NBN_PONAB
ID NBN_PONAB Reviewed; 754 AA.
AC Q5RCV3; Q5RFU1;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 25-MAY-2022, entry version 97.
DE RecName: Full=Nibrin;
DE AltName: Full=Nijmegen breakage syndrome protein 1 homolog;
GN Name=NBN;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 -!- 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. Interacts with RBBP8; the interaction links the role of the
CC MRN complex in DNA double-strand break sensing to resection (By
CC similarity). {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; CR857059; CAH89366.1; -; mRNA.
DR EMBL; CR858165; CAH90404.1; -; mRNA.
DR RefSeq; NP_001125200.1; NM_001131728.1.
DR RefSeq; NP_001191291.1; NM_001204362.1.
DR AlphaFoldDB; Q5RCV3; -.
DR STRING; 9601.ENSPPYP00000021011; -.
DR PRIDE; Q5RCV3; -.
DR GeneID; 100172091; -.
DR KEGG; pon:100172091; -.
DR CTD; 4683; -.
DR eggNOG; ENOG502QQ7Y; Eukaryota.
DR InParanoid; Q5RCV3; -.
DR OrthoDB; 831679at2759; -.
DR Proteomes; UP000001595; 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:0016605; C:PML body; IEA:UniProtKB-SubCell.
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:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
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: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; 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 2: Evidence at transcript level;
KW Cell cycle; Chromosome; DNA damage; DNA repair; Isopeptide bond; Meiosis;
KW Nucleus; Phosphoprotein; Reference proteome; Telomere; Ubl conjugation.
FT CHAIN 1..754
FT /note="Nibrin"
FT /id="PRO_0000231045"
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..402
FT /note="Interaction with MTOR, MAPKAP1 and RICTOR"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT REGION 326..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 396..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..475
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 736..743
FT /note="EEXXXDDL motif"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT COMPBIAS 326..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..475
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 278
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:O60934"
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 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 402
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT MOD_RES 673
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CROSSLNK 571
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CROSSLNK 582
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60934"
FT CONFLICT 164
FT /note="A -> P (in Ref. 1; CAH90404)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="K -> R (in Ref. 1; CAH89366)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="E -> K (in Ref. 1; CAH90404)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="Q -> R (in Ref. 1; CAH89366)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="S -> P (in Ref. 1; CAH90404)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="Missing (in Ref. 1; CAH89366)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="D -> G (in Ref. 1; CAH90404)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 754 AA; 85121 MW; B809C79F7910CBF8 CRC64;
MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIEKDQS ISRNHAVLTA NFSVTNLSQT
DEIPVLALKD NSKYGTFVNE EKMQNGFSRT LKSGDSITFG VFESKFRIEY EPLVACSSCL
DVSGKTALNQ AILQLGGFTV NNWTEECTHL VMVSVKVTIK TICALICGRP IVKPEYFTEF
LKAVQSKKQL PQIESFYPPL DEPSIGSKNV DLSGRQERKQ IFKGKTFIFL NAKQHKKLSS
AVVFGGGEAR LITEENEEEH NFFLAPGTCV VDTGITNSQT LIPDCQKKWI QSIMDMLQRQ
GLRPIPEAEI GLAVIFMTTK NYCDPQGHPS TGLKTTTPGP SLSQGLSVDE KLMPSAPVNT
TTYVADTESE QADTWDLSER PKEIKVSKME QKFRMLSQDA PTVKESCKTS SNNNSMVSNT
LAKMRIPNYQ LSPTKLPSIN KSKDRASQQQ QTNSIRNYFQ PSTKKRERDE ENQEMSSCKS
ARIEMSCSLL EQTQPAIPLL WKNKEQHLSE NEPVDTNSDN NLFTDTDLIS TVKNSASKSH
AAEKLRSNKK REMHDVTIED EVLEQLLKDT KPELEIEVKV QKQEEDVNIR KRPRMDVETN
DTFSDKAVPE SSKISQENEI GKKHELKEES LWSTKEISNN DKLQDHSEML PKKLLLTEFR
SLVIKNSTSR NPSGINGDYG LLKNFKKFKK VTYPGAGKLP HIIGGSDLIA HHARKNTELE
EWLRQEMEVQ NQHAKEESLA DDLFRYNPYL KRRR
