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nibrin; Nijmegen breakage syndrome protein 1; cell cycle regulatory protein p95 (NBN, NBS, NBS1, P95)

Function: 1) DNA damage signal sensing (DNA double-strand break repair) 2) recruits ATM, ATR, DNA-PKcs to the DNA damage sites 3) recruits MRE11 & RAD50 to DNA double-strand breaks via interaction with histone H2AX 4) telomere length maintenance - generates 3'overhang which serves as primer for telomerase 5) control of intra-S-phase checkpoint 6) G1 & G2 checkpoints (putative) 7) component of MRN complex 8) component of BASC complex 9) interacts with histone H2AFX; requires phosphorylation of H2AFX on Ser-139 10) interacts with TERF2 & KPNA2 11) phosphorylation by ATM in response to ionizing radiation; phosphorylation associated with intra-S phase checkpoint control & telomere maintenance Compartment: - nucleus, telomere - localizes to discrete nuclear foci after treatment with genotoxic agents (putative) Expression: - ubiquitous, expressed at high levels in testis Pathology: 1) defects in the nibrin gene are associated with a) Nijmegen breakage syndrome b) genetic susceptibility to breast cancer c) aplastic anemia d) childhood acute lymphoblastic leukemia (putative) 2) also see MRN complex

Interactions

molecular events

Related

acute lymphoblastic leukemia (ALL) aplastic anemia breast cancer NBN gene mutation; nibrin gene mutation NBS1 gene Nijmegen breakage syndrome; ataxia-telangiectasia variant 1

General

nuclear protein phosphoprotein

Properties

SIZE: entity length = 754 aa MW = 85 kD COMPARTMENT: cell nucleus MOTIF: forkhead-associated (FHA) domain {24-83} BRCA1 C-terminal (BRCT) motif SITE: 105-181 Ser phosphorylation site {S278} Thr phosphorylation site {T337} Ser phosphorylation site {S341} Ser phosphorylation site {S343} Ser phosphorylation site {S397} Ser phosphorylation site {S432} glutamine-rich region {448-451} MOTIF: glutamine residue (SEVERAL) nuclear translocation signal {461-467} Thr phosphorylation site {T602} Ser phosphorylation site {S615} EEXXXDDL {736-743}

References

  1. UniProt :accession O60934
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/NBS1ID160.html
  3. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/NBN
  4. NIEHS-SNPs http://egp.gs.washington.edu/data/nbs1/
  5. Varon R et al Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93:467-76, 1998 PMID: 9590180
  6. Carney JP et al The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93:477-86, 1998 PMID: 9590181

Component-of

MRN complex

Databases & Figures

OMIM correlations MORBIDMAP 602667 UniProt O60934 PFAM correlations Entrez Gene 4683 Kegg hsa:4683 Figures/diagrams/slides/tables related to nibrin