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Nbn

Protein FULL name:

nibrin [Mus musculus].


Nbn (Mus musculus) is product of expression of Nbn gene.






FUNCTION: 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 (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 and MRE11A. Interacts with histone H2AFX this requires phosphorylation of H2AFX on 'Ser-139'. Interacts with HJURP, INTS3, KPNA2 and TERF2 (By similarity).

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

TISSUE SPECIFICITY: High expression in the liver, heart and testis. Low expression in all other tissues analyzed. In the cerebellum the postmitotic Purkinje cells are marked specifically.

DEVELOPMENTAL STAGE: A low level of expression is observed in all tissues. Highly specific expression was observed in organs with physiologic DNA double strand breakage (DSB), such as testis, thymus and spleen. Enhanced expression is also found at sites of high proliferative activity. These are the subventricular layer of the telencephalon and the diencephalon, the liver, lung, kidney and gut, as well as striated and smooth muscle cells in various organs.

DOMAIN: The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AFX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage (By similarity).

DOMAIN: The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex (By similarity).

DOMAIN: The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response (By similarity).

PTM: Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance (By similarity).

SIMILARITY: Contains 1 BRCT domain.

SIMILARITY: Contains 1 FHA domain.


NCBI GenPept GI number(s): 145386524
Species: Mus musculus

Links to other databases:

Database ID Link
Uniprot Q9R207 Q9R207
PFAM: - Q9R207 (Link - using uniprot id)
InterPro: - Q9R207 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MWKLLPAAGAAPGEPYRLLAGVEYVVGRKNCGILIENDQSISRNHAVLTV
NFPVTSLSQTDEIPTLTIKDNSKYGTFVNEEKMQTGLSCTLKTGDRVTFG
VFESKFRVEYEPLVVCSSCLDVSGKTVLNQAILQLGGLTANNWTEECTHL
VMSAVKVTIKTICALICGRPIIKPEYFSEFLKAVESKKQPPDIESFYPPI
DEPAIGSKSVDLSGRHERKQIFKGKTFVFLNAKQHKKLSSAVAFGGGEAR
LMAEDDEEEQSFFSAPGTCVVDVGITNTQLIISHSQKKWIHLIMDTLQRN
GLRPIPEAEIGLAVIFMTTENYCNPQGQPCTELKTTTPGPSLSQVLSANG
KIIPSAPVNMTTYVADTESEPADTCMPLSERPEEVKIPGLEQSSRKLSQE
TFNIKEAPKPSSKANNVASDTLVRGKTPSYQLSPMKFPVANKNKDWTSQQ
QQNSIKNYFQPCTRKRERDEDNPELSSCKSSRMELSCSLLEQTQPAGPSL
WKSKEHQSQNATLDREADTSSVGGMDIELNRKSPDRKPLPTETLRPRKRK
DVDLATEEEVLEELLRSTKPELAVQVKVEKQEADDTIRKKPRMDAERNRP
LNGGSEPESNSALQEDEREKKDELQTESWSTKHEIANSDGLQDSSEELPR
KLLLTEFRSLVVSNHNSTSRNLCVNECGPLKNFKKFKKATFPGAGKLPHI
IGGSDLVGHHARKNTELEEWLKQEMEVQKQQAKEESLADDLFRYNPNVKR
R

Nbn (Mus musculus) belongs to following protein families:
References:

Title Authors Journal
Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome. Vissinga CS, Yeo TC, Woessner J, Massa HF, Wilson RK, Trask BJ, Concannon P Cytogenet Cell Genet Jan. 1, 1999
Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine development. Wilda M, Demuth I, Concannon P, Sperling K, Hameister H Hum Mol Genet July 22, 2000
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
The transcriptional landscape of the mammalian genome. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y Science Sept. 2, 2005
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


Last modification of this entry: Oct. 6, 2010.

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