BLM_HUMAN
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 03-AUG-2022, entry version 221.
DE RecName: Full=RecQ-like DNA helicase BLM {ECO:0000305};
DE EC=3.6.4.12 {ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030};
DE AltName: Full=Bloom syndrome protein;
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], AND FUNCTION.
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 STRUCTURE BY NMR OF 1200-1295.
RX PubMed=20739603; DOI=10.1093/jb/mvq097;
RA Sato A., Mishima M., Nagai A., Kim S.Y., Ito Y., Hakoshima T., Jee J.G.,
RA Kitano K.;
RT "Solution structure of the HRDC domain of human Bloom syndrome protein
RT BLM.";
RL J. Biochem. 148:517-525(2010).
RN [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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). Involved in 5'-end
CC resection of DNA during double-strand break (DSB) repair: unwinds DNA
CC and recruits DNA2 which mediates the cleavage of 5'-ssDNA
CC (PubMed:21325134). Negatively regulates sister chromatid exchange (SCE)
CC (PubMed:25901030). Stimulates DNA 4-way junction branch migration and
CC DNA Holliday junction dissolution (PubMed:25901030). Binds single-
CC stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction
CC (PubMed:20639533, PubMed:24257077, PubMed:25901030). Recruited by the
CC KHDC3L-OOEP scaffold to DNA replication forks where it is retained by
CC TRIM25 ubiquitination, it thereby promotes the restart of stalled
CC replication forks (By similarity). {ECO:0000250|UniProtKB:O88700,
CC ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:20639533,
CC ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288,
CC ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114,
CC ECO:0000269|PubMed:25901030, 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; EC=3.6.4.12;
CC Evidence={ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030};
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.
CC {ECO:0000250|UniProtKB:O88700}.
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 -!- 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="http://atlasgeneticsoncology.org/Genes/BLMID109.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/blm/";
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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 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 AlphaFoldDB; P54132; -.
DR BMRB; P54132; -.
DR SMR; P54132; -.
DR BioGRID; 107110; 221.
DR ComplexPortal; CPX-3301; BTR double Holliday Junction dissolution complex.
DR CORUM; P54132; -.
DR DIP; DIP-33322N; -.
DR ELM; P54132; -.
DR IntAct; P54132; 73.
DR MINT; P54132; -.
DR STRING; 9606.ENSP00000347232; -.
DR BindingDB; P54132; -.
DR ChEMBL; CHEMBL1293237; -.
DR GlyGen; P54132; 1 site.
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; P54132; -.
DR PeptideAtlas; P54132; -.
DR PRIDE; P54132; -.
DR ProteomicsDB; 56649; -.
DR ABCD; P54132; 1 sequenced antibody.
DR Antibodypedia; 704; 500 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 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; CGRFTMN; -.
DR OrthoDB; 445763at2759; -.
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 HDR through Homologous Recombination (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; 109 hits in 1089 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 133 other tissues.
DR ExpressionAtlas; P54132; baseline and differential.
DR Genevisible; P54132; HS.
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: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; IC: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:0006974; P:cellular response to DNA damage stimulus; 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: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; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
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 transcription, DNA-templated; 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:0048478; P:replication fork protection; NAS:UniProtKB.
DR GO; GO:0071139; P:resolution of 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 Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.150.80; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
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 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; SSF46785; SSF46785; 1.
DR SUPFAM; SSF47819; SSF47819; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR TIGRFAMs; TIGR00614; recQ_fam; 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.
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 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 /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 C-
FT 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 C-
FT 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 DNA Holliday junction binding."
FT /evidence="ECO:0000269|PubMed:24257077"
FT MUTAGEN 1121
FT /note="S->A: Decreased slightly DNA Holliday junction
FT binding."
FT /evidence="ECO:0000269|PubMed:24257077"
FT MUTAGEN 1125
FT /note="K->A: Decreased DNA Holliday junction binding."
FT /evidence="ECO:0000269|PubMed:24257077"
FT MUTAGEN 1139
FT /note="R->A: Decreased strongly DNA Holliday 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 DNA
FT Holliday junction binding."
FT /evidence="ECO:0000269|PubMed:20639533"
FT MUTAGEN 1237
FT /note="Y->A: No change in ssDNA binding. Increased DNA
FT Holliday junction binding."
FT /evidence="ECO:0000269|PubMed:20639533"
FT MUTAGEN 1239
FT /note="N->D: Reduced ssDNA binding. No change in DNA
FT Holliday junction binding."
FT /evidence="ECO:0000269|PubMed:20639533"
FT MUTAGEN 1243
FT /note="T->A: No change in ssDNA binding. Decreased DNA
FT Holliday junction binding."
FT /evidence="ECO:0000269|PubMed:20639533"
FT MUTAGEN 1244
FT /note="V->A: Reduced ssDNA binding. Increased DNA Holliday
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 C-
FT terminal domain with the HRDC domain."
FT /evidence="ECO:0000269|PubMed:25901030"
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 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
