Homo sapiens L. (human) [HSA]

FULL NAME: Nibrin


DESCRIPTION:
Component of the MRE11/RAD50/NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control 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. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability.

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:
Contains 1 FHA domain.
Contains 1 BRCT domain.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.


RELATED PATHWAY(S):
homologous recombination (HR)


RELATED DISEASE(S):
Nijmegen breakage syndrome (NBS)
aplastic anemia (AA)


Amino acids sequence

        10         20         30         40         50         60
MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA NFSVTNLSQT
        70         80         90        100        110        120
DEIPVLTLKD NSKYGTFVNE EKMQNGFSRT LKSGDGITFG VFGSKFRIEY EPLVACSSCL
       130        140        150        160        170        180
DVSGKTALNQ AILQLGGFTV NNWTEECTHL VMVSVKVTIK TICALICGRP IVKPEYFTEF
       190        200        210        220        230        240
LKAVESKKQP PQIESFYPPL DEPSIGSKNV DLSGRQERKQ IFKGKTFIFL NAKQHKKLSS
       250        260        270        280        290        300
AVVFGGGEAR LITEENEEEH NFFLAPGTCV VDTGITNSQT LIPDCQKKWI QSIMDMLQRQ
       310        320        330        340        350        360
GLRPIPEAEI GLAVIFMTTK NYCDPQGHPS TGLKTTTPGP SLSQGVSVDE KLMPSAPVNT
       370        380        390        400        410        420
TTYVADTESE QADTWDLSER PKEIKVSKME QKFRMLSQDA PTVKESCKTS SNNNSMVSNT
       430        440        450        460        470        480
LAKMRIPNYQ LSPTKLPSIN KSKDRASQQQ QTNSIRNYFQ PSTKKRERDE ENQEMSSCKS
       490        500        510        520        530        540
ARIETSCSLL EQTQPATPSL WKNKEQHLSE NEPVDTNSDN NLFTDTDLKS IVKNSASKSH
       550        560        570        580        590        600
AAEKLRSNKK REMDDVAIED EVLEQLFKDT KPELEIDVKV QKQEEDVNVR KRPRMDIETN
       610        620        630        640        650        660
DTFSDEAVPE SSKISQENEI GKKRELKEDS LWSAKEISNN DKLQDDSEML PKKLLLTEFR
       670        680        690        700        710        720
SLVIKNSTSR NPSGINDDYG QLKNFKKFKK VTYPGAGKLP HIIGGSDLIA HHARKNTELE
       730        740        750
EWLRQEMEVQ NQHAKEESLA DDLFRYNPYL KRRR  

Encoded by NBN gene

FULL NAME: nibrin


OTHER NAME(S):
AT-V1
AT-V2
ATV
FLJ10155
MGC87362
NBS
NBS1
P95


DESCRIPTION:
Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgtggaaac tgctgcccgc cgcgggcccg gcaggaggag aaccatacag acttttgact
        70         80         90        100        110        120
ggcgttgagt acgttgttgg aaggaaaaac tgtgccattc tgattgaaaa tgatcagtcg
       130        140        150        160        170        180
atcagccgaa atcatgctgt gttaactgct aacttttctg taaccaacct gagtcaaaca
       190        200        210        220        230        240
gatgaaatcc ctgtattgac attaaaagat aattctaagt atggtacctt tgttaatgag
       250        260        270        280        290        300
gaaaaaatgc agaatggctt ttcccgaact ttgaagtcgg gggatggtat tacttttgga
       310        320        330        340        350        360
gtgtttggaa gtaaattcag aatagagtat gagcctttgg ttgcatgctc ttcttgttta
       370        380        390        400        410        420
gatgtctctg ggaaaactgc tttaaatcaa gctatattgc aacttggagg atttactgta
       430        440        450        460        470        480
aacaattgga cagaagaatg cactcacctt gtcatggtat cagtgaaagt taccattaaa
       490        500        510        520        530        540
acaatatgtg cactcatttg tggacgtcca attgtaaagc cagaatattt tactgaattc
       550        560        570        580        590        600
ctgaaagcag ttgagtccaa gaagcagcct ccacaaattg aaagttttta cccacctctt
       610        620        630        640        650        660
gatgaaccat ctattggaag taaaaatgtt gatctgtcag gacggcagga aagaaaacaa
       670        680        690        700        710        720
atcttcaaag ggaaaacatt tatatttttg aatgccaaac agcataagaa attgagttcc
       730        740        750        760        770        780
gcagttgtct ttggaggtgg ggaagctagg ttgataacag aagagaatga agaagaacat
       790        800        810        820        830        840
aatttctttt tggctccggg aacgtgtgtt gttgatacag gaataacaaa ctcacagacc
       850        860        870        880        890        900
ttaattcctg actgtcagaa gaaatggatt cagtcaataa tggatatgct ccaaaggcaa
       910        920        930        940        950        960
ggtcttagac ctattcctga agcagaaatt ggattggcgg tgattttcat gactacaaag
       970        980        990       1000       1010       1020
aattactgtg atcctcaggg ccatcccagt acaggattaa agacaacaac tccaggacca
      1030       1040       1050       1060       1070       1080
agcctttcac aaggcgtgtc agttgatgaa aaactaatgc caagcgcccc agtgaacact
      1090       1100       1110       1120       1130       1140
acaacatacg tagctgacac agaatcagag caagcagata catgggattt gagtgaaagg
      1150       1160       1170       1180       1190       1200
ccaaaagaaa tcaaagtctc caaaatggaa caaaaattca gaatgctttc acaagatgca
      1210       1220       1230       1240       1250       1260
cccactgtaa aggagtcctg caaaacaagc tctaataata atagtatggt atcaaatact
      1270       1280       1290       1300       1310       1320
ttggctaaga tgagaatccc aaactatcag ctttcaccaa ctaaattgcc aagtataaat
      1330       1340       1350       1360       1370       1380
aaaagtaaag atagggcttc tcagcagcag cagaccaact ccatcagaaa ctactttcag
      1390       1400       1410       1420       1430       1440
ccgtctacca aaaaaaggga aagggatgaa gaaaatcaag aaatgtcttc atgcaaatca
      1450       1460       1470       1480       1490       1500
gcaagaatag aaacgtcttg ttctctttta gaacaaacac aacctgctac accctcattg
      1510       1520       1530       1540       1550       1560
tggaaaaata aggagcagca tctatctgag aatgagcctg tggacacaaa ctcagacaat
      1570       1580       1590       1600       1610       1620
aacttattta cagatacaga tttaaaatct attgtgaaaa attctgccag taaatctcat
      1630       1640       1650       1660       1670       1680
gctgcagaaa agctaagatc aaataaaaaa agggaaatgg atgatgtggc catagaagat
      1690       1700       1710       1720       1730       1740
gaagtattgg aacagttatt caaggacaca aaaccagagt tagaaattga tgtgaaagtt
      1750       1760       1770       1780       1790       1800
caaaaacagg aggaagatgt caatgttaga aaaaggccaa ggatggatat agaaacaaat
      1810       1820       1830       1840       1850       1860
gacactttca gtgatgaagc agtaccagaa agtagcaaaa tatctcaaga aaatgaaatt
      1870       1880       1890       1900       1910       1920
gggaagaaac gtgaactcaa ggaagactca ctatggtcag ctaaagaaat atctaacaat
      1930       1940       1950       1960       1970       1980
gacaaacttc aggatgatag tgagatgctt ccaaaaaagc tgttattgac tgaatttaga
      1990       2000       2010       2020       2030       2040
tcactggtga ttaaaaactc tacttccaga aatccatctg gcataaatga tgattatggt
      2050       2060       2070       2080       2090       2100
caactaaaaa atttcaagaa attcaaaaag gtcacatatc ctggagcagg aaaacttcca
      2110       2120       2130       2140       2150       2160
cacatcattg gaggatcaga tctaatagct catcatgctc gaaagaatac agaactagaa
      2170       2180       2190       2200       2210       2220
gagtggctaa ggcaggaaat ggaggtacaa aatcaacatg caaaagaaga gtctcttgct
      2230       2240       2250       2260
gatgatcttt ttagatacaa tccttattta aaaaggagaa gataa 

Last modification date: Oct. 2, 2011