Q9JIL9 (NBN_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 83. History...
Names and origin
|Protein names||Recommended name:|
Nijmegen breakage syndrome protein 1 homolog
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||750 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 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 By similarity.
Present at approximately equal levels in the heart at fetal day 17, at relatively constant levels at postnatal days 10, 17 and 21 and at slightly lower levels in the adult heart. Barely detectable in the brain. Not detected in kidney, very low levels in liver and skeletal muscle and moderate levels in heart, lung and brain (at protein level). Ref.1
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.
Contains 1 BRCT domain.
Contains 1 FHA domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 750||750||Nibrin||PRO_0000231046|
|Domain||24 – 83||60||FHA|
|Domain||105 – 181||77||BRCT|
|Motif||461 – 467||7||Nuclear localization signal By similarity|
|Motif||733 – 740||8||EEXXXDDL motif|
Amino acid modifications
|Modified residue||343||1||Phosphoserine; by ATM By similarity|
|Modified residue||433||1||Phosphoserine By similarity|
|Sequence conflict||67||1||T → I in AAF91228. Ref.1|
|Sequence conflict||84||1||Q → L in AAH85700. Ref.2|
|Sequence conflict||277||1||N → H in AAH85700. Ref.2|
|Sequence conflict||301||1||G → D in AAF91228. Ref.1|
|Sequence conflict||497||1||G → E in AAF91228. Ref.1|
|Sequence conflict||514||1||D → G in AAF91228. Ref.1|
|Sequence conflict||619||1||G → E in AAF91228. Ref.1|
|Sequence conflict||642||1||Q → P in AAH85700. Ref.2|
|Sequence conflict||672||1||V → P in AAF91228. Ref.1|
|||"The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT-1, AT-2 and HL-1 cardiomyocytes."|
Lanson N.A. Jr., Egeland D.B., Royals B.A., Claycomb W.C.
Nucleic Acids Res. 28:2882-2892(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
|||"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].
|+||Additional computationally mapped references.|
|AF218575 mRNA. Translation: AAF91228.1.|
BC085700 mRNA. Translation: AAH85700.1.
|RefSeq||NP_620228.1. NM_138873.2. |
3D structure databases
|SMR||Q9JIL9. Positions 217-327. |
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:621420. rat. |
|RGD||621420. Nbn. |
Gene expression databases
|GermOnline||ENSRNOG00000008580. Rattus norvegicus. |
Family and domain databases
|Gene3D||184.108.40.206. 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||SSF52113. BRCT. 1 hit. |
SSF49879. SMAD_FHA. 1 hit.
|PROSITE||PS50172. BRCT. False negative. |
PS50006. FHA_DOMAIN. 1 hit.
|Accession||Primary (citable) accession number: Q9JIL9|
Secondary accession number(s): Q5RKL2
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families