Q9R207 (NBN_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 101. History...
Names and origin
|Protein names||Recommended name:|
Cell cycle regulatory protein p95
Nijmegen breakage syndrome protein 1 homolog
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||751 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex By similarity.
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. Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection. Interacts with SP100; recruits NBN to PML bodies. Interacts with ATF2. Interacts with MTOR, MAPKAP1 isoform 2and RICTOR; indicative for an association with the mTORC2 complex. Ref.7
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. Ref.6
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. Ref.6
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.
The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex By similarity.
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.
Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance By similarity. Ref.8
Contains 1 BRCT domain.
Contains 1 FHA domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 751||751||Nibrin||PRO_0000231044|
|Domain||24 – 83||60||FHA|
|Domain||105 – 181||77||BRCT|
|Region||111 – 328||218||Mediates interaction with SP100|
|Region||221 – 403||183||Interaction with MTOR, MAPKAP1 and RICTOR By similarity|
|Motif||461 – 467||7||Nuclear localization signal By similarity|
|Motif||734 – 741||8||EEXXXDDL motif|
|Compositional bias||449 – 452||4||Poly-Gln|
Amino acid modifications
|Modified residue||343||1||Phosphoserine; by ATM Ref.8|
|Modified residue||398||1||Phosphoserine By similarity|
|Modified residue||433||1||Phosphoserine By similarity|
|Sequence conflict||9||1||G → S in AAH44773. Ref.4|
|Sequence conflict||11 – 12||2||AP → SL in AAC62113. Ref.3|
|Sequence conflict||325||1||P → Q in BAE22356. Ref.5|
|Sequence conflict||366||1||D → E in BAA76298. Ref.2|
|Sequence conflict||455||1||I → F in BAA76298. Ref.2|
|Sequence conflict||513||1||L → Q in AAH44773. Ref.4|
|Sequence conflict||664||1||N → K in AAH44773. Ref.4|
|Sequence conflict||676||1||E → D in AAH44773. Ref.4|
|Sequence conflict||679||1||P → S in AAH44773. Ref.4|
|||"Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome."|
Vissinga C.S., Yeo T.C., Woessner J., Massa H.F., Wilson R.K., Trask B.J., Concannon P.
Cytogenet. Cell Genet. 87:80-84(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Structure of the mouse Nijmegen breakage syndrome (Nibrin/Nbs1) protein."|
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain and Testis.
|||"Isolation of 50 cDNAs differentially expressed in embryonic forebrain as compared to mid and hindbrain: a strategy to identify candidate genes involved in human neurodevelopmental diseases."|
Mas C., Bourgeois F., Simonneau M.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain stem.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II and FVB/N.
Tissue: Colon and Mammary gland.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-613.
Tissue: Medulla oblongata.
|||"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. 9:1739-1744(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
|||"Recruitment of NBS1 into PML oncogenic domains via interaction with SP100 protein."|
Naka K., Ikeda K., Motoyama N.
Biochem. Biophys. Res. Commun. 299:863-871(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SP100.
|||"Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest."|
Yong W., Bao S., Chen H., Li D., Sanchez E.R., Shou W.
J. Biol. Chem. 282:14690-14694(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-343.
|||"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."|
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
|+||Additional computationally mapped references.|
|AF076687 mRNA. Translation: AAD20943.1.|
AB016988 mRNA. Translation: BAA76298.1.
AF092840 mRNA. Translation: AAC62113.1.
BC044773 mRNA. Translation: AAH44773.1.
BC055061 mRNA. Translation: AAH55061.1.
AK134960 mRNA. Translation: BAE22356.1.
AK031933 mRNA. Translation: BAC27610.1.
|RefSeq||NP_038780.3. NM_013752.3. |
3D structure databases
|SMR||Q9R207. Positions 217-326. |
Protein-protein interaction databases
|BioGrid||205163. 7 interactions.|
|IntAct||Q9R207. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000029879; ENSMUSP00000029879; ENSMUSG00000028224. |
|UCSC||uc008sbn.1. mouse. |
|MGI||MGI:1351625. Nbn. |
Gene expression databases
Family and domain databases
|Gene3D||188.8.131.52. 1 hit. |
184.108.40.20690. 1 hit.
|InterPro||IPR001357. BRCT_dom. |
|Pfam||PF00498. FHA. 1 hit. |
PF08599. Nbs1_C. 1 hit.
|PIRSF||PIRSF011869. Nibrin_animal. 1 hit. |
|SMART||SM00292. BRCT. 1 hit. |
SM00240. FHA. 1 hit.
|SUPFAM||SSF49879. SSF49879. 1 hit. |
SSF52113. SSF52113. 1 hit.
|PROSITE||PS50006. FHA_DOMAIN. 1 hit. |
|Accession||Primary (citable) accession number: Q9R207|
Secondary accession number(s): O88981 Q9R1X1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|