Protein: Nibrin (A0A0C4DG07)
Organism: Homo sapiens (Human)
Function: Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases. The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage. The MRN complex possesses single-strand endonuclease activity and double-strand- specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination. Within the MRN complex, nbn acts as a protein- protein adapter, which specifically recognizes and binds phosphorylated proteins, promoting their recruitment to DNA damage sites. Recruits mre11 and rad50 components of the MRN complex to DSBs in response to DNA damage. Promotes the recruitment of PI3/PI4-kinase family members atm, atr, and probably DNA-PKcs to the DNA damage sites, activating their functions. Mediates the recruitment of phosphorylated rbbp8/CtIP to DSBs, leading to cooperation between the MRN complex and rbbp8/CtIP to initiate end resection
Subcellular location: Nucleus
Sequence: MQNGFSRTLKSGDGITFGVFGSKFRIEYEPLVACSSCLDVSGKTALNQAILQLGGFTVNNWTEECTHLVMVSVKVTIKTICALICGRPIVKPEYFTEFLKAVESKKQPPQIESFYPPLDEPSIGSKNVDLSGRQERKQIFKGKTFIFLNAKQHKKLSSAVVFGGGEARLITEENEEEHNFFLAPGTCVVDTGITNSQTLIPDCQKKWIQSIMDMLQRQGLRPIPEAEIGLAVIFMTTKNYCDPQGHPSTGLKTTTPGPSLSQGVSVDEKLMPSAPVNTTTYVADTESEQADTWDLSERPKEIKVSKMEQKFRMLSQDAPTVKESCKTSSNNNSMVSNTLAKMRIPNYQLSPTKLPSINKSKDRASQQQQTNSIRNYFQPSTKKRERDEENQEMSSCKSARIETSCSLLEQTQPATPSLWKNKEQHLSENEPVDTNSDNNLFTDTDLKSIVKNSASKSHAAEKLRSNKKREMDDVAIEDEVLEQLFKDTKPELEIDVKVQKQEEDVNVRKRPRMDIETNDTFSDEAVPESSKISQENEIGKKRELKEDSLWSAKEISNNDKLQDDSEMLPKKLLLTEFRSLVIKNSTSRNPSGINDDYGQLKNFKKFKKVTYPGAGKLPHIIGGSDLIAHHARKNTELEEWLRQEMEVQNQHAKEESLADDLFRYNPYLKRRR
InterPro domains: - IPR040227: Nibrin-related (family) [2-671]
- IPR032429: Nibrin, second BRCT domain (domain) [134-243]
- IPR043014: Nibrin, second BRCT domain superfamily (homologous_superfamily) [129-244]
- IPR001357: BRCT domain (domain) [34-97]
- IPR036420: BRCT domain superfamily (homologous_superfamily) [25-120]
- IPR016592: Nibrin (family) [1-672]
- IPR013908: Nibrin, C-terminal (domain) [600-664]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0008134 (transcription factor binding), GO:0003676 (nucleic acid binding), GO:0003677 (DNA binding), GO:0140297 (DNA-binding transcription factor binding), GO:0003684 (damaged DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0048519 (negative regulation of biological process), GO:0022402 (cell cycle process), GO:0006807 (nitrogen compound metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0009892 (negative regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0048523 (negative regulation of cellular process), GO:0007165 (signal transduction), GO:0019222 (regulation of metabolic process), GO:0007049 (cell cycle), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0007154 (cell communication), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0044085 (cellular component biogenesis), GO:0051129 (negative regulation of cellular component organization), GO:0060255 (regulation of macromolecule metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0010948 (negative regulation of cell cycle process), GO:0051726 (regulation of cell cycle), GO:1901360 (organic cyclic compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0016043 (cellular component organization), GO:0045786 (negative regulation of cell cycle), GO:0051128 (regulation of cellular component organization), GO:0044260 (cellular macromolecule metabolic process), GO:0010564 (regulation of cell cycle process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0050790 (regulation of catalytic activity), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044093 (positive regulation of molecular function), GO:1903047 (mitotic cell cycle process), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0051130 (positive regulation of cellular component organization), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0033554 (cellular response to stress), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0000278 (mitotic cell cycle), GO:0007346 (regulation of mitotic cell cycle), GO:0051246 (regulation of protein metabolic process), GO:0007093 (mitotic cell cycle checkpoint signaling), GO:0072331 (signal transduction by p53 class mediator), GO:0022607 (cellular component assembly), GO:0051053 (negative regulation of DNA metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0045930 (negative regulation of mitotic cell cycle), GO:0006259 (DNA metabolic process), GO:0043085 (positive regulation of catalytic activity), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0000075 (cell cycle checkpoint signaling), GO:0010562 (positive regulation of phosphorus metabolic process), GO:0051052 (regulation of DNA metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0051054 (positive regulation of DNA metabolic process), GO:0042770 (signal transduction in response to DNA damage), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0010639 (negative regulation of organelle organization), GO:1901987 (regulation of cell cycle phase transition), GO:0051247 (positive regulation of protein metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0033043 (regulation of organelle organization), GO:0051338 (regulation of transferase activity), GO:0006996 (organelle organization), GO:0010638 (positive regulation of organelle organization), GO:0051174 (regulation of phosphorus metabolic process), GO:1901988 (negative regulation of cell cycle phase transition), GO:1902750 (negative regulation of cell cycle G2/M phase transition), GO:0045937 (positive regulation of phosphate metabolic process), GO:0006281 (DNA repair), GO:0044818 (mitotic G2/M transition checkpoint), GO:0044774 (mitotic DNA integrity checkpoint signaling), GO:1902749 (regulation of cell cycle G2/M phase transition), GO:0043549 (regulation of kinase activity), GO:0006275 (regulation of DNA replication), GO:0032205 (negative regulation of telomere maintenance), GO:2001251 (negative regulation of chromosome organization), GO:0033044 (regulation of chromosome organization), GO:0031401 (positive regulation of protein modification process), GO:0000077 (DNA damage checkpoint signaling), GO:0031570 (DNA integrity checkpoint signaling), GO:0030330 (DNA damage response, signal transduction by p53 class mediator), GO:0051347 (positive regulation of transferase activity), GO:0032204 (regulation of telomere maintenance), GO:0031399 (regulation of protein modification process), GO:1901991 (negative regulation of mitotic cell cycle phase transition), GO:0000723 (telomere maintenance), GO:0051276 (chromosome organization), GO:0019220 (regulation of phosphate metabolic process), GO:2001252 (positive regulation of chromosome organization), GO:0022616 (DNA strand elongation), GO:1901990 (regulation of mitotic cell cycle phase transition), GO:0032206 (positive regulation of telomere maintenance), GO:0001932 (regulation of protein phosphorylation), GO:0010389 (regulation of G2/M transition of mitotic cell cycle), GO:0030174 (regulation of DNA-templated DNA replication initiation), GO:0007095 (mitotic G2 DNA damage checkpoint signaling), GO:0010972 (negative regulation of G2/M transition of mitotic cell cycle), GO:0090329 (regulation of DNA-templated DNA replication), GO:0032200 (telomere organization), GO:0042327 (positive regulation of phosphorylation), GO:0001934 (positive regulation of protein phosphorylation), GO:0006302 (double-strand break repair), GO:0042325 (regulation of phosphorylation), GO:0044773 (mitotic DNA damage checkpoint signaling), GO:0033674 (positive regulation of kinase activity), GO:0071103 (DNA conformation change), GO:0016233 (telomere capping), GO:1904353 (regulation of telomere capping), GO:0031954 (positive regulation of protein autophosphorylation), GO:0032392 (DNA geometric change), GO:0031952 (regulation of protein autophosphorylation), GO:0032508 (DNA duplex unwinding)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0090734 (site of DNA damage), GO:0098687 (chromosomal region), GO:0140513 (nuclear protein-containing complex), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0005654 (nucleoplasm), GO:0016605 (PML body), GO:0043229 (intracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0016234 (inclusion body), GO:0043233 (organelle lumen), GO:0035861 (site of double-strand break), GO:0043227 (membrane-bounded organelle), GO:0000781 (chromosome, telomeric region), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0042405 (nuclear inclusion body), GO:0005730 (nucleolus), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0005694 (chromosome)