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Protein

Nibrin

Gene

Nbn

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

  • blastocyst growth Source: UniProtKB
  • DNA duplex unwinding Source: GO_Central
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via homologous recombination Source: GO_Central
  • in utero embryonic development Source: UniProtKB
  • isotype switching Source: UniProtKB
  • meiotic cell cycle Source: UniProtKB-KW
  • mitotic cell cycle checkpoint Source: UniProtKB
  • mitotic G2 DNA damage checkpoint Source: UniProtKB
  • negative regulation of neuron differentiation Source: RGD
  • negative regulation of viral entry into host cell Source: RGD
  • positive regulation of cell proliferation Source: RGD
  • regulation of fibroblast proliferation Source: UniProtKB
  • response to drug Source: RGD
  • signal transduction in response to DNA damage Source: GO_Central
  • telomere capping Source: GO_Central
  • telomere maintenance Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair, Meiosis

Names & Taxonomyi

Protein namesi
Recommended name:
Nibrin
Alternative name(s):
Nijmegen breakage syndrome protein 1 homolog
Gene namesi
Name:Nbn
Synonyms:Nbs1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621420. Nbn.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002310461 – 750NibrinAdd BLAST750

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei337PhosphothreonineBy similarity1
Modified residuei343Phosphoserine; by ATMBy similarity1
Modified residuei347PhosphoserineBy similarity1
Modified residuei433PhosphoserineCombined sources1
Modified residuei508PhosphoserineBy similarity1
Modified residuei517PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9JIL9.
PRIDEiQ9JIL9.

PTM databases

iPTMnetiQ9JIL9.
PhosphoSitePlusiQ9JIL9.

Expressioni

Tissue specificityi

Present at approximately equal levels in the heart at fetal day 17, at relatively constant levels at postnatal days 10, 17 and 21 and at slightly lower levels in the adult heart. Barely detectable in the brain. Not detected in kidney, very low levels in liver and skeletal muscle and moderate levels in heart, lung and brain (at protein level).1 Publication

Interactioni

Subunit structurei

Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50 and MRE11A. Interacts with histone H2AFX this requires phosphorylation of H2AFX on 'Ser-139'. Interacts with HJURP, INTS3, KPNA2 and TERF2. Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection. Interacts with SP100; recruits NBN to PML bodies. Interacts with ATF2. Interacts with MTOR, MAPKAP1 and RICTOR; indicative for an association with the mTORC2 complex (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012377.

Structurei

3D structure databases

ProteinModelPortaliQ9JIL9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 83FHAPROSITE-ProRule annotationAdd BLAST60
Domaini105 – 181BRCTAdd BLAST77

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni111 – 328Mediates interaction with SP100By similarityAdd BLAST218
Regioni221 – 403Interaction with MTOR, MAPKAP1 and RICTORBy similarityAdd BLAST183

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi461 – 467Nuclear localization signalBy similarity7
Motifi733 – 740EEXXXDDL motif8

Domaini

The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AFX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage.By similarity
The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex.By similarity
The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response.By similarity

Sequence similaritiesi

Contains 1 BRCT domain.Curated
Contains 1 FHA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IK5M. Eukaryota.
ENOG410Y1R8. LUCA.
HOGENOMiHOG000231654.
HOVERGENiHBG053070.
InParanoidiQ9JIL9.
KOiK10867.
PhylomeDBiQ9JIL9.

Family and domain databases

CDDicd00027. BRCT. 1 hit.
Gene3Di2.60.200.20. 1 hit.
3.40.50.10190. 1 hit.
InterProiIPR001357. BRCT_dom.
IPR013908. DNA-repair_Nbs1_C.
IPR000253. FHA_dom.
IPR032429. Nibrin_BRCT2.
IPR016592. Nibrin_met.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamiPF00498. FHA. 1 hit.
PF08599. Nbs1_C. 1 hit.
PF16508. NIBRIN_BRCT_II. 1 hit.
[Graphical view]
PIRSFiPIRSF011869. Nibrin_animal. 1 hit.
SMARTiSM00240. FHA. 1 hit.
SM01348. Nbs1_C. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF52113. SSF52113. 1 hit.
PROSITEiPS50006. FHA_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JIL9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWKLLPAASA APGEPCRLLA GVEYIVGRKN CAILIENDQS ISRNHAVLRV
60 70 80 90 100
NFPVTSLSQT DEIPTLTIKD NSKYGTFINE EKMQNGLSST LKTGDRVTFG
110 120 130 140 150
VFESKFRVEY EPLVVCSSCL DVSGKTVLNQ AILQLGGLTA NSWTEECTHL
160 170 180 190 200
AMSSVKVTIK TICALICGRP IVKPEYFSEF LKAVESKTQP PEIESFYPPI
210 220 230 240 250
DEPAIGNKSV DLSGRRERKQ IFKGKTFVFL NAKQHKKLGS AVVFGGGEAR
260 270 280 290 300
LMAEGGEEEQ SFFSAPGTCV VDVGITNTQL IITDSQRKWI HLIMDILQRH
310 320 330 340 350
GLRPIPEAEI GLAVIFMTTE SYCNPQGQPC TEVKTTTPGP SLSQGLSANG
360 370 380 390 400
KVIPSAPMNM TTYVADTESE PADTCMSLSE RPEEVKIFGL DQNSRKLLQG
410 420 430 440 450
TCNIKETSNQ SSNSNNAASN TLVRGKAPNY QLSPMKCPAA SKNKDWSSQQ
460 470 480 490 500
QLNSIKNYFQ PCSRKRERDE ENPEQSSCKS SRVELSCSLL EQTQPAGPSL
510 520 530 540 550
WKSKDHESQS ETLDRASNAS SVGGIDIKPN GKSPDSKSFS TEDLRARKRK
560 570 580 590 600
EVDLSTEEEV LEELLRSTKP ELAVQVKVEK QEADVSIRKK PRMDAERNQH
610 620 630 640 650
LNGGPVPESN SALQEDETGK KDELQIEAWS TKREVSNTDE LQDSSEELPR
660 670 680 690 700
KLLLTEFRSL VVHNNSSRNL CVLNGRGELK NFKKFKKATC PGAGKLPHII
710 720 730 740 750
GGSDLIGHHA RKNTELEEWL KHEMEVQKQQ AKEDSLADDL FRYNPNVKRR
Length:750
Mass (Da):83,150
Last modified:April 4, 2006 - v2
Checksum:i43A93B5497102A4A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67T → I in AAF91228 (PubMed:10908350).Curated1
Sequence conflicti84Q → L in AAH85700 (PubMed:15489334).Curated1
Sequence conflicti277N → H in AAH85700 (PubMed:15489334).Curated1
Sequence conflicti301G → D in AAF91228 (PubMed:10908350).Curated1
Sequence conflicti497G → E in AAF91228 (PubMed:10908350).Curated1
Sequence conflicti514D → G in AAF91228 (PubMed:10908350).Curated1
Sequence conflicti619G → E in AAF91228 (PubMed:10908350).Curated1
Sequence conflicti642Q → P in AAH85700 (PubMed:15489334).Curated1
Sequence conflicti672V → P in AAF91228 (PubMed:10908350).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF218575 mRNA. Translation: AAF91228.1.
BC085700 mRNA. Translation: AAH85700.1.
RefSeqiNP_620228.1. NM_138873.2.
UniGeneiRn.25214.

Genome annotation databases

GeneIDi85482.
KEGGirno:85482.
UCSCiRGD:621420. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF218575 mRNA. Translation: AAF91228.1.
BC085700 mRNA. Translation: AAH85700.1.
RefSeqiNP_620228.1. NM_138873.2.
UniGeneiRn.25214.

3D structure databases

ProteinModelPortaliQ9JIL9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012377.

PTM databases

iPTMnetiQ9JIL9.
PhosphoSitePlusiQ9JIL9.

Proteomic databases

PaxDbiQ9JIL9.
PRIDEiQ9JIL9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi85482.
KEGGirno:85482.
UCSCiRGD:621420. rat.

Organism-specific databases

CTDi4683.
RGDi621420. Nbn.

Phylogenomic databases

eggNOGiENOG410IK5M. Eukaryota.
ENOG410Y1R8. LUCA.
HOGENOMiHOG000231654.
HOVERGENiHBG053070.
InParanoidiQ9JIL9.
KOiK10867.
PhylomeDBiQ9JIL9.

Miscellaneous databases

PROiQ9JIL9.

Family and domain databases

CDDicd00027. BRCT. 1 hit.
Gene3Di2.60.200.20. 1 hit.
3.40.50.10190. 1 hit.
InterProiIPR001357. BRCT_dom.
IPR013908. DNA-repair_Nbs1_C.
IPR000253. FHA_dom.
IPR032429. Nibrin_BRCT2.
IPR016592. Nibrin_met.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamiPF00498. FHA. 1 hit.
PF08599. Nbs1_C. 1 hit.
PF16508. NIBRIN_BRCT_II. 1 hit.
[Graphical view]
PIRSFiPIRSF011869. Nibrin_animal. 1 hit.
SMARTiSM00240. FHA. 1 hit.
SM01348. Nbs1_C. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF52113. SSF52113. 1 hit.
PROSITEiPS50006. FHA_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNBN_RAT
AccessioniPrimary (citable) accession number: Q9JIL9
Secondary accession number(s): Q5RKL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: November 30, 2016
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.