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HMGN5 (High Mobility Group Nucleosome binding domain 5)

Written2016-04Michael Bustin, Takashi Furusawa
National Cancer Institute, NIH, Building 37, Room 3122, 37 Convent Drive, Bethesa, MD 20892, US.;;

Abstract HMGN5 is a member of the high mobility group nucleosome binding domain (HMGN) protein family. HMGN proteins are ubiquitously expressed in vertebrate cells. They are nuclear proteins that bind specifically to nucleosomes without specificity for the DNA sequence and affect the structure and function of chromatin. HMGN5 sequences have been detected in all vertebrate tissues examines. HMGN5 differs from the other members of the HMGN family in that it is significantly larger and its amino acid sequence varies significantly between different vertebrate species.

Keywords HMGN5, NSBP1, Chromatin

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nucleosomal binding protein 1
high-mobility group nucleosome binding domain 5
Other aliasNBP-45
LocusID (NCBI) 79366
Atlas_Id 52454
Location_base_pair Starts at 81113701 and ends at 81201942 bp from pter ( according to hg19-Feb_2009)  [Mapping HMGN5.png]
  Reproduced from: HMGN5/NSBP1: a new member of the HMGN protein family that affects chromatin structure and function. Rochman M, Malicet C, Bustin M. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):86-92. doi: 0.1016/j.bbagrm.2009.09.012. Review. PMID: 20123071.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BRWD3 (Xq21.1) / HMGN5 (Xq21.1)


  Organization of the human HMGN5 and mouse Hmgn5 gene. Exons are marked by red blocks and untranslated regions are marked by white boxes. The number of amino acids encoded by each exon is indicated. Reproduced from: HMGN5/NSBP1: a new member of the HMGN protein family that affects chromatin structure and function. Rochman M, Malicet C, Bustin M. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):86-92. doi: 0.1016/j.bbagrm.2009.09.012. Review. PMID: 20123071
Description NCBI Reference Sequence: NC_000023.11; Coding positions from 81,113,701 to 81,201,942 (length: 88,242 bp). Both human and mouse Hmgn5 genes are composed of 6 exons and 5 introns.
Transcription 849 bp cDNA for Human HMGN5. No splicing isoforms are reported as of April 2016.


  Schematic representation of structural domains of mouse and human HMGN5 proteins. Localization of each domain is related to the amino acid sequences of the proteins numbered on top of each scheme. Reproduced from: HMGN5/NSBP1: a new member of the HMGN protein family that affects chromatin structure and function. Rochman M, Malicet C, Bustin M. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):86-92. doi: 0.1016/j.bbagrm.2009.09.012. Review. PMID: 20123071
Description Reference sequence for HMGN5 protein: NP_110390.1. HMGN5 contains 282 amino acid residues with a molecular weight of 31525 Da. HMGN5 belongs to the HMGN protein family. HMGN5 contains a Nucleosome Bingding Domain (residue 12-36) for chromatin interaction.
Expression Expressed at low levels in most vertebrate cells.
Localisation Nucleus.
Function Modulates chromatin structure.
Homology HomoloGene (NCBI) Genes identified as putative homologs: NP_110390.1 HMGN5, Homo sapiens; XP_001144951.2 Hmgn5, Pan troglodytes; XP_001103630 Hmgn5 Macaca mulatta; XP_002699982.3 Hmgn5, Bos taurus.

Implicated in

Entity Clear cell renal cell carcinoma (ccRCC)
Note HMGN5 expression is detected in renal tissues from clear cell renal cell carcinoma (ccRCC) patients and in ccRCC cell lines, and its expression level is associated with tumor grade. Knockdown of HMGN5 induced cell cycle arrest and apoptosis, and inhibited invasion in ccRCC cell line 786-O. (Ji et al, 2012).
Entity Prostate Cancer
Note Knock down of HMGN5 inhibits the in vitro and in vivo growth of the human prostate cancer cell line DU145 by inducing cell cycle arrest and apoptosis (Jiang et al, 2010). Similar effect is also observed in the LNCaP prostate cancer cell line, too (Zhang et al, 2012). HMGN5 knockdown exhibit increased apoptosis rate in response to ionizing radiation (Su et al, 2015). The normal prostate epithelial cells which are induced Ectopic HMGN5 expression results in oncogenic phenotype such as colony formation and invasion (Guo et al, 2015). Tumorigenic activity of the cells which overexpress HMGN5 is suppressed by MIR340 (microRNA-340) (Wei et al, 2015).
Entity Gliomas
Note HMGN5 is highly expressed in both low-grade and high-grade glioma tissue samples than normal brain tissues. The down regulation of HMGN5 expression in human glioma cell line (U251 and U87) caused cell cycle arrest and apoptosis. (Qu et al, 2011).
Entity Bladder cancer
Note The protein level of HMGN5 in surgically removed bladder cancer specimens and human bladder cell lines is correlated with the increased tumor grade and pathologic stage. Knock down of HMGN5 reduced cell viability and cell cycle promotion (Wahafu et al, 2010; Gan et al, 2015). The expression level of HMGN5 is suppressed by MIR186 in human bladder cancer cells (Yao et al, 2015).
Entity Lung cancer
Note HMGN5 is highly expressed in lung cancer cell lines A549 and H1299. Downregulation of HMGN5 inhibits cell proliferation and colony formation (Chen et al, 2012). MIR326 downregulated HMGN5 expression in the non-small cell lung cancer (NSCLC) cell and inhibited cell proliferation and invasion of NSCLC (Li et al, 2016).
Entity Osteosarcoma
Note Both HMGN5 RNA and HMGN5 protein are highly expressed in human osteosarcoma tumor. The expression level is also upregulated in osteosarcoma cell lines SaO2 and HOS while other cell lines U-2OS and MG63 showed lower expression level. HMGN5 expression is induced by anticancer agents in these cell lines. Overexpression of HMGN5 in U-2OS and MG63 cells increased drug resistance by upregulating autophagy (Yang et al, 2014).
Entity Breast cancer
Note HMGN5 is highly expressed in breast cancer tissues when compared with the adjacent non-cancerous tissues. Clinical and histopathologic analysis revealed that HMGN5 expression level is correlated to the tumor grade and staging. Using the human breast cancer cell line MCA-MB-213 as a model, HMGN5 knockdown resulted in inhibition of migration and invasion, and induced cell death (Weng et al, 2015).


Knockdown of HMGN5 expression by RNA interference induces cell cycle arrest in human lung cancer cells
Chen P, Wang XL, Ma ZS, Xu Z, Jia B, Ren J, Hu YX, Zhang QH, Ma TG, Yan BD, Yan QZ, Li YL, Li Z, Yu JY, Gao R, Fan N, Li B, Yang JL
Asian Pac J Cancer Prev 2012;13(7):3223-8
PMID 22994738
Metabolomics reveals a role for the chromatin-binding protein HMGN5 in glutathione metabolism
Ciappio ED, Krausz KW, Rochman M, Furusawa T, Bonzo JA, Tessarollo L, Gonzalez FJ, Bustin M
PLoS One 2014 Jan 2;9(1):e84583
PMID 24392144
Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness
Furusawa T, Rochman M, Taher L, Dimitriadis EK, Nagashima K, Anderson S, Bustin M
Nat Commun 2015 Jan 22;6:6138
PMID 25609380
Knockdown of HMGN5 suppresses the viability and invasion of human urothelial bladder cancer 5637 cells in vitro and in vivo
Gan Y, Tan J, Yang J, Zhou Y, Dai Y, He L, Yao K, Tang Y
Med Oncol 2015 Apr;32(4):136
PMID 25796505
HMGNs, DNA repair and cancer
Gerlitz G
Biochim Biophys Acta 2010 Jan-Feb;1799(1-2):80-5
PMID 20004154
Evolution of high mobility group nucleosome-binding proteins and its implications for vertebrate chromatin specialization
González-Romero R, Eirín-Ló JM, Ausió J
Mol Biol Evol 2015 Jan;32(1):121-31
PMID 25281808
Expression of oncogenic HMGN5 increases the sensitivity of prostate cancer cells to gemcitabine
Guo Z, Zhang X, Li X, Xie F, Su B, Zhang M, Zhou L
Oncol Rep 2015 Mar;33(3):1519-25
PMID 25572120
HMGN5 blockade by siRNA enhances apoptosis, suppresses invasion and increases chemosensitivity to temozolomide in meningiomas
He J, Liu C, Wang B, Li N, Zuo G, Gao D
Int J Oncol 2015 Oct;47(4):1503-11
PMID 26315299
[Effect of nucleosomal binding protein 1 in androgen-independent prostatic carcinoma]
Huang C, Zhou LQ, Song G
Zhonghua Yi Xue Za Zhi 2008 Mar 11;88(10):657-60
PMID 18642763
Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of clear cell renal cell carcinoma cells in vitro and in vivo
Ji SQ, Yao L, Zhang XY, Li XS, Zhou LQ
J Exp Clin Cancer Res 2012 Mar 15;31:22
PMID 22420896
Downregulation of the nucleosome-binding protein 1 (NSBP1) gene can inhibit the in vitro and in vivo proliferation of prostate cancer cells
Jiang N, Zhou LQ, Zhang XY
Asian J Androl 2010 Sep;12(5):709-17
PMID 20531280
Characterization of a human gene encoding nucleosomal binding protein NSBP1
King LM, Francomano CA
Genomics 2001 Jan 15;71(2):163-73
PMID 11161810
High mobility group N proteins modulate the fidelity of the cellular transcriptional profile in a tissue- and variant-specific manner
Kugler JE, Horsch M, Huang D, Furusawa T, Rochman M, Garrett L, Becker L, Bohla A, Hölter SM, Prehn C, Rathkolb B, Racz I, Aguilar-Pimentel JA, Adler T, Adamski J, Beckers J, Busch DH, Eickelberg O, Klopstock T, Ollert M, Stöger T, Wolf E, Wurst W, Yildirim AÖ, Zimmer A, Gailus-Durner V, Fuchs H, Hrab de Angelis M, Garfinkel B, Orly J, Ovcharenko I, Bustin M
J Biol Chem 2013 Jun 7;288(23):16690-703
PMID 23620591
Suppression of nucleosome-binding protein 1 by miR-326 impedes cell proliferation and invasion in non-small cell lung cancer cells
Li D, Du X, Liu A, Li P
Oncol Rep 2016 Feb;35(2):1117-24
PMID 26548724
Distinct properties of human HMGN5 reveal a rapidly evolving but functionally conserved nucleosome binding protein
Malicet C, Rochman M, Postnikov Y, Bustin M
Mol Cell Biol 2011 Jul;31(13):2742-55
PMID 21518955
Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth
Moretti F, Rolando C, Winker M, Ivanek R, Rodriguez J, Von Kriegsheim A, Taylor V, Bustin M, Pertz O
Mol Cell Biol 2015 Jun 1;35(11):2035-50
PMID 25825524
HMGN5: a potential oncogene in gliomas
Qu J, Yan R, Chen J, Xu T, Zhou J, Wang M, Chen C, Yan Y, Lu Y
J Neurooncol 2011 Sep;104(3):729-36
PMID 21373965
HMGN5/NSBP1: a new member of the HMGN protein family that affects chromatin structure and function
Rochman M, Malicet C, Bustin M
Biochim Biophys Acta 2010 Jan-Feb;1799(1-2):86-92
The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription
Rochman M, Postnikov Y, Correll S, Malicet C, Wincovitch S, Karpova TS, McNally JG, Wu X, Bubunenko NA, Grigoryev S, Bustin M
Mol Cell 2009 Sep 11;35(5):642-56
PMID 19748358
NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression
Shirakawa H, Landsman D, Postnikov YV, Bustin M
J Biol Chem 2000 Mar 3;275(9):6368-74
PMID 10692437
HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation
Su B, Shi B, Tang Y, Guo Z, Yu X, He X, Li X, Gao X, Zhou L
Prostate 2015 Jan;75(1):33-44
PMID 25307178
Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life
Tang WY, Morey LM, Cheung YY, Birch L, Prins GS, Ho SM
Endocrinology 2012 Jan;153(1):42-55
PMID 22109888
Persistent hypomethylation in the promoter of nucleosomal binding protein 1 (Nsbp1) correlates with overexpression of Nsbp1 in mouse uteri neonatally exposed to diethylstilbestrol or genistein
Tang WY, Newbold R, Mardilovich K, Jefferson W, Cheng RY, Medvedovic M, Ho SM
Endocrinology 2008 Dec;149(12):5922-31
PMID 18669593
The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells
Wahafu W, He ZS, Zhang XY, Zhang CJ, Yao K, Hao H, Song G, He Q, Li XS, Zhou LQ
Tumour Biol 2011 Oct;32(5):931-9
PMID 21695596
microRNA-340 Suppresses Tumorigenic Potential of Prostate Cancer Cells by Targeting High-Mobility Group Nucleosome-Binding Domain 5
Wei P, Qiao B, Li Q, Han X, Zhang H, Huo Q, Sun J
DNA Cell Biol 2016 Jan;35(1):33-43
PMID 26394192
The high-mobility group nucleosome-binding domain 5 is highly expressed in breast cancer and promotes the proliferation and invasion of breast cancer cells
Weng M, Song F, Chen J, Wu J, Qin J, Jin T, Xu J
Tumour Biol 2015 Feb;36(2):959-66
High-mobility group nucleosome-binding domain 5 increases drug resistance in osteosarcoma through upregulating autophagy
Yang C, Gao R, Wang J, Yuan W, Wang C, Zhou X
Tumour Biol 2014 Jul;35(7):6357-63
PMID 24664583
MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1
Yao K, He L, Gan Y, Zeng Q, Dai Y, Tan J
Diagn Pathol 2015 Aug 20;10:146
PMID 26290438
High mobility group protein N5 (HMGN5) and lamina-associated polypeptide 2α (LAP2α) interact and reciprocally affect their genome-wide chromatin organization
Zhang S, Schones DE, Malicet C, Rochman M, Zhou M, Foisner R, Bustin M
J Biol Chem 2013 Jun 21;288(25):18104-9
PMID 23673662
Small interfering RNA targeting HMGN5 induces apoptosis via modulation of a mitochondrial pathway and Bcl-2 family proteins in prostate cancer cells
Zhang XY, Guo ZQ, Ji SQ, Zhang M, Jiang N, Li XS, Zhou LQ
Asian J Androl 2012 May;14(3):487-92
PMID 22504871
[Effects of inhibiting nucleosomal binding protein 1 on proliferation of human prostate cancer cells]
Zhou LQ, Song G, He ZS, Hao JR, Na YQ
Zhonghua Yi Xue Za Zhi 2007 Feb 6;87(6):404-8
PMID 17456383
The expression and clinical significance of high mobility group nucleosome binding domain 5 in human osteosarcoma
Zhou X, Yuan B, Yuan W, Wang C, Gao R, Wang J
Tumour Biol 2014 Jul;35(7):6539-47
PMID 24687550
Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD)
dela Peña I, Kim HJ, Sohn A, Kim BN, Han DH, Ryu JH, Shin CY, Noh M, Cheong JH
Behav Brain Funct 2014 May 6;10:17
PMID 24884696


This paper should be referenced as such :
Michael Bustin, Takashi Furusawa
HMGN5 (High Mobility Group Nucleosome binding domain 5)
Atlas Genet Cytogenet Oncol Haematol. 2017;21(1):3-6.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)HMGN5   8013
Entrez_Gene (NCBI)HMGN5  79366  high mobility group nucleosome binding domain 5
AliasesNBP-45; NSBP1
GeneCards (Weizmann)HMGN5
Ensembl hg19 (Hinxton)ENSG00000198157 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000198157 [Gene_View]  ENSG00000198157 [Sequence]  chrX:81113701-81201942 [Contig_View]  HMGN5 [Vega]
ICGC DataPortalENSG00000198157
TCGA cBioPortalHMGN5
Genatlas (Paris)HMGN5
SOURCE (Princeton)HMGN5
Genetics Home Reference (NIH)HMGN5
Genomic and cartography
GoldenPath hg38 (UCSC)HMGN5  -     chrX:81113701-81201942 -  Xq21.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HMGN5  -     Xq21.1   [Description]    (hg19-Feb_2009)
GoldenPathHMGN5 - Xq21.1 [CytoView hg19]  HMGN5 - Xq21.1 [CytoView hg38]
Mapping of homologs : NCBIHMGN5 [Mapview hg19]  HMGN5 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF250329 AK094058 AK315792 BC005342 DA745749
RefSeq transcript (Entrez)NM_030763
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)HMGN5
Cluster EST : UnigeneHs.282204 [ NCBI ]
CGAP (NCI)Hs.282204
Alternative Splicing GalleryENSG00000198157
Gene ExpressionHMGN5 [ NCBI-GEO ]   HMGN5 [ EBI - ARRAY_EXPRESS ]   HMGN5 [ SEEK ]   HMGN5 [ MEM ]
Gene Expression Viewer (FireBrowse)HMGN5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)79366
GTEX Portal (Tissue expression)HMGN5
Human Protein AtlasENSG00000198157-HMGN5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP82970   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP82970  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP82970
Splice isoforms : SwissVarP82970
Domaine pattern : Prosite (Expaxy)HMG14_17 (PS00355)   
Domains : Interpro (EBI)HMGN_fam   
Domain families : Pfam (Sanger)HMG14_17 (PF01101)   
Domain families : Pfam (NCBI)pfam01101   
Domain families : Smart (EMBL)HMG17 (SM00527)  
Conserved Domain (NCBI)HMGN5
DMDM Disease mutations79366
Blocks (Seattle)HMGN5
Human Protein Atlas [tissue]ENSG00000198157-HMGN5 [tissue]
Peptide AtlasP82970
IPIIPI00006157   IPI00646652   IPI00643588   IPI00642320   IPI00644714   IPI00643151   
Protein Interaction databases
IntAct (EBI)P82970
Ontologies - Pathways
Ontology : AmiGOchromatin  chromatin binding  RNA binding  nucleus  nucleus  chromatin organization  regulation of transcription, DNA-templated  positive regulation of cell proliferation  positive regulation of gene expression  nucleosomal DNA binding  negative regulation of apoptotic process  positive regulation of transcription, DNA-templated  negative regulation of cell cycle arrest  
Ontology : EGO-EBIchromatin  chromatin binding  RNA binding  nucleus  nucleus  chromatin organization  regulation of transcription, DNA-templated  positive regulation of cell proliferation  positive regulation of gene expression  nucleosomal DNA binding  negative regulation of apoptotic process  positive regulation of transcription, DNA-templated  negative regulation of cell cycle arrest  
NDEx NetworkHMGN5
Atlas of Cancer Signalling NetworkHMGN5
Wikipedia pathwaysHMGN5
Orthology - Evolution
GeneTree (enSembl)ENSG00000198157
Phylogenetic Trees/Animal Genes : TreeFamHMGN5
Homologs : HomoloGeneHMGN5
Homology/Alignments : Family Browser (UCSC)HMGN5
Gene fusions - Rearrangements
Fusion : FusionGDB25457   
Fusion : Fusion_HubBRWD3--HMGN5    HMGN5--SH3BGRL    OPTN--HMGN5   
Fusion : QuiverHMGN5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHMGN5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HMGN5
Exome Variant ServerHMGN5
ExAC (Exome Aggregation Consortium)ENSG00000198157
GNOMAD BrowserENSG00000198157
Varsome BrowserHMGN5
Genetic variants : HAPMAP79366
Genomic Variants (DGV)HMGN5 [DGVbeta]
DECIPHERHMGN5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHMGN5 
ICGC Data PortalHMGN5 
TCGA Data PortalHMGN5 
Broad Tumor PortalHMGN5
OASIS PortalHMGN5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHMGN5  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DHMGN5
Mutations and Diseases : HGMDHMGN5
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)X-chromosome gene database
BioMutasearch HMGN5
DgiDB (Drug Gene Interaction Database)HMGN5
DoCM (Curated mutations)HMGN5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HMGN5 (select a term)
NCG5 (London)HMGN5
Cancer3DHMGN5(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry HMGN5
NextProtP82970 [Medical]
Target ValidationHMGN5
Huge Navigator HMGN5 [HugePedia]
snp3D : Map Gene to Disease79366
BioCentury BCIQHMGN5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD79366
Chemical/Pharm GKB GenePA31789
Clinical trialHMGN5
canSAR (ICR)HMGN5 (select the gene name)
DataMed IndexHMGN5
PubMed37 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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