Search Results

Overview

Uniprot IDO60934
Protein NameNibrin
Gene NameNBN
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
288 LIPDCQKKWIQSIMD
388 PKEIKVSKMEQKFRM
435 NYQLSPTKLPSINKS
441 TKLPSINKSKDRASQ
479 NQEMSSCKSARIETS
533 TDLKSIVKNSASKSH
582 EIDVKVQKQEEDVNV
622 SQENEIGKKRELKED
623 QENEIGKKRELKEDS

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)

Protein Sequence

10 MWKLLPAAGP 20 AGGEPYRLLT 30 GVEYVVGRKN 40 CAILIENDQS 50 ISRNHAVLTA 60 NFSVTNLSQT 70 DEIPVLTLKD 80 NSKYGTFVNE 90 EKMQNGFSRT 100 LKSGDGITFG 110 VFGSKFRIEY 120 EPLVACSSCL 130 DVSGKTALNQ 140 AILQLGGFTV 150 NNWTEECTHL 160 VMVSVKVTIK 170 TICALICGRP 180 IVKPEYFTEF 190 LKAVESKKQP 200 PQIESFYPPL 210 DEPSIGSKNV 220 DLSGRQERKQ 230 IFKGKTFIFL 240 NAKQHKKLSS 250 AVVFGGGEAR 260 LITEENEEEH 270 NFFLAPGTCV 280 VDTGITNSQT 290 LIPDCQKKWI 300 QSIMDMLQRQ 310 GLRPIPEAEI 320 GLAVIFMTTK 330 NYCDPQGHPS 340 TGLKTTTPGP 350 SLSQGVSVDE 360 KLMPSAPVNT 370 TTYVADTESE 380 QADTWDLSER 390 PKEIKVSKME 400 QKFRMLSQDA 410 PTVKESCKTS 420 SNNNSMVSNT 430 LAKMRIPNYQ 440 LSPTKLPSIN 450 KSKDRASQQQ 460 QTNSIRNYFQ 470 PSTKKRERDE 480 ENQEMSSCKS 490 ARIETSCSLL 500 EQTQPATPSL 510 WKNKEQHLSE 520 NEPVDTNSDN 530 NLFTDTDLKS 540 IVKNSASKSH 550 AAEKLRSNKK 560 REMDDVAIED 570 EVLEQLFKDT 580 KPELEIDVKV 590 QKQEEDVNVR 600 KRPRMDIETN 610 DTFSDEAVPE 620 SSKISQENEI 630 GKKRELKEDS 640 LWSAKEISNN 650 DKLQDDSEML 660 PKKLLLTEFR 670 SLVIKNSTSR 680 NPSGINDDYG 690 QLKNFKKFKK 700 VTYPGAGKLP 710 HIIGGSDLIA 720 HHARKNTELE 730 EWLRQEMEVQ 740 NQHAKEESLA 750 DDLFRYNPYL KRRR

Gene Ontology

Classification GO ID Description
Biological Process GO:0051321 meiotic cell cycle
Cellular Component GO:0098687 chromosomal region
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0005829 cytosol
Cellular Component GO:0030870 Mre11 complex
Cellular Component GO:0042405 nuclear inclusion body
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Cellular Component GO:0005657 replication fork
Cellular Component GO:0035861 site of double-strand break
Molecular Function GO:0140463 chromatin-protein adaptor activity
Molecular Function GO:0003684 damaged DNA binding
Molecular Function GO:0140297 DNA-binding transcription factor binding
Molecular Function GO:0042393 histone binding
Molecular Function GO:0140031 phosphorylation-dependent protein binding
Molecular Function GO:0043539 protein serine/threonine kinase activator activity
Biological Process GO:0001832 blastocyst growth
Biological Process GO:0000077 DNA damage checkpoint signaling
Biological Process GO:0030330 DNA damage response, signal transduction by p53 class mediator
Biological Process GO:0000729 DNA double-strand break processing
Biological Process GO:0110025 DNA strand resection involved in replication fork processing
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0097681 double-strand break repair via alternative nonhomologous end joining
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0035825 homologous recombination
Biological Process GO:0045190 isotype switching
Biological Process GO:0007095 mitotic G2 DNA damage checkpoint signaling
Biological Process GO:0044818 mitotic G2/M transition checkpoint
Biological Process GO:1904354 negative regulation of telomere capping
Biological Process GO:2000781 positive regulation of double-strand break repair
Biological Process GO:1905168 positive regulation of double-strand break repair via homologous recombination
Biological Process GO:0032206 positive regulation of telomere maintenance
Biological Process GO:0031848 protection from non-homologous end joining at telomere
Biological Process GO:0070534 protein K63-linked ubiquitination
Biological Process GO:1990166 protein localization to site of double-strand break
Biological Process GO:0062176 R-loop processing
Biological Process GO:0051726 regulation of cell cycle
Biological Process GO:0030174 regulation of DNA-templated DNA replication initiation
Biological Process GO:0090656 t-circle formation
Biological Process GO:0000723 telomere maintenance
Biological Process GO:0043247 telomere maintenance in response to DNA damage
Biological Process GO:0090737 telomere maintenance via telomere trimming
Biological Process GO:0031860 telomeric 3' overhang formation

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[2] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[3] Yan M, Tu H, Tang S, Gai Z, Shi Q et al.. Lactylated Proteomic Analysis Reveals Functional Implications of Lysine Lactylation In Asthenozoospermia.. Mol Cell Proteomics 24(12):101439. 2025 Dec. PMID: 41192556.

[4] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.