAD10 endonuclease. Interacts with RTT107. Ref.4 Ref.11 Ref.12 Ref.13 Ref.16
Subcellular location	Nucleus. Cytoplasm Ref.6 Ref.7.
Post-translational modification	Phosphorylated by ATR (MEC1) and ATM (TEL1) upon DNA damage. This appears to be required for the function with the RAD1-RAD10 endonuclease. Ref.9 Ref.13 Ref.14 Ref.17
Miscellaneous	Present with 274 molecules/cell in log phase SD medium. Ref.8
Sequence similarities	Belongs to the SLX4 family.

Ontologies

Keywords
Biological process	DNA damage DNA recombination DNA repair
Cellular component	Cytoplasm Nucleus
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA-dependent DNA replication Inferred from genetic interaction Ref.6. Source: SGD double-strand break repair via single-strand annealing, removal of nonhomologous ends Inferred from mutant phenotype Ref.16. Source: SGD
Cellular component	Slx1-Slx4 complex Inferred from physical interaction Ref.6. Source: SGD cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	5'-flap endonuclease activity Inferred from direct assay Ref.6. Source: SGD protein binding Inferred from physical interaction Ref.4. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SLX1	P38324	4	EBI-37788,EBI-21016

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 748	748	Structure-specific endonuclease subunit SLX4		PRO_0000270574
Regions
	Compositional bias	568 – 573	6	Poly-Glu
Amino acid modifications
	Modified residue	72	1	Phosphothreonine; by ATR and ATM Ref.13
	Modified residue	113	1	Phosphothreonine; by ATR and ATM Potential
	Modified residue	289	1	Phosphoserine; by ATR and ATM Ref.13
	Modified residue	319	1	Phosphothreonine; by ATR and ATM Potential
	Modified residue	329	1	Phosphoserine; by ATR and ATM Ref.13
	Modified residue	355	1	Phosphoserine; by ATR and ATM Potential
	Modified residue	388	1	Phosphoserine Ref.17
	Modified residue	486	1	Phosphoserine Ref.14
	Modified residue	499	1	Phosphoserine Ref.17

Sequences

	Sequence		Length	Mass (Da)
	Q12098 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 52C0FD889C8C5835	FASTA	748	84,362
	10 20 30 40 50 60 MELQRAQRNL KFLQNEDYVN VTDQTNLNGE SQNAYSLGME TQVPEMQFSL SSDDDSIGTQ 70 80 90 100 110 120 VKSVTAQKSP MTQETTKNDT ERNKDVDKSC NPVSTSHPDL GGSNIEENIF INTQIQSRLD 130 140 150 160 170 180 DAEEETNLKL KLEKFKYSFK SSNADDTHSN ANVTAKRRPA IRKANSKLKT KPKTKRDPKI 190 200 210 220 230 240 IKNITDFNIN NYERSRTASL LKQLSGKHKK VLDIIKTQNE GNSDKPPRAR NNKGEKATFD 250 260 270 280 290 300 TYSEQEWKDI MKLLLQKFPQ SEETDLNEVQ KFLYGSEKSS NSLDNQESSQ QRLWTASQLP 310 320 330 340 350 360 PELPDEAIQP EQEERIRDTQ SAVNFLSLSQ VMDDKSEIMK DEESIIISRG DSTSSQEYGN 370 380 390 400 410 420 GLEPQQPVGN VVGEDIELAV GTRINAFSLT DYKACKPMSV EVSRRCENST DNDYDNISIV 430 440 450 460 470 480 SDTTDETSTL FPLDQYRYVF IENDERPPLA TDTIGSTQFF TPNTSPLDGI IDLTQESFKA 490 500 510 520 530 540 VRSLISPLKV ENNKTGVTSQ ASNQVQVPAT RTPTIIPQKN LTTTLKTEEE KNNIGSSIRV 550 560 570 580 590 600 KLLQESVVKL NPKLVKHNFY RVEANDSEEE ETEFDDQFCI ADIQLVDSSK ISTKDSTQNP 610 620 630 640 650 660 TTSNDIIDTS AASSIASPEK FCEIMMSQSM KELRQSLKTV GLKPMRTKVE IIQSLQTASQ 670 680 690 700 710 720 ILSTANPDNK GEHGGVANFS KIEIFDHLTE LIEAFPDFLE RIYTFEPIPL NELIEKLFSA 730 740 EPFVSQIDEM TIREWADVQG ICLRNDKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XII." Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., Heuss-Neitzel D., Hilbert H. , Hilger F., Kleine K., Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., Hani J., Hoheisel J.D. Nature 387:87-90(1997) [PubMed: 9169871] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed: 17322287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae." Mullen J.R., Kaliraman V., Ibrahim S.S., Brill S.J. Genetics 157:103-118(2001) [PubMed: 11139495] [Abstract] Cited for: FUNCTION, INTERACTION WITH SLX1.
[5]	"Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae." Kaliraman V., Brill S.J. Curr. Genet. 41:389-400(2002) [PubMed: 12228808] [Abstract] Cited for: FUNCTION.
[6]	"Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3." Fricke W.M., Brill S.J. Genes Dev. 17:1768-1778(2003) [PubMed: 12832395] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[8]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[9]	"Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage." Flott S., Rouse J. Biochem. J. 391:325-333(2005) [PubMed: 15975089] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION BY MEC1 AND TEL1.
[10]	"Multiple endonucleases function to repair covalent topoisomerase I complexes in Saccharomyces cerevisiae." Deng C., Brown J.A., You D., Brown J.M. Genetics 170:591-600(2005) [PubMed: 15834151] [Abstract] Cited for: FUNCTION.
[11]	"Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs." Zappulla D.C., Maharaj A.S.R., Connelly J.J., Jockusch R.A., Sternglanz R. BMC Mol. Biol. 7:40-40(2006) [PubMed: 17094803] [Abstract] Cited for: INTERACTION WITH RTT107.
[12]	"Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4." Roberts T.M., Kobor M.S., Bastin-Shanower S.A., Ii M., Horte S.A., Gin J.W., Emili A., Rine J., Brill S.J., Brown G.W. Mol. Biol. Cell 17:539-548(2006) [PubMed: 16267268] [Abstract] Cited for: FUNCTION, INTERACTION WITH RTT107.
[13]	"Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast." Flott S., Alabert C., Toh G.W., Toth R., Sugawara N., Campbell D.G., Haber J.E., Pasero P., Rouse J. Mol. Cell. Biol. 27:6433-6445(2007) [PubMed: 17636031] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAD1 AND SLX1, PHOSPHORYLATION AT THR-72; SER-289 AND SER-329 BY MEC1 AND TEL1.
[14]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed: 17563356] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, MASS SPECTROMETRY.
[15]	"Mutants defective in Rad1-Rad10-Slx4 exhibit a unique pattern of viability during mating-type switching in Saccharomyces cerevisiae." Lyndaker A.M., Goldfarb T., Alani E. Genetics 179:1807-1821(2008) [PubMed: 18579504] [Abstract] Cited for: FUNCTION.
[16]	"Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates." Li F., Dong J., Pan X., Oum J.-H., Boeke J.D., Lee S.E. Mol. Cell 30:325-335(2008) [PubMed: 18471978] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAD1.
[17]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388 AND SER-499, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z73307 Genomic DNA. Translation: CAA97706.1. U53881 Genomic DNA. Translation: AAB82394.1. X91258 Genomic DNA. Translation: CAA62650.1. AY692839 Genomic DNA. Translation: AAT92858.1. BK006945 Genomic DNA. Translation: DAA09446.1.
PIR	S59327.
RefSeq	NP_013236.1. NM_001182022.1.
3D structure databases
ProteinModelPortal	Q12098.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-1771N.
IntAct	Q12098. 3 interactions.
MINT	MINT-402900.
STRING	Q12098.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YLR135W; YLR135W; YLR135W.
GeneID	850826.
KEGG	sce:YLR135W.
NMPDR	fig|4932.3.peg.4229.
Organism-specific databases
CYGD	YLR135w.
SGD	S000004125. SLX4.
Phylogenomic databases
eggNOG	fuNOG12019.
OMA	NTQIQSR.
OrthoDB	EOG4K0TXX.
Gene expression databases
ArrayExpress	Q12098.
Genevestigator	Q12098.
Family and domain databases
InterPro	IPR018574. Structure-sp_endonuc_su_SLX4. [Graphical view]
KO	K15079.
Pfam	PF09494. Slx4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	967085.

Entry information

Entry name

SLX4_YEAST

Accession

Primary (citable) accession number: Q12098
Secondary accession number(s): D6VYD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	November 1, 1996
Last modified:	December 14, 2011
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program