ID BLM_HUMAN Reviewed; 1417 AA. AC P54132; Q52M96; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 230. DE RecName: Full=RecQ-like DNA helicase BLM {ECO:0000305}; DE EC=5.6.2.4 {ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:9388193}; DE AltName: Full=Bloom syndrome protein; DE AltName: Full=DNA 3'-5' helicase BLM {ECO:0000305}; DE AltName: Full=DNA helicase, RecQ-like type 2; DE Short=RecQ2; DE AltName: Full=RecQ protein-like 3; GN Name=BLM; Synonyms=RECQ2, RECQL3; 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 [MRNA], AND VARIANTS BLM ARG-672; ILE-843 AND SER-1055. RX PubMed=7585968; DOI=10.1016/0092-8674(95)90105-1; RA Ellis N.A., Groden J., Ye T.-Z., Straughen J., Lennon D.J., Ciocci S., RA Proytcheva M., German J.; RT "The Bloom's syndrome gene product is homologous to RecQ helicases."; RL Cell 83:655-666(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=B-cell; RX PubMed=9388193; DOI=10.1074/jbc.272.49.30611; RA Karow J.K., Chakraverty R.K., Hickson I.D.; RT "The Bloom's syndrome gene product is a 3'-5' DNA helicase."; RL J. Biol. Chem. 272:30611-30614(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-137; MET-298; GLN-591; RP LEU-868; ILE-1205; LYS-1213 AND ILE-1321. RG NIEHS SNPs program; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP NUCLEAR LOCALIZATION SIGNAL. RX PubMed=9388480; DOI=10.1006/bbrc.1997.7648; RA Kaneko H., Orii K.O., Matsui E., Shimozawa N., Fukao T., Matsumoto T., RA Shimamoto A., Furuichi Y., Hayakawa S., Kasahara K., Kondo N.; RT "BLM (the causative gene of Bloom syndrome) protein translocation into the RT nucleus by a nuclear localization signal."; RL Biochem. Biophys. Res. Commun. 240:348-353(1997). RN [6] RP IDENTIFICATION OF BLM AS MEMBER OF BASC. RX PubMed=10783165; RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.; RT "BASC, a super complex of BRCA1-associated proteins involved in the RT recognition and repair of aberrant DNA structures."; RL Genes Dev. 14:927-939(2000). RN [7] RP INTERACTION WITH FANCD2, AND PHOSPHORYLATION. RX PubMed=15257300; DOI=10.1038/sj.emboj.7600277; RA Pichierri P., Franchitto A., Rosselli F.; RT "BLM and the FANC proteins collaborate in a common pathway in response to RT stalled replication forks."; RL EMBO J. 23:3154-3163(2004). RN [8] RP FUNCTION IN DNA REPAIR. RX PubMed=12019152; RA Langland G., Elliott J., Li Y., Creaney J., Dixon K., Groden J.; RT "The BLM helicase is necessary for normal DNA double-strand break repair."; RL Cancer Res. 62:2766-2770(2002). RN [9] RP IDENTIFICATION IN A COMPLEX WITH RMI1, AND PHOSPHORYLATION. RX PubMed=15775963; DOI=10.1038/sj.emboj.7600622; RA Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W.; RT "BLAP75, an essential component of Bloom's syndrome protein complexes that RT maintain genome integrity."; RL EMBO J. 24:1465-1476(2005). RN [10] RP INTERACTION WITH RMI1. RX PubMed=16595695; DOI=10.1074/jbc.c600051200; RA Raynard S., Bussen W., Sung P.; RT "A double Holliday junction dissolvasome comprising BLM, topoisomerase III RT alpha, and BLAP75."; RL J. Biol. Chem. 281:13861-13864(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499 AND THR-508, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [12] RP INTERACTION WITH SUPV3L1. RX PubMed=17961633; DOI=10.1016/j.mad.2007.09.001; RA Pereira M., Mason P., Szczesny R.J., Maddukuri L., Dziwura S., RA Jedrzejczak R., Paul E., Wojcik A., Dybczynska L., Tudek B., Bartnik E., RA Klysik J., Bohr V.A., Stepien P.P.; RT "Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the RT SUV3 gene results in mouse embryonic lethality."; RL Mech. Ageing Dev. 128:609-617(2007). RN [13] RP INTERACTION WITH RMI1. RX PubMed=18923082; DOI=10.1101/gad.1708608; RA Xu D., Guo R., Sobeck A., Bachrati C.Z., Yang J., Enomoto T., Brown G.W., RA Hoatlin M.E., Hickson I.D., Wang W.; RT "RMI, a new OB-fold complex essential for Bloom syndrome protein to RT maintain genome stability."; RL Genes Dev. 22:2843-2855(2008). RN [14] RP INTERACTION WITH RMI1. RX PubMed=18923083; DOI=10.1101/gad.1725108; RA Singh T.R., Ali A.M., Busygina V., Raynard S., Fan Q., Du C.-H., RA Andreassen P.R., Sung P., Meetei A.R.; RT "BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component RT of the Bloom helicase-double Holliday junction dissolvasome."; RL Genes Dev. 22:2856-2868(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; THR-57; THR-114; SER-358; RP SER-419; SER-422; SER-1295; SER-1296 AND SER-1310, AND IDENTIFICATION BY RP 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499, AND IDENTIFICATION BY RP 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 [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-863, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-168; THR-171; RP SER-419; SER-422 AND SER-426, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP FUNCTION, AND INTERACTION WITH DNA2. RX PubMed=21325134; DOI=10.1101/gad.2003811; RA Nimonkar A.V., Genschel J., Kinoshita E., Polaczek P., Campbell J.L., RA Wyman C., Modrich P., Kowalczykowski S.C.; RT "BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection RT machineries for human DNA break repair."; RL Genes Dev. 25:350-362(2011). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; THR-171; SER-328; RP SER-338; SER-358; SER-422; SER-464; SER-499; SER-1197 AND SER-1310, AND RP IDENTIFICATION BY MASS SPECTROMETRY [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 [22] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH SPIDR AND RAD51, INTERACTION RP WITH RMI1; SPIDR AND TOP3A, AND SUBCELLULAR LOCATION. RX PubMed=23509288; DOI=10.1073/pnas.1220921110; RA Wan L., Han J., Liu T., Dong S., Xie F., Chen H., Huang J.; RT "Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase RT with homologous recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 110:10646-10651(2013). RN [23] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-484, 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 [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-331 AND LYS-594, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [25] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-24; LYS-31; LYS-38; LYS-56; RP LYS-63; LYS-87; LYS-91; LYS-105; LYS-116; LYS-129; LYS-195; LYS-205; RP LYS-331; LYS-344; LYS-347; LYS-451; LYS-476; LYS-484; LYS-498; LYS-513; RP LYS-514; LYS-531; LYS-535; LYS-588; LYS-594; LYS-604; LYS-1125; LYS-1199; RP LYS-1207; LYS-1329; LYS-1372 AND LYS-1395, AND IDENTIFICATION BY MASS RP 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 [26] RP DECREASE IN SUMYOYLATION (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL RP INFECTION). RX PubMed=32690953; DOI=10.1038/s41564-020-0753-6; RA Volcic M., Sparrer K.M.J., Koepke L., Hotter D., Sauter D., Stuerzel C.M., RA Scherer M., Stamminger T., Hofmann T.G., Arhel N.J., Wiesmueller L., RA Kirchhoff F.; RT "Vpu modulates DNA repair to suppress innate sensing and hyper-integration RT of HIV-1."; RL Nat. Microbiol. 5:1247-1261(2020). RN [27] RP FUNCTION, AND DEUBIQUITINATION BY USP37. RX PubMed=34606619; DOI=10.1093/nar/gkab842; RA Wu C., Chang Y., Chen J., Su Y., Li L., Chen Y., Li Y., Wu J., Huang J., RA Zhao F., Wang W., Yin H., Wang S., Jin M., Lou Z., Zhu W.G., Luo K., RA Zhang J., Yuan J.; RT "USP37 regulates DNA damage response through stabilizing and RT deubiquitinating BLM."; RL Nucleic Acids Res. 49:11224-11240(2021). RN [28] RP STRUCTURE BY NMR OF 1210-1294, MUTAGENESIS OF LYS-1227; TYR-1237; ASN-1239; RP THR-1243 AND VAL-1244, DNA-BINDING, DOMAIN, AND REGION. RX PubMed=20639533; DOI=10.1093/nar/gkq586; RA Kim Y.M., Choi B.S.; RT "Structure and function of the regulatory HRDC domain from human Bloom RT syndrome protein."; RL Nucleic Acids Res. 38:7764-7777(2010). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1068-1209, MUTAGENESIS OF RP 1094-SER--VAL-1103; SER-1121; LYS-1125 AND ARG-1139, DNA-BINDING, AND RP REGION. RX PubMed=24257077; DOI=10.1038/srep03294; RA Kim S.Y., Hakoshima T., Kitano K.; RT "Structure of the RecQ C-terminal domain of human Bloom syndrome protein."; RL Sci. Rep. 3:3294-3294(2013). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 640-1298 IN COMPLEX WITH DNA; ADP RP AND ZINC IONS, FUNCTION, DNA-BINDING, CATALYTIC ACTIVITY, COFACTOR, RP ZINC-BINDING MOTIF, DNA-BINDING DOMAIN, AND MUTAGENESIS OF ASN-1164. RX PubMed=24816114; DOI=10.1107/s139900471400501x; RA Swan M.K., Legris V., Tanner A., Reaper P.M., Vial S., Bordas R., RA Pollard J.R., Charlton P.A., Golec J.M., Bertrand J.A.; RT "Structure of human Bloom's syndrome helicase in complex with ADP and RT duplex DNA."; RL Acta Crystallogr. D 70:1465-1475(2014). RN [31] RP STRUCTURE BY NMR OF 1067-1210. RX PubMed=24435566; DOI=10.1007/s10858-014-9812-8; RA Park C.J., Ko J., Ryu K.S., Choi B.S.; RT "Solution structure of the RecQ C-terminal domain of human Bloom syndrome RT protein."; RL J. Biomol. NMR 58:141-147(2014). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 636-1298 IN COMPLEX WITH DNA; ADP RP AND ZINC IONS, FUNCTION, DNA-BINDING, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, RP AND MUTAGENESIS OF HIS-666; SER-729 AND LYS-1270. RX PubMed=25901030; DOI=10.1093/nar/gkv373; RA Newman J.A., Savitsky P., Allerston C.K., Bizard A.H., Ozer O., Sarlos K., RA Liu Y., Pardon E., Steyaert J., Hickson I.D., Gileadi O.; RT "Crystal structure of the Bloom's syndrome heli case indicates a role for RT the HRDC domain in conformational changes."; RL Nucleic Acids Res. 43:5221-5235(2015). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 362-414 OF HOMODIMER, SUBUNIT, RP HOMOOLIGOMERIZATION, DOMAIN, AND REGION. RX PubMed=28228481; DOI=10.1074/jbc.m116.761510; RA Shi J., Chen W.F., Zhang B., Fan S.H., Ai X., Liu N.N., Rety S., Xi X.G.; RT "A helical bundle in the N-terminal domain of the BLM helicase mediates RT dimer and potentially hexamer formation."; RL J. Biol. Chem. 292:5909-5920(2017). RN [34] RP VARIANT BLM PHE-1036. RX PubMed=9285778; DOI=10.1093/hmg/6.9.1427; RA Foucault F., Vaury C., Barakat A., Thibout D., Planchon P., Jaulin C., RA Praz F., Amor-Gueret M.; RT "Characterization of a new BLM mutation associated with a topoisomerase II RT alpha defect in a patient with Bloom's syndrome."; RL Hum. Mol. Genet. 6:1427-1434(1997). RN [35] RP VARIANT BLM ARG-878. RX PubMed=10862105; RX DOI=10.1002/1098-1004(200006)15:6<584::aid-humu28>3.0.co;2-i; RA Barakat A., Ababou M., Onclercq R., Dutertre S., Chadli E., Hda N., RA Benslimane A., Amor-Gueret M.; RT "Identification of a novel BLM missense mutation (2706T>C) in a Moroccan RT patient with Bloom's syndrome."; RL Hum. Mutat. 15:584-585(2000). CC -!- FUNCTION: ATP-dependent DNA helicase that unwinds single- and double- CC stranded DNA in a 3'-5' direction (PubMed:9388193, PubMed:24816114, CC PubMed:25901030). Participates in DNA replication and repair CC (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). CC Involved in 5'-end resection of DNA during double-strand break (DSB) CC repair: unwinds DNA and recruits DNA2 which mediates the cleavage of CC 5'-ssDNA (PubMed:21325134). Negatively regulates sister chromatid CC exchange (SCE) (PubMed:25901030). Stimulates DNA 4-way junction branch CC migration and DNA Holliday junction dissolution (PubMed:25901030). CC Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday CC junction (PubMed:20639533, PubMed:24257077, PubMed:25901030). Recruited CC by the KHDC3L-OOEP scaffold to DNA replication forks where it is CC retained by TRIM25 ubiquitination, it thereby promotes the restart of CC stalled replication forks (By similarity). CC {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, CC ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, CC ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, CC ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, CC ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193}. CC -!- FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby CC suppressing immune sensing and proviral hyper-integration. CC {ECO:0000269|PubMed:32690953}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Couples ATP hydrolysis with the unwinding of duplex DNA by CC translocating in the 3'-5' direction.; EC=5.6.2.4; CC Evidence={ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, CC ECO:0000269|PubMed:9388193}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, CC ECO:0000269|PubMed:9388193}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:24816114, CC ECO:0000269|PubMed:25901030}; CC -!- SUBUNIT: Monomer (PubMed:28228481). Homodimer (via N-terminus) CC (PubMed:28228481). Homotetramer (via N-terminus); dimer of dimers CC (PubMed:28228481). Homohexamer (via N-terminus) (PubMed:28228481). CC Self-association negatively regulates DNA unwinding amplitude and rate. CC Oligomeric complexes dissociate into monomer in presence of ATP CC (PubMed:28228481). Part of the BRCA1-associated genome surveillance CC complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 CC and the RAD50-MRE11-NBS1 protein complex. This association could be a CC dynamic process changing throughout the cell cycle and within CC subnuclear domains. Interacts with RMI complex. Interacts directly with CC RMI1 (via N-terminal region) component of RMI complex. Found in a CC complex, at least composed of BLM, RAD51 and SPIDR; the complex CC formation is mediated by SPIDR. Interacts with the KHDC3L/FILIA- CC OOEP/FLOPED scaffold complex and TRIM25 at DNA replication forks (By CC similarity). Interacts with ubiquitinated FANCD2 (PubMed:15257300). CC Interacts with SUPV3L1 (PubMed:17961633). Interacts with TOP3A (via N- CC terminal region). Interacts with SPIDR (via C-terminal region); the CC interaction is direct and required to target BLM to sites of DNA CC damage. {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:15257300, CC ECO:0000269|PubMed:15775963, ECO:0000269|PubMed:16595695, CC ECO:0000269|PubMed:17961633, ECO:0000269|PubMed:18923082, CC ECO:0000269|PubMed:18923083, ECO:0000269|PubMed:21325134, CC ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:28228481}. CC -!- INTERACTION: CC P54132; Q9BX63: BRIP1; NbExp=16; IntAct=EBI-621372, EBI-3509650; CC P54132; P39748: FEN1; NbExp=4; IntAct=EBI-621372, EBI-707816; CC P54132; Q9BQ15: NABP2; NbExp=6; IntAct=EBI-621372, EBI-2120336; CC P54132; P53350: PLK1; NbExp=4; IntAct=EBI-621372, EBI-476768; CC P54132; O75771: RAD51D; NbExp=4; IntAct=EBI-621372, EBI-1055693; CC P54132; Q9H9A7: RMI1; NbExp=15; IntAct=EBI-621372, EBI-621339; CC P54132; P27694: RPA1; NbExp=4; IntAct=EBI-621372, EBI-621389; CC P54132; P42677: RPS27; NbExp=4; IntAct=EBI-621372, EBI-356336; CC P54132; Q14159: SPIDR; NbExp=11; IntAct=EBI-621372, EBI-11318692; CC P54132; P54274: TERF1; NbExp=3; IntAct=EBI-621372, EBI-710997; CC P54132; Q15554: TERF2; NbExp=8; IntAct=EBI-621372, EBI-706637; CC P54132; Q13472: TOP3A; NbExp=9; IntAct=EBI-621372, EBI-621345; CC P54132; Q96RL1: UIMC1; NbExp=2; IntAct=EBI-621372, EBI-725300; CC P54132; Q14191: WRN; NbExp=9; IntAct=EBI-621372, EBI-368417; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23509288}. CC Note=Together with SPIDR, is redistributed in discrete nuclear DNA CC damage-induced foci following hydroxyurea (HU) or camptothecin (CPT) CC treatment. Accumulated at sites of DNA damage in a RMI complex- and CC SPIDR-dependent manner. CC -!- DOMAIN: The N-terminal region mediates dimerization and CC homooligomerization (PubMed:28228481). Both the helicase ATP-binding CC domain and the helicase C-terminal domain form intramolecular CC interactions with the HRDC domain in a ATP-dependent manner CC (PubMed:25901030). The HRDC domain is required for single-stranded DNA CC (ssDNA) and DNA Holliday junction binding (PubMed:20639533). CC {ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:25901030, CC ECO:0000269|PubMed:28228481}. CC -!- PTM: Poly-ubiquitinated by TRIM25 at Lys-259 (By similarity). CC Deubiquitinated by USP37; leading to stabilization in order to sustain CC the DNA damage response (PubMed:34606619). CC {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:34606619}. CC -!- PTM: Phosphorylated in response to DNA damage. Phosphorylation requires CC the FANCA-FANCC-FANCE-FANCF-FANCG protein complex, as well as the CC presence of RMI1. {ECO:0000269|PubMed:15257300, CC ECO:0000269|PubMed:15775963}. CC -!- PTM: (Microbial infection) Sumoylation of BLM is decreased by HIV-1 Vpu CC protein, unleashing end degradation of viral cDNA. CC {ECO:0000269|PubMed:32690953}. CC -!- DISEASE: Bloom syndrome (BLM) [MIM:210900]: An autosomal recessive CC disorder. It is characterized by proportionate pre- and postnatal CC growth deficiency, sun-sensitive telangiectatic hypo- and CC hyperpigmented skin, predisposition to malignancy, and chromosomal CC instability. {ECO:0000269|PubMed:10862105, ECO:0000269|PubMed:7585968, CC ECO:0000269|PubMed:9285778}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the helicase family. RecQ subfamily. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=BLMbase; Note=BLM mutation db; CC URL="http://structure.bmc.lu.se/idbase/BLMbase/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/109/BLM"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/blm/"; 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; U39817; AAA87850.1; -; mRNA. DR EMBL; AY886902; AAW62255.1; -; Genomic_DNA. DR EMBL; BC093622; AAH93622.1; -; mRNA. DR EMBL; BC101567; AAI01568.1; -; mRNA. DR EMBL; BC115030; AAI15031.1; -; mRNA. DR EMBL; BC115032; AAI15033.1; -; mRNA. DR CCDS; CCDS10363.1; -. DR PIR; A57570; A57570. DR RefSeq; NP_000048.1; NM_000057.3. DR RefSeq; NP_001274175.1; NM_001287246.1. DR RefSeq; NP_001274176.1; NM_001287247.1. DR RefSeq; NP_001274177.1; NM_001287248.1. DR PDB; 2KV2; NMR; -; A=1210-1294. DR PDB; 2MH9; NMR; -; A=1067-1210. DR PDB; 2RRD; NMR; -; A=1200-1295. DR PDB; 3WE2; X-ray; 2.70 A; A/B=1068-1209. DR PDB; 3WE3; X-ray; 2.90 A; A/B=1068-1209. DR PDB; 4CDG; X-ray; 2.79 A; A/B=636-1298. DR PDB; 4CGZ; X-ray; 3.20 A; A=636-1298. DR PDB; 4O3M; X-ray; 2.30 A; A=640-1298. DR PDB; 5LUP; X-ray; 2.03 A; A/B/C/D/E/F/G/H/I/J/K/L=362-414. DR PDB; 5MK5; X-ray; 2.16 A; A/B/C/D=362-414. DR PDB; 5U6K; X-ray; 2.60 A; L/M/N/O=297-309. DR PDB; 7AUC; X-ray; 1.53 A; A=636-1070, A=1202-1298. DR PDB; 7AUD; X-ray; 2.96 A; A/B/C/D/E/F=636-1070, A/B/C/D/E/F=1202-1298. DR PDB; 7XUW; X-ray; 1.80 A; A=550-570. DR PDB; 7XV0; X-ray; 1.50 A; B=146-165. DR PDBsum; 2KV2; -. DR PDBsum; 2MH9; -. DR PDBsum; 2RRD; -. DR PDBsum; 3WE2; -. DR PDBsum; 3WE3; -. DR PDBsum; 4CDG; -. DR PDBsum; 4CGZ; -. DR PDBsum; 4O3M; -. DR PDBsum; 5LUP; -. DR PDBsum; 5MK5; -. DR PDBsum; 5U6K; -. DR PDBsum; 7AUC; -. DR PDBsum; 7AUD; -. DR PDBsum; 7XUW; -. DR PDBsum; 7XV0; -. DR AlphaFoldDB; P54132; -. DR BMRB; P54132; -. DR SMR; P54132; -. DR BioGRID; 107110; 246. DR ComplexPortal; CPX-3301; BTR double Holliday Junction dissolution complex. DR CORUM; P54132; -. DR DIP; DIP-33322N; -. DR ELM; P54132; -. DR IntAct; P54132; 77. DR MINT; P54132; -. DR STRING; 9606.ENSP00000347232; -. DR BindingDB; P54132; -. DR ChEMBL; CHEMBL1293237; -. DR GlyGen; P54132; 3 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P54132; -. DR PhosphoSitePlus; P54132; -. DR BioMuta; BLM; -. DR DMDM; 1705486; -. DR EPD; P54132; -. DR jPOST; P54132; -. DR MassIVE; P54132; -. DR MaxQB; P54132; -. DR PaxDb; 9606-ENSP00000347232; -. DR PeptideAtlas; P54132; -. DR ProteomicsDB; 56649; -. DR Pumba; P54132; -. DR ABCD; P54132; 1 sequenced antibody. DR Antibodypedia; 704; 556 antibodies from 37 providers. DR DNASU; 641; -. DR Ensembl; ENST00000355112.8; ENSP00000347232.3; ENSG00000197299.13. DR Ensembl; ENST00000680772.1; ENSP00000506117.1; ENSG00000197299.13. DR GeneID; 641; -. DR KEGG; hsa:641; -. DR MANE-Select; ENST00000355112.8; ENSP00000347232.3; NM_000057.4; NP_000048.1. DR UCSC; uc002bpr.5; human. DR AGR; HGNC:1058; -. DR CTD; 641; -. DR DisGeNET; 641; -. DR GeneCards; BLM; -. DR GeneReviews; BLM; -. DR HGNC; HGNC:1058; BLM. DR HPA; ENSG00000197299; Tissue enhanced (bone marrow, lymphoid tissue, salivary gland). DR MalaCards; BLM; -. DR MIM; 210900; phenotype. DR MIM; 604610; gene. DR neXtProt; NX_P54132; -. DR OpenTargets; ENSG00000197299; -. DR Orphanet; 125; Bloom syndrome. DR PharmGKB; PA25369; -. DR VEuPathDB; HostDB:ENSG00000197299; -. DR eggNOG; KOG0351; Eukaryota. DR GeneTree; ENSGT00940000156800; -. DR HOGENOM; CLU_001103_1_1_1; -. DR InParanoid; P54132; -. DR OMA; FHVMEDI; -. DR OrthoDB; 5474026at2759; -. DR PhylomeDB; P54132; -. DR TreeFam; TF317801; -. DR BRENDA; 3.6.4.12; 2681. DR PathwayCommons; P54132; -. DR Reactome; R-HSA-174414; Processive synthesis on the C-strand of the telomere. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-912446; Meiotic recombination. DR Reactome; R-HSA-9701192; Defective homologous recombination repair (HRR) due to BRCA1 loss of function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; P54132; -. DR SIGNOR; P54132; -. DR BioGRID-ORCS; 641; 128 hits in 1175 CRISPR screens. DR ChiTaRS; BLM; human. DR EvolutionaryTrace; P54132; -. DR GeneWiki; Bloom_syndrome_protein; -. DR GenomeRNAi; 641; -. DR Pharos; P54132; Tchem. DR PRO; PR:P54132; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P54132; Protein. DR Bgee; ENSG00000197299; Expressed in parotid gland and 134 other cell types or tissues. DR ExpressionAtlas; P54132; baseline and differential. DR GO; GO:0005694; C:chromosome; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000800; C:lateral element; IDA:UniProtKB. DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0031422; C:RecQ family helicase-topoisomerase III complex; IPI:ComplexPortal. DR GO; GO:0005657; C:replication fork; ISS:BHF-UCL. DR GO; GO:0043138; F:3'-5' DNA helicase activity; IBA:GO_Central. DR GO; GO:1905773; F:8-hydroxy-2'-deoxyguanosine DNA binding; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0003678; F:DNA helicase activity; IDA:UniProtKB. DR GO; GO:1990814; F:DNA/DNA annealing activity; IDA:GO_Central. DR GO; GO:0061749; F:forked DNA-dependent helicase activity; IDA:UniProtKB. DR GO; GO:0000400; F:four-way junction DNA binding; IDA:UniProtKB. DR GO; GO:0009378; F:four-way junction helicase activity; IDA:UniProtKB. DR GO; GO:0051880; F:G-quadruplex DNA binding; IDA:UniProtKB. DR GO; GO:0004386; F:helicase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0140677; F:molecular function activator activity; IDA:DisProt. DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0061821; F:telomeric D-loop binding; IDA:BHF-UCL. DR GO; GO:0061849; F:telomeric G-quadruplex DNA binding; IDA:BHF-UCL. DR GO; GO:0000403; F:Y-form DNA binding; IDA:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0072757; P:cellular response to camptothecin; IDA:UniProtKB. DR GO; GO:0072711; P:cellular response to hydroxyurea; IDA:UniProtKB. DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0000729; P:DNA double-strand break processing; IDA:UniProtKB. DR GO; GO:0032508; P:DNA duplex unwinding; IDA:UniProtKB. DR GO; GO:0006310; P:DNA recombination; NAS:UniProtKB. DR GO; GO:0006281; P:DNA repair; NAS:UniProtKB. DR GO; GO:0006260; P:DNA replication; ISS:BHF-UCL. DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IBA:GO_Central. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:ComplexPortal. DR GO; GO:0044806; P:G-quadruplex DNA unwinding; IDA:BHF-UCL. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IDA:UniProtKB. DR GO; GO:0051782; P:negative regulation of cell division; IMP:UniProtKB. DR GO; GO:0045910; P:negative regulation of DNA recombination; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:UniProtKB. DR GO; GO:0090329; P:regulation of DNA-templated DNA replication; IMP:UniProtKB. DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB. DR GO; GO:0071139; P:resolution of DNA recombination intermediates; IDA:ComplexPortal. DR GO; GO:0010165; P:response to X-ray; IDA:UniProtKB. DR GO; GO:0090656; P:t-circle formation; TAS:BHF-UCL. DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central. DR GO; GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome. DR GO; GO:0061820; P:telomeric D-loop disassembly; IDA:BHF-UCL. DR CDD; cd18016; DEXHc_RecQ2_BLM; 1. DR CDD; cd18794; SF2_C_RecQ; 1. DR DisProt; DP03061; -. DR Gene3D; 1.10.150.80; HRDC domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR012532; BDHCT. DR InterPro; IPR032439; BDHCT_assoc. DR InterPro; IPR032437; BLM_N. DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom. DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS. DR InterPro; IPR004589; DNA_helicase_ATP-dep_RecQ. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR010997; HRDC-like_sf. DR InterPro; IPR002121; HRDC_dom. DR InterPro; IPR044876; HRDC_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR032284; RecQ_Zn-bd. DR InterPro; IPR018982; RQC_domain. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR NCBIfam; TIGR00614; recQ_fam; 1. DR PANTHER; PTHR13710:SF105; BLOOM SYNDROME PROTEIN; 1. DR PANTHER; PTHR13710; DNA HELICASE RECQ FAMILY MEMBER; 1. DR Pfam; PF08072; BDHCT; 1. DR Pfam; PF16204; BDHCT_assoc; 1. DR Pfam; PF16202; BLM_N; 1. DR Pfam; PF00270; DEAD; 1. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF00570; HRDC; 1. DR Pfam; PF16124; RecQ_Zn_bind; 1. DR Pfam; PF09382; RQC; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SMART; SM00341; HRDC; 1. DR SMART; SM00956; RQC; 1. DR SUPFAM; SSF47819; HRDC-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS50967; HRDC; 1. DR Genevisible; P54132; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Disease variant; DNA damage; KW DNA repair; DNA replication; DNA-binding; Dwarfism; Helicase; Hydrolase; KW Isomerase; Isopeptide bond; Metal-binding; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc. FT CHAIN 1..1417 FT /note="RecQ-like DNA helicase BLM" FT /id="PRO_0000205039" FT DOMAIN 676..851 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541, FT ECO:0000305|PubMed:24816114" FT DOMAIN 877..1024 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542, FT ECO:0000305|PubMed:24816114" FT DOMAIN 1212..1292 FT /note="HRDC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00328, FT ECO:0000269|PubMed:20639533, ECO:0000305|PubMed:20639533" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 203..227 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 250..291 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 301..600 FT /note="Necessary for interaction with SPIDR" FT /evidence="ECO:0000269|PubMed:23509288" FT REGION 362..414 FT /note="Necessary for dimerization and homooligomerization" FT /evidence="ECO:0000269|PubMed:28228481" FT REGION 870..873 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:25901030" FT REGION 897..899 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT REGION 1000..1003 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT REGION 1094..1139 FT /note="DNA Holliday junction binding" FT /evidence="ECO:0000269|PubMed:24257077" FT REGION 1110..1112 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT REGION 1121..1125 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT REGION 1160..1166 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT REGION 1227..1244 FT /note="Necessary for ssDNA and DNA Holliday junction FT binding" FT /evidence="ECO:0000269|PubMed:20639533" FT REGION 1289..1417 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 795..798 FT /note="DEAH box" FT MOTIF 1334..1349 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 203..217 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 250..289 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1289..1307 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1330..1353 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1354..1394 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 668..672 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CDG, FT ECO:0007744|PDB:4CGZ, ECO:0007744|PDB:4O3M" FT BINDING 692..696 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CDG, FT ECO:0007744|PDB:4CGZ, ECO:0007744|PDB:4O3M" FT BINDING 982 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:25901030, FT ECO:0007744|PDB:4CDG, ECO:0007744|PDB:4CGZ" FT BINDING 1036 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CDG, FT ECO:0007744|PDB:4CGZ, ECO:0007744|PDB:4O3M" FT BINDING 1055 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CDG, FT ECO:0007744|PDB:4CGZ, ECO:0007744|PDB:4O3M" FT BINDING 1063 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CDG, FT ECO:0007744|PDB:4CGZ, ECO:0007744|PDB:4O3M" FT BINDING 1066 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CDG, FT ECO:0007744|PDB:4CGZ, ECO:0007744|PDB:4O3M" FT BINDING 1242 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:25901030, FT ECO:0007744|PDB:4CDG, ECO:0007744|PDB:4CGZ" FT SITE 717 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:25901030" FT SITE 808 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:25901030" FT SITE 920 FT /note="3' overhang DNA-binding; via amide nitrogen" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT SITE 946 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT SITE 968 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT SITE 1110 FT /note="3' overhang DNA-binding" FT /evidence="ECO:0000269|PubMed:24816114, FT ECO:0000269|PubMed:25901030, ECO:0007744|PDB:4CGZ, FT ECO:0007744|PDB:4O3M" FT MOD_RES 28 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 48 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 57 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 114 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 168 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 171 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 338 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 358 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 419 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 422 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 426 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 464 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 499 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 508 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:16964243" FT MOD_RES 863 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1197 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1295 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1296 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1310 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 24 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 31 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 38 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 56 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 63 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 87 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 91 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 105 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 116 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 129 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 195 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 205 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 331 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 344 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="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 451 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 476 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 484 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 498 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 513 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 514 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 531 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 535 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 588 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 594 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 604 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1125 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1199 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1207 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1329 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1372 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1395 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 137 FT /note="K -> R (in dbSNP:rs28384988)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022295" FT VARIANT 298 FT /note="T -> M (in dbSNP:rs28384991)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022296" FT VARIANT 591 FT /note="R -> Q (in dbSNP:rs28385012)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022297" FT VARIANT 672 FT /note="Q -> R (in BLM; dbSNP:rs747281324)" FT /evidence="ECO:0000269|PubMed:7585968" FT /id="VAR_006901" FT VARIANT 841 FT /note="I -> T (in BLM; dbSNP:rs767086502)" FT /id="VAR_016032" FT VARIANT 843 FT /note="T -> I (in BLM; dbSNP:rs137853152)" FT /evidence="ECO:0000269|PubMed:7585968" FT /id="VAR_006902" FT VARIANT 868 FT /note="P -> L (in dbSNP:rs2227935)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022298" FT VARIANT 878 FT /note="C -> R (in BLM)" FT /evidence="ECO:0000269|PubMed:10862105" FT /id="VAR_016033" FT VARIANT 891 FT /note="G -> E (in BLM; dbSNP:rs763471784)" FT /id="VAR_009138" FT VARIANT 901 FT /note="C -> Y (in BLM; dbSNP:rs758311406)" FT /id="VAR_009139" FT VARIANT 1036 FT /note="C -> F (in BLM; dbSNP:rs137853153)" FT /evidence="ECO:0000269|PubMed:9285778" FT /id="VAR_009140" FT VARIANT 1043 FT /note="A -> D (in dbSNP:rs2229035)" FT /id="VAR_051731" FT VARIANT 1055 FT /note="C -> S (in BLM; dbSNP:rs367543029)" FT /evidence="ECO:0000269|PubMed:7585968" FT /id="VAR_006903" FT VARIANT 1205 FT /note="V -> I (in dbSNP:rs28385141)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022299" FT VARIANT 1209 FT /note="S -> T (in dbSNP:rs1801256)" FT /id="VAR_014912" FT VARIANT 1213 FT /note="E -> K (in dbSNP:rs28385142)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022300" FT VARIANT 1321 FT /note="V -> I (in dbSNP:rs7167216)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022301" FT MUTAGEN 666 FT /note="H->A: Reduced intramolecular association between FT both the helicase ATP-binding domain and the helicase FT C-terminal domain with the HRDC domain. No change in forked FT duplex DNA helicase activity. No change in DNA 4-way FT junction branch migration and Holliday junction dissolution FT activities. No change in suppression of enhanced sister FT chromatide exchange activity." FT /evidence="ECO:0000269|PubMed:25901030" FT MUTAGEN 729 FT /note="S->A: Reduced intramolecular interaction between FT both the helicase ATP-binding domain and the helicase FT C-terminal domain with the HRDC domain. No change in forked FT duplex DNA helicase activity. No change in DNA 4-way FT junction branch migration and Holliday junction dissolution FT activities. No change in suppression of enhanced sister FT chromatide exchange activity." FT /evidence="ECO:0000269|PubMed:25901030" FT MUTAGEN 1094..1103 FT /note="Missing: Decreased DNAHolliday junction binding." FT /evidence="ECO:0000269|PubMed:24257077" FT MUTAGEN 1121 FT /note="S->A: Decreased slightly DNAHolliday junction FT binding." FT /evidence="ECO:0000269|PubMed:24257077" FT MUTAGEN 1125 FT /note="K->A: Decreased DNAHolliday junction binding." FT /evidence="ECO:0000269|PubMed:24257077" FT MUTAGEN 1139 FT /note="R->A: Decreased strongly DNAHolliday junction FT binding." FT /evidence="ECO:0000269|PubMed:24257077" FT MUTAGEN 1164 FT /note="N->A: Reduced strongly DNA helicase activity." FT /evidence="ECO:0000269|PubMed:24816114" FT MUTAGEN 1227 FT /note="K->E: Reduced ssDNA binding. No change in FT DNAHolliday junction binding." FT /evidence="ECO:0000269|PubMed:20639533" FT MUTAGEN 1237 FT /note="Y->A: No change in ssDNA binding. Increased FT DNAHolliday junction binding." FT /evidence="ECO:0000269|PubMed:20639533" FT MUTAGEN 1239 FT /note="N->D: Reduced ssDNA binding. No change in FT DNAHolliday junction binding." FT /evidence="ECO:0000269|PubMed:20639533" FT MUTAGEN 1243 FT /note="T->A: No change in ssDNA binding. Decreased FT DNAHolliday junction binding." FT /evidence="ECO:0000269|PubMed:20639533" FT MUTAGEN 1244 FT /note="V->A: Reduced ssDNA binding. Increased DNAHolliday FT junction binding." FT /evidence="ECO:0000269|PubMed:20639533" FT MUTAGEN 1270 FT /note="K->V: Reduced intramolecular interaction between FT both the helicase ATP-binding domain and the helicase FT C-terminal domain with the HRDC domain." FT /evidence="ECO:0000269|PubMed:25901030" FT HELIX 151..154 FT /evidence="ECO:0007829|PDB:7XV0" FT HELIX 365..383 FT /evidence="ECO:0007829|PDB:5LUP" FT HELIX 388..391 FT /evidence="ECO:0007829|PDB:5LUP" FT HELIX 397..411 FT /evidence="ECO:0007829|PDB:5LUP" FT TURN 559..562 FT /evidence="ECO:0007829|PDB:7XUW" FT HELIX 640..643 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 652..661 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 672..680 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 685..688 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 695..705 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 706..713 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 717..729 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 734..737 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 745..753 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 755..757 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 762..765 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 767..770 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 774..785 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 789..796 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 797..800 FT /evidence="ECO:0007829|PDB:4CDG" FT TURN 804..807 FT /evidence="ECO:0007829|PDB:7AUD" FT HELIX 809..814 FT /evidence="ECO:0007829|PDB:4CDG" FT TURN 818..820 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 826..830 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 835..845 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 846..848 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 851..853 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 862..868 FT /evidence="ECO:0007829|PDB:7AUC" FT TURN 871..873 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 874..885 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 891..894 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 898..910 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 915..919 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 924..935 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 941..945 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 947..950 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 960..965 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 970..977 FT /evidence="ECO:0007829|PDB:7AUC" FT TURN 978..983 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 987..993 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 995..1007 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1013..1031 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1037..1044 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1054..1057 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1059..1061 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1064..1067 FT /evidence="ECO:0007829|PDB:7AUC" FT TURN 1069..1071 FT /evidence="ECO:0007829|PDB:4CDG" FT STRAND 1074..1076 FT /evidence="ECO:0007829|PDB:4CDG" FT HELIX 1078..1090 FT /evidence="ECO:0007829|PDB:4O3M" FT STRAND 1096..1099 FT /evidence="ECO:0007829|PDB:3WE2" FT HELIX 1111..1119 FT /evidence="ECO:0007829|PDB:4O3M" FT TURN 1129..1136 FT /evidence="ECO:0007829|PDB:4O3M" FT HELIX 1139..1151 FT /evidence="ECO:0007829|PDB:4O3M" FT STRAND 1154..1161 FT /evidence="ECO:0007829|PDB:4O3M" FT STRAND 1163..1166 FT /evidence="ECO:0007829|PDB:4CGZ" FT STRAND 1167..1173 FT /evidence="ECO:0007829|PDB:4O3M" FT HELIX 1177..1181 FT /evidence="ECO:0007829|PDB:4O3M" FT STRAND 1188..1190 FT /evidence="ECO:0007829|PDB:4CDG" FT HELIX 1195..1197 FT /evidence="ECO:0007829|PDB:4CDG" FT STRAND 1207..1209 FT /evidence="ECO:0007829|PDB:2RRD" FT HELIX 1210..1233 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1237..1239 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1243..1252 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1257..1260 FT /evidence="ECO:0007829|PDB:7AUC" FT STRAND 1263..1265 FT /evidence="ECO:0007829|PDB:2KV2" FT HELIX 1268..1283 FT /evidence="ECO:0007829|PDB:7AUC" FT HELIX 1284..1288 FT /evidence="ECO:0007829|PDB:7AUC" SQ SEQUENCE 1417 AA; 159000 MW; 423DF5F381194E11 CRC64; MAAVPQNNLQ EQLERHSART LNNKLSLSKP KFSGFTFKKK TSSDNNVSVT NVSVAKTPVL RNKDVNVTED FSFSEPLPNT TNQQRVKDFF KNAPAGQETQ RGGSKSLLPD FLQTPKEVVC TTQNTPTVKK SRDTALKKLE FSSSPDSLST INDWDDMDDF DTSETSKSFV TPPQSHFVRV STAQKSKKGK RNFFKAQLYT TNTVKTDLPP PSSESEQIDL TEEQKDDSEW LSSDVICIDD GPIAEVHINE DAQESDSLKT HLEDERDNSE KKKNLEEAEL HSTEKVPCIE FDDDDYDTDF VPPSPEEIIS ASSSSSKCLS TLKDLDTSDR KEDVLSTSKD LLSKPEKMSM QELNPETSTD CDARQISLQQ QLIHVMEHIC KLIDTIPDDK LKLLDCGNEL LQQRNIRRKL LTEVDFNKSD ASLLGSLWRY RPDSLDGPME GDSCPTGNSM KELNFSHLPS NSVSPGDCLL TTTLGKTGFS ATRKNLFERP LFNTHLQKSF VSSNWAETPR LGKKNESSYF PGNVLTSTAV KDQNKHTASI NDLERETQPS YDIDNFDIDD FDDDDDWEDI MHNLAASKSS TAAYQPIKEG RPIKSVSERL SSAKTDCLPV SSTAQNINFS ESIQNYTDKS AQNLASRNLK HERFQSLSFP HTKEMMKIFH KKFGLHNFRT NQLEAINAAL LGEDCFILMP TGGGKSLCYQ LPACVSPGVT VVISPLRSLI VDQVQKLTSL DIPATYLTGD KTDSEATNIY LQLSKKDPII KLLYVTPEKI CASNRLISTL ENLYERKLLA RFVIDEAHCV SQWGHDFRQD YKRMNMLRQK FPSVPVMALT ATANPRVQKD ILTQLKILRP QVFSMSFNRH NLKYYVLPKK PKKVAFDCLE WIRKHHPYDS GIIYCLSRRE CDTMADTLQR DGLAALAYHA GLSDSARDEV QQKWINQDGC QVICATIAFG MGIDKPDVRF VIHASLPKSV EGYYQESGRA GRDGEISHCL LFYTYHDVTR LKRLIMMEKD GNHHTRETHF NNLYSMVHYC ENITECRRIQ LLAYFGENGF NPDFCKKHPD VSCDNCCKTK DYKTRDVTDD VKSIVRFVQE HSSSQGMRNI KHVGPSGRFT MNMLVDIFLG SKSAKIQSGI FGKGSAYSRH NAERLFKKLI LDKILDEDLY INANDQAIAY VMLGNKAQTV LNGNLKVDFM ETENSSSVKK QKALVAKVSQ REEMVKKCLG ELTEVCKSLG KVFGVHYFNI FNTVTLKKLA ESLSSDPEVL LQIDGVTEDK LEKYGAEVIS VLQKYSEWTS PAEDSSPGIS LSSSRGPGRS AAEELDEEIP VSSHYFASKT RNERKRKKMP ASQRSKRRKT ASSGSKAKGG SATCRKISSK TKSSSIIGSS SASHTSQATS GANSKLGIMA PPKPINRPFL KPSYAFS //