MDC1_HUMAN
ID MDC1_HUMAN Reviewed; 2089 AA.
AC Q14676; A2AB04; A2BF04; A2RRA8; A7YY86; B0S8A2; Q0EFC2; Q2L6H7; Q2TAZ4;
AC Q5JP55; Q5JP56; Q5ST83; Q68CQ3; Q86Z06; Q96QC2;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 3.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Mediator of DNA damage checkpoint protein 1;
DE AltName: Full=Nuclear factor with BRCT domains 1;
GN Name=MDC1; Synonyms=KIAA0170, NFBD1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS MET-536;
RP PRO-1540 AND ARG-1545.
RC TISSUE=Myelomonocyte;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-268.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-251;
RP ALA-586; ASP-1509; PRO-1540 AND ARG-1545.
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-371;
RP LEU-386; PRO-1180; ASP-1509 AND ARG-1545.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=16702430; DOI=10.1534/genetics.106.057034;
RA Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M.,
RA Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K.,
RA Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A.,
RA Wanner V., Sano K., Macquin C., Ikeo K., Tokunaga K., Gojobori T.,
RA Inoko H., Bahram S.;
RT "Rapid evolution of major histocompatibility complex class I genes in
RT primates generates new disease alleles in humans via hitchhiking
RT diversity.";
RL Genetics 173:1555-1570(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-268 AND
RP ARG-1545.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-1545.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 279-2089 (ISOFORM 4), AND VARIANTS MET-536; PRO-1540
RP AND ARG-1545.
RC TISSUE=Pancreas;
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 [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14695167;
RA Mochan T.A., Venere M., DiTullio R.A. Jr., Halazonetis T.D.;
RT "53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways
RT activating ataxia-telangiectasia mutated (ATM) in response to DNA damage.";
RL Cancer Res. 63:8586-8591(2003).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12475977; DOI=10.1074/jbc.m210749200;
RA Shang Y.L., Bodero A.J., Chen P.-L.;
RT "NFBD1, a novel nuclear protein with signature motifs of FHA and BRCT, and
RT an internal 41-amino acid repeat sequence, is an early participant in DNA
RT damage response.";
RL J. Biol. Chem. 278:6323-6329(2003).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ATM- AND CELL
RP CYCLE-DEPENDENT PHOSPHORYLATION, AND DOMAINS NLS1 AND NLS2.
RX PubMed=12499369; DOI=10.1074/jbc.m211392200;
RA Xu X., Stern D.F.;
RT "NFBD1/KIAA0170 is a chromatin-associated protein involved in DNA damage
RT signaling pathways.";
RL J. Biol. Chem. 278:8795-8803(2003).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHEK2.
RX PubMed=12551934; DOI=10.1074/jbc.c300001200;
RA Peng A., Chen P.-L.;
RT "NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2
RT phosphorylation in response to DNA damage.";
RL J. Biol. Chem. 278:8873-8876(2003).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRCA1 AND BARD1.
RX PubMed=12611903; DOI=10.1074/jbc.c300060200;
RA Lou Z., Chini C.C.S., Minter-Dykhouse K., Chen J.;
RT "Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization
RT and phosphorylation in DNA damage checkpoint control.";
RL J. Biol. Chem. 278:13599-13602(2003).
RN [13]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP INTERACTION WITH THE MRN COMPLEX, PHOSPHORYLATION BY ATM, AND MUTAGENESIS
RP OF ARG-58.
RX PubMed=12607003; DOI=10.1038/nature01445;
RA Goldberg M., Stucki M., Falck J., D'Amours D., Rahman D., Pappin D.,
RA Bartek J., Jackson S.P.;
RT "MDC1 is required for the intra-S-phase DNA damage checkpoint.";
RL Nature 421:952-956(2003).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CHEK2, PHOSPHORYLATION BY
RP ATM AND CHEK2, AND MUTAGENESIS OF ARG-58; SER-72; ASN-96; GLY-97 AND
RP THR-98.
RX PubMed=12607004; DOI=10.1038/nature01447;
RA Lou Z., Minter-Dykhouse K., Wu X., Chen J.;
RT "MDC1 is coupled to activated CHK2 in mammalian DNA damage response
RT pathways.";
RL Nature 421:957-961(2003).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH THE MRN COMPLEX; ATM;
RP FANCD2; H2AX; SMC1A AND TP53BP1, AND PHOSPHORYLATION BY ATM.
RX PubMed=12607005; DOI=10.1038/nature01446;
RA Stewart G.S., Wang B., Bignell C.R., Taylor A.M.R., Elledge S.J.;
RT "MDC1 is a mediator of the mammalian DNA damage checkpoint.";
RL Nature 421:961-966(2003).
RN [16]
RP REVIEW.
RX PubMed=15279781; DOI=10.1016/j.dnarep.2004.03.007;
RA Stucki M., Jackson S.P.;
RT "MDC1/NFBD1: a key regulator of the DNA damage response in higher
RT eukaryotes.";
RL DNA Repair 3:953-957(2004).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH H2AX.
RX PubMed=15201865; DOI=10.1038/sj.emboj.7600269;
RA Lukas C., Melander F., Stucki M., Falck J., Bekker-Jensen S., Goldberg M.,
RA Lerenthal Y., Jackson S.P., Bartek J., Lukas J.;
RT "Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-
RT dependent chromatin retention.";
RL EMBO J. 23:2674-2683(2004).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH THE PRKDC COMPLEX.
RX PubMed=15377652; DOI=10.1074/jbc.c400375200;
RA Lou Z., Chen B.P.-C., Asaithamby A., Minter-Dykhouse K., Chen D.J.,
RA Chen J.;
RT "MDC1 regulates DNA-PK autophosphorylation in response to DNA damage.";
RL J. Biol. Chem. 279:46359-46362(2004).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17693683; DOI=10.1074/mcp.m700120-mcp200;
RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J.,
RA Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.;
RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling
RT network: indicating the involvement of ribonucleoside-diphosphate reductase
RT M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal
RT transduction.";
RL Mol. Cell. Proteomics 6:1952-1967(2007).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-372; SER-376; THR-378;
RP SER-513; THR-523 AND SER-780, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [22]
RP INTERACTION WITH RNF8.
RX PubMed=18006705; DOI=10.1126/science.1150034;
RA Kolas N.K., Chapman J.R., Nakada S., Ylanko J., Chahwan R., Sweeney F.D.,
RA Panier S., Mendez M., Wildenhain J., Thomson T.M., Pelletier L.,
RA Jackson S.P., Durocher D.;
RT "Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase.";
RL Science 318:1637-1640(2007).
RN [23]
RP INTERACTION WITH CEP164.
RX PubMed=18283122; DOI=10.1101/gad.1627708;
RA Sivasubramaniam S., Sun X., Pan Y.R., Wang S., Lee E.Y.;
RT "Cep164 is a mediator protein required for the maintenance of genomic
RT stability through modulation of MDC1, RPA, and CHK1.";
RL Genes Dev. 22:587-600(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1403 AND THR-1425, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; THR-301; SER-394;
RP SER-397; SER-402; THR-404; THR-449; SER-453; THR-455; SER-495; SER-498;
RP SER-513; SER-780; SER-793; SER-1033; SER-1068; THR-1198; SER-1399;
RP SER-1400; THR-1403; THR-1425; THR-1466; THR-1548; THR-1589; SER-1604;
RP THR-1630; THR-1664; THR-1671; SER-1681; THR-1697; SER-1702; SER-1711;
RP SER-1775 AND THR-1858, VARIANT [LARGE SCALE ANALYSIS] PRO-1540, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-329; THR-331;
RP SER-372; SER-376; THR-378; SER-402; THR-404; SER-411; THR-449; SER-453;
RP THR-455; THR-1157 AND THR-1466, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-812 AND LYS-1402, AND
RP IDENTIFICATION BY MASS 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 [29]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH APTX.
RX PubMed=20008512; DOI=10.1093/nar/gkp1149;
RA Becherel O.J., Jakob B., Cherry A.L., Gueven N., Fusser M., Kijas A.W.,
RA Peng C., Katyal S., McKinnon P.J., Chen J., Epe B., Smerdon S.J.,
RA Taucher-Scholz G., Lavin M.F.;
RT "CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in
RT the DNA damage response.";
RL Nucleic Acids Res. 38:1489-1503(2010).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; SER-168; SER-329;
RP THR-331; SER-402; THR-404; SER-485; SER-513; SER-955; SER-1068; SER-1399;
RP THR-1403; THR-1425; THR-1589; SER-1775; THR-1800 AND SER-1820, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; THR-301; SER-329;
RP SER-402; THR-404; THR-455; SER-495; SER-498; THR-1567 AND SER-1820, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
RP SUMOYLATION AT LYS-1840, UBIQUITINATION BY RNF4, MUTAGENESIS OF LYS-1840,
RP AND INTERACTION WITH TP53BP1.
RX PubMed=22635276; DOI=10.1038/emboj.2012.158;
RA Luo K., Zhang H., Wang L., Yuan J., Lou Z.;
RT "Sumoylation of MDC1 is important for proper DNA damage response.";
RL EMBO J. 31:3008-3019(2012).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; THR-146; SER-168;
RP SER-299; SER-376; SER-453; THR-455; SER-485; SER-495; SER-498; SER-513;
RP THR-523; SER-780; SER-998; SER-1086; THR-1157; SER-1399; SER-1400;
RP THR-1403; THR-1425; SER-1564; THR-1589; THR-1671; SER-1775 AND SER-1820,
RP AND 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 [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; SER-168; SER-329;
RP SER-485; SER-780; THR-1157; THR-1198; THR-1239; THR-1280; THR-1302 AND
RP THR-1608, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1943, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [36]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1840, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [37]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-616 AND LYS-1413, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [38]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-616; LYS-1413; LYS-1740; LYS-1790
RP AND LYS-1840, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [39]
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 1883-2089 IN COMPLEX WITH
RP PHOSPHORYLATED H2AX.
RX PubMed=16377563; DOI=10.1016/j.cell.2005.09.038;
RA Stucki M., Clapperton J.A., Mohammad D., Yaffe M.B., Smerdon S.J.,
RA Jackson S.P.;
RT "MDC1 directly binds phosphorylated histone H2AX to regulate cellular
RT responses to DNA double-strand breaks.";
RL Cell 123:1213-1226(2005).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 1891-2086, AND INTERACTION WITH
RP PHOSPHORYLATED H2AX.
RX PubMed=16049003; DOI=10.1074/jbc.c500273200;
RA Lee M.S., Edwards R.A., Thede G.L., Glover J.N.M.;
RT "Structure of the BRCT repeat domain of MDC1 and its specificity for the
RT free COOH-terminal end of the gamma-H2AX histone tail.";
RL J. Biol. Chem. 280:32053-32056(2005).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 1891-2089 IN COMPLEX WITH
RP PHOSPHORYLATED HISTONE TETRAPEPTIDE.
RX PubMed=20159462; DOI=10.1016/j.str.2009.12.008;
RA Campbell S.J., Edwards R.A., Glover J.N.;
RT "Comparison of the structures and peptide binding specificities of the BRCT
RT domains of MDC1 and BRCA1.";
RL Structure 18:167-176(2010).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 1884-2089.
RX PubMed=22139841; DOI=10.1074/jbc.m111.307868;
RA Singh N., Wiltshire T.D., Thompson J.R., Mer G., Couch F.J.;
RT "Molecular basis for the association of microcephalin (MCPH1) protein with
RT the cell division cycle protein 27 (Cdc27) subunit of the anaphase-
RT promoting complex.";
RL J. Biol. Chem. 287:2854-2862(2012).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-10 AND 19-138, AND
RP PHOSPHORYLATION AT THR-4.
RX PubMed=22234877; DOI=10.1093/nar/gkr1296;
RA Liu J., Luo S., Zhao H., Liao J., Li J., Yang C., Xu B., Stern D.F., Xu X.,
RA Ye K.;
RT "Structural mechanism of the phosphorylation-dependent dimerization of the
RT MDC1 forkhead-associated domain.";
RL Nucleic Acids Res. 40:3898-3912(2012).
CC -!- FUNCTION: Required for checkpoint mediated cell cycle arrest in
CC response to DNA damage within both the S phase and G2/M phases of the
CC cell cycle. May serve as a scaffold for the recruitment of DNA repair
CC and signal transduction proteins to discrete foci of DNA damage marked
CC by 'Ser-139' phosphorylation of histone H2AX. Also required for
CC downstream events subsequent to the recruitment of these proteins.
CC These include phosphorylation and activation of the ATM, CHEK1 and
CC CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2
CC may also be activated independently by a parallel pathway mediated by
CC TP53BP1. {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369,
CC ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003,
CC ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005,
CC ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167,
CC ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652}.
CC -!- SUBUNIT: Homodimer. Interacts with several proteins involved in the DNA
CC damage response, although not all these interactions may be direct.
CC Interacts with H2AX, which requires phosphorylation of H2AX on 'Ser-
CC 139'. Interacts with the MRN complex, composed of MRE11, RAD50, and
CC NBN. Interacts with CHEK2, which requires ATM-mediated phosphorylation
CC of 'Thr-68' within the FHA domain of CHEK2. Interacts constitutively
CC with the BRCA1-BARD1 complex, SMC1A and TP53BP1. Interacts with ATM and
CC FANCD2, and these interactions are reduced upon DNA damage. Also
CC interacts with the PRKDC complex, composed of XRCC6/KU70, XRCC5/KU80
CC and PRKDC/XRCC7. This interaction may be required for PRKDC
CC autophosphorylation, which is essential for DNA double strand break
CC (DSB) repair. When phosphorylated by ATM, interacts with RNF8 (via FHA
CC domain). Interacts with CEP164. When phosphorylated, interacts with
CC APTX (via FHA-like domain). {ECO:0000269|PubMed:12551934,
CC ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004,
CC ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903,
CC ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652,
CC ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563,
CC ECO:0000269|PubMed:18006705, ECO:0000269|PubMed:18283122,
CC ECO:0000269|PubMed:20008512, ECO:0000269|PubMed:20159462,
CC ECO:0000269|PubMed:22635276}.
CC -!- INTERACTION:
CC Q14676; Q13315: ATM; NbExp=3; IntAct=EBI-495644, EBI-495465;
CC Q14676; P38398: BRCA1; NbExp=4; IntAct=EBI-495644, EBI-349905;
CC Q14676; P16104: H2AX; NbExp=21; IntAct=EBI-495644, EBI-494830;
CC Q14676; O60934: NBN; NbExp=33; IntAct=EBI-495644, EBI-494844;
CC Q14676; O96028: NSD2; NbExp=3; IntAct=EBI-495644, EBI-2693298;
CC Q14676; O96028-1: NSD2; NbExp=3; IntAct=EBI-495644, EBI-15910280;
CC Q14676; Q06609: RAD51; NbExp=3; IntAct=EBI-495644, EBI-297202;
CC Q14676; O76064: RNF8; NbExp=11; IntAct=EBI-495644, EBI-373337;
CC Q14676; O76064-1: RNF8; NbExp=2; IntAct=EBI-495644, EBI-15964690;
CC Q14676; Q99816: TSG101; NbExp=5; IntAct=EBI-495644, EBI-346882;
CC Q14676; O43070: nbs1; Xeno; NbExp=2; IntAct=EBI-495644, EBI-2125045;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12475977,
CC ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934,
CC ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004,
CC ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903,
CC ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865,
CC ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:20008512}. Chromosome
CC {ECO:0000250}. Note=Associated with chromatin. Relocalizes to discrete
CC nuclear foci following DNA damage, this requires 'Ser-139'
CC phosphorylation of H2AX. Colocalizes with APTX at sites of DNA double-
CC strand breaks.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q14676-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14676-2; Sequence=VSP_014593;
CC Name=3;
CC IsoId=Q14676-3; Sequence=VSP_034104;
CC Name=4;
CC IsoId=Q14676-4; Sequence=VSP_014593, VSP_034103;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis.
CC {ECO:0000269|PubMed:12499369}.
CC -!- DOMAIN: Tandemly repeated BRCT domains are characteristic of proteins
CC involved in DNA damage signaling. In MDC1, these repeats are required
CC for localization to chromatin which flanks sites of DNA damage marked
CC by 'Ser-139' phosphorylation of H2AX. {ECO:0000269|PubMed:12499369}.
CC -!- PTM: Phosphorylated upon exposure to ionizing radiation (IR),
CC ultraviolet radiation (UV), and hydroxyurea (HU). Phosphorylation in
CC response to IR requires ATM, NBN, and possibly CHEK2. Also
CC phosphorylated during the G2/M phase of the cell cycle and during
CC activation of the mitotic spindle checkpoint. Phosphorylation at Thr-4
CC by ATM stabilizes and enhances homodimerization via the FHA domain.
CC {ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004,
CC ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:22234877}.
CC -!- PTM: Sumoylation at Lys-1840 by PIAS4 following DNA damage promotes
CC ubiquitin-mediated degradation. {ECO:0000269|PubMed:22635276}.
CC -!- PTM: Ubiquitinated by RNF4, leading to proteasomal degradation;
CC undergoes 'Lys-48'-linked polyubiquitination.
CC {ECO:0000269|PubMed:22635276}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11487.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAH18685.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; D79992; BAA11487.2; ALT_INIT; mRNA.
DR EMBL; CR749828; CAH18685.1; ALT_TERM; mRNA.
DR EMBL; BA000025; BAB63322.1; -; Genomic_DNA.
DR EMBL; AB088099; BAC54931.1; -; Genomic_DNA.
DR EMBL; AB202097; BAE78617.1; -; Genomic_DNA.
DR EMBL; AB103605; BAF31266.1; -; Genomic_DNA.
DR EMBL; AL662797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL845353; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX248307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX927283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759873; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR788240; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR936878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03321.1; -; Genomic_DNA.
DR EMBL; BC110645; AAI10646.1; -; mRNA.
DR EMBL; BC152556; AAI52557.1; -; mRNA.
DR CCDS; CCDS34384.1; -. [Q14676-1]
DR RefSeq; NP_055456.2; NM_014641.2. [Q14676-1]
DR RefSeq; XP_005249551.1; XM_005249494.4. [Q14676-1]
DR RefSeq; XP_011513303.1; XM_011515001.2. [Q14676-1]
DR RefSeq; XP_011513305.1; XM_011515003.2. [Q14676-1]
DR RefSeq; XP_016867008.1; XM_017011519.1. [Q14676-1]
DR PDB; 2ADO; X-ray; 1.45 A; A/B=1891-2086.
DR PDB; 2AZM; X-ray; 2.41 A; A/B=1883-2089.
DR PDB; 2ETX; X-ray; 1.33 A; A/B=1884-2089.
DR PDB; 3K05; X-ray; 1.33 A; A/B=1891-2089.
DR PDB; 3UEO; X-ray; 2.60 A; E/F=325-336.
DR PDB; 3UMZ; X-ray; 1.65 A; A/B=27-138.
DR PDB; 3UN0; X-ray; 2.30 A; A/B=26-138.
DR PDB; 3UNM; X-ray; 1.80 A; A/B=27-138.
DR PDB; 3UNN; X-ray; 1.70 A; A=27-138, B=1-8.
DR PDB; 3UOT; X-ray; 1.80 A; A/B=19-138, D/E=1-10.
DR PDBsum; 2ADO; -.
DR PDBsum; 2AZM; -.
DR PDBsum; 2ETX; -.
DR PDBsum; 3K05; -.
DR PDBsum; 3UEO; -.
DR PDBsum; 3UMZ; -.
DR PDBsum; 3UN0; -.
DR PDBsum; 3UNM; -.
DR PDBsum; 3UNN; -.
DR PDBsum; 3UOT; -.
DR AlphaFoldDB; Q14676; -.
DR SMR; Q14676; -.
DR BioGRID; 115014; 420.
DR CORUM; Q14676; -.
DR DIP; DIP-33603N; -.
DR IntAct; Q14676; 171.
DR MINT; Q14676; -.
DR STRING; 9606.ENSP00000365588; -.
DR BindingDB; Q14676; -.
DR GlyGen; Q14676; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14676; -.
DR PhosphoSitePlus; Q14676; -.
DR SwissPalm; Q14676; -.
DR BioMuta; MDC1; -.
DR CPTAC; CPTAC-3234; -.
DR CPTAC; CPTAC-3235; -.
DR CPTAC; CPTAC-931; -.
DR EPD; Q14676; -.
DR jPOST; Q14676; -.
DR MassIVE; Q14676; -.
DR MaxQB; Q14676; -.
DR PaxDb; Q14676; -.
DR PeptideAtlas; Q14676; -.
DR PRIDE; Q14676; -.
DR ProteomicsDB; 60105; -. [Q14676-1]
DR ProteomicsDB; 60106; -. [Q14676-2]
DR ProteomicsDB; 60107; -. [Q14676-3]
DR ProteomicsDB; 60108; -. [Q14676-4]
DR Antibodypedia; 1870; 496 antibodies from 33 providers.
DR CPTC; Q14676; 5 antibodies.
DR DNASU; 9656; -.
DR Ensembl; ENST00000376406.8; ENSP00000365588.3; ENSG00000137337.16. [Q14676-1]
DR Ensembl; ENST00000383566.8; ENSP00000373060.4; ENSG00000206481.11.
DR Ensembl; ENST00000420019.6; ENSP00000396484.2; ENSG00000224587.9. [Q14676-1]
DR Ensembl; ENST00000420320.6; ENSP00000416511.2; ENSG00000225589.9. [Q14676-1]
DR Ensembl; ENST00000427406.6; ENSP00000387429.2; ENSG00000234012.9. [Q14676-1]
DR Ensembl; ENST00000435664.6; ENSP00000404318.2; ENSG00000231135.9.
DR Ensembl; ENST00000440369.6; ENSP00000415212.2; ENSG00000228575.9. [Q14676-1]
DR Ensembl; ENST00000449153.6; ENSP00000409167.2; ENSG00000237095.9. [Q14676-1]
DR GeneID; 9656; -.
DR KEGG; hsa:9656; -.
DR MANE-Select; ENST00000376406.8; ENSP00000365588.3; NM_014641.3; NP_055456.2.
DR UCSC; uc003nrg.5; human. [Q14676-1]
DR CTD; 9656; -.
DR DisGeNET; 9656; -.
DR GeneCards; MDC1; -.
DR HGNC; HGNC:21163; MDC1.
DR HPA; ENSG00000137337; Low tissue specificity.
DR MIM; 607593; gene.
DR neXtProt; NX_Q14676; -.
DR OpenTargets; ENSG00000137337; -.
DR PharmGKB; PA134942837; -.
DR VEuPathDB; HostDB:ENSG00000137337; -.
DR eggNOG; KOG2043; Eukaryota.
DR GeneTree; ENSGT00940000161757; -.
DR HOGENOM; CLU_003038_0_0_1; -.
DR InParanoid; Q14676; -.
DR OMA; HGDCETD; -.
DR OrthoDB; 670424at2759; -.
DR PhylomeDB; Q14676; -.
DR TreeFam; TF329580; -.
DR PathwayCommons; Q14676; -.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR SignaLink; Q14676; -.
DR SIGNOR; Q14676; -.
DR BioGRID-ORCS; 9656; 140 hits in 1077 CRISPR screens.
DR ChiTaRS; MDC1; human.
DR EvolutionaryTrace; Q14676; -.
DR GeneWiki; MDC1; -.
DR GenomeRNAi; 9656; -.
DR Pharos; Q14676; Tbio.
DR PRO; PR:Q14676; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q14676; protein.
DR Bgee; ENSG00000137337; Expressed in right testis and 93 other tissues.
DR ExpressionAtlas; Q14676; baseline and differential.
DR Genevisible; Q14676; HS.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0070975; F:FHA domain binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; TAS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR IDEAL; IID00568; -.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF16770; RTT107_BRCT_5; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR PROSITE; PS50172; BRCT; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Chromosome;
KW DNA damage; DNA repair; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..2089
FT /note="Mediator of DNA damage checkpoint protein 1"
FT /id="PRO_0000096316"
FT DOMAIN 54..105
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DOMAIN 1892..1970
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1991..2082
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 1..150
FT /note="Interaction with CHEK2"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..220
FT /note="Interaction with the MRN complex"
FT REGION 145..568
FT /note="Required for nuclear localization (NLS1)"
FT REGION 185..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 482..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..1887
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1148..1610
FT /note="Interaction with the PRKDC complex"
FT REGION 1698..2089
FT /note="Required for nuclear localization (NLS2)"
FT COMPBIAS 1..19
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..275
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..507
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..687
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 816..902
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 913..952
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 982..996
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1017..1031
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1114..1158
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1166..1233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1248..1274
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1290..1390
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1401..1513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1535..1568
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1576..1609
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1619..1636
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1662..1718
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1802..1833
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1835..1879
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 4
FT /note="Phosphothreonine; by ATM"
FT /evidence="ECO:0000269|PubMed:22234877"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 146
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:17693683, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5U2M8"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 301
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 331
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 378
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 404
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 449
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 455
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 504
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 523
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5U2M8"
FT MOD_RES 780
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 793
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 812
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 955
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 998
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1033
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1068
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 1086
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1157
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1198
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 1239
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1280
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1302
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1399
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1400
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1402
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1403
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1425
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1466
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 1548
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1567
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1589
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1604
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1608
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1630
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1664
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1671
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1681
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1697
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1702
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1711
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1775
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1800
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1820
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1858
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1943
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CROSSLNK 616
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 616
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1413
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 1413
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1740
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1790
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1840
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000269|PubMed:22635276"
FT CROSSLNK 1840
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 741..1004
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014593"
FT VAR_SEQ 1029..1787
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034103"
FT VAR_SEQ 1124..1410
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034104"
FT VARIANT 179
FT /note="R -> C (in dbSNP:rs28986464)"
FT /id="VAR_051160"
FT VARIANT 251
FT /note="E -> K (in dbSNP:rs2517560)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_022843"
FT VARIANT 268
FT /note="R -> K (in dbSNP:rs9262152)"
FT /evidence="ECO:0000269|PubMed:14574404,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_022844"
FT VARIANT 371
FT /note="E -> K (in dbSNP:rs2075015)"
FT /evidence="ECO:0000269|PubMed:16702430"
FT /id="VAR_022845"
FT VARIANT 386
FT /note="P -> L (in dbSNP:rs28986465)"
FT /evidence="ECO:0000269|PubMed:16702430"
FT /id="VAR_051161"
FT VARIANT 536
FT /note="I -> M (in dbSNP:rs58344693)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8724849"
FT /id="VAR_043922"
FT VARIANT 586
FT /note="S -> A (in dbSNP:rs2844707)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_022846"
FT VARIANT 917
FT /note="R -> S (in dbSNP:rs28986467)"
FT /id="VAR_051162"
FT VARIANT 1100
FT /note="P -> A (in dbSNP:rs28994869)"
FT /id="VAR_051163"
FT VARIANT 1112
FT /note="S -> F (in dbSNP:rs28987085)"
FT /id="VAR_051164"
FT VARIANT 1180
FT /note="S -> P (in dbSNP:rs9461623)"
FT /evidence="ECO:0000269|PubMed:16702430"
FT /id="VAR_051165"
FT VARIANT 1509
FT /note="E -> D (in dbSNP:rs3132589)"
FT /evidence="ECO:0000269|PubMed:16702430, ECO:0000269|Ref.3"
FT /id="VAR_022847"
FT VARIANT 1540
FT /note="S -> P (in dbSNP:rs3130645)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8724849, ECO:0000269|Ref.3,
FT ECO:0007744|PubMed:18669648"
FT /id="VAR_022848"
FT VARIANT 1545
FT /note="Q -> R (in dbSNP:rs17292678)"
FT /evidence="ECO:0000269|PubMed:14574404,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16702430,
FT ECO:0000269|PubMed:8724849, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.6"
FT /id="VAR_043923"
FT VARIANT 1745
FT /note="P -> R (in dbSNP:rs28994871)"
FT /id="VAR_051166"
FT VARIANT 1791
FT /note="V -> E (in dbSNP:rs28994873)"
FT /id="VAR_051167"
FT VARIANT 1855
FT /note="D -> E (in dbSNP:rs28994874)"
FT /id="VAR_051168"
FT VARIANT 1883
FT /note="R -> Q (in dbSNP:rs28994875)"
FT /id="VAR_051169"
FT VARIANT 1904
FT /note="R -> Q (in dbSNP:rs28994876)"
FT /id="VAR_051170"
FT MUTAGEN 58
FT /note="R->A: Abrogates binding to the MRE11 complex and to
FT CHEK2."
FT /evidence="ECO:0000269|PubMed:12607003,
FT ECO:0000269|PubMed:12607004"
FT MUTAGEN 72
FT /note="S->A: Abrogates binding to CHEK2."
FT /evidence="ECO:0000269|PubMed:12607004"
FT MUTAGEN 96
FT /note="N->A: Abrogates binding to CHEK2; when associated
FT with A-97 and A-98."
FT /evidence="ECO:0000269|PubMed:12607004"
FT MUTAGEN 97
FT /note="G->A: Abrogates binding to CHEK2; when associated
FT with A-96 and A-98."
FT /evidence="ECO:0000269|PubMed:12607004"
FT MUTAGEN 98
FT /note="T->A: Abrogates binding to CHEK2; when associated
FT with A-96 and A-97."
FT /evidence="ECO:0000269|PubMed:12607004"
FT MUTAGEN 1840
FT /note="K->R: Suppresses RNF4-mediated ubiquitination,
FT accumulates at sites of DNA damage, defective homologous
FT recombination."
FT /evidence="ECO:0000269|PubMed:22635276"
FT CONFLICT 638
FT /note="L -> P (in Ref. 2; CAH18685)"
FT /evidence="ECO:0000305"
FT CONFLICT 645..1326
FT /note="Missing (in Ref. 2; CAH18685)"
FT /evidence="ECO:0000305"
FT CONFLICT 1005
FT /note="G -> GS (in Ref. 3; BAB63322)"
FT /evidence="ECO:0000305"
FT CONFLICT 1041
FT /note="T -> A (in Ref. 1; BAA11487 and 7; AAI52557)"
FT /evidence="ECO:0000305"
FT CONFLICT 1266
FT /note="Y -> S (in Ref. 4; BAE78617)"
FT /evidence="ECO:0000305"
FT CONFLICT 1283
FT /note="P -> T (in Ref. 4; BAE78617)"
FT /evidence="ECO:0000305"
FT CONFLICT 1533
FT /note="A -> T (in Ref. 4; BAC54931/BAF31266)"
FT /evidence="ECO:0000305"
FT CONFLICT 1536
FT /note="E -> A (in Ref. 5; BX248307)"
FT /evidence="ECO:0000305"
FT CONFLICT 1664
FT /note="T -> S (in Ref. 4; BAE78617)"
FT /evidence="ECO:0000305"
FT CONFLICT 1668
FT /note="Q -> R (in Ref. 2; CAH18685)"
FT /evidence="ECO:0000305"
FT CONFLICT 1734
FT /note="A -> T (in Ref. 4; BAE78617)"
FT /evidence="ECO:0000305"
FT CONFLICT 1843
FT /note="E -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 2048
FT /note="H -> R (in Ref. 2)"
FT /evidence="ECO:0000305"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:3UOT"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:3UN0"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 51..59
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:3UMZ"
FT TURN 101..104
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:3UMZ"
FT STRAND 1894..1897
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 1903..1911
FT /evidence="ECO:0007829|PDB:2ETX"
FT TURN 1920..1922
FT /evidence="ECO:0007829|PDB:2ETX"
FT STRAND 1924..1927
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 1935..1943
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 1951..1959
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 1966..1968
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 1973..1978
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 1983..1992
FT /evidence="ECO:0007829|PDB:2ETX"
FT TURN 1995..1998
FT /evidence="ECO:0007829|PDB:2ETX"
FT STRAND 2000..2003
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 2011..2020
FT /evidence="ECO:0007829|PDB:2ETX"
FT STRAND 2024..2026
FT /evidence="ECO:0007829|PDB:3K05"
FT STRAND 2037..2040
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 2043..2048
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 2050..2055
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 2063..2071
FT /evidence="ECO:0007829|PDB:2ETX"
FT HELIX 2076..2079
FT /evidence="ECO:0007829|PDB:2ETX"
SQ SEQUENCE 2089 AA; 226666 MW; A8B880A25617EC96 CRC64;
MEDTQAIDWD VEEEEETEQS SESLRCNVEP VGRLHIFSGA HGPEKDFPLH LGKNVVGRMP
DCSVALPFPS ISKQHAEIEI LAWDKAPILR DCGSLNGTQI LRPPKVLSPG VSHRLRDQEL
ILFADLLCQY HRLDVSLPFV SRGPLTVEET PRVQGETQPQ RLLLAEDSEE EVDFLSERRM
VKKSRTTSSS VIVPESDEEG HSPVLGGLGP PFAFNLNSDT DVEEGQQPAT EEASSAARRG
ATVEAKQSEA EVVTEIQLEK DQPLVKERDN DTKVKRGAGN GVVPAGVILE RSQPPGEDSD
TDVDDDSRPP GRPAEVHLER AQPFGFIDSD TDAEEERIPA TPVVIPMKKR KIFHGVGTRG
PGAPGLAHLQ ESQAGSDTDV EEGKAPQAVP LEKSQASMVI NSDTDDEEEV SAALTLAHLK
ESQPAIWNRD AEEDMPQRVV LLQRSQTTTE RDSDTDVEEE ELPVENREAV LKDHTKIRAL
VRAHSEKDQP PFGDSDDSVE ADKSSPGIHL ERSQASTTVD INTQVEKEVP PGSAIIHIKK
HQVSVEGTNQ TDVKAVGGPA KLLVVSLEEA WPLHGDCETD AEEGTSLTAS VVADVRKSQL
PAEGDAGAEW AAAVLKQERA HEVGAQGGPP VAQVEQDLPI SRENLTDLVV DTDTLGESTQ
PQREGAQVPT GREREQHVGG TKDSEDNYGD SEDLDLQATQ CFLENQGLEA VQSMEDEPTQ
AFMLTPPQEL GPSHCSFQTT GTLDEPWEVL ATQPFCLRES EDSETQPFDT HLEAYGPCLS
PPRAIPGDQH PESPVHTEPM GIQGRGRQTV DKVMGIPKET AERVGPERGP LERETEKLLP
ERQTDVTGEE ELTKGKQDRE QKQLLARDTQ RQESDKNGES ASPERDRESL KVEIETSEEI
QEKQVQKQTL PSKAFEREVE RPVANRECDP AELEEKVPKV ILERDTQRGE PEGGSQDQKG
QASSPTPEPG VGAGDLPGPT SAPVPSGSQS GGRGSPVSPR RHQKGLLNCK MPPAEKASRI
RAAEKVSRGD QESPDACLPP TVPEAPAPPQ KPLNSQSQKH LAPPPLLSPL LPSIKPTVRK
TRQDGSQEAP EAPLSSELEP FHPKPKIRTR KSSRMTPFPA TSAAPEPHPS TSTAQPVTPK
PTSQATRSRT NRSSVKTPEP VVPTAPELQP STSTDQPVTS EPTSQVTRGR KSRSSVKTPE
TVVPTALELQ PSTSTDRPVT SEPTSQATRG RKNRSSVKTP EPVVPTAPEL QPSTSTDQPV
TSEPTYQATR GRKNRSSVKT PEPVVPTAPE LRPSTSTDRP VTPKPTSRTT RSRTNMSSVK
TPETVVPTAP ELQISTSTDQ PVTPKPTSRT TRSRTNMSSV KNPESTVPIA PELPPSTSTE
QPVTPEPTSR ATRGRKNRSS GKTPETLVPT APKLEPSTST DQPVTPEPTS QATRGRTNRS
SVKTPETVVP TAPELQPSTS TDQPVTPEPT SQATRGRTDR SSVKTPETVV PTAPELQASA
STDQPVTSEP TSRTTRGRKN RSSVKTPETV VPAAPELQPS TSTDQPVTPE PTSRATRGRT
NRSSVKTPES IVPIAPELQP STSRNQLVTP EPTSRATRCR TNRSSVKTPE PVVPTAPEPH
PTTSTDQPVT PKLTSRATRR KTNRSSVKTP KPVEPAASDL EPFTPTDQSV TPEAIAQGGQ
SKTLRSSTVR AMPVPTTPEF QSPVTTDQPI SPEPITQPSC IKRQRAAGNP GSLAAPIDHK
PCSAPLEPKS QASRNQRWGA VRAAESLTAI PEPASPQLLE TPIHASQIQK VEPAGRSRFT
PELQPKASQS RKRSLATMDS PPHQKQPQRG EVSQKTVIIK EEEEDTAEKP GKEEDVVTPK
PGKRKRDQAE EEPNRIPSRS LRRTKLNQES TAPKVLFTGV VDARGERAVL ALGGSLAGSA
AEASHLVTDR IRRTVKFLCA LGRGIPILSL DWLHQSRKAG FFLPPDEYVV TDPEQEKNFG
FSLQDALSRA RERRLLEGYE IYVTPGVQPP PPQMGEIISC CGGTYLPSMP RSYKPQRVVI
TCPQDFPHCS IPLRVGLPLL SPEFLLTGVL KQEAKPEAFV LSPLEMSST
