Welcome! Click here to login or here to register.
Home
Proteins
DNA damage
Diseases
Homologs
Pathways
Keywords
Publications
Draw a picture
 
Search
 
Links
Help
Contact





Bujnicki Lab Homepage

RAD50

Protein FULL name:

DNA repair protein RAD50 [Homo sapiens].


RAD50 (Homo sapiens) is product of expression of RAD50 gene.


RAD50 is involved in:

DDS in Homo sapiens
     


Keywords:



FUNCTION: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand- specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation.

COFACTOR: Binds 1 zinc ion per homodimer (By similarity).

SUBUNIT: Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11A and NBN. Found in a complex with TERF2. Interacts with RINT1. Interacts with BRCA1 via its N-terminal domain. Interacts with DCLRE1C/Artemis.

INTERACTION: P41235:HNF4A; NbExp=1; IntAct=EBI-495494, EBI-1049011;

SUBCELLULAR LOCATION: Nucleus. Telomere. Note=Localizes to discrete nuclear foci after treatment with genotoxic agents.

TISSUE SPECIFICITY: Expressed at very low level in most tissues, except in testis where it is expressed at higher level. Expressed in fibroblasts.

DOMAIN: The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc- hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11A homodimer (By similarity).

PTM: Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity).

MISCELLANEOUS: In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells.

SIMILARITY: Belongs to the SMC family. RAD50 subfamily.

SIMILARITY: Contains 1 zinc-hook domain.

SEQUENCE CAUTION: Sequence=AAH62603.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;


NCBI GenPept GI number(s): 19924129
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q92878 Q92878
PFAM: - Q92878 (Link - using uniprot id)
InterPro: - Q92878 (Link - using uniprot id)
CATH: None  
SCOP: None  
PDB: - -


Protein sequence:
MSRIEKMSILGVRSFGIEDKDKQIITFFSPLTILVGPNGAGKTTIIECLK
YICTGDFPPGTKGNTFVHDPKVAQETDVRAQIRLQFRDVNGELIAVQRSM
VCTQKSKKTEFKTLEGVITRTKHGEKVSLSSKCAEIDREMISSLGVSKAV
LNNVIFCHQEDSNWPLSEGKALKQKFDEIFSATRYIKALETLRQVRQTQG
QKVKEYQMELKYLKQYKEKACEIRDQITSKEAQLTSSKEIVKSYENELDP
LKNRLKEIEHNLSKIMKLDNEIKALDSRKKQMEKDNSELEEKMEKVFQGT
DEQLNDLYHNHQRTVREKERKLVDCHRELEKLNKESRLLNQEKSELLVEQ
GRLQLQADRHQEHIRARDSLIQSLATQLELDGFERGPFSERQIKNFHKLV
RERQEGEAKTANQLMNDFAEKETLKQKQIDEIRDKKTGLGRIIELKSEIL
SKKQNELKNVKYELQQLEGSSDRILELDQELIKAERELSKAEKNSNVETL
KMEVISLQNEKADLDRTLRKLDQEMEQLNHHTTTRTQMEMLTKDKADKDE
QIRKIKSRHSDELTSLLGYFPNKKQLEDWLHSKSKEINQTRDRLAKLNKE
LASSEQNKNHINNELKRKEEQLSSYEDKLFDVCGSQDFESDLDRLKEEIE
KSSKQRAMLAGATAVYSQFITQLTDENQSCCPVCQRVFQTEAELQEVISD
LQSKLRLAPDKLKSTESELKKKEKRRDEMLGLVPMRQSIIDLKEKEIPEL
RNKLQNVNRDIQRLKNDIEEQETLLGTIMPEEESAKVCLTDVTIMERFQM
ELKDVERKIAQQAAKLQGIDLDRTVQQVNQEKQEKQHKLDTVSSKIELNR
KLIQDQQEQIQHLKSTTNELKSEKLQISTNLQRRQQLEEQTVELSTEVQS
LYREIKDAKEQVSPLETTLEKFQQEKEELINKKNTSNKIAQDKLNDIKEK
VKNIHGYMKDIENYIQDGKDDYKKQKETELNKVIAQLSECEKHKEKINED
MRLMRQDIDTQKIQERWLQDNLTLRKRNEELKEVEEERKQHLKEMGQMQV
LQMKSEHQKLEENIDNIKRNHNLALGRQKGYEEEIIHFKKELREPQFRDA
EEKYREMMIVMRTTELVNKDLDIYYKTLDQAIMKFHSMKMEEINKIIRDL
WRSTYRGQDIEYIEIRSDADENVSASDKRRNYNYRVVMLKGDTALDMRGR
CSAGQKVLASLIIRLALAETFCLNCGIIALDEPTTNLDRENIESLAHALV
EIIKSRSQQRNFQLLVITHDEDFVELLGRSEYVEKFYRIKKNIDQCSEIV
KCSVSSLGFNVH

RAD50 (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair. Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH Mol Cell Biol Sept. 1, 1996
The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd, Hays L, Morgan WF, Petrini JH Cell May 1, 1998
The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Paull TT, Gellert M Mol Cell June 1, 1998
Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. Trujillo KM, Yuan SS, Lee EY, Sung P J Biol Chem Aug. 21, 1998
Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH Science July 1, 1999
Molecular cloning and characterization of splice variants of human RAD50 gene. Kim KK, Shin BA, Seo KH, Kim PN, Koh JT, Kim JH, Park BR Gene July 22, 1999
BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J Genes Dev April 15, 2000
Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products. Zhao S, Weng YC, Yuan SS, Lin YT, Hsu HC, Lin SC, Gerbino E, Song MH, Zdzienicka MZ, Gatti RA, Shay JW, Ziv Y, Shiloh Y, Lee EY Nature May 25, 2000
Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T Nat Genet July 1, 2000
RINT-1, a novel Rad50-interacting protein, participates in radiation-induced G(2)/M checkpoint control. Xiao J, Liu CC, Chen PL, Lee WH J Biol Chem March 2, 2001
Human Rad50/Mre11 is a flexible complex that can tether DNA ends. de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C Mol Cell Nov. 1, 2001
Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Stracker TH, Carson CT, Weitzman MD Nature July 18, 2002
DNA end-binding specificity of human Rad50/Mre11 is influenced by ATP. de Jager M, Wyman C, van Gent DC, Kanaar R Nucleic Acids Res Oct. 15, 2002
Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility. Heikkinen K, Karppinen SM, Soini Y, Makinen M, Winqvist R J Med Genet Dec. 1, 2003
Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Lee JH, Paull TT Science April 2, 2004
Large-scale characterization of HeLa cell nuclear phosphoproteins. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP Proc Natl Acad Sci U S A Aug. 17, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ Mol Cell Biol Oct. 1, 2004
Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in response to DNA damage. Chen L, Morio T, Minegishi Y, Nakada S, Nagasawa M, Komatsu K, Chessa L, Villa A, Lecis D, Delia D, Mizutani S Cancer Sci Jan. 1, 2005
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M Cell Nov. 3, 2006
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science May 25, 2007
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A Aug. 5, 2008
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal Jan. 1, 2009
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science Aug. 14, 2009


Last modification of this entry: Oct. 15, 2010.

Add your own comment!

There is no comment yet.
Welcome stranger! Click here to login or here to register.
Valid HTML 4.01! This site is Emacs powered. Made with Django.