Reviewed, UniProtKB/Swiss-Prot Q9R207 (NBN_MOUSE)

Names and origin

Protein names

Recommended name:
    Nibrin
Alternative name(s):
    Nijmegen breakage syndrome protein 1 homolog
    Cell cycle regulatory protein p95

Gene names

Name:	Nbn
Synonyms:	Nbs1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	751 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 By similarity.
Subunit structure	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 By similarity.
Subcellular location	Nucleus. Telomere By similarity. Note: Localizes to discrete nuclear foci after treatment with genotoxic agents By similarity.
Tissue specificity	High expression in the liver, heart and testis. Low expression in all other tissues analyzed. In the cerebellum the postmitotic Purkinje cells are marked specifically. Ref.6
Developmental stage	A low level of expression is observed in all tissues. Highly specific expression was observed in organs with physiologic DNA double strand breakage (DSB), such as testis, thymus and spleen. Enhanced expression is also found at sites of high proliferative activity. These are the subventricular layer of the telencephalon and the diencephalon, the liver, lung, kidney and gut, as well as striated and smooth muscle cells in various organs. Ref.6
Domain	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.
Post-translational modification	Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance By similarity. Ref.7
Sequence similarities	Contains 1 BRCT domain. Contains 1 FHA domain.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair Meiosis
Cellular component	Chromosomal protein Nucleus Telomere
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	G1/S transition checkpoint Inferred from sequence or structural similarity. Source: UniProtKB blastocyst growth Inferred from mutant phenotype. Source: UniProtKB cell proliferation Inferred from mutant phenotype. Source: MGI double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB isotype switching Inferred from direct assay. Source: UniProtKB meiosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic cell cycle G2/M transition DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB neuromuscular process controlling balance Inferred from mutant phenotype. Source: MGI regulation of fibroblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB telomere maintenance Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	Mre11 complex Inferred from sequence or structural similarity. Source: UniProtKB nuclear inclusion body Inferred from sequence or structural similarity. Source: UniProtKB replication fork Inferred from direct assay. Source: MGI
Molecular function	damaged DNA binding Inferred from direct assay. Source: MGI protein N-terminus binding Inferred from sequence or structural similarity. Source: UniProtKB transcription factor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 751	751	Nibrin		PRO_0000231044
Regions
	Domain	24 – 83	60	FHA
	Domain	105 – 181	77	BRCT
	Motif	461 – 467	7	Nuclear localization signal By similarity
	Motif	734 – 741	8	EEXXXDDL motif
	Compositional bias	449 – 452	4	Poly-Gln
Amino acid modifications
	Modified residue	337	1	Phosphothreonine By similarity
	Modified residue	341	1	Phosphoserine By similarity
	Modified residue	343	1	Phosphoserine; by ATM By similarity
	Modified residue	398	1	Phosphoserine Ref.7
	Modified residue	433	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	9	1	G → S in AAH44773. Ref.4
	Sequence conflict	11 – 12	2	AP → SL in AAC62113. Ref.3
	Sequence conflict	325	1	P → Q in BAE22356. Ref.5
	Sequence conflict	366	1	D → E in BAA76298. Ref.2
	Sequence conflict	455	1	I → F in BAA76298. Ref.2
	Sequence conflict	513	1	L → Q in AAH44773. Ref.4
	Sequence conflict	664	1	N → K in AAH44773. Ref.4
	Sequence conflict	676	1	E → D in AAH44773. Ref.4
	Sequence conflict	679	1	P → S in AAH44773. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9R207-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: C9F597CC08227B2C	FASTA	751	83,795
	10 20 30 40 50 60 MWKLLPAAGA APGEPYRLLA GVEYVVGRKN CGILIENDQS ISRNHAVLTV NFPVTSLSQT 70 80 90 100 110 120 DEIPTLTIKD NSKYGTFVNE EKMQTGLSCT LKTGDRVTFG VFESKFRVEY EPLVVCSSCL 130 140 150 160 170 180 DVSGKTVLNQ AILQLGGLTA NNWTEECTHL VMSAVKVTIK TICALICGRP IIKPEYFSEF 190 200 210 220 230 240 LKAVESKKQP PDIESFYPPI DEPAIGSKSV DLSGRHERKQ IFKGKTFVFL NAKQHKKLSS 250 260 270 280 290 300 AVAFGGGEAR LMAEDDEEEQ SFFSAPGTCV VDVGITNTQL IISHSQKKWI HLIMDTLQRN 310 320 330 340 350 360 GLRPIPEAEI GLAVIFMTTE NYCNPQGQPC TELKTTTPGP SLSQVLSANG KIIPSAPVNM 370 380 390 400 410 420 TTYVADTESE PADTCMPLSE RPEEVKIPGL EQSSRKLSQE TFNIKEAPKP SSKANNVASD 430 440 450 460 470 480 TLVRGKTPSY QLSPMKFPVA NKNKDWTSQQ QQNSIKNYFQ PCTRKRERDE DNPELSSCKS 490 500 510 520 530 540 SRMELSCSLL EQTQPAGPSL WKSKEHQSQN ATLDREADTS SVGGMDIELN RKSPDRKPLP 550 560 570 580 590 600 TETLRPRKRK DVDLATEEEV LEELLRSTKP ELAVQVKVEK QEADDTIRKK PRMDAERNRP 610 620 630 640 650 660 LNGGSEPESN SALQEDEREK KDELQTESWS TKHEIANSDG LQDSSEELPR KLLLTEFRSL 670 680 690 700 710 720 VVSNHNSTSR NLCVNECGPL KNFKKFKKAT FPGAGKLPHI IGGSDLVGHH ARKNTELEEW 730 740 750 LKQEMEVQKQ QAKEESLADD LFRYNPNVKR R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome." Vissinga C.S., Yeo T.C., Woessner J., Massa H.F., Wilson R.K., Trask B.J., Concannon P. Cytogenet. Cell Genet. 87:80-84(1999) [PubMed: 10640816] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of the mouse Nijmegen breakage syndrome (Nibrin/Nbs1) protein." Saito T. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain and Testis.
[3]	"Isolation of 50 cDNAs differentially expressed in embryonic forebrain as compared to mid and hindbrain: a strategy to identify candidate genes involved in human neurodevelopmental diseases." Mas C., Bourgeois F., Simonneau M. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain stem.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Czech II and FVB/N. Tissue: Colon and Mammary gland.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-613. Strain: C57BL/6J. Tissue: Medulla oblongata.
[6]	"Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine development." Wilda M., Demuth I., Concannon P., Sperling K., Hameister H. Hum. Mol. Genet. 9:1739-1744(2000) [PubMed: 10915761] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[7]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF076687 mRNA. Translation: AAD20943.1. AB016988 mRNA. Translation: BAA76298.1. AF092840 mRNA. Translation: AAC62113.1. BC044773 mRNA. Translation: AAH44773.1. BC055061 mRNA. Translation: AAH55061.1. AK134960 mRNA. Translation: BAE22356.1. AK031933 mRNA. Translation: BAC27610.1.
IPI	IPI00316857.
RefSeq	NP_038780.3.
UniGene	Mm.20866
3D structure databases
SMR	Q9R207. Positions 2-123, 113-249, 216-327.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9R207.
PTM databases
PhosphoSite	Q9R207.
Proteomic databases
PRIDE	Q9R207.
Genome annotation databases
Ensembl	ENSMUST00000029879; ENSMUSP00000029879; ENSMUSG00000028224; Mus musculus. [Genome view]
GeneID	27354.
KEGG	mmu:27354.
UCSC	uc008sbn.1. mouse.
Organism-specific databases
CTD	27354.
MGI	MGI:1351625. Nbn.
Phylogenomic databases
HOGENOM	HBG444442.
HOVERGEN	Q9R207.
InParanoid	Q9R207.
OMA	QEMEVQN.
OrthoDB	EOG92NMKB.
Gene expression databases
ArrayExpress	Q9R207.
Bgee	Q9R207.
CleanEx	MM_NBN.
Genevestigator	Q9R207.
GermOnline	ENSMUSG00000028224. Mus musculus.
Family and domain databases
InterPro	IPR001357. BRCT. IPR013908. DNA-repair_Nbs1_C. IPR000253. FHA. IPR016592. Nibrin_met. IPR008984. SMAD_FHA_domain. [Graphical view]
Gene3D	G3DSA:2.60.200.20. FHA. 1 hit.
Pfam	PF00498. FHA. 1 hit. PF08599. Nbs1_C. 1 hit. [Graphical view]
PIRSF	PIRSF011869. Nibrin_animal. 1 hit.
SMART	SM00292. BRCT. 1 hit. SM00240. FHA. 1 hit. [Graphical view]
PROSITE	PS50172. BRCT. False negative. PS50006. FHA_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	305208.
SOURCE	Search...

Entry information

Entry name

NBN_MOUSE

Accession

Primary (citable) accession number: Q9R207
Secondary accession number(s): O88981 , Q3UY57, Q811I6, Q8CCY0, Q9R1X1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	May 1, 2000
Last modified:	January 19, 2010
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)