SLX1_HUMAN
ID SLX1_HUMAN Reviewed; 275 AA.
AC Q9BQ83; B7ZME1; Q6NTG6;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Structure-specific endonuclease subunit SLX1 {ECO:0000255|HAMAP-Rule:MF_03100};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03100};
DE AltName: Full=GIY-YIG domain-containing protein 1 {ECO:0000255|HAMAP-Rule:MF_03100};
GN Name=SLX1A {ECO:0000255|HAMAP-Rule:MF_03100};
GN Synonyms=GIYD1 {ECO:0000255|HAMAP-Rule:MF_03100}, SLX1;
GN and
GN Name=SLX1B {ECO:0000255|HAMAP-Rule:MF_03100}; Synonyms=GIYD2, SLX1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=B-cell, Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION.
RX PubMed=15358107; DOI=10.1016/j.bbrc.2004.07.038;
RA Hildebrandt M.A.T., Salavaggione O.E., Martin Y.N., Flynn H.C., Jalal S.,
RA Wieben E.D., Weinshilboum R.M.;
RT "Human SULT1A3 pharmacogenetics: gene duplication and functional genomic
RT studies.";
RL Biochem. Biophys. Res. Commun. 321:870-878(2004).
RN [4]
RP FUNCTION, INTERACTION WITH SLX4, AND MUTAGENESIS OF GLU-82.
RX PubMed=19596235; DOI=10.1016/j.cell.2009.06.030;
RA Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P.,
RA Elledge S.J., Harper J.W.;
RT "Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is
RT required for DNA repair.";
RL Cell 138:63-77(2009).
RN [5]
RP FUNCTION, INTERACTION WITH SLX4, MUTAGENESIS OF ARG-41 AND GLU-82, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19596236; DOI=10.1016/j.cell.2009.06.029;
RA Fekairi S., Scaglione S., Chahwan C., Taylor E.R., Tissier A., Coulon S.,
RA Dong M.-Q., Ruse C., Yates J.R. III, Russell P., Fuchs R.P., McGowan C.H.,
RA Gaillard P.-H.L.;
RT "Human SLX4 is a Holliday junction resolvase subunit that binds multiple
RT DNA repair/recombination endonucleases.";
RL Cell 138:78-89(2009).
RN [6]
RP FUNCTION, AND INTERACTION WITH SLX4.
RX PubMed=19595721; DOI=10.1016/j.molcel.2009.06.020;
RA Munoz I.M., Hain K., Declais A.-C., Gardiner M., Toh G.W.,
RA Sanchez-Pulido L., Heuckmann J.M., Toth R., Macartney T., Eppink B.,
RA Kanaar R., Ponting C.P., Lilley D.M.J., Rouse J.;
RT "Coordination of structure-specific nucleases by human SLX4/BTBD12 is
RT required for DNA repair.";
RL Mol. Cell 35:116-127(2009).
CC -!- FUNCTION: Catalytic subunit of the SLX1-SLX4 structure-specific
CC endonuclease that resolves DNA secondary structures generated during
CC DNA repair and recombination. Has endonuclease activity towards
CC branched DNA substrates, introducing single-strand cuts in duplex DNA
CC close to junctions with ss-DNA. Has a preference for 5'-flap
CC structures, and promotes symmetrical cleavage of static and migrating
CC Holliday junctions (HJs). Resolves HJs by generating two pairs of
CC ligatable, nicked duplex products. {ECO:0000255|HAMAP-Rule:MF_03100,
CC ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19596235,
CC ECO:0000269|PubMed:19596236}.
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC -!- SUBUNIT: Forms a heterodimer with SLX4.
CC -!- INTERACTION:
CC Q9BQ83; Q8IY92: SLX4; NbExp=10; IntAct=EBI-2370858, EBI-2370740;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03100,
CC ECO:0000269|PubMed:19596236}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BQ83-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BQ83-2; Sequence=VSP_033331;
CC -!- SIMILARITY: Belongs to the SLX1 family. {ECO:0000255|HAMAP-
CC Rule:MF_03100}.
CC -!- CAUTION: Found in a segmental duplication on p arm of chromosome 16
CC giving rise to two identical copies of this gene sharing exons with
CC SULT1A3 and SULT1A4. {ECO:0000305}.
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DR EMBL; AC106782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000754; AAH00754.1; -; mRNA.
DR EMBL; BC000803; AAH00803.1; -; mRNA.
DR EMBL; BC015990; AAH15990.1; -; mRNA.
DR EMBL; BC019306; AAH19306.1; -; mRNA.
DR EMBL; BC069007; AAH69007.1; -; mRNA.
DR EMBL; BC130545; AAI30546.1; -; mRNA.
DR EMBL; BC130547; AAI30548.1; -; mRNA.
DR EMBL; BC144462; AAI44463.1; -; mRNA.
DR CCDS; CCDS10648.1; -. [Q9BQ83-1]
DR CCDS; CCDS10649.1; -. [Q9BQ83-2]
DR CCDS; CCDS32431.1; -. [Q9BQ83-1]
DR CCDS; CCDS32432.1; -. [Q9BQ83-2]
DR RefSeq; NP_001014999.1; NM_001014999.2. [Q9BQ83-1]
DR RefSeq; NP_001015000.1; NM_001015000.2. [Q9BQ83-2]
DR RefSeq; NP_076949.1; NM_024044.3. [Q9BQ83-1]
DR RefSeq; NP_835145.1; NM_178044.2. [Q9BQ83-2]
DR AlphaFoldDB; Q9BQ83; -.
DR SMR; Q9BQ83; -.
DR BioGRID; 122479; 46.
DR BioGRID; 139225; 32.
DR IntAct; Q9BQ83; 70.
DR STRING; 9606.ENSP00000251303; -.
DR iPTMnet; Q9BQ83; -.
DR PhosphoSitePlus; Q9BQ83; -.
DR BioMuta; SLX1A; -.
DR DMDM; 74732820; -.
DR MassIVE; Q9BQ83; -.
DR PaxDb; Q9BQ83; -.
DR PeptideAtlas; Q9BQ83; -.
DR PRIDE; Q9BQ83; -.
DR Antibodypedia; 26716; 59 antibodies from 16 providers.
DR Antibodypedia; 63854; 7 antibodies from 5 providers.
DR DNASU; 79008; -.
DR Ensembl; ENST00000251303.11; ENSP00000251303.7; ENSG00000132207.18. [Q9BQ83-1]
DR Ensembl; ENST00000330181.9; ENSP00000328940.5; ENSG00000181625.17. [Q9BQ83-1]
DR Ensembl; ENST00000345535.8; ENSP00000333945.4; ENSG00000132207.18. [Q9BQ83-2]
DR Ensembl; ENST00000351581.4; ENSP00000335316.4; ENSG00000181625.17. [Q9BQ83-2]
DR GeneID; 548593; -.
DR GeneID; 79008; -.
DR KEGG; hsa:548593; -.
DR KEGG; hsa:79008; -.
DR MANE-Select; ENST00000251303.11; ENSP00000251303.7; NM_001014999.3; NP_001014999.1.
DR UCSC; uc002dsx.4; human. [Q9BQ83-1]
DR CTD; 548593; -.
DR CTD; 79008; -.
DR DisGeNET; 548593; -.
DR DisGeNET; 79008; -.
DR GeneCards; SLX1A; -.
DR GeneCards; SLX1B; -.
DR HGNC; HGNC:20922; SLX1A.
DR HGNC; HGNC:28748; SLX1B.
DR HPA; ENSG00000132207; Low tissue specificity.
DR HPA; ENSG00000181625; Low tissue specificity.
DR MIM; 615822; gene.
DR MIM; 615823; gene.
DR neXtProt; NX_Q9BQ83; -.
DR OpenTargets; ENSG00000132207; -.
DR PharmGKB; PA142671738; -.
DR VEuPathDB; HostDB:ENSG00000132207; -.
DR VEuPathDB; HostDB:ENSG00000181625; -.
DR eggNOG; KOG3005; Eukaryota.
DR GeneTree; ENSGT00390000013368; -.
DR HOGENOM; CLU_030739_0_0_1; -.
DR InParanoid; Q9BQ83; -.
DR OMA; LQFEHAW; -.
DR OrthoDB; 844266at2759; -.
DR PhylomeDB; Q9BQ83; -.
DR TreeFam; TF352344; -.
DR PathwayCommons; Q9BQ83; -.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; Q9BQ83; -.
DR BioGRID-ORCS; 548593; 29 hits in 594 CRISPR screens.
DR BioGRID-ORCS; 79008; 14 hits in 210 CRISPR screens.
DR ChiTaRS; SLX1A; human.
DR Pharos; Q9BQ83; Tbio.
DR PRO; PR:Q9BQ83; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9BQ83; protein.
DR Bgee; ENSG00000132207; Expressed in granulocyte and 95 other tissues.
DR ExpressionAtlas; Q9BQ83; baseline and differential.
DR Genevisible; Q9BQ83; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0033557; C:Slx1-Slx4 complex; IDA:UniProtKB.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB.
DR GO; GO:0008821; F:crossover junction endodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0010792; P:DNA double-strand break processing involved in repair via single-strand annealing; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:1904357; P:negative regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL.
DR GO; GO:1904431; P:positive regulation of t-circle formation; ISS:BHF-UCL.
DR GO; GO:0090656; P:t-circle formation; IMP:BHF-UCL.
DR GO; GO:0010833; P:telomere maintenance via telomere lengthening; IMP:BHF-UCL.
DR GO; GO:0061820; P:telomeric D-loop disassembly; IMP:BHF-UCL.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.1440.10; -; 1.
DR HAMAP; MF_03100; Endonuc_su_Slx1; 1.
DR InterPro; IPR000305; GIY-YIG_endonuc.
DR InterPro; IPR035901; GIY-YIG_endonuc_sf.
DR InterPro; IPR027520; Slx1.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01541; GIY-YIG; 1.
DR SUPFAM; SSF82771; SSF82771; 1.
DR PROSITE; PS50164; GIY_YIG; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA damage; DNA recombination; DNA repair;
KW Endonuclease; Hydrolase; Metal-binding; Nuclease; Nucleus;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..275
FT /note="Structure-specific endonuclease subunit SLX1"
FT /id="PRO_0000332120"
FT DOMAIN 12..95
FT /note="GIY-YIG"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03100"
FT ZN_FING 186..238
FT /note="SLX1-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03100"
FT REGION 148..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..164
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 81..194
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033331"
FT MUTAGEN 41
FT /note="R->A: Abolishes endonucleolytic activity."
FT /evidence="ECO:0000269|PubMed:19596236"
FT MUTAGEN 82
FT /note="E->A: Abolishes endonucleolytic activity."
FT /evidence="ECO:0000269|PubMed:19596235,
FT ECO:0000269|PubMed:19596236"
SQ SEQUENCE 275 AA; 30771 MW; 57DF055F2E59CF70 CRC64;
MGPAGVAARP GRFFGVYLLY CLNPRYRGRV YVGFTVNTAR RVQQHNGGRK KGGAWRTSGR
GPWEMVLVVH GFPSSVAALR FEWAWQHPHA SRRLAHVGPR LRGETAFAFH LRVLAHMLRA
PPWARLPLTL RWVRPDLRQD LCLPPPPHVP LAFGPPPPQA PAPRRRAGPF DDAEPEPDQG
DPGACCSLCA QTIQDEEGPL CCPHPGCLLR AHVICLAEEF LQEEPGQLLP LEGQCPCCEK
SLLWGDLIWL CQMDTEKEVE DSELEEAHWT DLLET
