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HBP1 (HMG-box transcription factor 1)

Written2009-03K Eric Paulson, Amy S Yee
Departments of Biochemistry, Radiation Oncology, Tufts Medical School, Boston, MA 02111, USA (KEP); Department of Biochemistry, Tufts Medical School, Boston, MA 02111, USA (ASY)

(Note : for Links provided by Atlas : click)

Identity

Other aliasFLJ16340
HGNC (Hugo) HBP1
LocusID (NCBI) 26959
Atlas_Id 40791
Location 7q22.3  [Link to chromosome band 7q22]
Location_base_pair Starts at 106809406 and ends at 106842974 bp from pter ( according to hg19-Feb_2009)  [Mapping HBP1.png]
Local_order The HBP1 gene is located between the PRKAR2B gene (left) and the COG5 gene (right).
Fusion genes
(updated 2016)
COPE (19p13.11) / HBP1 (7q22.3)HBP1 (7q22.3) / HBP1 (7q22.3)HBP1 (7q22.3) / JAZF1 (7p15.2)
HBP1 (7q22.3) / LRP1 (12q13.3)

DNA/RNA

 
  HBP1 Locus on 7q22. Chromosome 7, band q22 is shown at the top of the diagram with the distance on the forward strand marked as indicated. The HBP1 gene is located between the PRKAR2B gene (left) and the COG5 gene (right). Coding exons are shown in bold red, while non-coding are shown with open red boxes. cDNA coding sequence is shown in dark green.
Description Sequence length 33515; cDNA length 2829; Coding sequence 1545. The gene is comprised of 11 exons; max. exon length 1121, min. exon length 54. Number of SNPs 6.
Transcription The consensus normal transcript is 2829 nt and the coding sequence is 1545 nt. The consensus normal transcript is produced from 11 exons. The first exon is non-coding. There are 16 different mRNAs produced, including 13 different alternatively spliced variants. Several of these alternatively spliced variants appear to be produced only in tumor cells.
Pseudogene None known.

Protein

 
  HBP1 Protein Schematic. HBP1 contains two defined domains; an ataxin homology domain (gray) and an HMG box DNA binding domain (red). There are two Rb-interacting motifs (black line) and a p38 MAP kinase-interacting region (yellow). A repression domain (aa200-400) encompasses the Ataxin homology domain.
Description HBP1 encodes a 515 amino acid, 62-kDa, transcriptional repressor. On western blots, HBP1 runs anomolously at 75 kD. HBP1 represses numerous target genes when overexpressed, including N-Myc, cyclin D1 and c-myc. The protein contains two known domains: an HMG box DNA binding domain and a repression domain that contains an ataxin homology domain.
Expression HBP1 mRNA is expressed in several human organs and tissues: brain; uterus; testis; mixed; uncharacterized tissue; lung; bladder; kidney; heart; lymph node; blood; prostate; trachea; esophagus; cervix; skin; adrenal gland; eye; intestine; vascular; amniotic fluid; mouth; embryonic tissue; spleen; thymus; placenta; connective tissue; liver; mammary gland; muscle; pancreas; stomach; ovary; ascites; ganglia; bone; pharynx; thyroid; adipose tissue; parathyroid; ear; pineal gland; nerve; bone marrow; umbilical cord.
Localisation HBP1 is predominantly a nuclear protein.
Function Cell Cycle. HBP1 was isolated as a cell cycle inhibitor and HMG-box transcriptional repressor. HBP1 binds to Rb and p107 via an LXCXE and IXCXE binding motif as part of HBP1 function in cell cycle regulation. HBP1 expression was uniquely associated with oncogene-mediated senescence in an RB-dependent manner.
Growth and Differentiation. Liver-specific expression of HBP1 was shown to inhibit liver regeneration. In addition, ectopic expression of HBP1 regulates differentiation in muscle cells. Similarly, transgenic mice overexpressing HBP1 exhibited altered thymus cellularity and decreased thymocyte development. Finally, HBP1 expression is maintained in the developing testis beyond the onset of spermatogenesis, and the expression of HBP1 in XY germ cells appears to correlate with the onset of mitotic arrest. The repression domain of HBP1 contains an Ataxin homology domain which interacts with the Sin3 corepressor PAH2 domain, thus recruiting HDAC1 to a repression complex.
Signaling and Transcription. HBP1 inhibits a number of genes through direct binding to its cognate recognition sequence, including N-myc and p47 phox. In addition, HBP1 is an inhibitor of Wnt signaling and blocks beta-catenin/LEF/TCF complexes. Wnt target genes regulated by HBP1 include c-myc and cyclin D1. HBP1 is regulated by p38 MAP kinase signaling and contains both a p38 MAP kinase docking sequence and a p38 MAP kinase phosphorylation site. Phosphorylation results in HBP1 protein stabilization and increased repression function. p38 MAP kinase phosphorylation is also required for HBP1 induction of premature senescence. HBP1 mRNA is stabilized by the green tea compound epigallo-catechin galate (EGCG), resulting in increased HBP1 protein and HBP1-dependent repression of Wnt signaling.
Homology HBP1 contains two recognized homology motifs; an Ataxin homology domain and an HMG box DNA binding domain.

Mutations

Somatic In an analysis of 76 breast tumors, 10 HBP1 mutations/variants were identified that were associated with fully invasive breast cancer. Some of these mutants/variants were shown to be the result of genomic mutations.

Implicated in

Note
  
Entity Breast Cancer
Disease Aberrations in HBP1 are associated with invasive breast cancer. The HBP1 gene is either mutated or reduced in breast cancer. As cited above in the "Somatic Mutation section", HBP1 mutations/variants were associated with fully invasive breast cancer, some of which arose from genomic mutations. In a new analysis, a subset of invasive breast cancer tumors had markedly reduced expression of the HBP1 mRNA.
Prognosis Statistical analysis of a breast cancer patient database predicted that reduced HBP1 mRNA levels were associated with a decreased relapse-free survival and recurrence with distant metastases (Paulson et al., 2007).
  

Bibliography

HBP1 repression of the p47phox gene: cell cycle regulation via the NADPH oxidase.
Berasi SP, Xiu M, Yee AS, Paulson KE.
Mol Cell Biol. 2004 Apr;24(7):3011-24.
PMID 15024088
 
Activation and repression of p21(WAF1/CIP1) transcription by RB binding proteins.
Gartel AL, Goufman E, Tevosian SG, Shih H, Yee AS, Tyner AL.
Oncogene. 1998 Dec 31;17(26):3463-9.
PMID 10030670
 
Suppression of Wnt signaling by the green tea compound (-)-epigallocatechin 3-gallate (EGCG) in invasive breast cancer cells. Requirement of the transcriptional repressor HBP1.
Kim J, Zhang X, Rieger-Christ KM, Summerhayes IC, Wazer DE, Paulson KE, Yee AS.
J Biol Chem. 2006 Apr 21;281(16):10865-75. Epub 2006 Feb 22.
PMID 16495219
 
The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A.
Lavender P, Vandel L, Bannister AJ, Kouzarides T.
Oncogene. 1997 Jun 5;14(22):2721-8.
PMID 9178770
 
Involvement of retinoblastoma protein and HBP1 in histone H1(0) gene expression.
Lemercier C, Duncliffe K, Boibessot I, Zhang H, Verdel A, Angelov D, Khochbin S.
Mol Cell Biol. 2000 Sep;20(18):6627-37.
PMID 10958660
 
Alterations of the HBP1 transcriptional repressor are associated with invasive breast cancer.
Paulson KE, Rieger-Christ K, McDevitt MA, Kuperwasser C, Kim J, Unanue VE, Zhang X, Hu M, Ruthazer R, Berasi SP, Huang CY, Giri D, Kaufman S, Dugan JM, Blum J, Netto G, Wazer DE, Summerhayes IC, Yee AS.
Cancer Res. 2007 Jul 1;67(13):6136-45.
PMID 17616670
 
Negative regulation of the Wnt-beta-catenin pathway by the transcriptional repressor HBP1.
Sampson EM, Haque ZK, Ku MC, Tevosian SG, Albanese C, Pestell RG, Paulson KE, Yee AS.
EMBO J. 2001 Aug 15;20(16):4500-11.
PMID 11500377
 
Human high mobility group box transcription factor 1 affects thymocyte development and transgene variegation.
Sekkali B, Szabat E, Ktistaki E, Tolaini M, Roderick K, Harker N, Patel A, Williams K, Norton T, Kioussis D.
J Immunol. 2005 Oct 15;175(8):5203-12.
PMID 16210625
 
Regulation of differentiation by HBP1, a target of the retinoblastoma protein.
Shih HH, Tevosian SG, Yee AS.
Mol Cell Biol. 1998 Aug;18(8):4732-43.
PMID 9671483
 
HMG box transcriptional repressor HBP1 maintains a proliferation barrier in differentiated liver tissue.
Shih HH, Xiu M, Berasi SP, Sampson EM, Leiter A, Paulson KE, Yee AS.
Mol Cell Biol. 2001 Sep;21(17):5723-32.
PMID 11486012
 
Evidence for the involvement of miRNA in redox regulated angiogenic response of human microvascular endothelial cells.
Shilo S, Roy S, Khanna S, Sen CK.
Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):471-7. Epub 2008 Feb 7.
PMID 18258815
 
HMG box transcription factor gene Hbp1 is expressed in germ cells of the developing mouse testis.
Smith JM, Bowles J, Wilson M, Koopman P.
Dev Dyn. 2004 Jun;230(2):366-70.
PMID 15162515
 
HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations.
Swanson KA, Knoepfler PS, Huang K, Kang RS, Cowley SM, Laherty CD, Eisenman RN, Radhakrishnan I.
Nat Struct Mol Biol. 2004 Aug;11(8):738-46. Epub 2004 Jul 4.
PMID 15235594
 
HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma family.
Tevosian SG, Shih HH, Mendelson KG, Sheppard KA, Paulson KE, Yee AS.
Genes Dev. 1997 Feb 1;11(3):383-96.
PMID 9030690
 
The transcriptional repressor HBP1 is a target of the p38 mitogen-activated protein kinase pathway in cell cycle regulation.
Xiu M, Kim J, Sampson E, Huang CY, Davis RJ, Paulson KE, Yee AS.
Mol Cell Biol. 2003 Dec;23(23):8890-901.
PMID 14612426
 
The HBP1 transcriptional repressor and the p38 MAP kinase: unlikely partners in G1 regulation and tumor suppression.
Yee AS, Paulson EK, McDevitt MA, Rieger-Christ K, Summerhayes I, Berasi SP, Kim J, Huang CY, Zhang X.
Gene. 2004 Jul 7;336(1):1-13.
PMID 15225871
 
The HBP1 transcriptional repressor participates in RAS-induced premature senescence.
Zhang X, Kim J, Ruthazer R, McDevitt MA, Wazer DE, Paulson KE, Yee AS.
Mol Cell Biol. 2006 Nov;26(22):8252-66. Epub 2006 Sep 11.
PMID 16966377
 
Human HMG box transcription factor HBP1: a role in hCD2 LCR function.
Zhuma T, Tyrrell R, Sekkali B, Skavdis G, Saveliev A, Tolaini M, Roderick K, Norton T, Smerdon S, Sedgwick S, Festenstein R, Kioussis D.
EMBO J. 1999 Nov 15;18(22):6396-406.
PMID 10562551
 
The AXH domain adopts alternative folds the solution structure of HBP1 AXH.
de Chiara C, Menon RP, Adinolfi S, de Boer J, Ktistaki E, Kelly G, Calder L, Kioussis D, Pastore A.
Structure. 2005 May;13(5):743-53.
PMID 15893665
 

Citation

This paper should be referenced as such :
Paulson, KE ; Yee, AS
HBP1 (HMG-box transcription factor 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):124-126.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HBP1ID40791ch7q22.html


External links

Nomenclature
HGNC (Hugo)HBP1   23200
Cards
AtlasHBP1ID40791ch7q22
Entrez_Gene (NCBI)HBP1  26959  HMG-box transcription factor 1
Aliases
GeneCards (Weizmann)HBP1
Ensembl hg19 (Hinxton)ENSG00000105856 [Gene_View]  chr7:106809406-106842974 [Contig_View]  HBP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000105856 [Gene_View]  chr7:106809406-106842974 [Contig_View]  HBP1 [Vega]
ICGC DataPortalENSG00000105856
TCGA cBioPortalHBP1
AceView (NCBI)HBP1
Genatlas (Paris)HBP1
WikiGenes26959
SOURCE (Princeton)HBP1
Genetics Home Reference (NIH)HBP1
Genomic and cartography
GoldenPath hg19 (UCSC)HBP1  -     chr7:106809406-106842974 +  7q22.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)HBP1  -     7q22.3   [Description]    (hg38-Dec_2013)
EnsemblHBP1 - 7q22.3 [CytoView hg19]  HBP1 - 7q22.3 [CytoView hg38]
Mapping of homologs : NCBIHBP1 [Mapview hg19]  HBP1 [Mapview hg38]
OMIM616714   
Gene and transcription
Genbank (Entrez)AF019214 AF182038 AK025284 AK074353 AK122785
RefSeq transcript (Entrez)NM_001244262 NM_012257
RefSeq genomic (Entrez)NC_000007 NC_018918 NT_007933 NW_004929332
Consensus coding sequences : CCDS (NCBI)HBP1
Cluster EST : UnigeneHs.162032 [ NCBI ]
CGAP (NCI)Hs.162032
Alternative Splicing GalleryENSG00000105856
Gene ExpressionHBP1 [ NCBI-GEO ]   HBP1 [ EBI - ARRAY_EXPRESS ]   HBP1 [ SEEK ]   HBP1 [ MEM ]
Gene Expression Viewer (FireBrowse)HBP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)26959
GTEX Portal (Tissue expression)HBP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60381   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60381  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60381
Splice isoforms : SwissVarO60381
PhosPhoSitePlusO60381
Domaine pattern : Prosite (Expaxy)AXH (PS51148)    HMG_BOX_2 (PS50118)   
Domains : Interpro (EBI)Ataxin-1_HBP1    Ataxin_AXH_dom    HMG_box_dom   
Domain families : Pfam (Sanger)AXH (PF08517)    HMG_box (PF00505)   
Domain families : Pfam (NCBI)pfam08517    pfam00505   
Domain families : Smart (EMBL)AXH (SM00536)  HMG (SM00398)  
Conserved Domain (NCBI)HBP1
DMDM Disease mutations26959
Blocks (Seattle)HBP1
PDB (SRS)2E6O    3QVE   
PDB (PDBSum)2E6O    3QVE   
PDB (IMB)2E6O    3QVE   
PDB (RSDB)2E6O    3QVE   
Structural Biology KnowledgeBase2E6O    3QVE   
SCOP (Structural Classification of Proteins)2E6O    3QVE   
CATH (Classification of proteins structures)2E6O    3QVE   
SuperfamilyO60381
Human Protein AtlasENSG00000105856
Peptide AtlasO60381
HPRD13634
IPIIPI00550468   IPI00607765   IPI00099615   IPI00910910   IPI00945896   IPI00944899   IPI00946845   IPI00946213   IPI00945567   
Protein Interaction databases
DIP (DOE-UCLA)O60381
IntAct (EBI)O60381
FunCoupENSG00000105856
BioGRIDHBP1
STRING (EMBL)HBP1
ZODIACHBP1
Ontologies - Pathways
QuickGOO60381
Ontology : AmiGODNA binding  RNA binding  protein binding  nucleoplasm  transcription, DNA-templated  regulation of transcription, DNA-templated  cell cycle arrest  Wnt signaling pathway  positive regulation of potassium ion transport  
Ontology : EGO-EBIDNA binding  RNA binding  protein binding  nucleoplasm  transcription, DNA-templated  regulation of transcription, DNA-templated  cell cycle arrest  Wnt signaling pathway  positive regulation of potassium ion transport  
NDEx NetworkHBP1
Atlas of Cancer Signalling NetworkHBP1
Wikipedia pathwaysHBP1
Orthology - Evolution
OrthoDB26959
GeneTree (enSembl)ENSG00000105856
Phylogenetic Trees/Animal Genes : TreeFamHBP1
HOVERGENO60381
HOGENOMO60381
Homologs : HomoloGeneHBP1
Homology/Alignments : Family Browser (UCSC)HBP1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHBP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HBP1
dbVarHBP1
ClinVarHBP1
1000_GenomesHBP1 
Exome Variant ServerHBP1
ExAC (Exome Aggregation Consortium)HBP1 (select the gene name)
Genetic variants : HAPMAP26959
Genomic Variants (DGV)HBP1 [DGVbeta]
DECIPHER (Syndromes)7:106809406-106842974  ENSG00000105856
CONAN: Copy Number AnalysisHBP1 
Mutations
ICGC Data PortalHBP1 
TCGA Data PortalHBP1 
Broad Tumor PortalHBP1
OASIS PortalHBP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHBP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHBP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch HBP1
DgiDB (Drug Gene Interaction Database)HBP1
DoCM (Curated mutations)HBP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HBP1 (select a term)
intoGenHBP1
NCG5 (London)HBP1
Cancer3DHBP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM616714   
Orphanet
MedgenHBP1
Genetic Testing Registry HBP1
NextProtO60381 [Medical]
TSGene26959
GENETestsHBP1
Huge Navigator HBP1 [HugePedia]
snp3D : Map Gene to Disease26959
BioCentury BCIQHBP1
ClinGenHBP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD26959
Chemical/Pharm GKB GenePA134901346
Clinical trialHBP1
Miscellaneous
canSAR (ICR)HBP1 (select the gene name)
Probes
Litterature
PubMed43 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHBP1
EVEXHBP1
GoPubMedHBP1
iHOPHBP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:32:53 CEST 2017

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