RAD50_HUMAN
ID RAD50_HUMAN Reviewed; 1312 AA.
AC Q92878; B9EGF5; O43254; Q6GMT7; Q6P5X3; Q9UP86;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=DNA repair protein RAD50;
DE Short=hRAD50;
DE EC=3.6.-.-;
GN Name=RAD50;
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] (ISOFORM 1), INTERACTION WITH MRE11, AND TISSUE
RP SPECIFICITY.
RX PubMed=8756642; DOI=10.1128/mcb.16.9.4832;
RA Dolganov G.M., Maser R.S., Novikov A., Tosto L., Chong S., Bressan D.A.,
RA Petrini J.H.J.;
RT "Human Rad50 is physically associated with human Mre11: identification of a
RT conserved multiprotein complex implicated in recombinational DNA repair.";
RL Mol. Cell. Biol. 16:4832-4841(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RX PubMed=10415333; DOI=10.1016/s0378-1119(99)00215-2;
RA Kim K.K., Shin B.A., Seo K.H., Kim P.N., Koh J.T., Kim J.H., Park B.R.;
RT "Molecular cloning and characterization of splice variants of human RAD50
RT gene.";
RL Gene 235:59-67(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS GLU-616; ALA-697;
RP HIS-964 AND MET-973.
RC TISSUE=Testis;
RA Offenberg H.H.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [7]
RP FUNCTION IN DSB REPAIR, AND IDENTIFICATION IN THE MRN COMPLEX WITH MRE11
RP AND NBN.
RX PubMed=9590181; DOI=10.1016/s0092-8674(00)81175-7;
RA Carney J.P., Maser R.S., Olivares H., Davis E.M., Le Beau M.,
RA Yates J.R. III, Hays L., Morgan W.F., Petrini J.H.J.;
RT "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage
RT of double-strand break repair to the cellular DNA damage response.";
RL Cell 93:477-486(1998).
RN [8]
RP FUNCTION IN DSB REPAIR, AND IDENTIFICATION IN THE MRN COMPLEX WITH MRE11
RP AND NBN.
RX PubMed=9705271; DOI=10.1074/jbc.273.34.21447;
RA Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P.;
RT "Nuclease activities in a complex of human recombination and DNA repair
RT factors Rad50, Mre11, and p95.";
RL J. Biol. Chem. 273:21447-21450(1998).
RN [9]
RP FUNCTION, ATP-BINDING, AND MUTAGENESIS OF LYS-42 AND ASP-1231.
RX PubMed=9651580; DOI=10.1016/s1097-2765(00)80097-0;
RA Paull T.T., Gellert M.;
RT "The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA
RT double-strand breaks.";
RL Mol. Cell 1:969-979(1998).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH BRCA1.
RX PubMed=10426999; DOI=10.1126/science.285.5428.747;
RA Zhong Q., Chen C.-F., Li S., Chen Y., Wang C.-C., Xiao J., Chen P.-L.,
RA Sharp Z.D., Lee W.-H.;
RT "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage
RT response.";
RL Science 285:747-750(1999).
RN [11]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE BASC COMPLEX WITH BRCA1;
RP MSH2; MSH6; MLH1; ATM; BLM; MRE11 AND NBN.
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 [12]
RP IDENTIFICATION IN THE MRN COMPLEX WITH MRE11 AND NBN.
RX PubMed=10839544; DOI=10.1038/35013083;
RA Zhao S., Weng Y.-C., Yuan S.-S.F., Lin Y.-T., Hsu H.-C., Lin S.-C.,
RA Gerbino E., Song M.-H., Zdzienicka M.Z., Gatti R.A., Shay J.W., Ziv Y.,
RA Shiloh Y., Lee E.Y.-H.P.;
RT "Functional link between ataxia-telangiectasia and Nijmegen breakage
RT syndrome gene products.";
RL Nature 405:473-477(2000).
RN [13]
RP FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION
RP IN THE A COMPLEX WITH TERF2, AND SUBCELLULAR LOCATION.
RX PubMed=10888888; DOI=10.1038/77139;
RA Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.;
RT "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human
RT telomeres.";
RL Nat. Genet. 25:347-352(2000).
RN [14]
RP INTERACTION WITH RINT1.
RX PubMed=11096100; DOI=10.1074/jbc.m008893200;
RA Xiao J., Liu C.-C., Chen P.-L., Lee W.-H.;
RT "RINT-1, a novel Rad50-interacting protein, participates in radiation-
RT induced G2/M checkpoint control.";
RL J. Biol. Chem. 276:6105-6111(2001).
RN [15]
RP FUNCTION, AND INTRAMOLECULAR COILED-COIL DOMAINS.
RX PubMed=11741547; DOI=10.1016/s1097-2765(01)00381-1;
RA de Jager M., van Noort J., van Gent D.C., Dekker C., Kanaar R., Wyman C.;
RT "Human Rad50/Mre11 is a flexible complex that can tether DNA ends.";
RL Mol. Cell 8:1129-1135(2001).
RN [16]
RP INACTIVATION BY ADENOVIRUS ONCOPROTEINS.
RX PubMed=12124628; DOI=10.1038/nature00863;
RA Stracker T.H., Carson C.T., Weitzman M.D.;
RT "Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair
RT complex.";
RL Nature 418:348-352(2002).
RN [17]
RP ATP-BINDING.
RX PubMed=12384589; DOI=10.1093/nar/gkf574;
RA de Jager M., Wyman C., van Gent D.C., Kanaar R.;
RT "DNA end-binding specificity of human Rad50/Mre11 is influenced by ATP.";
RL Nucleic Acids Res. 30:4425-4431(2002).
RN [18]
RP INTERACTION WITH DCLRE1C.
RX PubMed=15456891; DOI=10.1128/mcb.24.20.9207-9220.2004;
RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D.,
RA Legerski R.J.;
RT "Artemis is a phosphorylation target of ATM and ATR and is involved in the
RT G2/M DNA damage checkpoint response.";
RL Mol. Cell. Biol. 24:9207-9220(2004).
RN [19]
RP FUNCTION IN ATM ACTIVATION.
RX PubMed=15064416; DOI=10.1126/science.1091496;
RA Lee J.-H., Paull T.T.;
RT "Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1
RT complex.";
RL Science 304:93-96(2004).
RN [20]
RP INTERACTION WITH DCLRE1C.
RX PubMed=15723659; DOI=10.1111/j.1349-7006.2005.00019.x;
RA Chen L., Morio T., Minegishi Y., Nakada S., Nagasawa M., Komatsu K.,
RA Chessa L., Villa A., Lecis D., Delia D., Mizutani S.;
RT "Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in
RT response to DNA damage.";
RL Cancer Sci. 96:134-141(2005).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015;
RA Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.;
RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage
RT response.";
RL Mol. Cell 18:577-587(2005).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635 AND THR-690, 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 [24]
RP INVOLVEMENT IN NBSLD.
RX PubMed=19409520; DOI=10.1016/j.ajhg.2009.04.010;
RA Waltes R., Kalb R., Gatei M., Kijas A.W., Stumm M., Sobeck A., Wieland B.,
RA Varon R., Lerenthal Y., Lavin M.F., Schindler D., Doerk T.;
RT "Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder.";
RL Am. J. Hum. Genet. 84:605-616(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-690, 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 [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-959, 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 [27]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL12.
RX PubMed=20943970; DOI=10.1128/jvi.01506-10;
RA Balasubramanian N., Bai P., Buchek G., Korza G., Weller S.K.;
RT "Physical interaction between the herpes simplex virus type 1 exonuclease,
RT UL12, and the DNA double-strand break-sensing MRN complex.";
RL J. Virol. 84:12504-12514(2010).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635 AND THR-690, 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 [29]
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635 AND THR-690, 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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [32]
RP IDENTIFICATION IN THE MRN COMPLEX, INTERACTION WITH MCM8 AND MCM9, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26215093; DOI=10.1038/ncomms8744;
RA Lee K.Y., Im J.S., Shibata E., Park J., Handa N., Kowalczykowski S.C.,
RA Dutta A.;
RT "MCM8-9 complex promotes resection of double-strand break ends by MRE11-
RT RAD50-NBS1 complex.";
RL Nat. Commun. 6:7744-7744(2015).
RN [33]
RP INTERACTION WITH MRNIP.
RX PubMed=27568553; DOI=10.1016/j.celrep.2016.07.087;
RA Staples C.J., Barone G., Myers K.N., Ganesh A., Gibbs-Seymour I.,
RA Patil A.A., Beveridge R.D., Daye C., Beniston R., Maslen S., Ahel I.,
RA Skehel J.M., Collis S.J.;
RT "MRNIP/C5orf45 interacts with the MRN complex and contributes to the DNA
RT damage response.";
RL Cell Rep. 16:2565-2575(2016).
RN [34]
RP VARIANTS LEU-94 AND HIS-224.
RX PubMed=14684699; DOI=10.1136/jmg.40.12.e131;
RA Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R.;
RT "Mutation screening of Mre11 complex genes: indication of RAD50 involvement
RT in breast and ovarian cancer susceptibility.";
RL J. Med. Genet. 40:E131-E131(2003).
CC -!- FUNCTION: Component of the MRN complex, which plays a central role in
CC double-strand break (DSB) repair, DNA recombination, maintenance of
CC telomere integrity and meiosis. The complex possesses single-strand
CC endonuclease activity and double-strand-specific 3'-5' exonuclease
CC activity, which are provided by MRE11. RAD50 may be required to bind
CC DNA ends and hold them in close proximity. This could facilitate
CC searches for short or long regions of sequence homology in the
CC recombining DNA templates, and may also stimulate the activity of DNA
CC ligases and/or restrict the nuclease activity of MRE11 to prevent
CC nucleolytic degradation past a given point (PubMed:11741547,
CC PubMed:9590181, PubMed:9705271, PubMed:9651580). The complex may also
CC be required for DNA damage signaling via activation of the ATM kinase
CC (PubMed:15064416). In telomeres the MRN complex may modulate t-loop
CC formation (PubMed:10888888). {ECO:0000269|PubMed:10888888,
CC ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:15064416,
CC ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580,
CC ECO:0000269|PubMed:9705271}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per homodimer. {ECO:0000250};
CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers
CC RAD50/MRE11 associated with a single NBN (PubMed:8756642,
CC PubMed:9590181, PubMed:9705271, PubMed:10839544, PubMed:26215093). As
CC part of the MRN complex, interacts with MCM8 and MCM9; the interaction
CC recruits the complex to DNA repair sites (PubMed:26215093). Component
CC of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM,
CC BLM, RAD50, MRE11 and NBN (PubMed:10783165). Found in a complex with
CC TERF2 (PubMed:10888888). Interacts with RINT1 (PubMed:11096100).
CC Interacts with BRCA1 via its N-terminal domain (PubMed:10426999).
CC Interacts with DCLRE1C/Artemis (PubMed:15456891, PubMed:15723659).
CC Interacts with MRNIP (PubMed:27568553). Interacts with CYREN (via XLF
CC motif) (By similarity). {ECO:0000250|UniProtKB:P70388,
CC ECO:0000269|PubMed:10426999, ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:10839544, ECO:0000269|PubMed:10888888,
CC ECO:0000269|PubMed:11096100, ECO:0000269|PubMed:15456891,
CC ECO:0000269|PubMed:15723659, ECO:0000269|PubMed:26215093,
CC ECO:0000269|PubMed:27568553, ECO:0000269|PubMed:8756642,
CC ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9705271}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein UL12 (PubMed:20943970). {ECO:0000269|PubMed:20943970}.
CC -!- INTERACTION:
CC Q92878; P46100: ATRX; NbExp=5; IntAct=EBI-495494, EBI-396461;
CC Q92878; O75943: RAD17; NbExp=2; IntAct=EBI-495494, EBI-968231;
CC Q92878; Q92878: RAD50; NbExp=5; IntAct=EBI-495494, EBI-495494;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:26215093}. Chromosome,
CC telomere {ECO:0000269|PubMed:10888888}. Chromosome
CC {ECO:0000269|PubMed:26215093}. Note=Localizes to discrete nuclear foci
CC after treatment with genotoxic agents. {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:26215093}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=RAD50-1, RAD50-2;
CC IsoId=Q92878-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92878-2; Sequence=VSP_012591;
CC Name=3; Synonyms=RAD50-3;
CC IsoId=Q92878-3; Sequence=VSP_012590;
CC -!- TISSUE SPECIFICITY: Expressed at very low level in most tissues, except
CC in testis where it is expressed at higher level. Expressed in
CC fibroblasts. {ECO:0000269|PubMed:8756642}.
CC -!- DOMAIN: The zinc-hook, which separates the large intramolecular coiled
CC coil regions, contains 2 Cys residues that coordinate one molecule of
CC zinc with the help of the 2 Cys residues of the zinc-hook of another
CC RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of
CC the homodimer, which constitute the ATP-binding domain, interact with
CC the MRE11 homodimer (By similarity). {ECO:0000250}.
CC -!- DISEASE: Nijmegen breakage syndrome-like disorder (NBSLD) [MIM:613078]:
CC A disorder similar to Nijmegen breakage syndrome and characterized by
CC chromosomal instability, radiation sensitivity, microcephaly, growth
CC retardation, short stature and bird-like face. Immunodeficiency is
CC absent. {ECO:0000269|PubMed:19409520}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In case of infection by adenovirus E4, the MRN complex
CC is inactivated and degraded by viral oncoproteins, thereby preventing
CC concatenation of viral genomes in infected cells.
CC -!- SIMILARITY: Belongs to the SMC family. RAD50 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH62603.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; U63139; AAB07119.1; -; mRNA.
DR EMBL; AF057299; AAD50325.1; -; mRNA.
DR EMBL; AF057300; AAD50326.1; -; mRNA.
DR EMBL; Z75311; CAA99729.1; -; mRNA.
DR EMBL; AC116366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62329.1; -; Genomic_DNA.
DR EMBL; BC062603; AAH62603.1; ALT_SEQ; mRNA.
DR EMBL; BC073850; AAH73850.1; -; mRNA.
DR EMBL; BC136436; AAI36437.1; -; mRNA.
DR CCDS; CCDS34233.1; -. [Q92878-1]
DR RefSeq; NP_005723.2; NM_005732.3. [Q92878-1]
DR PDB; 5GOX; X-ray; 2.40 A; A/B=585-766.
DR PDBsum; 5GOX; -.
DR AlphaFoldDB; Q92878; -.
DR SMR; Q92878; -.
DR BioGRID; 115417; 235.
DR ComplexPortal; CPX-4442; MRN complex.
DR CORUM; Q92878; -.
DR DIP; DIP-33606N; -.
DR IntAct; Q92878; 95.
DR MINT; Q92878; -.
DR STRING; 9606.ENSP00000368100; -.
DR GlyGen; Q92878; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92878; -.
DR PhosphoSitePlus; Q92878; -.
DR BioMuta; RAD50; -.
DR DMDM; 60392986; -.
DR CPTAC; CPTAC-3286; -.
DR CPTAC; CPTAC-954; -.
DR EPD; Q92878; -.
DR jPOST; Q92878; -.
DR MassIVE; Q92878; -.
DR MaxQB; Q92878; -.
DR PaxDb; Q92878; -.
DR PeptideAtlas; Q92878; -.
DR PRIDE; Q92878; -.
DR ProteomicsDB; 75562; -. [Q92878-1]
DR ProteomicsDB; 75563; -. [Q92878-2]
DR ProteomicsDB; 75564; -. [Q92878-3]
DR Antibodypedia; 14460; 469 antibodies from 35 providers.
DR CPTC; Q92878; 2 antibodies.
DR DNASU; 10111; -.
DR Ensembl; ENST00000378823.8; ENSP00000368100.4; ENSG00000113522.14. [Q92878-1]
DR GeneID; 10111; -.
DR KEGG; hsa:10111; -.
DR MANE-Select; ENST00000378823.8; ENSP00000368100.4; NM_005732.4; NP_005723.2.
DR UCSC; uc003kxi.4; human. [Q92878-1]
DR CTD; 10111; -.
DR DisGeNET; 10111; -.
DR GeneCards; RAD50; -.
DR HGNC; HGNC:9816; RAD50.
DR HPA; ENSG00000113522; Low tissue specificity.
DR MalaCards; RAD50; -.
DR MIM; 604040; gene.
DR MIM; 613078; phenotype.
DR neXtProt; NX_Q92878; -.
DR OpenTargets; ENSG00000113522; -.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR Orphanet; 240760; Nijmegen breakage syndrome-like disorder.
DR PharmGKB; PA34175; -.
DR VEuPathDB; HostDB:ENSG00000113522; -.
DR eggNOG; KOG0962; Eukaryota.
DR GeneTree; ENSGT00390000018781; -.
DR HOGENOM; CLU_006184_0_0_1; -.
DR InParanoid; Q92878; -.
DR OMA; CFGVNCG; -.
DR PhylomeDB; Q92878; -.
DR TreeFam; TF101217; -.
DR PathwayCommons; Q92878; -.
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
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; Q92878; -.
DR SIGNOR; Q92878; -.
DR BioGRID-ORCS; 10111; 75 hits in 1086 CRISPR screens.
DR ChiTaRS; RAD50; human.
DR GeneWiki; Rad50; -.
DR GenomeRNAi; 10111; -.
DR Pharos; Q92878; Tbio.
DR PRO; PR:Q92878; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q92878; protein.
DR Bgee; ENSG00000113522; Expressed in corpus callosum and 112 other tissues.
DR ExpressionAtlas; Q92878; baseline and differential.
DR Genevisible; Q92878; HS.
DR GO; GO:0070533; C:BRCA1-C complex; IPI:ComplexPortal.
DR GO; GO:0098687; C:chromosomal region; IC:ComplexPortal.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0000794; C:condensed nuclear chromosome; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030870; C:Mre11 complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IDA:BHF-UCL.
DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IBA:GO_Central.
DR GO; GO:0051880; F:G-quadruplex DNA binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB.
DR GO; GO:0043047; F:single-stranded telomeric DNA binding; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; IBA:GO_Central.
DR GO; GO:0000729; P:DNA double-strand break processing; IC:ComplexPortal.
DR GO; GO:0032508; P:DNA duplex unwinding; IMP:BHF-UCL.
DR GO; GO:0006310; P:DNA recombination; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB.
DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; IC:ComplexPortal.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0035825; P:homologous recombination; IC:ComplexPortal.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:1904354; P:negative regulation of telomere capping; IDA:BHF-UCL.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IDA:BHF-UCL.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR GO; GO:0000019; P:regulation of mitotic recombination; IDA:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; TAS:BHF-UCL.
DR GO; GO:0000722; P:telomere maintenance via recombination; IBA:GO_Central.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB.
DR GO; GO:0031860; P:telomeric 3' overhang formation; IMP:BHF-UCL.
DR CDD; cd03240; ABC_Rad50; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR045171; ABC_Rad50.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR038729; Rad50/SbcC_AAA.
DR InterPro; IPR004584; Rad50_eukaryotes.
DR InterPro; IPR013134; Zn_hook_RAD50.
DR Pfam; PF13476; AAA_23; 1.
DR Pfam; PF04423; Rad50_zn_hook; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR TIGRFAMs; TIGR00606; rad50; 1.
DR PROSITE; PS51131; ZN_HOOK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Chromosome; Coiled coil; DNA damage; DNA repair; Host-virus interaction;
KW Hydrolase; Meiosis; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Telomere; Zinc.
FT CHAIN 1..1312
FT /note="DNA repair protein RAD50"
FT /id="PRO_0000138641"
FT DOMAIN 635..734
FT /note="Zinc-hook"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00471"
FT COILED 228..359
FT /evidence="ECO:0000255"
FT COILED 401..598
FT /evidence="ECO:0000255"
FT COILED 635..673
FT /evidence="ECO:0000255"
FT COILED 706..734
FT /evidence="ECO:0000255"
FT COILED 789..1079
FT /evidence="ECO:0000255"
FT BINDING 36..43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 681
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00471"
FT BINDING 684
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00471"
FT MOD_RES 635
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 690
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 959
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..139
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10415333"
FT /id="VSP_012590"
FT VAR_SEQ 1..5
FT /note="MSRIE -> MLIFSVRDMFA (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_012591"
FT VARIANT 94
FT /note="I -> L (in dbSNP:rs28903085)"
FT /evidence="ECO:0000269|PubMed:14684699"
FT /id="VAR_025526"
FT VARIANT 127
FT /note="V -> I (in dbSNP:rs28903086)"
FT /id="VAR_029168"
FT VARIANT 191
FT /note="T -> I (in dbSNP:rs2230017)"
FT /id="VAR_022085"
FT VARIANT 193
FT /note="R -> W (in dbSNP:rs28903087)"
FT /id="VAR_029169"
FT VARIANT 224
FT /note="R -> H (in dbSNP:rs28903088)"
FT /evidence="ECO:0000269|PubMed:14684699"
FT /id="VAR_025527"
FT VARIANT 315
FT /note="V -> L (in dbSNP:rs28903090)"
FT /id="VAR_034436"
FT VARIANT 469
FT /note="G -> A (in dbSNP:rs55653181)"
FT /id="VAR_061779"
FT VARIANT 616
FT /note="K -> E (in dbSNP:rs1047380)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020958"
FT VARIANT 697
FT /note="V -> A (in dbSNP:rs1047382)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020959"
FT VARIANT 842
FT /note="V -> A (in dbSNP:rs28903093)"
FT /id="VAR_029170"
FT VARIANT 964
FT /note="Y -> H (in dbSNP:rs1047386)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020960"
FT VARIANT 973
FT /note="K -> M (in dbSNP:rs1129482)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020961"
FT VARIANT 1038
FT /note="R -> G (in dbSNP:rs1047387)"
FT /id="VAR_020962"
FT MUTAGEN 42
FT /note="K->N: Abolishes ability to degrade ATP."
FT /evidence="ECO:0000269|PubMed:9651580"
FT MUTAGEN 1231
FT /note="D->A: Abolishes ability to degrade ATP."
FT /evidence="ECO:0000269|PubMed:9651580"
FT CONFLICT 204
FT /note="K -> E (in Ref. 3; CAA99729)"
FT /evidence="ECO:0000305"
FT CONFLICT 723
FT /note="E -> K (in Ref. 6; AAH62603/AAH73850)"
FT /evidence="ECO:0000305"
FT CONFLICT 733
FT /note="V -> A (in Ref. 3; CAA99729)"
FT /evidence="ECO:0000305"
FT HELIX 586..632
FT /evidence="ECO:0007829|PDB:5GOX"
FT HELIX 638..673
FT /evidence="ECO:0007829|PDB:5GOX"
FT TURN 674..676
FT /evidence="ECO:0007829|PDB:5GOX"
FT STRAND 682..684
FT /evidence="ECO:0007829|PDB:5GOX"
FT HELIX 691..704
FT /evidence="ECO:0007829|PDB:5GOX"
FT TURN 705..707
FT /evidence="ECO:0007829|PDB:5GOX"
FT HELIX 708..731
FT /evidence="ECO:0007829|PDB:5GOX"
FT HELIX 733..744
FT /evidence="ECO:0007829|PDB:5GOX"
FT HELIX 746..764
FT /evidence="ECO:0007829|PDB:5GOX"
SQ SEQUENCE 1312 AA; 153892 MW; 1F208C3817FC41FC CRC64;
MSRIEKMSIL GVRSFGIEDK DKQIITFFSP LTILVGPNGA GKTTIIECLK YICTGDFPPG
TKGNTFVHDP KVAQETDVRA QIRLQFRDVN GELIAVQRSM VCTQKSKKTE FKTLEGVITR
TKHGEKVSLS SKCAEIDREM ISSLGVSKAV LNNVIFCHQE DSNWPLSEGK ALKQKFDEIF
SATRYIKALE TLRQVRQTQG QKVKEYQMEL KYLKQYKEKA CEIRDQITSK EAQLTSSKEI
VKSYENELDP LKNRLKEIEH NLSKIMKLDN EIKALDSRKK QMEKDNSELE EKMEKVFQGT
DEQLNDLYHN HQRTVREKER KLVDCHRELE KLNKESRLLN QEKSELLVEQ GRLQLQADRH
QEHIRARDSL IQSLATQLEL DGFERGPFSE RQIKNFHKLV RERQEGEAKT ANQLMNDFAE
KETLKQKQID EIRDKKTGLG RIIELKSEIL SKKQNELKNV KYELQQLEGS SDRILELDQE
LIKAERELSK AEKNSNVETL KMEVISLQNE KADLDRTLRK LDQEMEQLNH HTTTRTQMEM
LTKDKADKDE QIRKIKSRHS DELTSLLGYF PNKKQLEDWL HSKSKEINQT RDRLAKLNKE
LASSEQNKNH INNELKRKEE QLSSYEDKLF DVCGSQDFES DLDRLKEEIE KSSKQRAMLA
GATAVYSQFI TQLTDENQSC CPVCQRVFQT EAELQEVISD LQSKLRLAPD KLKSTESELK
KKEKRRDEML GLVPMRQSII DLKEKEIPEL RNKLQNVNRD IQRLKNDIEE QETLLGTIMP
EEESAKVCLT DVTIMERFQM ELKDVERKIA QQAAKLQGID LDRTVQQVNQ EKQEKQHKLD
TVSSKIELNR KLIQDQQEQI QHLKSTTNEL KSEKLQISTN LQRRQQLEEQ TVELSTEVQS
LYREIKDAKE QVSPLETTLE KFQQEKEELI NKKNTSNKIA QDKLNDIKEK VKNIHGYMKD
IENYIQDGKD DYKKQKETEL NKVIAQLSEC EKHKEKINED MRLMRQDIDT QKIQERWLQD
NLTLRKRNEE LKEVEEERKQ HLKEMGQMQV LQMKSEHQKL EENIDNIKRN HNLALGRQKG
YEEEIIHFKK ELREPQFRDA EEKYREMMIV MRTTELVNKD LDIYYKTLDQ AIMKFHSMKM
EEINKIIRDL WRSTYRGQDI EYIEIRSDAD ENVSASDKRR NYNYRVVMLK GDTALDMRGR
CSAGQKVLAS LIIRLALAET FCLNCGIIAL DEPTTNLDRE NIESLAHALV EIIKSRSQQR
NFQLLVITHD EDFVELLGRS EYVEKFYRIK KNIDQCSEIV KCSVSSLGFN VH
