Homo sapiens L. (human) [HSA]

FULL NAME: DNA repair protein RAD50


DESCRIPTION:
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.
Subcellular location - Nucleus. Chromosome › telomere. Note: Localizes to discrete nuclear foci after treatment with genotoxic agents.

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.


STRUCTURE SIMILARITY:
Belongs to the SMC family. RAD50 subfamily.
Contains 1 zinc-hook domain.


SUBUNIT STRUCTURE:
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.


CATALYTIC ACTIVITY:
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.


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


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated upon DNA damage, probably by ATM or ATR.


RELATED PATHWAY(S):
homologous recombination (HR)
non-homologous end-joining (NHEJ)


RELATED DISEASE(S):
Nijmegen breakage syndrome-like disorder (NBSLD)


Amino acids sequence

        10         20         30         40         50         60
MSRIEKMSIL GVRSFGIEDK DKQIITFFSP LTILVGPNGA GKTTIIECLK YICTGDFPPG
        70         80         90        100        110        120
TKGNTFVHDP KVAQETDVRA QIRLQFRDVN GELIAVQRSM VCTQKSKKTE FKTLEGVITR
       130        140        150        160        170        180
TKHGEKVSLS SKCAEIDREM ISSLGVSKAV LNNVIFCHQE DSNWPLSEGK ALKQKFDEIF
       190        200        210        220        230        240
SATRYIKALE TLRQVRQTQG QKVKEYQMEL KYLKQYKEKA CEIRDQITSK EAQLTSSKEI
       250        260        270        280        290        300
VKSYENELDP LKNRLKEIEH NLSKIMKLDN EIKALDSRKK QMEKDNSELE EKMEKVFQGT
       310        320        330        340        350        360
DEQLNDLYHN HQRTVREKER KLVDCHRELE KLNKESRLLN QEKSELLVEQ GRLQLQADRH
       370        380        390        400        410        420
QEHIRARDSL IQSLATQLEL DGFERGPFSE RQIKNFHKLV RERQEGEAKT ANQLMNDFAE
       430        440        450        460        470        480
KETLKQKQID EIRDKKTGLG RIIELKSEIL SKKQNELKNV KYELQQLEGS SDRILELDQE
       490        500        510        520        530        540
LIKAERELSK AEKNSNVETL KMEVISLQNE KADLDRTLRK LDQEMEQLNH HTTTRTQMEM
       550        560        570        580        590        600
LTKDKADKDE QIRKIKSRHS DELTSLLGYF PNKKQLEDWL HSKSKEINQT RDRLAKLNKE
       610        620        630        640        650        660
LASSEQNKNH INNELKRKEE QLSSYEDKLF DVCGSQDFES DLDRLKEEIE KSSKQRAMLA
       670        680        690        700        710        720
GATAVYSQFI TQLTDENQSC CPVCQRVFQT EAELQEVISD LQSKLRLAPD KLKSTESELK
       730        740        750        760        770        780
KKEKRRDEML GLVPMRQSII DLKEKEIPEL RNKLQNVNRD IQRLKNDIEE QETLLGTIMP
       790        800        810        820        830        840
EEESAKVCLT DVTIMERFQM ELKDVERKIA QQAAKLQGID LDRTVQQVNQ EKQEKQHKLD
       850        860        870        880        890        900
TVSSKIELNR KLIQDQQEQI QHLKSTTNEL KSEKLQISTN LQRRQQLEEQ TVELSTEVQS
       910        920        930        940        950        960
LYREIKDAKE QVSPLETTLE KFQQEKEELI NKKNTSNKIA QDKLNDIKEK VKNIHGYMKD
       970        980        990       1000       1010       1020
IENYIQDGKD DYKKQKETEL NKVIAQLSEC EKHKEKINED MRLMRQDIDT QKIQERWLQD
      1030       1040       1050       1060       1070       1080
NLTLRKRNEE LKEVEEERKQ HLKEMGQMQV LQMKSEHQKL EENIDNIKRN HNLALGRQKG
      1090       1100       1110       1120       1130       1140
YEEEIIHFKK ELREPQFRDA EEKYREMMIV MRTTELVNKD LDIYYKTLDQ AIMKFHSMKM
      1150       1160       1170       1180       1190       1200
EEINKIIRDL WRSTYRGQDI EYIEIRSDAD ENVSASDKRR NYNYRVVMLK GDTALDMRGR
      1210       1220       1230       1240       1250       1260
CSAGQKVLAS LIIRLALAET FCLNCGIIAL DEPTTNLDRE NIESLAHALV EIIKSRSQQR
      1270       1280       1290       1300       1310
NFQLLVITHD EDFVELLGRS EYVEKFYRIK KNIDQCSEIV KCSVSSLGFN VH

Encoded by RAD50 gene

FULL NAME: RAD50 homolog (S. cerevisiae)


OTHER NAME(S):
NBSLD
RAD502
hRad50


DESCRIPTION:
The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]


Nucleic acid sequence

        10         20         30         40         50         60
atgtcccgga tcgaaaagat gagcattctg ggcgtgcgga gttttggaat agaggacaaa
        70         80         90        100        110        120
gataagcaaa ttatcacttt cttcagcccc cttacaattt tggttggacc caatggggcg
       130        140        150        160        170        180
ggaaagacga ccatcattga atgtctaaaa tatatttgta ctggagattt ccctcctgga
       190        200        210        220        230        240
accaaaggaa atacatttgt acacgatccc aaggttgctc aagaaacaga tgtgagagcc
       250        260        270        280        290        300
cagattcgtc tgcaatttcg tgatgtcaat ggagaactta tagctgtgca aagatctatg
       310        320        330        340        350        360
gtgtgtactc agaaaagcaa aaagacagaa tttaaaactc tggaaggagt cattactaga
       370        380        390        400        410        420
acaaagcatg gtgaaaaggt cagtctgagc tctaagtgtg cagaaattga ccgagaaatg
       430        440        450        460        470        480
atcagttctc ttggggtttc caaggctgtg ctaaataatg tcattttctg tcatcaagaa
       490        500        510        520        530        540
gattctaatt ggcctttaag tgaaggaaag gctttgaagc aaaagtttga tgagattttt
       550        560        570        580        590        600
tcagcaacaa gatacattaa agccttagaa acacttcggc aggtacgtca gacacaaggt
       610        620        630        640        650        660
cagaaagtaa aagaatatca aatggaacta aaatatctga agcaatataa ggaaaaagct
       670        680        690        700        710        720
tgtgagattc gtgatcagat tacaagtaag gaagcccagt taacatcttc aaaggaaatt
       730        740        750        760        770        780
gtcaaatcct atgagaatga acttgatcca ttgaagaatc gtctaaaaga aattgaacat
       790        800        810        820        830        840
aatctctcta aaataatgaa acttgacaat gaaattaaag ccttggatag ccgaaagaag
       850        860        870        880        890        900
caaatggaga aagataatag tgaactggaa gagaaaatgg aaaaggtttt tcaagggact
       910        920        930        940        950        960
gatgagcaac taaatgactt atatcacaat caccagagaa cagtaaggga gaaagaaagg
       970        980        990       1000       1010       1020
aaattggtag actgtcatcg tgaactggaa aaactaaata aagaatctag gcttctcaat
      1030       1040       1050       1060       1070       1080
caggaaaaat cagaactgct tgttgaacag ggtcgtctac agctgcaagc agatcgccat
      1090       1100       1110       1120       1130       1140
caagaacata tccgagctag agattcatta attcagtctt tggcaacaca gctagaattg
      1150       1160       1170       1180       1190       1200
gatggctttg agcgtggacc attcagtgaa agacagatta aaaattttca caaacttgtg
      1210       1220       1230       1240       1250       1260
agagagagac aagaagggga agcaaaaact gccaaccaac tgatgaatga ctttgcagaa
      1270       1280       1290       1300       1310       1320
aaagagactc tgaaacaaaa acagatagat gagataagag ataagaaaac tggactggga
      1330       1340       1350       1360       1370       1380
agaataattg agttaaaatc agaaatccta agtaagaagc agaatgagct gaaaaatgtg
      1390       1400       1410       1420       1430       1440
aagtatgaat tacagcagtt ggaaggatct tcagacagga ttcttgaact ggaccaggag
      1450       1460       1470       1480       1490       1500
ctcataaaag ctgaacgtga gttaagcaag gctgagaaaa acagcaatgt agaaacctta
      1510       1520       1530       1540       1550       1560
aaaatggaag taataagtct ccaaaatgaa aaagcagact tagacaggac cctgcgtaaa
      1570       1580       1590       1600       1610       1620
cttgaccagg agatggagca gttaaaccat catacaacaa cacgtaccca aatggagatg
      1630       1640       1650       1660       1670       1680
ctgaccaaag acaaagctga caaagatgaa caaatcagaa aaataaaatc taggcacagt
      1690       1700       1710       1720       1730       1740
gatgaattaa cctcactgtt gggatatttt cccaacaaaa aacagcttga agactggcta
      1750       1760       1770       1780       1790       1800
catagtaaat caaaagaaat taatcagacc agggacagac ttgccaaatt gaacaaggaa
      1810       1820       1830       1840       1850       1860
ctagcttcat ctgagcagaa taaaaatcat ataaataatg aactaaaaag aaaggaagag
      1870       1880       1890       1900       1910       1920
cagttgtcca gttacgaaga caagctgttt gatgtttgtg gtagccagga ttttgaaagt
      1930       1940       1950       1960       1970       1980
gatttagaca ggcttaaaga ggaaattgaa aaatcatcaa aacagcgagc catgctggct
      1990       2000       2010       2020       2030       2040
ggagccacag cagtttactc ccagttcatt actcagctaa cagacgaaaa ccagtcatgt
      2050       2060       2070       2080       2090       2100
tgccccgttt gtcagagagt ttttcagaca gaggctgagt tacaagaagt catcagtgat
      2110       2120       2130       2140       2150       2160
ttgcagtcta aactgcgact tgctccagat aaactcaagt caacagaatc agagctaaaa
      2170       2180       2190       2200       2210       2220
aaaaaggaaa agcggcgtga tgaaatgctg ggacttgtgc ccatgaggca aagcataatt
      2230       2240       2250       2260       2270       2280
gatttgaagg agaaggaaat accagaatta agaaacaaac tgcagaatgt caatagagac
      2290       2300       2310       2320       2330       2340
atacagcgcc taaagaacga catagaagaa caagaaacac tcttgggtac aataatgcct
      2350       2360       2370       2380       2390       2400
gaagaagaaa gtgccaaagt atgcctgaca gatgttacaa ttatggagag gttccagatg
      2410       2420       2430       2440       2450       2460
gaacttaaag atgttgaaag aaaaattgca caacaagcag ctaagctaca aggaatagac
      2470       2480       2490       2500       2510       2520
ttagatcgaa ctgtccaaca agtcaaccag gagaaacaag agaaacagca caagttagac
      2530       2540       2550       2560       2570       2580
acagtttcta gtaagattga attgaatcgt aagcttatac aggaccagca ggaacagatt
      2590       2600       2610       2620       2630       2640
caacatctaa aaagtacaac aaatgagcta aaatctgaga aacttcagat atccactaat
      2650       2660       2670       2680       2690       2700
ttgcaacgtc gtcagcaact ggaggagcag actgtggaat tatccactga agttcagtct
      2710       2720       2730       2740       2750       2760
ttgtacagag agataaagga tgctaaagag caggtaagcc ctttggaaac aacattggaa
      2770       2780       2790       2800       2810       2820
aagttccagc aagaaaaaga agaattaatc aacaaaaaaa atacaagcaa caaaatagca
      2830       2840       2850       2860       2870       2880
caggataaac tgaatgatat taaagagaag gttaaaaata ttcatggcta tatgaaagac
      2890       2900       2910       2920       2930       2940
attgagaatt atattcaaga tgggaaagac gactataaga agcaaaaaga aactgaactt
      2950       2960       2970       2980       2990       3000
aataaagtaa tagctcaact aagtgaatgc gagaaacaca aagaaaagat aaatgaagat
      3010       3020       3030       3040       3050       3060
atgagactca tgagacaaga tattgataca cagaagatac aagaaaggtg gctacaagat
      3070       3080       3090       3100       3110       3120
aaccttactt taagaaaaag aaatgaggaa ctaaaagaag ttgaagaaga aagaaaacaa
      3130       3140       3150       3160       3170       3180
catttgaagg aaatgggtca aatgcaggtt ttgcaaatga aaagtgaaca tcagaagttg
      3190       3200       3210       3220       3230       3240
gaagagaaca tagacaatat aaaaagaaat cataatttgg cattagggcg acagaaaggt
      3250       3260       3270       3280       3290       3300
tatgaagaag aaattattca ttttaagaaa gaacttcgag aaccacaatt tcgggatgct
      3310       3320       3330       3340       3350       3360
gaggaaaagt atagagaaat gatgattgtt atgaggacaa cagaacttgt gaacaaggat
      3370       3380       3390       3400       3410       3420
ctggatattt attataagac tcttgaccaa gcaataatga aatttcacag tatgaaaatg
      3430       3440       3450       3460       3470       3480
gaagaaatca ataaaattat acgtgacctg tggcgaagta cctatcgtgg acaagatatt
      3490       3500       3510       3520       3530       3540
gaatacatag aaatacggtc tgatgccgat gaaaatgtat cagcttctga taaaaggcgg
      3550       3560       3570       3580       3590       3600
aattataact accgagtggt gatgctgaag ggagacacag ccttggatat gcgaggacga
      3610       3620       3630       3640       3650       3660
tgcagtgctg gacaaaaggt attagcctca ctcatcattc gcctggccct ggctgaaacg
      3670       3680       3690       3700       3710       3720
ttctgcctca actgtggcat cattgccttg gatgagccaa caacaaatct tgaccgagaa
      3730       3740       3750       3760       3770       3780
aacattgaat ctcttgcaca tgctctggtt gagataataa aaagtcgctc acagcagcgt
      3790       3800       3810       3820       3830       3840
aacttccagc ttctggtaat cactcatgat gaagattttg tggagctttt aggacgttct
      3850       3860       3870       3880       3890       3900
gaatatgtgg agaaattcta caggattaaa aagaacatcg atcagtgctc agagattgtg
      3910       3920       3930
aaatgcagtg ttagctccct gggattcaat gttcattaa  

Last modification date: Feb. 6, 2012