Homo sapiens Protein: NBN | |||||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-28011.6 | ||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||
Gene Symbol | NBN | ||||||||||||||||||||||||||||||||||||||||
Protein Name | nibrin | ||||||||||||||||||||||||||||||||||||||||
Synonyms | AT-V1; AT-V2; ATV; NBS; NBS1; P95; | ||||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000265433 | ||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-28009 (NBN) | ||||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||||
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. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex. {ECO:0000269PubMed:10888888, ECO:0000269PubMed:15616588, ECO:0000269PubMed:19759395, ECO:0000269PubMed:23762398, ECO:0000269PubMed:9705271}. | ||||||||||||||||||||||||||||||||||||||||
Subcellular Localization | Nucleus {ECO:0000250}. Nucleus, PML body {ECO:0000269PubMed:12470659, ECO:0000269PubMed:15916964}. Chromosome, telomere {ECO:0000250}. Note=Localizes to discrete nuclear foci after treatment with genotoxic agents. {ECO:0000250}. | ||||||||||||||||||||||||||||||||||||||||
Disease Associations | Nijmegen breakage syndrome (NBS) [MIM:251260]: A disorder characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies. {ECO:0000269PubMed:9590180}. Note=The disease is caused by mutations affecting the gene represented in this entry.Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269PubMed:14684699}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Aplastic anemia (AA) [MIM:609135]: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.Note=Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). | ||||||||||||||||||||||||||||||||||||||||
Tissue Specificity | Ubiquitous. Expressed at high levels in testis. | ||||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 111 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||||
InterPro |
IPR000253
Forkhead-associated (FHA) domain IPR001357 BRCT domain IPR008984 SMAD/FHA domain IPR013908 DNA repair Nbs1, C-terminal IPR016592 Nibrin |
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PFAM |
PF00498
PF00533 PF12738 PF08599 |
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PRINTS | |||||||||||||||||||||||||||||||||||||||||
PIRSF |
PIRSF011869
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SMART |
SM00240
SM00292 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||||
SwissProt | O60934 | ||||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-O60934 | ||||||||||||||||||||||||||||||||||||||||
TrEMBL | E5RGR7 | ||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 4683 | ||||||||||||||||||||||||||||||||||||||||
UniGene | Hs.652803 | ||||||||||||||||||||||||||||||||||||||||
RefSeq | NP_002476 | ||||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:7652 | ||||||||||||||||||||||||||||||||||||||||
OMIM | 602667 | ||||||||||||||||||||||||||||||||||||||||
CCDS | CCDS6249 | ||||||||||||||||||||||||||||||||||||||||
HPRD | 04050 | ||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||
EMBL | AB013139 AF051334 AF058696 AF069291 AK223256 AK312410 AY566246 BC108650 BC136802 BC136803 BX640816 CH471060 | ||||||||||||||||||||||||||||||||||||||||
GenPept | AAC39732 AAC39752 AAC62232 AAI08651 AAI36803 AAI36804 AAS59158 BAA28616 BAD96976 BAG35323 CAH56160 EAW91660 | ||||||||||||||||||||||||||||||||||||||||