NBN_CHICK
ID NBN_CHICK Reviewed; 753 AA.
AC Q9DE07;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Nibrin;
DE AltName: Full=Nijmegen breakage syndrome protein 1 homolog;
GN Name=NBN; Synonyms=NBS1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11062235; DOI=10.1074/jbc.c000578200;
RA Tauchi H., Kobayashi J., Morishima K., Matsuura S., Nakamura A.,
RA Shiraishi T., Ito E., Masnada D., Delia D., Komatsu K.;
RT "The forkhead-associated domain of NBS1 is essential for nuclear foci
RT formation after irradiation but not essential for hRAD50.hMRE11.NBS1
RT complex DNA repair activity.";
RL J. Biol. Chem. 276:12-15(2001).
RN [2]
RP FUNCTION IN DNA DSB REPAIR.
RX PubMed=12422221; DOI=10.1038/nature01125;
RA Tauchi H., Kobayashi J., Morishima K., van Gent D.C., Shiraishi T.,
RA Verkaik N.S., vanHeems D., Ito E., Nakamura A., Sonoda E., Takata M.,
RA Takeda S., Matsuura S., Komatsu K.;
RT "Nbs1 is essential for DNA repair by homologous recombination in higher
RT vertebrate cells.";
RL Nature 420:93-98(2002).
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 (PubMed:12422221). The complex is
CC involved in double-strand break (DSB) repair, DNA recombination,
CC maintenance of telomere integrity, cell cycle checkpoint control and
CC meiosis (PubMed:12422221). The complex possesses single-strand
CC endonuclease activity and double-strand-specific 3'-5' exonuclease
CC activity, which are provided by MRE11 (By similarity). RAD50 may be
CC required to bind DNA ends and hold them in close proximity (By
CC similarity). NBN modulate the DNA damage signal sensing by recruiting
CC PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the
CC DNA damage sites and activating their functions (By similarity). It can
CC also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction
CC with the histone H2AX (By similarity). NBN also functions in telomere
CC length maintenance by generating the 3' overhang which serves as a
CC primer for telomerase dependent telomere elongation (By similarity).
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 (By similarity). The roles of NBS1/MRN encompass DNA damage sensor,
CC signal transducer, and effector, which enable cells to maintain DNA
CC integrity and genomic stability (By similarity). Forms a complex with
CC RBBP8 to link DNA double-strand break sensing to resection (By
CC similarity). {ECO:0000250|UniProtKB:O60934,
CC ECO:0000269|PubMed:12422221}.
CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers
CC RAD50/MRE11 associated with a single NBN. Interacts with RBBP8; the
CC interaction links the role of the MRN complex in DNA double-strand
CC break sensing to resection. {ECO:0000250|UniProtKB:O60934}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O60934}.
CC Chromosome, telomere {ECO:0000250|UniProtKB:O60934}.
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.
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; AF230342; AAG47947.1; -; mRNA.
DR RefSeq; NP_989668.1; NM_204337.1.
DR AlphaFoldDB; Q9DE07; -.
DR SMR; Q9DE07; -.
DR STRING; 9031.ENSGALP00000041080; -.
DR PaxDb; Q9DE07; -.
DR PRIDE; Q9DE07; -.
DR GeneID; 374246; -.
DR KEGG; gga:374246; -.
DR CTD; 4683; -.
DR VEuPathDB; HostDB:geneid_374246; -.
DR eggNOG; ENOG502QQ7Y; Eukaryota.
DR InParanoid; Q9DE07; -.
DR OrthoDB; 831679at2759; -.
DR PhylomeDB; Q9DE07; -.
DR Reactome; R-GGA-217106; Chk1-controlled and DNA-damage induced centrosome duplication.
DR Reactome; R-GGA-351433; ATM mediated phosphorylation of repair proteins.
DR Reactome; R-GGA-351442; ATM mediated response to DNA double-strand break.
DR Reactome; R-GGA-351444; Recruitment of repair and signaling proteins to double-strand breaks.
DR PRO; PR:Q9DE07; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0030870; C:Mre11 complex; ISS:UniProtKB.
DR GO; GO:0042405; C:nuclear inclusion body; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0006302; P:double-strand break repair; 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:0048145; P:regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; ISS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.40.50.10190; -; 1.
DR Gene3D; 3.40.50.10980; -; 1.
DR InterPro; IPR001357; BRCT_dom.
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; PF00533; BRCT; 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; SM00292; BRCT; 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; Meiosis; Nucleus;
KW Phosphoprotein; Reference proteome; Telomere.
FT CHAIN 1..753
FT /note="Nibrin"
FT /id="PRO_0000231047"
FT DOMAIN 22..81
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DOMAIN 101..191
FT /note="BRCT"
FT REGION 442..606
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 735..742
FT /note="EEXXXDDL motif"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT COMPBIAS 458..486
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..512
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..568
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..606
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 343
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:O60934"
SQ SEQUENCE 753 AA; 83987 MW; 410BBE74123D9B06 CRC64;
MWKLVPAAGP GEPFRLLVGT EYVVGRKNCA FLIQDDQSIS RSHAVLTVSR PETTHSQSVS
VPVLTIKDTS KYGTFVNGSK LSGASRSLQS GDRVNFGVFE SKFRVEYESL VVCSSCLDVA
QKTALNEAIQ QLGGLVVNEW TKECTHLIME SVKVTVKTIC ALICGRPIVK PEFFSELMKA
VQSRQQLPTP ESFYPSVDEP AIGIDNMDLS GHPERKKIFS GKTFVFLTAK QHKKLGPAVI
LGGGEAKLMA EERKETSLLV SPEVCVVDVG VTNSQILGSE SMRNWTDSIL AVLESNNLRA
IPEAEIGLAV IFMSTEIYCN PQRQPDNKAV TASTASKVRP VSSQSSTVDE TIMPTAAADY
STLNVADTEI EEQTCMEIER TTSQTTRREK VAFQQAAVRE NPSTSGTVNA GMLISRVNRT
SGFGQKNHPH SPSKILEVDK PRECTPRQQS NSITNYFHVA RKRERAEEGE ETSLSKQAKL
EKKPLPVSEC TESSASSAWN SEKEQHGKGN NIQLGRESGE LASDKTDIKI TFSENPAPKK
RKELDDVSED VETLEMVFES RDLDWEEQTA NGDQEAQSNK RKKRCLETKG SRTEEGNTKQ
REENEMLRKE EVGSVLTLED KSKIKEESSV SIRNKLINHN KLEDDSSRLP SKLLLTEFRS
LVVSCPRSNS PTMRNTKCRG QNNFKTFRKV PYPGAGQLPY IIGGSDLVAH QARKNSELEE
WLREELEEQN RRAREESLAD DLFRYDPNVK RRR
