O60934 (NBN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nibrin

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

Gene names

Name:	NBN
Synonyms:	NBS, NBS1, P95

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	754 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. Ref.11 Ref.16 Ref.21
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 By similarity. Interacts with histone H2AFX this requires phosphorylation of H2AFX on 'Ser-139'. Interacts with HJURP, INTS3, KPNA2 and TERF2. Ref.2 Ref.12 Ref.17 Ref.19 Ref.25 Ref.29
Subcellular location	Nucleus By similarity. Chromosome › telomere By similarity. Note: Localizes to discrete nuclear foci after treatment with genotoxic agents By similarity.
Tissue specificity	Ubiquitous. Expressed at high levels in testis.
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. Ref.20 The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex. Ref.20 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. Ref.20
Post-translational modification	Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance. Ref.13 Ref.14 Ref.15 Ref.18 Ref.24 Ref.26 Ref.27 Ref.28
Involvement in disease	Defects in NBN are the cause of Nijmegen breakage syndrome (NBS) [MIM:251260]. NBS is an autosomal recessive syndrome characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies. Defects in NBN are a cause of susceptibility to breast cancer (BC) [MIM:114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Ref.32 Defects in NBN may be associated with aplastic anemia (AA) [MIM:609135]. A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. Note=Defects in NBN might play a role in the pathogenesis of childhood acute lymphoblastic leukemia (ALL).
Miscellaneous	In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells.
Sequence similarities	Contains 1 BRCT domain. Contains 1 FHA domain.
Sequence caution	The sequence AAI08651.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence starting in position 550. The sequence BAD96976.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH56160.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair Meiosis
Cellular component	Chromosome Nucleus Telomere
Coding sequence diversity	Polymorphism
Disease	Disease mutation
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator Traceable author statement Ref.2. Source: UniProtKB DNA duplex unwinding Inferred from mutant phenotype. Source: BHF-UCL cell cycle arrest Traceable author statement Ref.2. Source: UniProtKB double-strand break repair via homologous recombination Traceable author statement. Source: Reactome meiosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic cell cycle G1/S transition checkpoint Inferred from direct assay. Source: UniProtKB mitotic cell cycle G2/M transition DNA damage checkpoint Inferred from direct assay. Source: UniProtKB positive regulation of kinase activity Inferred from direct assay. Source: BHF-UCL positive regulation of protein autophosphorylation Inferred from direct assay. Source: BHF-UCL regulation of DNA-dependent DNA replication initiation Traceable author statement Ref.2. Source: UniProtKB telomere maintenance Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Mre11 complex Inferred from direct assay Ref.2. Source: UniProtKB nuclear chromosome, telomeric region Inferred from direct assay Ref.16. Source: BHF-UCL nuclear inclusion body Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay Ref.16. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome
Molecular function	protein N-terminus binding Inferred from physical interaction Ref.2. Source: UniProtKB transcription factor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
H2AFX	P16104	9	EBI-494844,EBI-494830
MDC1	Q14676	8	EBI-494844,EBI-495644

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 754	754	Nibrin		PRO_0000231043
Regions
	Domain	24 – 83	60	FHA
	Domain	105 – 181	77	BRCT
	Motif	461 – 467	7	Nuclear localization signal
	Motif	736 – 743	8	EEXXXDDL motif
	Compositional bias	448 – 451	4	Poly-Gln
Amino acid modifications
	Modified residue	278	1	Phosphoserine; by ATM Ref.14
	Modified residue	337	1	Phosphothreonine Ref.28
	Modified residue	341	1	Phosphoserine Ref.28
	Modified residue	343	1	Phosphoserine; by ATM Ref.13 Ref.15 Ref.18 Ref.26 Ref.28
	Modified residue	397	1	Phosphoserine Ref.15 Ref.26 Ref.27
	Modified residue	432	1	Phosphoserine Ref.24 Ref.27
	Modified residue	602	1	Phosphothreonine Ref.28
	Modified residue	615	1	Phosphoserine Ref.15
Natural variations
	Natural variant	93	1	S → L in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant. Ref.31 Corresponds to variant rs12721593 [ dbSNP | Ensembl ].		VAR_025792
	Natural variant	95	1	D → N in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant. Ref.31		VAR_025793
	Natural variant	105	1	K → N. Ref.7 Corresponds to variant rs13312858 [ dbSNP | Ensembl ].		VAR_025794
	Natural variant	142	1	N → S. Corresponds to variant rs769414 [ dbSNP | Ensembl ].		VAR_051226
	Natural variant	150	1	L → F in BC. Ref.32		VAR_025795
	Natural variant	171	1	I → V in some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant; associated with aplastic anemia at homozygosity. Ref.31 Ref.34		VAR_025796
	Natural variant	185	1	E → Q. Ref.1 Ref.2 Ref.5 Ref.7 Ref.32 Ref.33 Corresponds to variant rs1805794 [ dbSNP | Ensembl ].		VAR_025797
	Natural variant	210	1	V → F. Ref.31		VAR_025798
	Natural variant	215	1	R → W. Ref.31 Corresponds to variant rs34767364 [ dbSNP | Ensembl ].		VAR_025799
	Natural variant	216	1	Q → K. Ref.7 Corresponds to variant rs769416 [ dbSNP | Ensembl ].		VAR_025800
	Natural variant	266	1	P → L. Ref.7 Corresponds to variant rs769420 [ dbSNP | Ensembl ].		VAR_025801
	Natural variant	408	1	K → E. Corresponds to variant rs34120922 [ dbSNP | Ensembl ].		VAR_051227
	Natural variant	497	1	T → A. Ref.7 Corresponds to variant rs3026268 [ dbSNP | Ensembl ].		VAR_025802
	Natural variant	574	1	L → I. Ref.32		VAR_025803
	Natural variant	679	1	Y → H Found in a renal cell carcinoma sample; somatic mutation. Ref.35		VAR_064738
Experimental info
	Mutagenesis	28	1	R → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.13 Ref.20
	Mutagenesis	45	1	H → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.13 Ref.20
	Mutagenesis	136 – 137	2	GG → EE: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.20
	Mutagenesis	176	1	Y → A: Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation. Ref.13 Ref.20
	Mutagenesis	343	1	S → A: Abrogates ATM-dependent phosphorylation. Ref.15 Ref.20
	Mutagenesis	397	1	S → A: Abrogates ATM-dependent phosphorylation. No loss of interaction with KPNA2. Ref.15 Ref.19 Ref.20
	Mutagenesis	465 – 466	2	KR → AA: Blocks the association with KPNA2, and reduces nuclear foci formation in response to ionizing radiation. Ref.20
	Mutagenesis	583	1	Q → K: No loss of interaction with KPNA2. Ref.19 Ref.20
	Mutagenesis	615	1	S → A: Abrogates ATM-dependent phosphorylation. Ref.15 Ref.20
	Mutagenesis	736 – 737	2	EE → AA: Decreases ATM binding. Ref.20
	Mutagenesis	741 – 742	2	DD → AA: Decreases ATM binding. Ref.20
	Mutagenesis	745 – 746	2	RY → AA: Decreases ATM binding. Ref.20
	Sequence conflict	247	1	G → R in BAD96976. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	O60934 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: CD602F09BA73DAB6	FASTA	754	84,959
	10 20 30 40 50 60 MWKLLPAAGP AGGEPYRLLT GVEYVVGRKN CAILIENDQS ISRNHAVLTA NFSVTNLSQT 70 80 90 100 110 120 DEIPVLTLKD NSKYGTFVNE EKMQNGFSRT LKSGDGITFG VFGSKFRIEY EPLVACSSCL 130 140 150 160 170 180 DVSGKTALNQ AILQLGGFTV NNWTEECTHL VMVSVKVTIK TICALICGRP IVKPEYFTEF 190 200 210 220 230 240 LKAVESKKQP PQIESFYPPL DEPSIGSKNV DLSGRQERKQ IFKGKTFIFL NAKQHKKLSS 250 260 270 280 290 300 AVVFGGGEAR LITEENEEEH NFFLAPGTCV VDTGITNSQT LIPDCQKKWI QSIMDMLQRQ 310 320 330 340 350 360 GLRPIPEAEI GLAVIFMTTK NYCDPQGHPS TGLKTTTPGP SLSQGVSVDE KLMPSAPVNT 370 380 390 400 410 420 TTYVADTESE QADTWDLSER PKEIKVSKME QKFRMLSQDA PTVKESCKTS SNNNSMVSNT 430 440 450 460 470 480 LAKMRIPNYQ LSPTKLPSIN KSKDRASQQQ QTNSIRNYFQ PSTKKRERDE ENQEMSSCKS 490 500 510 520 530 540 ARIETSCSLL EQTQPATPSL WKNKEQHLSE NEPVDTNSDN NLFTDTDLKS IVKNSASKSH 550 560 570 580 590 600 AAEKLRSNKK REMDDVAIED EVLEQLFKDT KPELEIDVKV QKQEEDVNVR KRPRMDIETN 610 620 630 640 650 660 DTFSDEAVPE SSKISQENEI GKKRELKEDS LWSAKEISNN DKLQDDSEML PKKLLLTEFR 670 680 690 700 710 720 SLVIKNSTSR NPSGINDDYG QLKNFKKFKK VTYPGAGKLP HIIGGSDLIA HHARKNTELE 730 740 750 EWLRQEMEVQ NQHAKEESLA DDLFRYNPYL KRRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome." Varon R., Vissinga C., Platzer M., Cerosaletti K.M., Chrzanowska K.H., Saar K., Beckmann G., Seemanova E., Cooper P.R., Nowak N.J., Stumm M., Weemaes C.M.R., Gatti R.A., Wilson R.K., Digweed M., Rosenthal A., Sperling K., Concannon P., Reis A. Cell 93:467-476(1998) [PubMed: 9590180] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN NIJMEGEN BREAKAGE SYNDROME, VARIANT GLN-185.
[2]	"The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response." Carney J.P., Maser R.S., Olivares H., Davis E.M., Le Beau M., Yates J.R. III, Hays L., Morgan W.F., Petrini J.H.J. Cell 93:477-486(1998) [PubMed: 9590181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 189-209; 238-250; 289-299; 300-320; 335-351; 395-405; 409-423; 426-441; 457-465; 503-529; 552-568; 595-613; 625-635; 653-660; 671-683 AND 736-745, VARIANT GLN-185, INTERACTION WITH MRE11 AND RAD50.
[3]	"Positional cloning of the gene for Nijmegen breakage syndrome." Matsuura S., Tauchi H., Nakamura A., Kondo N., Sakamoto S., Endo S., Smeets D., Solder B., Belohradsky B.H., Kaloustian V.M., Oshimura M., Isomura M., Nakamura Y., Komatsu K. Nat. Genet. 19:179-181(1998) [PubMed: 9620777] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1." Tauchi H., Matsuura S., Isomura M., Kinjo T., Nakamura A., Sakamoto S., Kondo N., Endo S., Komatsu K., Nakamura Y. Genomics 55:242-247(1999) [PubMed: 9933573] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Fibroblast.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-185. Tissue: Brain.
[6]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Synovial cell.
[7]	NIEHS SNPs program Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASN-105; GLN-185; LYS-216; LEU-266 AND ALA-497.
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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]. Tissue: Brain, Skin and Testis.
[10]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 58-754. Tissue: Colon endothelium.
[11]	"Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95." Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P. J. Biol. Chem. 273:21447-21450(1998) [PubMed: 9705271] [Abstract] Cited for: FUNCTION IN DSB REPAIR, IDENTIFICATION IN THE MRN COMPLEX WITH MRE11A AND RAD50.
[12]	"Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization." Desai-Mehta A., Cerosaletti K.M., Concannon P. Mol. Cell. Biol. 21:2184-2191(2001) [PubMed: 11238951] [Abstract] Cited for: INTERACTION WITH MRE11.
[13]	"ATM-dependent phosphorylation of nibrin in response to radiation exposure." Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., Kozlov S., Lavin M.F., Gatti R.A., Concannon P., Khanna K.K. Nat. Genet. 25:115-119(2000) [PubMed: 10802669] [Abstract] Cited for: PHOSPHORYLATION AT SER-343, MUTAGENESIS OF ARG-28; HIS-45; 136-GLY-GLY-137 AND TYR-176.
[14]	"Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products." Zhao S., Weng Y.-C., Yuan S.-S.F., Lin Y.-T., Hsu H.-C., Lin S.-C., Gerbino E., Song M.-H., Zdzienicka M.Z., Gatti R.A., Shay J.W., Ziv Y., Shiloh Y., Lee E.Y.-H.P. Nature 405:473-477(2000) [PubMed: 10839544] [Abstract] Cited for: PHOSPHORYLATION AT SER-278.
[15]	"ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response." Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N., O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G., Livingston D.M., Weaver D.T. Nature 405:477-482(2000) [PubMed: 10839545] [Abstract] Cited for: PHOSPHORYLATION AT SER-343; SER-397 AND SER-615, MUTAGENESIS OF SER-343; SER-397 AND SER-615.
[16]	"Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres." Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T. Nat. Genet. 25:347-352(2000) [PubMed: 10888888] [Abstract] Cited for: FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH TERF2.
[17]	"NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain." Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K., Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K. Curr. Biol. 12:1846-1851(2002) [PubMed: 12419185] [Abstract] Cited for: INTERACTION WITH H2AFX.
[18]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1." Tseng S.-F., Chang C.-Y., Wu K.-J., Teng S.-C. J. Biol. Chem. 280:39594-39600(2005) [PubMed: 16188882] [Abstract] Cited for: INTERACTION WITH KPNA2, MUTAGENESIS OF SER-397; 465-LYS-ARG-466 AND GLN-583.
[20]	"Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage." Falck J., Coates J., Jackson S.P. Nature 434:605-611(2005) [PubMed: 15758953] [Abstract] Cited for: DOMAIN, MUTAGENESIS OF 736-GLU-GLU-737; 741-ASP-ASP-742 AND 745-ARG-TYR-746.
[21]	"Nbs1 is required for ATR-dependent phosphorylation events." Stiff T., Reis C., Alderton G.K., Woodbine L., O'Driscoll M., Jeggo P.A. EMBO J. 24:199-208(2005) [PubMed: 15616588] [Abstract] Cited for: FUNCTION.
[22]	"The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control." Zhang Y., Zhou J., Lim C.U. Cell Res. 16:45-54(2006) [PubMed: 16467875] [Abstract] Cited for: REVIEW.
[23]	"Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex." Stracker T.H., Carson C.T., Weitzman M.D. Nature 418:348-352(2002) [PubMed: 12124628] [Abstract] Cited for: INACTIVATION BY ADENOVIRUS ONCOPROTEINS.
[24]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells." Kato T., Sato N., Hayama S., Yamabuki T., Ito T., Miyamoto M., Kondo S., Nakamura Y., Daigo Y. Cancer Res. 67:8544-8553(2007) [PubMed: 17823411] [Abstract] Cited for: INTERACTION WITH HJURP.
[26]	"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-343 AND SER-397, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[27]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397 AND SER-432, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-337; SER-341; SER-343 AND THR-602, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[29]	"SOSS complexes participate in the maintenance of genomic stability." Huang J., Gong Z., Ghosal G., Chen J. Mol. Cell 35:384-393(2009) [PubMed: 19683501] [Abstract] Cited for: INTERACTION WITH INTS3.
[30]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]	"Mutations in the Nijmegen breakage syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL)." Varon R., Reis A., Henze G., von Einsiedel H.G., Sperling K., Seeger K. Cancer Res. 61:3570-3572(2001) [PubMed: 11325820] [Abstract] Cited for: VARIANTS LEU-93; ASN-95; VAL-171; PHE-210 AND TRP-215, POSSIBLE INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA.
[32]	"Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility." Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R. J. Med. Genet. 40:E131-E131(2003) [PubMed: 14684699] [Abstract] Cited for: VARIANT BC PHE-150, VARIANTS GLN-185 AND ILE-574.
[33]	"Polymorphisms in DNA repair and metabolic genes in bladder cancer." Sanyal S., Festa F., Sakano S., Zhang Z., Steineck G., Norming U., Wijkstroem H., Larsson P., Kumar R., Hemminki K. Carcinogenesis 25:729-734(2004) [PubMed: 14688016] [Abstract] Cited for: VARIANT GLN-185.
[34]	"First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability." Shimada H., Shimizu K., Mimaki S., Sakiyama T., Mori T., Shimasaki N., Yokota J., Nakachi K., Ohta T., Ohki M. Hum. Genet. 115:372-376(2004) [PubMed: 15338273] [Abstract] Cited for: VARIANT VAL-171.
[35]	"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma." Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A. Nature 469:539-542(2011) [PubMed: 21248752] [Abstract] Cited for: VARIANT HIS-679.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF051334 mRNA. Translation: AAC39732.1. AF058696 mRNA. Translation: AAC39752.1. AB013139 Genomic DNA. Translation: BAA28616.1. AF069291 Genomic DNA. Translation: AAC62232.1. AK312410 mRNA. Translation: BAG35323.1. AK223256 mRNA. Translation: BAD96976.1. Different initiation. AY566246 Genomic DNA. Translation: AAS59158.1. CH471060 Genomic DNA. Translation: EAW91660.1. BC108650 mRNA. Translation: AAI08651.1. Sequence problems. BC136802 mRNA. Translation: AAI36803.1. BC136803 mRNA. Translation: AAI36804.1. BX640816 mRNA. Translation: CAH56160.1. Different initiation.
IPI	IPI00299463.
PIR	T00393.
RefSeq	NP_002476.2. NM_002485.4.
UniGene	Hs.492208.
3D structure databases
ProteinModelPortal	O60934.
SMR	O60934. Positions 12-327.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-33605N.
IntAct	O60934. 6 interactions.
MINT	MINT-203482.
STRING	O60934.
PTM databases
PhosphoSite	O60934.
Proteomic databases
PRIDE	O60934.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265433; ENSP00000265433; ENSG00000104320.
GeneID	4683.
KEGG	hsa:4683.
UCSC	uc003yej.1. human.
Organism-specific databases
CTD	4683.
GeneCards	GC08M091015.
H-InvDB	HIX0007638.
HGNC	HGNC:7652. NBN.
HPA	CAB003836. HPA001429.
MIM	114480. phenotype. 251260. phenotype. 602667. gene. 609135. phenotype.
neXtProt	NX_O60934.
Orphanet	647. Nijmegen breakage syndrome.
PharmGKB	PA31457.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000000521.
HOVERGEN	HBG053070.
InParanoid	O60934.
OMA	QEMEVQN.
OrthoDB	EOG45MN4Q.
PhylomeDB	O60934.
Enzyme and pathway databases
Pathway_Interaction_DB	bard1pathway. BARD1 signaling events. telomerasepathway. Regulation of Telomerase.
Reactome	REACT_111183. Meiosis. REACT_216. DNA Repair.
Gene expression databases
ArrayExpress	O60934.
Bgee	O60934.
CleanEx	HS_NBN.
Genevestigator	O60934.
GermOnline	ENSG00000104320. Homo sapiens.
Family and domain databases
InterPro	IPR001357. BRCT. IPR013908. DNA-repair_Nbs1_C. IPR000253. FHA_dom. IPR016592. Nibrin_met. IPR008984. SMAD_FHA_domain. [Graphical view]
Gene3D	G3DSA:2.60.200.20. FHA. 1 hit.
KO	K10867.
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]
SUPFAM	SSF52113. BRCT. 1 hit. SSF49879. SMAD_FHA. 1 hit.
PROSITE	PS50172. BRCT. False negative. PS50006. FHA_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	18054.
SOURCE	Search...

Entry information

Entry name

NBN_HUMAN

Accession

Primary (citable) accession number: O60934
Secondary accession number(s): B2R626 , B2RNC5, O60672, Q32NF7, Q53FM6, Q63HR6, Q7LDM2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	August 1, 1998
Last modified:	January 25, 2012
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.