Written | 2009-03 | K 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) |
Identity |
Alias (NCBI) | FLJ16340 |
HGNC (Hugo) | HBP1 |
LocusID (NCBI) | 26959 |
Atlas_Id | 40791 |
Location | 7q22.3 [Link to chromosome band 7q22] |
Location_base_pair | Starts at 107169003 and ends at 107202522 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping HBP1.png] |
Local_order | The HBP1 gene is located between the PRKAR2B gene (left) and the COG5 gene (right). |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
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 |
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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 |
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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 ] |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
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