NBN_RAT
ID NBN_RAT Reviewed; 750 AA.
AC Q9JIL9; Q5RKL2;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Nibrin;
DE AltName: Full=Nijmegen breakage syndrome protein 1 homolog;
GN Name=Nbn; Synonyms=Nbs1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10908350; DOI=10.1093/nar/28.15.2882;
RA Lanson N.A. Jr., Egeland D.B., Royals B.A., Claycomb W.C.;
RT "The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-
RT immortalized AT-1, AT-2 and HL-1 cardiomyocytes.";
RL Nucleic Acids Res. 28:2882-2892(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Component of the MRE11-RAD50-NBN (MRN complex) which plays a
CC critical role in the cellular response to DNA damage and the
CC maintenance of chromosome integrity. The complex is involved in double-
CC strand break (DSB) repair, DNA recombination, maintenance of telomere
CC integrity, cell cycle checkpoint control and meiosis. The complex
CC possesses single-strand endonuclease activity and double-strand-
CC specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50
CC may be required to bind DNA ends and hold them in close proximity. NBN
CC modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase
CC family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites
CC and activating their functions. It can also recruit MRE11 and RAD50 to
CC the proximity of DSBs by an interaction with the histone H2AX. NBN also
CC functions in telomere length maintenance by generating the 3' overhang
CC which serves as a primer for telomerase dependent telomere elongation.
CC NBN is a major player in the control of intra-S-phase checkpoint and
CC there is some evidence that NBN is involved in G1 and G2 checkpoints.
CC The roles of NBS1/MRN encompass DNA damage sensor, signal transducer,
CC and effector, which enable cells to maintain DNA integrity and genomic
CC stability. Forms a complex with RBBP8 to link DNA double-strand break
CC sensing to resection. Enhances AKT1 phosphorylation possibly by
CC association with the mTORC2 complex (By similarity).
CC {ECO:0000250|UniProtKB:O60934}.
CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers
CC RAD50/MRE11 associated with a single NBN (By similarity). As part of
CC the MRN complex, interacts with MCM9; the interaction recruits the
CC complex to DNA repair sites (By similarity). Component of the BASC
CC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50,
CC MRE11 and NBN (By similarity). Interacts with histone H2AX this
CC requires phosphorylation of H2AX on 'Ser-139' (By similarity).
CC Interacts with HJURP, INTS3, KPNA2 and TERF2 (By similarity). Interacts
CC with RBBP8; the interaction links the role of the MRN complex in DNA
CC double-strand break sensing to resection (By similarity). Interacts
CC with SP100; recruits NBN to PML bodies (By similarity). Interacts with
CC ATF2 (By similarity). Interacts with MTOR, MAPKAP1 isoform 2 and
CC RICTOR; indicative for an association with the mTORC2 complex (By
CC similarity). Interacts with MRNIP (By similarity). Interacts with UFL1;
CC promoting UFL1 recruitment to double-strand breaks following DNA damage
CC (By similarity). Interacts with CYREN (via XLF motif) (By similarity).
CC {ECO:0000250|UniProtKB:O60934, ECO:0000250|UniProtKB:Q9R207}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O60934}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:O60934}. Chromosome, telomere
CC {ECO:0000250|UniProtKB:O60934}. Chromosome
CC {ECO:0000250|UniProtKB:O60934}. Note=Localizes to discrete nuclear foci
CC after treatment with genotoxic agents. Acetylation of 'Lys-5' of
CC histone H2AX (H2AXK5ac) promotes NBN/NBS1 assembly at the sites of DNA
CC damage. {ECO:0000250|UniProtKB:O60934}.
CC -!- TISSUE SPECIFICITY: Present at approximately equal levels in the heart
CC at fetal day 17, at relatively constant levels at postnatal days 10, 17
CC and 21 and at slightly lower levels in the adult heart. Barely
CC detectable in the brain. Not detected in kidney, very low levels in
CC liver and skeletal muscle and moderate levels in heart, lung and brain
CC (at protein level). {ECO:0000269|PubMed:10908350}.
CC -!- DOMAIN: The FHA and BRCT domains are likely to have a crucial role for
CC both binding to histone H2AX and for relocalization of MRE11/RAD50
CC complex to the vicinity of DNA damage. {ECO:0000250|UniProtKB:O60934}.
CC -!- DOMAIN: The C-terminal domain contains a MRE11-binding site, and this
CC interaction is required for the nuclear localization of the MRN
CC complex. {ECO:0000250|UniProtKB:O60934}.
CC -!- DOMAIN: The EEXXXDDL motif at the C-terminus is required for the
CC interaction with ATM and its recruitment to sites of DNA damage and
CC promote the phosphorylation of ATM substrates, leading to the events of
CC DNA damage response. {ECO:0000250|UniProtKB:O60934}.
CC -!- PTM: Phosphorylated by ATM in response of ionizing radiation, and such
CC phosphorylation is responsible intra-S phase checkpoint control and
CC telomere maintenance. {ECO:0000250|UniProtKB:O60934}.
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DR EMBL; AF218575; AAF91228.1; -; mRNA.
DR EMBL; BC085700; AAH85700.1; -; mRNA.
DR RefSeq; NP_620228.1; NM_138873.2.
DR AlphaFoldDB; Q9JIL9; -.
DR STRING; 10116.ENSRNOP00000012377; -.
DR iPTMnet; Q9JIL9; -.
DR PhosphoSitePlus; Q9JIL9; -.
DR PaxDb; Q9JIL9; -.
DR GeneID; 85482; -.
DR KEGG; rno:85482; -.
DR UCSC; RGD:621420; rat.
DR CTD; 4683; -.
DR RGD; 621420; Nbn.
DR eggNOG; ENOG502QQ7Y; Eukaryota.
DR InParanoid; Q9JIL9; -.
DR OrthoDB; 831679at2759; -.
DR PhylomeDB; Q9JIL9; -.
DR Reactome; R-RNO-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-RNO-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-RNO-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-RNO-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-RNO-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-RNO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-RNO-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-RNO-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-RNO-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-RNO-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-RNO-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-69473; G2/M DNA damage checkpoint.
DR PRO; PR:Q9JIL9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070533; C:BRCA1-C complex; ISO:RGD.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:RGD.
DR GO; GO:0030870; C:Mre11 complex; ISS:UniProtKB.
DR GO; GO:0042405; C:nuclear inclusion body; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0016605; C:PML body; ISO:RGD.
DR GO; GO:0005657; C:replication fork; ISO:RGD.
DR GO; GO:0035861; C:site of double-strand break; ISO:RGD.
DR GO; GO:0003684; F:damaged DNA binding; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISS:UniProtKB.
DR GO; GO:0001832; P:blastocyst growth; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISO:RGD.
DR GO; GO:0032508; P:DNA duplex unwinding; ISO:RGD.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0045190; P:isotype switching; ISS:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:RGD.
DR GO; GO:1904354; P:negative regulation of telomere capping; ISO:RGD.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IMP:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISO:RGD.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; ISO:RGD.
DR GO; GO:0048145; P:regulation of fibroblast proliferation; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0090656; P:t-circle formation; ISO:RGD.
DR GO; GO:0000723; P:telomere maintenance; ISS:UniProtKB.
DR GO; GO:0090737; P:telomere maintenance via telomere trimming; ISO:RGD.
DR GO; GO:0031860; P:telomeric 3' overhang formation; ISO:RGD.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.40.50.10190; -; 1.
DR Gene3D; 3.40.50.10980; -; 1.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR013908; DNA-repair_Nbs1_C.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR040227; Nibrin-rel.
DR InterPro; IPR032429; Nibrin_BRCT2.
DR InterPro; IPR043014; Nibrin_BRCT2_sf.
DR InterPro; IPR016592; Nibrin_met.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR PANTHER; PTHR12162; PTHR12162; 1.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF08599; Nbs1_C; 1.
DR Pfam; PF16508; NIBRIN_BRCT_II; 1.
DR PIRSF; PIRSF011869; Nibrin_animal; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM01348; Nbs1_C; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Chromosome; DNA damage; DNA repair; Isopeptide bond; Meiosis;
KW Nucleus; Phosphoprotein; Reference proteome; Telomere; Ubl conjugation.
FT CHAIN 1..750
FT /note="Nibrin"
FT /id="PRO_0000231046"
FT DOMAIN 24..83
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DOMAIN 105..181
FT /note="BRCT"
FT REGION 111..328
FT /note="Mediates interaction with SP100"
FT /evidence="ECO:0000250|UniProtKB:Q9R207"
FT REGION 221..403
FT /note="Interaction with MTOR, MAPKAP1 and RICTOR"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT REGION 429..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..550
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..622
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 461..467
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOTIF 733..740
FT /note="EEXXXDDL motif"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT COMPBIAS 442..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..477
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..597
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 343
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CROSSLNK 528
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CROSSLNK 569
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CROSSLNK 580
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CONFLICT 67
FT /note="T -> I (in Ref. 1; AAF91228)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="Q -> L (in Ref. 2; AAH85700)"
FT /evidence="ECO:0000305"
FT CONFLICT 277
FT /note="N -> H (in Ref. 2; AAH85700)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="G -> D (in Ref. 1; AAF91228)"
FT /evidence="ECO:0000305"
FT CONFLICT 497
FT /note="G -> E (in Ref. 1; AAF91228)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="D -> G (in Ref. 1; AAF91228)"
FT /evidence="ECO:0000305"
FT CONFLICT 619
FT /note="G -> E (in Ref. 1; AAF91228)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="Q -> P (in Ref. 2; AAH85700)"
FT /evidence="ECO:0000305"
FT CONFLICT 672
FT /note="V -> P (in Ref. 1; AAF91228)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 750 AA; 83150 MW; 43A93B5497102A4A CRC64;
MWKLLPAASA APGEPCRLLA GVEYIVGRKN CAILIENDQS ISRNHAVLRV NFPVTSLSQT
DEIPTLTIKD NSKYGTFINE EKMQNGLSST LKTGDRVTFG VFESKFRVEY EPLVVCSSCL
DVSGKTVLNQ AILQLGGLTA NSWTEECTHL AMSSVKVTIK TICALICGRP IVKPEYFSEF
LKAVESKTQP PEIESFYPPI DEPAIGNKSV DLSGRRERKQ IFKGKTFVFL NAKQHKKLGS
AVVFGGGEAR LMAEGGEEEQ SFFSAPGTCV VDVGITNTQL IITDSQRKWI HLIMDILQRH
GLRPIPEAEI GLAVIFMTTE SYCNPQGQPC TEVKTTTPGP SLSQGLSANG KVIPSAPMNM
TTYVADTESE PADTCMSLSE RPEEVKIFGL DQNSRKLLQG TCNIKETSNQ SSNSNNAASN
TLVRGKAPNY QLSPMKCPAA SKNKDWSSQQ QLNSIKNYFQ PCSRKRERDE ENPEQSSCKS
SRVELSCSLL EQTQPAGPSL WKSKDHESQS ETLDRASNAS SVGGIDIKPN GKSPDSKSFS
TEDLRARKRK EVDLSTEEEV LEELLRSTKP ELAVQVKVEK QEADVSIRKK PRMDAERNQH
LNGGPVPESN SALQEDETGK KDELQIEAWS TKREVSNTDE LQDSSEELPR KLLLTEFRSL
VVHNNSSRNL CVLNGRGELK NFKKFKKATC PGAGKLPHII GGSDLIGHHA RKNTELEEWL
KHEMEVQKQQ AKEDSLADDL FRYNPNVKRR
