CPLM-001027

Genbank Nucleotide ID

Protein Synonyms/Alias

Cell cycle regulatory protein p95; Nijmegen breakage syndrome protein 1

Homo sapiens (Human)

Position	Peptide	Type	References
3	*****MWKLLPAAGP	ubiquitination	[1, 2]
82	GTFVNEEKMQNGFSR	ubiquitination	[2]
334	GHPSTGLKTTTPGPS	ubiquitination	[2]
544	SKSHAAEKLRSNKKR	acetylation	[3]
665	EFRSLVIKNSTSRNP	ubiquitination	[4]
683	NDDYGQLKNFKKFKK	ubiquitination	[4, 5, 6]
715	LIAHHARKNTELEEW	ubiquitination	[2]

[1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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.

DOMAIN 24 83 FHA.
DOMAIN 105 181 BRCT.
REGION 111 328 Mediates interaction with SP100 (By
MOTIF 461 467 Nuclear localization signal.
MOTIF 736 743 EEXXXDDL motif.
MOD_RES 278 278 Phosphoserine; by ATM.
MOD_RES 343 343 Phosphoserine; by ATM.
MOD_RES 397 397 Phosphoserine.
MOD_RES 402 402 Phosphothreonine.
MOD_RES 432 432 Phosphoserine.
MOD_RES 615 615 Phosphoserine.

Cell cycle; Chromosome; Complete proteome; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; Meiosis; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Telomere.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0030870; C:Mre11 complex; IDA:UniProtKB.
GO:0000784; C:nuclear chromosome, telomeric region; IDA:BHF-UCL.
GO:0042405; C:nuclear inclusion body; IDA:UniProtKB.
GO:0005730; C:nucleolus; IDA:BHF-UCL.
GO:0016605; C:PML body; IDA:UniProtKB.
GO:0005657; C:replication fork; IEA:Compara.
GO:0003684; F:damaged DNA binding; IEA:Compara.
GO:0006915; P:apoptotic process; IEA:Compara.
GO:0001832; P:blastocyst growth; IEA:Compara.
GO:0007050; P:cell cycle arrest; TAS:UniProtKB.
GO:0008283; P:cell proliferation; IEA:Compara.
GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; TAS:UniProtKB.
GO:0032508; P:DNA duplex unwinding; IMP:BHF-UCL.
GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome.
GO:0045190; P:isotype switching; IEA:Compara.
GO:0007126; P:meiosis; IEA:UniProtKB-KW.
GO:0007095; P:mitotic G2 DNA damage checkpoint; IDA:UniProtKB.
GO:0050885; P:neuromuscular process controlling balance; IEA:Compara.
GO:0033674; P:positive regulation of kinase activity; IDA:BHF-UCL.
GO:0031954; P:positive regulation of protein autophosphorylation; IDA:BHF-UCL.
GO:0030174; P:regulation of DNA-dependent DNA replication initiation; TAS:UniProtKB.
GO:0000723; P:telomere maintenance; IMP:UniProtKB.

IPR001357; BRCT_dom.
IPR013908; DNA-repair_Nbs1_C.
IPR000253; FHA_dom.
IPR016592; Nibrin_met.
IPR008984; SMAD_FHA_domain.

PF00498; FHA
PF08599; Nbs1_C

SM00292; BRCT
SM00240; FHA

PS50172; BRCT
PS50006; FHA_DOMAIN