NBN
entrez
4683
canonical
uniprot
O60934
canonical
ensembl
ENSG00000104320
resolver
ensp
ENSP00000265433
resolver
ensp
ENSP00000386924
resolver
ensp
ENSP00000428252
resolver
ensp
ENSP00000429971
resolver
ensp
ENSP00000513229
resolver
ensp
ENSP00000513234
resolver
ensp
ENSP00000513235
resolver
ensp
ENSP00000513245
resolver
ensp
ENSP00000639957
resolver
enst
ENST00000265433
resolver
enst
ENST00000409330
resolver
enst
ENST00000517337
resolver
enst
ENST00000523444
resolver
enst
ENST00000697292
resolver
enst
ENST00000697298
resolver
enst
ENST00000697299
resolver
enst
ENST00000697310
resolver
enst
ENST00000969898
resolver
genesymbol
NBN
resolver
genesymbol_syn
NBS
resolver
genesymbol_syn
NBS1
resolver
genesymbol_syn
P95
resolver
hgnc
HGNC:7652
resolver
uniprot
A0A0C4DG07
resolver
uniprot
B2R626
resolver
uniprot
B2RNC5
resolver
uniprot
E5RGN7
resolver
uniprot
O60672
resolver
uniprot
Q32NF7
resolver
uniprot
Q53FM6
resolver
uniprot
Q63HR6
resolver
uniprot
Q7LDM2
resolver
uniprot_entry
A0A0C4DG07_HUMAN
resolver
uniprot_entry
NBN_HUMAN
resolver
uniprot_sec
B2R626
resolver
uniprot_sec
B2RNC5
resolver
uniprot_sec
E5RGN7
resolver
uniprot_sec
O60672
resolver
uniprot_sec
Q32NF7
resolver
uniprot_sec
Q53FM6
resolver
uniprot_sec
Q63HR6
resolver
uniprot_sec
Q7LDM2
resolver
amino_acid_sequence
MWKLLPAAGPAGGEPYRLLTGVEYVVGRKNCAILIENDQSISRNHAVLTANFSVTNLSQTDEIPVLTLKDNSKYGTFVNEEKMQNGFSRTLKSGDGITFGVFGSKFRIEYEPLVACSSCLDVSGKTALNQAILQLGGFTVNNWTEECTHLVMVSVKVTIKTICALICGRPIVKPEYFTEFLKAVESKKQPPQIESFYPPLDEPSIGSKNVDLSGRQERKQIFKGKTFIFLNAKQHKKLSSAVVFGGGEARLITEENEEEHNFFLAPGTCVVDTGITNSQTLIPDCQKKWIQSIMDMLQRQGLRPIPEAEIGLAVIFMTTKNYCDPQGHPSTGLKTTTPGPSLSQGVSVDEKLMPSAPVNTTTYVADTESEQADTWDLSERPKEIKVSKMEQKFRMLSQDAPTVKESCKTSSNNNSMVSNTLAKMRIPNYQLSPTKLPSINKSKDRASQQQQTNSIRNYFQPSTKKRERDEENQEMSSCKSARIETSCSLLEQTQPATPSLWKNKEQHLSENEPVDTNSDNNLFTDTDLKSIVKNSASKSHAAEKLRSNKKREMDDVAIEDEVLEQLFKDTKPELEIDVKVQKQEEDVNVRKRPRMDIETNDTFSDEAVPESSKISQENEIGKKRELKEDSLWSAKEISNNDKLQDDSEMLPKKLLLTEFRSLVIKNSTSRNPSGINDDYGQLKNFKKFKKVTYPGAGKLPHIIGGSDLIAHHARKNTELEEWLRQEMEVQNQHAKEESLADDLFRYNPYLKRRR
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:9590180}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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:0000269|PubMed:14684699}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:15338273}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Note=Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). {ECO:0000269|PubMed:11325820}.
uniprot
proteins
function
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 (PubMed:10888888, PubMed:15616588, PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:19759395, PubMed:23115235, PubMed:28216226, PubMed:28867292, PubMed:9705271). 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 (PubMed:19759395, PubMed:28867292, PubMed:9705271). 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 (PubMed:19759395, PubMed:9705271). 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 (PubMed:19759395, PubMed:28867292, PubMed:9705271). 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 (PubMed:12419185, PubMed:15616588, PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890, PubMed:19759395, PubMed:19804756, PubMed:23762398, PubMed:24534091, PubMed:27814491, PubMed:27889449, PubMed:33836577). Recruits MRE11 and RAD50 components of the MRN complex to DSBs in response to DNA damage (PubMed:12419185, PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:24534091, PubMed:26438602). Promotes the recruitment of PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites, activating their functions (PubMed:15064416, PubMed:15616588, PubMed:15790808, PubMed:16622404, PubMed:22464731, PubMed:30952868, PubMed:35076389). Mediates the recruitment of phosphorylated RBBP8/CtIP to DSBs, leading to cooperation between the MRN complex and RBBP8/CtIP to initiate end resection (PubMed:19759395, PubMed:27814491, PubMed:27889449, PubMed:33836577). RBBP8/CtIP specifically promotes the endonuclease activity of the MRN complex to clear DNA ends containing protein adducts (PubMed:27814491, PubMed:27889449, PubMed:30787182, PubMed:33836577). The MRN complex is also required for the processing of R-loops (PubMed:31537797). NBN also functions in telomere length maintenance via its interaction with TERF2: interaction with TERF2 during G1 phase preventing recruitment of DCLRE1B/Apollo to telomeres (PubMed:10888888, PubMed:28216226). NBN also promotes DNA repair choice at dysfunctional telomeres: NBN phosphorylation by CDK2 promotes non-homologous end joining repair at telomeres, while unphosphorylated NBN promotes microhomology-mediated end-joining (MMEJ) repair (PubMed:28216226). Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex (PubMed:23762398). {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15616588, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:19804756, ECO:0000269|PubMed:22464731, ECO:0000269|PubMed:23115235, ECO:0000269|PubMed:23762398, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26438602, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:33836577, ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:9705271}.
uniprot
proteins
mass_dalton
84959
uniprot
proteins
mutagenesis
MUTAGEN 28; /note="R->A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Decreased ability to recognize and bind phosphorylated proteins, such as MDC1. In RRHK mutant; abolished ability to recognize and bind phosphorylated proteins, such as RBBP8; when associated with A-43, A-45 and M-160."; /evidence="ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:19804756, ECO:0000269|PubMed:30787182"; MUTAGEN 42; /note="S->A: Decreased ability to recognize and bind phosphorylated proteins."; /evidence="ECO:0000269|PubMed:19804756"; MUTAGEN 43; /note="R->A: In RRHK mutant; abolished ability to recognize and bind phosphorylated proteins, such as RBBP8; when associated with A-28, A-45 and M-160."; /evidence="ECO:0000269|PubMed:30787182"; MUTAGEN 45; /note="H->A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Decreased ability to recognize and bind phosphorylated proteins, such as MDC1. In RRHK mutant; abolished ability to recognize and bind phosphorylated proteins, such as RBBP8; when associated with A-28, A-43, and M-160."; /evidence="ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:30787182"; MUTAGEN 136..137; /note="GG->EE: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation."; /evidence="ECO:0000269|PubMed:10802669"; MUTAGEN 160; /note="K->M: Decreased ability to recognize and bind phosphorylated proteins, such as MDC1. In RRHK mutant; abolished ability to recognize and bind phosphorylated proteins, such as RBBP8; when associated with A-28, A-43 and A-45."; /evidence="ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:19804756, ECO:0000269|PubMed:30787182"; MUTAGEN 176; /note="Y->A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation."; /evidence="ECO:0000269|PubMed:10802669"; MUTAGEN 233; /note="K->A: Abolished recruitment to DNA damage sites."; /evidence="ECO:0000269|PubMed:18582474"; MUTAGEN 233; /note="K->R: Does not affect recruitment to DNA damage sites."; /evidence="ECO:0000269|PubMed:18582474"; MUTAGEN 247; /note="G->R: Abolished recruitment to DNA damage sites."; /evidence="ECO:0000269|PubMed:18582474"; MUTAGEN 270; /note="V->P: Abolished recruitment to DNA damage sites."; /evidence="ECO:0000269|PubMed:18582474"; MUTAGEN 271; /note="V->R: Abolished recruitment to DNA damage sites."; /evidence="ECO:0000269|PubMed:18582474"; MUTAGEN 343; /note="S->A: Abrogates ATM-dependent phosphorylation."; /evidence="ECO:0000269|PubMed:10839545"; MUTAGEN 388; /note="K->R: Abolished lactylation, leading to decreased recruitment of the MRN complex to DNA damage sites."; /evidence="ECO:0000269|PubMed:38961290"; MUTAGEN 397; /note="S->A: Abrogates ATM-dependent phosphorylation. No loss of interaction with KPNA2."; /evidence="ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:16188882"; MUTAGEN 432; /note="S->A: Does not affect interaction with TERF2."; /evidence="ECO:0000269|PubMed:28216226"; MUTAGEN 432; /note="S->D: Mimics phosphorylation; impaired interaction with TERF2."; /evidence="ECO:0000269|PubMed:28216226"; MUTAGEN 465..466; /note="KR->AA: Blocks the association with KPNA2, and reduces nuclear foci formation in response to ionizing radiation."; /evidence="ECO:0000269|PubMed:16188882"; MUTAGEN 583; /note="Q->K: No loss of interaction with KPNA2."; /evidence="ECO:0000269|PubMed:16188882"; MUTAGEN 615; /note="S->A: Abrogates ATM-dependent phosphorylation."; /evidence="ECO:0000269|PubMed:10839545"; MUTAGEN 665; /note="K->R: Does not affect ubiquitination by PELI1; when associated with R-683."; /evidence="ECO:0000269|PubMed:30952868"; MUTAGEN 683; /note="K->R: Does not affect ubiquitination by PELI1; when associated with R-665."; /evidence="ECO:0000269|PubMed:30952868"; MUTAGEN 686..690; /note="KKFKK->RFKR: Abolished ubiquitination by PELI1."; /evidence="ECO:0000269|PubMed:30952868"; MUTAGEN 735; /note="K->R: Abolished ubiquitination by the SCF(SKP2) complex."; /evidence="ECO:0000269|PubMed:22464731"; MUTAGEN 736..737; /note="EE->AA: Decreases ATM-binding."; /evidence="ECO:0000269|PubMed:15758953"; MUTAGEN 741..742; /note="DD->AA: Decreases ATM-binding."; /evidence="ECO:0000269|PubMed:15758953"; MUTAGEN 744..746; /note="FRY->AAA: Impaired interaction with ATM."; /evidence="ECO:0000269|PubMed:35076389"; MUTAGEN 744; /note="F->A: Impaired interaction with ATM."; /evidence="ECO:0000269|PubMed:35076389"; MUTAGEN 745..746; /note="RY->AA: Decreases ATM binding."; /evidence="ECO:0000269|PubMed:15758953"; MUTAGEN 745; /note="R->A: Does not affect interaction with ATM."; /evidence="ECO:0000269|PubMed:35076389"; MUTAGEN 746; /note="Y->A: Impaired interaction with ATM."; /evidence="ECO:0000269|PubMed:35076389"; MUTAGEN 751; /note="K->R: Does not affect ubiquitination by the SCF(SKP2) complex."; /evidence="ECO:0000269|PubMed:22464731
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance (PubMed:10766245, PubMed:10802669, PubMed:10839544, PubMed:10839545). Phosphorylated at Ser-432 by CDK2 in S/G2 phases abolishes interaction with TERF2, enabling DCLRE1B/Apollo recruitment to telomeres (PubMed:28216226). Phosphorylation at Ser-432 in response to dysfunctional telomeres promotes non-homologous end joining repair at telomeres, while dephosphorylation by PPP1CA promotes microhomology-mediated end-joining (MMEJ) repair (PubMed:28216226). {ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839544, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:28216226}.; PTM: Ubiquitinated at Lys-435 via 'Lys-6'-linked ubiquitin chains by RNF8, promoting NBN recruitment to DNA double-strand breaks (DSBs) (PubMed:23115235). Ubiquitinated at Lys-686 and Lys-689 via 'Lys-63'-linked ubiquitin chains by PELI1: ubiquitination takes place following PELI1 phosphorylation and promotes ATM activation and DNA repair (PubMed:30952868). Ubiquitinated at Lys-735 via 'Lys-63'-linked ubiquitin chains by the SCF(SKP2) complex: ubiquitination takes place following SKP2 phosphorylation and promotes ATM activation and DNA repair (PubMed:22464731). {ECO:0000269|PubMed:22464731, ECO:0000269|PubMed:23115235, ECO:0000269|PubMed:30952868}.; PTM: Lactylation at Lys-388 by KAT5 in response to DNA damage promotes recruitment of the MRN complex to DNA damage sites (PubMed:38961290). Delactylated by HDAC3 (PubMed:38961290). {ECO:0000269|PubMed:38961290}.
uniprot
proteins
protein_family
Nibrin family
uniprot
proteins
pubmed
10766245
uniprot
proteins
pubmed
10783165
uniprot
proteins
pubmed
10802669
uniprot
proteins
pubmed
10839544
uniprot
proteins
pubmed
10839545
uniprot
proteins
pubmed
10888888
uniprot
proteins
pubmed
11238951
uniprot
proteins
pubmed
11325820
uniprot
proteins
pubmed
12419185
uniprot
proteins
pubmed
12470659
uniprot
proteins
pubmed
14684699
uniprot
proteins
pubmed
14688016
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15064416
uniprot
proteins
pubmed
15338273
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616588
uniprot
proteins
pubmed
15758953
uniprot
proteins
pubmed
15790808
uniprot
proteins
pubmed
15916964
uniprot
proteins
pubmed
16188882
uniprot
proteins
pubmed
16467875
uniprot
proteins
pubmed
16622404
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17823411
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18411307
uniprot
proteins
pubmed
18582474
uniprot
proteins
pubmed
18583988
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18678890
uniprot
proteins
pubmed
19338747
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19683501
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19759395
uniprot
proteins
pubmed
19804756
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20943970
uniprot
proteins
pubmed
21248752
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22464731
uniprot
proteins
pubmed
23115235
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23762398
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24534091
uniprot
proteins
pubmed
26215093
uniprot
proteins
pubmed
26438602
uniprot
proteins
pubmed
27568553
uniprot
proteins
pubmed
27814491
uniprot
proteins
pubmed
27889449
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28216226
uniprot
proteins
pubmed
28867292
uniprot
proteins
pubmed
30787182
uniprot
proteins
pubmed
30886146
uniprot
proteins
pubmed
30952868
uniprot
proteins
pubmed
31537797
uniprot
proteins
pubmed
33836577
uniprot
proteins
pubmed
35076389
uniprot
proteins
pubmed
36577401
uniprot
proteins
pubmed
38961290
uniprot
proteins
pubmed
9590180
uniprot
proteins
pubmed
9590181
uniprot
proteins
pubmed
9620777
uniprot
proteins
pubmed
9705271
uniprot
proteins
pubmed
9933573
uniprot
proteins
sequence_length
754
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:26215093}. Chromosome {ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:19338747, ECO:0000269|PubMed:23115235, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26438602}. Nucleus, PML body {ECO:0000269|PubMed:12470659, ECO:0000269|PubMed:15916964}. Chromosome, telomere {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:28216226}. Note=Localizes to discrete nuclear foci after treatment with genotoxic agents (PubMed:10783165, PubMed:26215093, PubMed:26438602). Localizes to DNA double-strand breaks (DSBs); recruited to DNA damage sites via association with phosphorylated proteins, such as phosphorylated H2AX, phosphorylated MDC1 and phosphorylated RAD17 (PubMed:12419185, PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890, PubMed:19338747, PubMed:23115235, PubMed:24534091, PubMed:26438602). Acetylation of 'Lys-5' of histone H2AX (H2AXK5ac) promotes NBN/NBS1 assembly at the sites of DNA damage (PubMed:26438602). {ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:23115235, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26438602}.
uniprot
proteins