SLX4_HUMAN
ID SLX4_HUMAN Reviewed; 1834 AA.
AC Q8IY92; Q69YT8; Q8TF15; Q96JP1;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Structure-specific endonuclease subunit SLX4;
DE AltName: Full=BTB/POZ domain-containing protein 12;
GN Name=SLX4; Synonyms=BTBD12, KIAA1784, KIAA1987;
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] OF 1-669 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 668-1834 (ISOFORMS 1/2), AND
RP VARIANTS SER-671; MET-952; LEU-1122 AND VAL-1221.
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1612-1834 (ISOFORMS 1/2).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1469, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287 AND SER-1469, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP FUNCTION, INTERACTION WITH SLX4IP; ERCC4; SLX1A; MSH2; MUS81; PLK1; TERF2
RP AND TERF2IP, AND SUBCELLULAR LOCATION.
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 [8]
RP FUNCTION, INTERACTION WITH ERCC4; SLX1A AND MUS81, AND SUBCELLULAR
RP 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 [9]
RP FUNCTION, AND INTERACTION WITH ERCC4; SLX1A AND MUS81-EME1.
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).
RN [10]
RP FUNCTION, AND INTERACTION WITH ERCC4.
RX PubMed=19595722; DOI=10.1016/j.molcel.2009.06.019;
RA Andersen S.L., Bergstralh D.T., Kohl K.P., LaRocque J.R., Moore C.B.,
RA Sekelsky J.;
RT "Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA
RT structure-specific endonucleases in DNA repair and recombination.";
RL Mol. Cell 35:128-135(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1044, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP INVOLVEMENT IN FANCP.
RX PubMed=21240277; DOI=10.1038/ng.751;
RA Stoepker C., Hain K., Schuster B., Hilhorst-Hofstee Y., Rooimans M.A.,
RA Steltenpool J., Oostra A.B., Eirich K., Korthof E.T., Nieuwint A.W.,
RA Jaspers N.G., Bettecken T., Joenje H., Schindler D., Rouse J.,
RA de Winter J.P.;
RT "SLX4, a coordinator of structure-specific endonucleases, is mutated in a
RT new Fanconi anemia subtype.";
RL Nat. Genet. 43:138-141(2011).
RN [15]
RP INVOLVEMENT IN FANCP.
RX PubMed=21240275; DOI=10.1038/ng.750;
RA Kim Y., Lach F.P., Desetty R., Hanenberg H., Auerbach A.D.,
RA Smogorzewska A.;
RT "Mutations of the SLX4 gene in Fanconi anemia.";
RL Nat. Genet. 43:142-146(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169; SER-1028; SER-1044;
RP SER-1070; SER-1185 AND SER-1469, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1180 AND LYS-1575, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1575, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [20]
RP INTERACTION WITH ERCC4.
RX PubMed=25538220; DOI=10.15252/embj.201489184;
RA Perez-Oliva A.B., Lachaud C., Szyniarowski P., Munoz I., Macartney T.,
RA Hickson I., Rouse J., Alessi D.R.;
RT "USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage
RT responses.";
RL EMBO J. 34:326-343(2015).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-291; LYS-1112; LYS-1179; LYS-1180
RP AND LYS-1575, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-68; LYS-291; LYS-347; LYS-359;
RP LYS-412; LYS-458; LYS-835; LYS-902; LYS-970; LYS-1081; LYS-1093; LYS-1112;
RP LYS-1120; LYS-1169; LYS-1179; LYS-1180; LYS-1575; LYS-1576 AND LYS-1657,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [23]
RP VARIANTS PHE-38; TRP-141; ALA-197; CYS-204; GLN-237; ARG-284; THR-378;
RP THR-385; VAL-386; VAL-424; LYS-457; GLU-458; THR-505; ASN-506; MET-568;
RP PRO-579; SER-671; LYS-787; VAL-870; GLY-894; LEU-929; GLN-942; MET-952;
RP LEU-975; LYS-1007; TRP-1060; LEU-1122; TYR-1123; VAL-1221; PHE-1271;
RP VAL-1286; GLY-1287; GLY-1342; PHE-1421; SER-1476; TRP-1550; VAL-1694;
RP CYS-1814 AND SER-1834, CHARACTERIZATION OF VARIANTS THR-378; LYS-787;
RP TRP-1550 AND CYS-1814, AND NO ASSOCIATION WITH BREAST CANCER.
RX PubMed=22911665; DOI=10.1002/humu.22206;
RA Bakker J.L., van Mil S.E., Crossan G., Sabbaghian N., De Leeneer K.,
RA Poppe B., Adank M., Gille H., Verheul H., Meijers-Heijboer H.,
RA de Winter J.P., Claes K., Tischkowitz M., Waisfisz Q.;
RT "Analysis of the novel Fanconi anemia gene SLX4/FANCP in familial breast
RT cancer cases.";
RL Hum. Mutat. 34:70-73(2013).
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 originating from replication and
CC recombination intermediates and from DNA damage. Component of the SLX1-
CC SLX4 structure-specific endonuclease that resolves DNA secondary
CC structures generated during DNA repair and recombination. Has
CC endonuclease activity towards branched DNA substrates, introducing
CC single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a
CC preference for 5'-flap structures, and promotes symmetrical cleavage of
CC static and migrating Holliday junctions (HJs). Resolves HJs by
CC generating two pairs of ligatable, nicked duplex products. Interacts
CC with the structure-specific ERCC4-ERCC1 endonuclease and promotes the
CC cleavage of bubble structures. Interacts with the structure-specific
CC MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and
CC replication fork-like structures. SLX4 is required for recovery from
CC alkylation-induced DNA damage and is involved in the resolution of DNA
CC double-strand breaks. {ECO:0000269|PubMed:19595721,
CC ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235,
CC ECO:0000269|PubMed:19596236}.
CC -!- SUBUNIT: Forms a heterodimer with SLX1A/GIYD1. Interacts with
CC ERCC4/XPF; catalytic subunit of the ERCC4-ERCC1 endonuclease. Interacts
CC with MUS81; catalytic subunit of the MUS81-EME1 endonuclease. Interacts
CC with MSH2; component of the MSH2-MSH3 mismatch repair complex.
CC Interacts with TERF2-TERF2IP. Interacts with PLK1 and SLX4IP.
CC {ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19595722,
CC ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19596236,
CC ECO:0000269|PubMed:25538220}.
CC -!- INTERACTION:
CC Q8IY92; Q96AY2: EME1; NbExp=4; IntAct=EBI-2370740, EBI-2370825;
CC Q8IY92; P07992: ERCC1; NbExp=6; IntAct=EBI-2370740, EBI-750962;
CC Q8IY92; Q92889: ERCC4; NbExp=10; IntAct=EBI-2370740, EBI-2370770;
CC Q8IY92; P43246: MSH2; NbExp=5; IntAct=EBI-2370740, EBI-355888;
CC Q8IY92; Q96NY9: MUS81; NbExp=13; IntAct=EBI-2370740, EBI-2370806;
CC Q8IY92; P53350: PLK1; NbExp=8; IntAct=EBI-2370740, EBI-476768;
CC Q8IY92; Q9BQ83: SLX1B; NbExp=10; IntAct=EBI-2370740, EBI-2370858;
CC Q8IY92; Q5VYV7: SLX4IP; NbExp=4; IntAct=EBI-2370740, EBI-2370881;
CC Q8IY92; Q15554: TERF2; NbExp=5; IntAct=EBI-2370740, EBI-706637;
CC Q8IY92; Q9NYB0: TERF2IP; NbExp=4; IntAct=EBI-2370740, EBI-750109;
CC Q8IY92-2; B3KX63: MUS81; NbExp=3; IntAct=EBI-10175993, EBI-10175987;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19596235,
CC ECO:0000269|PubMed:19596236}. Note=Localizes to sites of DNA damage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IY92-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IY92-2; Sequence=VSP_035295, VSP_035296;
CC -!- DISEASE: Fanconi anemia complementation group P (FANCP) [MIM:613951]: A
CC disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair. Some
CC individuals affected by Fanconi anemia of complementation group P have
CC skeletal anomalies. {ECO:0000269|PubMed:21240275,
CC ECO:0000269|PubMed:21240277}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SLX4 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SLX4 structure-specific endonuclease subunit homolog
CC (S.cerevisiae) (SLX4); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/SLX4";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC006111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB075867; BAB85573.1; -; mRNA.
DR EMBL; AB058687; BAB47413.1; -; mRNA.
DR EMBL; AL442083; CAH10659.1; -; mRNA.
DR CCDS; CCDS10506.2; -. [Q8IY92-1]
DR RefSeq; NP_115820.2; NM_032444.3. [Q8IY92-1]
DR PDB; 4M7C; X-ray; 2.05 A; C/D=1014-1025.
DR PDB; 4UYI; X-ray; 1.86 A; A=668-796.
DR PDB; 4ZOU; X-ray; 2.15 A; A=669-787.
DR PDB; 7BU5; X-ray; 1.80 A; B=1550-1610.
DR PDBsum; 4M7C; -.
DR PDBsum; 4UYI; -.
DR PDBsum; 4ZOU; -.
DR PDBsum; 7BU5; -.
DR AlphaFoldDB; Q8IY92; -.
DR SMR; Q8IY92; -.
DR BioGRID; 124097; 67.
DR ComplexPortal; CPX-484; SLX4-TERF2 complex.
DR IntAct; Q8IY92; 165.
DR STRING; 9606.ENSP00000294008; -.
DR iPTMnet; Q8IY92; -.
DR PhosphoSitePlus; Q8IY92; -.
DR BioMuta; SLX4; -.
DR DMDM; 205371796; -.
DR EPD; Q8IY92; -.
DR jPOST; Q8IY92; -.
DR MassIVE; Q8IY92; -.
DR MaxQB; Q8IY92; -.
DR PaxDb; Q8IY92; -.
DR PeptideAtlas; Q8IY92; -.
DR PRIDE; Q8IY92; -.
DR ProteomicsDB; 71127; -. [Q8IY92-1]
DR ProteomicsDB; 71128; -. [Q8IY92-2]
DR Antibodypedia; 24180; 91 antibodies from 14 providers.
DR DNASU; 84464; -.
DR Ensembl; ENST00000294008.4; ENSP00000294008.3; ENSG00000188827.11. [Q8IY92-1]
DR GeneID; 84464; -.
DR KEGG; hsa:84464; -.
DR MANE-Select; ENST00000294008.4; ENSP00000294008.3; NM_032444.4; NP_115820.2.
DR UCSC; uc002cvp.3; human. [Q8IY92-1]
DR CTD; 84464; -.
DR DisGeNET; 84464; -.
DR GeneCards; SLX4; -.
DR GeneReviews; SLX4; -.
DR HGNC; HGNC:23845; SLX4.
DR HPA; ENSG00000188827; Tissue enhanced (testis).
DR MalaCards; SLX4; -.
DR MIM; 613278; gene.
DR MIM; 613951; phenotype.
DR neXtProt; NX_Q8IY92; -.
DR OpenTargets; ENSG00000188827; -.
DR Orphanet; 84; Fanconi anemia.
DR PharmGKB; PA134983583; -.
DR VEuPathDB; HostDB:ENSG00000188827; -.
DR eggNOG; ENOG502R4G8; Eukaryota.
DR GeneTree; ENSGT00390000014091; -.
DR HOGENOM; CLU_003520_0_0_1; -.
DR InParanoid; Q8IY92; -.
DR OMA; QMMDESD; -.
DR OrthoDB; 288384at2759; -.
DR PhylomeDB; Q8IY92; -.
DR TreeFam; TF106446; -.
DR PathwayCommons; Q8IY92; -.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; Q8IY92; -.
DR SIGNOR; Q8IY92; -.
DR BioGRID-ORCS; 84464; 61 hits in 1120 CRISPR screens.
DR ChiTaRS; SLX4; human.
DR GeneWiki; SLX4; -.
DR GenomeRNAi; 84464; -.
DR Pharos; Q8IY92; Tbio.
DR PRO; PR:Q8IY92; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8IY92; protein.
DR Bgee; ENSG00000188827; Expressed in right hemisphere of cerebellum and 114 other tissues.
DR Genevisible; Q8IY92; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0033557; C:Slx1-Slx4 complex; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IBA:GO_Central.
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:0006260; P:DNA replication; IEA:InterPro.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; IBA:GO_Central.
DR GO; GO:0000706; P:meiotic DNA double-strand break processing; IBA:GO_Central.
DR GO; GO:1904357; P:negative regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:1904431; P:positive regulation of t-circle formation; ISS:BHF-UCL.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IDA:ComplexPortal.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR GO; GO:0072429; P:response to intra-S DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0090656; P:t-circle formation; IMP:BHF-UCL.
DR GO; GO:0061820; P:telomeric D-loop disassembly; IMP:BHF-UCL.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR006642; Rad18_UBZ4.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR018574; Structure-sp_endonuc_su_Slx4.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF09494; Slx4; 1.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS51908; ZF_UBZ4; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; DNA damage;
KW DNA recombination; DNA repair; Fanconi anemia; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1834
FT /note="Structure-specific endonuclease subunit SLX4"
FT /id="PRO_0000186219"
FT DOMAIN 691..764
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT ZN_FING 293..323
FT /note="UBZ4-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT ZN_FING 333..361
FT /note="UBZ4-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 1..669
FT /note="Interaction with SLX4IP, ERCC4/XPF and MSH2"
FT /evidence="ECO:0000269|PubMed:19596235"
FT REGION 24..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 69..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 452..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 561..610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..1834
FT /note="Interaction with PLK1 and TERF2-TERF2IP"
FT /evidence="ECO:0000269|PubMed:19596235"
FT REGION 826..846
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 902..1151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1195..1504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1328..1648
FT /note="Interaction with MUS81"
FT REGION 1516..1564
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1605..1746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1632..1834
FT /note="Interaction with SLX1"
FT COILED 801..870
FT /evidence="ECO:0000255"
FT COMPBIAS 76..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 153..171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..206
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..610
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 826..844
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 902..917
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 964..978
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 983..1006
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1045..1077
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1086..1109
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1122..1141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1243..1296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1476..1504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1605..1644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1695..1725
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 336
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 356
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1028
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1044
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1070
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P1D7"
FT MOD_RES 1135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P1D7"
FT MOD_RES 1185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1464
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P1D7"
FT MOD_RES 1469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 1610
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P1D7"
FT CROSSLNK 68
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 291
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 347
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 359
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 412
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 458
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 835
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 902
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 970
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1081
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1093
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1112
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1169
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1179
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1180
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 1575
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1576
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1657
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..312
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11853319"
FT /id="VSP_035295"
FT VAR_SEQ 313..316
FT /note="QHVN -> MFSF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11853319"
FT /id="VSP_035296"
FT VARIANT 38
FT /note="L -> F (in dbSNP:rs141167501)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068982"
FT VARIANT 141
FT /note="G -> W (in dbSNP:rs137976282)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068983"
FT VARIANT 197
FT /note="V -> A (in dbSNP:rs147826749)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068984"
FT VARIANT 204
FT /note="R -> C (in dbSNP:rs79842542)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068985"
FT VARIANT 237
FT /note="R -> Q (in dbSNP:rs138615800)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068986"
FT VARIANT 284
FT /note="H -> R"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068987"
FT VARIANT 378
FT /note="P -> T (likely benign variant; does not modify the
FT functional properties of the protein)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068988"
FT VARIANT 385
FT /note="P -> T (in dbSNP:rs115694169)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068989"
FT VARIANT 386
FT /note="M -> V (in dbSNP:rs113490934)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068990"
FT VARIANT 424
FT /note="A -> V (in dbSNP:rs551823420)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068991"
FT VARIANT 457
FT /note="N -> K (in dbSNP:rs74319927)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068992"
FT VARIANT 458
FT /note="K -> E (in dbSNP:rs149126845)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068993"
FT VARIANT 505
FT /note="A -> T"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068994"
FT VARIANT 506
FT /note="S -> N (in dbSNP:rs765859186)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068995"
FT VARIANT 568
FT /note="V -> M (in dbSNP:rs371825444)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068996"
FT VARIANT 579
FT /note="L -> P (in dbSNP:rs772504776)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068997"
FT VARIANT 671
FT /note="L -> S (in dbSNP:rs77985244)"
FT /evidence="ECO:0000269|PubMed:11347906,
FT ECO:0000269|PubMed:22911665"
FT /id="VAR_068998"
FT VARIANT 787
FT /note="E -> K (does not modify the functional properties of
FT the protein; dbSNP:rs140600202)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_068999"
FT VARIANT 870
FT /note="A -> V (in dbSNP:rs149584080)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069000"
FT VARIANT 894
FT /note="V -> G (in dbSNP:rs145137472)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069001"
FT VARIANT 929
FT /note="P -> L (in dbSNP:rs117707719)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069002"
FT VARIANT 942
FT /note="E -> Q (in dbSNP:rs114014006)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069003"
FT VARIANT 952
FT /note="A -> M (requires 2 nucleotide substitutions;
FT dbSNP:rs863224277)"
FT /evidence="ECO:0000269|PubMed:11347906,
FT ECO:0000269|PubMed:22911665"
FT /id="VAR_069004"
FT VARIANT 975
FT /note="P -> L (in dbSNP:rs114472821)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069005"
FT VARIANT 1007
FT /note="Q -> K (in dbSNP:rs138798067)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069006"
FT VARIANT 1060
FT /note="R -> W (in dbSNP:rs144273492)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069007"
FT VARIANT 1122
FT /note="P -> L (in dbSNP:rs714181)"
FT /evidence="ECO:0000269|PubMed:11347906,
FT ECO:0000269|PubMed:22911665"
FT /id="VAR_019326"
FT VARIANT 1123
FT /note="S -> Y (in dbSNP:rs144647122)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069008"
FT VARIANT 1221
FT /note="A -> V (in dbSNP:rs3827530)"
FT /evidence="ECO:0000269|PubMed:11347906,
FT ECO:0000269|PubMed:22911665"
FT /id="VAR_019729"
FT VARIANT 1271
FT /note="S -> F (in dbSNP:rs3810813)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_019327"
FT VARIANT 1286
FT /note="A -> V (in dbSNP:rs149011965)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069009"
FT VARIANT 1287
FT /note="V -> G (in dbSNP:rs1596520811)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069010"
FT VARIANT 1342
FT /note="S -> G (in dbSNP:rs140051968)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069011"
FT VARIANT 1367
FT /note="A -> T (in dbSNP:rs17136464)"
FT /id="VAR_046337"
FT VARIANT 1421
FT /note="I -> F (in dbSNP:rs141567438)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069012"
FT VARIANT 1476
FT /note="T -> S (in dbSNP:rs372321470)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069013"
FT VARIANT 1550
FT /note="R -> W (does not modify the functional properties of
FT the protein; dbSNP:rs77021998)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069014"
FT VARIANT 1677
FT /note="P -> S (in dbSNP:rs7196345)"
FT /id="VAR_046338"
FT VARIANT 1694
FT /note="A -> V (in dbSNP:rs761226343)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069015"
FT VARIANT 1814
FT /note="R -> C (in dbSNP:rs767720336)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069016"
FT VARIANT 1834
FT /note="N -> S (does not modify the functional properties of
FT the protein; dbSNP:rs111738042)"
FT /evidence="ECO:0000269|PubMed:22911665"
FT /id="VAR_069017"
FT HELIX 668..682
FT /evidence="ECO:0007829|PDB:4UYI"
FT TURN 683..686
FT /evidence="ECO:0007829|PDB:4UYI"
FT STRAND 693..696
FT /evidence="ECO:0007829|PDB:4UYI"
FT STRAND 702..705
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 707..713
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 715..724
FT /evidence="ECO:0007829|PDB:4UYI"
FT STRAND 726..730
FT /evidence="ECO:0007829|PDB:4UYI"
FT STRAND 733..739
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 745..757
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 764..766
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 767..776
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 780..787
FT /evidence="ECO:0007829|PDB:4UYI"
FT HELIX 1016..1019
FT /evidence="ECO:0007829|PDB:4M7C"
FT STRAND 1560..1562
FT /evidence="ECO:0007829|PDB:7BU5"
FT HELIX 1566..1568
FT /evidence="ECO:0007829|PDB:7BU5"
FT HELIX 1571..1579
FT /evidence="ECO:0007829|PDB:7BU5"
FT TURN 1580..1582
FT /evidence="ECO:0007829|PDB:7BU5"
FT HELIX 1588..1602
FT /evidence="ECO:0007829|PDB:7BU5"
FT STRAND 1603..1605
FT /evidence="ECO:0007829|PDB:7BU5"
SQ SEQUENCE 1834 AA; 200012 MW; 9131E88628DB15D5 CRC64;
MKLSVNEAQL GFYLGSLSHL SACPGIDPRS SEDQPESLKT GQMMDESDED FKELCASFFQ
RVKKHGIKEV SGERKTQKAA SNGTQIRSKL KRTKQTATKT KTLQGPAEKK PPSGSQAPRT
KKQRVTKWQA SEPAHSVNGE GGVLASAPDP PVLRETAQNT QTGNQQEPSP NLSREKTREN
VPNSDSQPPP SCLTTAVPSP SKPRTAQLVL QRMQQFKRAD PERLRHASEE CSLEAAREEN
VPKDPQEEMM AGNVYGLGPP APESDAAVAL TLQQEFARVG ASAHDDSLEE KGLFFCQICQ
KNLSAMNVTR REQHVNRCLD EAEKTLRPSV PQIPECPICG KPFLTLKSRT SHLKQCAVKM
EVGPQLLLQA VRLQTAQPEG SSSPPMFSFS DHSRGLKRRG PTSKKEPRKR RKVDEAPSED
LLVAMALSRS EMEPGAAVPA LRLESAFSER IRPEAENKSR KKKPPVSPPL LLVQDSETTG
RQIEDRVALL LSEEVELSST PPLPASRILK EGWERAGQCP PPPERKQSFL WEGSALTGAW
AMEDFYTARL VPPLVPQRPA QGLMQEPVPP LVPPEHSELS ERRSPALHGT PTAGCGSRGP
SPSASQREHQ ALQDLVDLAR EGLSASPWPG SGGLAGSEGT AGLDVVPGGL PLTGFVVPSQ
DKHPDRGGRT LLSLGLLVAD FGAMVNNPHL SDVQFQTDSG EVLYAHKFVL YARCPLLIQY
VNNEGFSAVE DGVLTQRVLL GDVSTEAART FLHYLYTADT GLPPGLSSEL SSLAHRFGVS
ELVHLCEQVP IATDSEGKPW EEKEAENCES RAENFQELLR SMWADEEEEA ETLLKSKDHE
EDQENVNEAE MEEIYEFAAT QRKLLQEERA AGAGEDADWL EGGSPVSGQL LAGVQVQKQW
DKVEEMEPLE PGRDEAATTW EKMGQCALPP PQGQHSGARG AEAPEQEAPE EALGHSSCSS
PSRDCQAERK EGSLPHSDDA GDYEQLFSST QGEISEPSQI TSEPEEQSGA VRERGLEVSH
RLAPWQASPP HPCRFLLGPP QGGSPRGSHH TSGSSLSTPR SRGGTSQVGS PTLLSPAVPS
KQKRDRSILT LSKEPGHQKG KERRSVLECR NKGVLMFPEK SPSIDLTQSN PDHSSSRSQK
SSSKLNEEDE VILLLDSDEE LELEQTKMKS ISSDPLEEKK ALEISPRSCE LFSIIDVDAD
QEPSQSPPRS EAVLQQEDEG ALPENRGSLG RRGAPWLFCD RESSPSEAST TDTSWLVPAT
PLASRSRDCS SQTQISSLRS GLAVQAVTQH TPRASVGNRE GNEVAQKFSV IRPQTPPPQT
PSSCLTPVSP GTSDGRRQGH RSPSRPHPGG HPHSSPLAPH PISGDRAHFS RRFLKHSPPG
PSFLNQTPAG EVVEVGDSDD EQEVASHQAN RSPPLDSDPP IPIDDCCWHM EPLSPIPIDH
WNLERTGPLS TSSPSRRMNE AADSRDCRSP GLLDTTPIRG SCTTQRKLQE KSSGAGSLGN
SRPSFLNSAL WDVWDGEEQR PPETPPPAQM PSAGGAQKPE GLETPKGANR KKNLPPKVPI
TPMPQYSIME TPVLKKELDR FGVRPLPKRQ MVLKLKEIFQ YTHQTLDSDS EDESQSSQPL
LQAPHCQTLA SQTYKPSRAG VHAQQEATTG PGAHRPKGPA KTKGPRHQRK HHESITPPSR
SPTKEAPPGL NDDAQIPASQ ESVATSVDGS DSSLSSQSSS SCEFGAAFES AGEEEGEGEV
SASQAAVQAA DTDEALRCYI RSKPALYQKV LLYQPFELRE LQAELRQNGL RVSSRRLLDF
LDTHCITFTT AATRREKLQG RRRQPRGKKK VERN
