Affinage

DBP

D site-binding protein · UniProt Q10586

Round 2 corrected
Length
325 aa
Mass
34.3 kDa
Annotated
2026-04-28
130 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DBP is a PAR-domain basic leucine zipper (bZIP) transcription factor that functions as a principal circadian clock output regulator, linking the core CLOCK–BMAL1 oscillator to rhythmic gene expression in liver, brain, and neuroendocrine tissues. CLOCK–BMAL1 drives Dbp transcription through intronic and extragenic E-box elements accompanied by circadian chromatin remodeling between permissive (H3K9ac, H3K4me3) and facultative heterochromatin (H3K9me2, HP1α) states, with sustained transcriptional bursting dependent on rapid proteasomal turnover of the BMAL1–CLOCK complex (PMID:16474407, PMID:22981862). DBP protein accumulates with a high-amplitude circadian rhythm and directly activates D-box-containing promoters of genes governing cholesterol/bile acid metabolism (CYP7A1), xenobiotic detoxification (CYP2A4/5, CYP2C6, CAR), the core clock (mPer1), and reproductive neuroendocrine signaling (Kiss1), functioning redundantly with the PAR bZIP factors TEF and HLF (PMID:8405996, PMID:10490589, PMID:16814730, PMID:21458520). Dbp-null mice exhibit a shortened free-running circadian period, reduced locomotor activity amplitude, disrupted sleep consolidation, and impaired EEG slow-wave and theta rhythms, while compound loss of all three PAR bZIPs causes xenobiotic hypersensitivity, premature aging, and cardiovascular dysfunction (PMID:9362490, PMID:10632591, PMID:16814730, PMID:20686175).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1990 High

    Identification of DBP as a liver-enriched bZIP transcription factor with strict circadian protein accumulation established the first known mammalian transcriptional activator whose abundance oscillates with a free-running circadian rhythm.

    Evidence cDNA cloning from rat liver, Western blots across tissues and circadian time-points, nuclear run-on transcription assays

    PMID:2261643 PMID:2331750

    Open questions at the time
    • Mechanism driving circadian mRNA/protein oscillation unknown
    • In vivo target genes beyond albumin not identified
    • Post-transcriptional mechanism restricting protein to liver not defined
  2. 1992 High

    Demonstration that DBP directly binds and transactivates hepatic cytochrome P450 (CYP2C6) and sialyltransferase promoters extended DBP's role from albumin regulation to liver-specific drug metabolism and glycosylation programs.

    Evidence DNase I footprinting, EMSA, cotransfection reporter assays in HepG2 cells

    PMID:1588973 PMID:1737800

    Open questions at the time
    • No loss-of-function evidence yet linking DBP to CYP2C6 expression in vivo
    • Relative contributions of DBP versus other liver-enriched factors (C/EBP, HNF) not delineated
  3. 1993 High

    Identification of DBP as a direct activator of cholesterol 7α-hydroxylase (CYP7A1) connected the circadian DBP oscillation to a rate-limiting metabolic step—bile acid synthesis—providing the first functional link between circadian clock output and intermediary metabolism.

    Evidence Cotransfection assays, supershift of evening nuclear extracts confirming DBP occupancy at CYP7A1 promoter

    PMID:8405996

    Open questions at the time
    • No genetic validation in Dbp-null animals for CYP7A1 regulation
    • Contribution of other D-box activators (TEF, HLF) not assessed
  4. 1993 Medium

    Evidence that DBP synergizes with C/EBP to restore factor IX transcription from the Leyden -5 mutant promoter after puberty explained the clinical recovery in haemophilia B Leyden by invoking pubertal DBP induction.

    Evidence Gel-shift assays and cotransfection transactivation assays with mutant factor IX promoter

    PMID:8499951

    Open questions at the time
    • Mechanism of pubertal DBP induction not defined
    • In vivo confirmation in patient-derived cells lacking
    • Relative importance of DBP versus androgen-responsive factors not resolved
  5. 1997 High

    Generation of Dbp-null mice established that DBP is dispensable for core clock function but required for normal circadian period length and locomotor activity amplitude, positioning DBP as a clock output regulator rather than a core oscillator component.

    Evidence Dbp-knockout mice, locomotor activity recording under constant darkness, in situ hybridization in SCN

    PMID:9362490

    Open questions at the time
    • Molecular targets responsible for shortened period not identified
    • Redundancy with TEF/HLF not tested genetically
  6. 2000 High

    Phenotyping of Dbp-null mice for sleep architecture revealed that DBP regulates circadian modulation of sleep consolidation, EEG delta power, theta frequency, and paradoxical sleep rebound, establishing DBP as a transcriptional link between the clock and sleep homeostasis.

    Evidence EEG/EMG recordings in Dbp−/− mice under LD and DD, sleep deprivation and recovery protocols

    PMID:10632591

    Open questions at the time
    • Downstream transcriptional targets mediating sleep phenotypes unknown
    • Brain region-specific versus systemic DBP contributions not dissected
  7. 2000 High

    Discovery that CLOCK binds E-box elements in Dbp introns and that Clock mutation abolishes rhythmic Dbp transcription defined the upstream molecular mechanism placing Dbp as a direct first-order target of the CLOCK–BMAL1 heterodimer, while DBP feeds forward onto Per1 cooperatively with CLOCK–BMAL1.

    Evidence Clock-mutant mouse Dbp mRNA analysis, EMSA with E-box probes, Per1 promoter cotransfection assays

    PMID:10733528 PMID:10848603

    Open questions at the time
    • Chromatin context of E-box activation not characterized
    • Quantitative contribution of DBP to Per1 amplitude versus direct CLOCK–BMAL1 drive unclear
  8. 2006 High

    Comprehensive ChIP analysis revealed that BMAL1–CLOCK binding at Dbp E-boxes drives daily chromatin transitions between permissive euchromatin (H3K9ac, H3K4me3) and repressive heterochromatin (H3K9me2, HP1α), providing the first genome-locus-specific model of how circadian transcription factors remodel chromatin.

    Evidence Time-resolved ChIP for BMAL1, CLOCK, H3K9ac, H3K4me3, H3K9me2, HP1α at Dbp locus; E-box mutant reporter analysis

    PMID:16474407

    Open questions at the time
    • Identity of histone methyltransferases/demethylases mediating these transitions unknown
    • Whether similar chromatin cycling occurs at all CLOCK–BMAL1 targets not established
  9. 2006 High

    Triple PAR bZIP knockout (Dbp/Tef/Hlf−/−) demonstrated that these factors collectively govern xenobiotic detoxification gene programs, with compound loss causing xenobiotic hypersensitivity, premature aging, and death—resolving the long-standing question of functional redundancy among PAR bZIP members.

    Evidence Triple-KO mouse generation, transcriptome profiling of liver/kidney, xenobiotic challenge survival experiments

    PMID:16814730

    Open questions at the time
    • Individual contributions of DBP, TEF, and HLF not separable in triple-KO
    • Non-hepatic detoxification roles not examined
  10. 2011 Medium

    Cell-autonomous gain- and loss-of-function experiments showed DBP and its D-box antagonist E4BP4 are critical determinants of circadian period at the single-cell level, and identification of Kiss1 as a direct DBP target in the AVPV linked the circadian clock to the preovulatory GnRH/LH surge.

    Evidence siRNA/overexpression of DBP in Rat-1 fibroblasts with bioluminescent reporters; Kiss1 promoter D-box reporter assays and AVPV in situ hybridization

    PMID:21458520 PMID:21635892

    Open questions at the time
    • In vivo reproductive phenotype of Dbp-null females not reported
    • Whether DBP's period-setting role depends on its transcriptional targets or direct protein interactions unknown
  11. 2012 High

    Live-cell imaging of BMAL1 at Dbp locus arrays revealed that BMAL1–CLOCK act as 'Kamikaze activators' requiring proteasome-dependent rapid turnover to sustain transcriptional bursting, fundamentally revising the model of how circadian transcription factors activate target genes.

    Evidence Fluorescent BMAL1 live imaging at tandem Dbp repeat arrays, proteasome inhibition (MG132), single-copy Dbp-luciferase burst analysis

    PMID:22981862

    Open questions at the time
    • Ubiquitin ligase(s) targeting BMAL1–CLOCK at Dbp not identified
    • Whether Kamikaze mechanism generalizes to all circadian target promoters not tested
    • Relationship between burst frequency and chromatin state transitions unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include the identity of the E3 ligase(s) that mediate BMAL1–CLOCK turnover at the Dbp locus, the brain region–specific transcriptional targets through which DBP controls sleep architecture and seizure susceptibility, and the individual versus redundant contributions of DBP relative to TEF and HLF at specific promoters in vivo.
  • No structural model of DBP–D-box DNA complex available
  • Post-transcriptional mechanisms restricting DBP protein to specific tissues not characterized
  • Genome-wide direct target map (ChIP-seq for DBP) in vivo not published in the timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1430728 Metabolism 4
Partners
ARNTLCLOCKESR1HLFNFIL3TEF

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 DBP was cloned as a transcriptional activator binding the D site of the albumin promoter; it belongs to the bZIP family (related to Fos, Jun, CREB, C/EBP) but lacks a canonical leucine zipper. DBP protein accumulates only in liver despite mRNA being present in most tissues, establishing that tissue specificity is determined post-transcriptionally. DBP expression is rapidly down-regulated during chemically induced liver regeneration, suggesting a role in hepatocyte proliferation control. cDNA cloning, Northern and Western blot across multiple rat tissues, liver regeneration model Cell High 2331750
1990 DBP protein accumulates in rat hepatocyte nuclei according to a strict circadian rhythm, reaching maximum around 8 p.m. and falling below detection during morning hours. The oscillation is free-running (circadian, not simply diurnal), is regulated at the transcriptional level, and may be under negative control of glucocorticoid hormones. The albumin gene, a putative DBP target, is transcribed more efficiently in the evening than in the morning, consistent with DBP driving rhythmic albumin transcription. Western blot of nuclear extracts across time-points, nuclear run-on transcription assay, glucocorticoid treatment experiments Cell High 2261643
1991 Chicken VBP (vitellogenin gene-binding protein) is the avian ortholog of rat DBP; both are bZIP proteins that dimerize and bind DNA as dimers. Despite only three amino acid differences in their basic/hinge regions, DBP's albumin D-site is a poor binding site for VBP, indicating distinct optimal DNA-binding sites. Their leucine zippers are functionally compatible (forming heterodimers) but define a novel bZIP subfamily. cDNA expression library screening, DNA-binding assays, dimerization studies, sequence comparison Molecular and cellular biology Medium 1922023
1992 DBP directly binds to and transactivates the CYP2C6 promoter in hepatoma cells through a sequence between -38 and -103 bp upstream of the transcription start site. DNase I footprinting with partially purified DBP confirmed a specific footprint at -43 to -64 bp. Gel-shift/Western immunoblot showed DBP binding is age-dependent, appearing only after 3 weeks of age in rats and reaching maximum by 7 weeks, paralleling the postnatal rise in CYP2C6 expression. Transient transfection in HepG2 cells, DNase I footprinting, gel mobility shift assay, Western immunoblot Molecular and cellular biology High 1588973
1992 DBP, along with HNF-1α and LAP/C/EBP, regulates the liver-restricted promoter of the alpha-2,6-sialyltransferase gene. Footprinting and deletion analysis identified a consensus DBP/LAP binding cis-element essential for liver-specific expression; expression vectors encoding DBP trans-activated the sialyltransferase promoter in cotransfection assays, demonstrating that tissue-specific glycosylation can be regulated transcriptionally by the same liver-enriched factors controlling other liver-specific genes. DNase I footprinting, 5' deletion analysis, site-directed mutagenesis, cotransfection assays The Journal of biological chemistry Medium 1737800
1993 DBP directly activates the cholesterol 7α-hydroxylase (C7αH) gene promoter through a cognate DNA site at approximately -225 bp, as shown by cotransfection assays. In nuclear extracts prepared by a novel method recovering near-quantitative DBP, the predominant binding activity at this promoter site in the evening (when DBP is high) was shown to contain DBP by supershift, providing direct evidence that DBP drives the circadian expression of C7αH, the rate-limiting enzyme in bile acid synthesis. Cotransfection assays, novel nuclear extract preparation, DNase I footprinting, gel shift/supershift assay Genes & development High 8405996
1993 DBP synergizes with C/EBP to compensate for the haemophilia B Leyden factor IX -5 mutation. The -5 nucleotide substitution disrupts binding of proteins to one of three newly identified transcription factor binding sites in the factor IX promoter. Post-pubertal induction of DBP (which is induced at puberty) allows DBP and C/EBP to synergistically restore transcriptional activity of the mutant -5 promoter, explaining the clinical recovery seen after puberty in Leyden patients. Transcription factor binding site characterization, gel-shift assays, cotransfection/transactivation assays Nature genetics Medium 8499951
1994 Human DBP gene was cloned and chromosomally localized to 19q13; human TEF to 22q13. The coding sequences, particularly the bZIP domain and PAR region, are highly conserved between human and rat DBP. Conservation of exon-intron boundaries around the bZIP-encoding exon suggests derivation from a common ancestral gene shared with TEF and HLF. DBP mRNA was detected in all tissues examined (brain, lung, liver, spleen, kidney), consistent with broad but rhythmically controlled expression. cDNA cloning, FISH chromosomal mapping, somatic cell hybrid analysis, Northern blot Genomics Medium 7835883
1997 DBP mRNA oscillates strongly in the suprachiasmatic nucleus (SCN) of the hypothalamus, with peak levels ~4 hours earlier than in liver, indicating tissue-specific control of circadian DBP expression. Dbp-null mice display reduced locomotor activity and a shorter free-running circadian period, establishing DBP as a modulator of circadian behavioral outputs. Since DBP-/- mice remain rhythmic and DBP is not required for circadian expression of its own gene, DBP functions in the circadian output pathway rather than as a core clock component. In situ hybridization in SCN, generation and analysis of Dbp-null mice (locomotor activity, free-running period) The EMBO journal High 9362490
1999 DBP drives circadian expression of the Cyp2a4 (steroid 15α-hydroxylase) and Cyp2a5 (coumarin 7-hydroxylase) genes in mouse liver. In vitro DNase I footprinting on Cyp2a4 and Cyp2a5 promoters and cotransfection in HepG2 cells confirmed DBP can activate these promoters. Genetic validation using Dbp-null mice showed significantly impaired circadian amplitude of CYP2A4 and CYP2A5 mRNA and protein, establishing DBP as a major factor controlling their rhythmic hepatic expression. DNase I footprinting, cotransfection assays, Dbp-null mouse experiments (mRNA and protein quantification) Molecular and cellular biology High 10490589
2000 DBP activates the mPer1 promoter by directly binding to it, and this activation is cooperative with CLOCK-BMAL1. Dbp transcription is itself activated by CLOCK-BMAL1 through E-boxes and repressed by mPER and mCRY proteins, placing DBP within the core circadian feedback loop as both a target and an amplifier of CLOCK-BMAL1 activity acting on Per1. Reporter gene assays (cotransfection), direct promoter binding assays Molecular and cellular biology Medium 10848603
2000 Loss of DBP (Dbp-/- mice) reduces the amplitude of circadian modulation of sleep time and sleep episode consolidation under both light-dark and constant-dark conditions without affecting total sleep duration. DBP deficiency also reduces amplitude of sleep-wake-dependent changes in slow-wave sleep delta power, increases hippocampal theta peak frequency, and abolishes the paradoxical sleep rebound after sleep deprivation, establishing DBP as a transcriptional regulator of both circadian and homeostatic aspects of sleep. EEG/EMG recordings in Dbp-/- mice, sleep deprivation experiments, quantitative EEG analysis The Journal of neuroscience High 10632591
2000 CLOCK is required for circadian Dbp transcription. Genetic experiments with Clock-mutant mice and biochemical studies demonstrated that CLOCK binds to E-box motifs within putative enhancer regions in the first and second introns of the Dbp gene to drive its rhythmic expression. The same E-box mechanism that controls core clock gene mPeriod1 expression also directly controls the rhythmic transcription of the clock output regulator Dbp. Analysis of Clock-mutant mice (Dbp mRNA levels), electrophoretic mobility shift assays, reporter gene assays with E-box mutants Genes & development High 10733528
2004 DEC2 (but not DEC1) suppresses DBP-mediated transcriptional activation of the cholesterol 7α-hydroxylase (CYP7A) gene by binding to an E-box (CACATG) at -219/-214 of CYP7A, overwhelming DBP's potent enhancement. This establishes a mechanistic antagonism where the clock-controlled repressor DEC2 opposes the clock-controlled activator DBP to regulate rhythmic cytochrome P450 expression in the liver. Transfection reporter assays, electrophoretic mobility shift assays (EMSA) Genes to cells Medium 15066123
2005 Hippocampal over-expression of DBP (via rAAV) in adult rats upregulates molecular clock constituents and the DBP target gene pyridoxal kinase. DBP over-expression inhibits spatial learning (but not memory), enhances susceptibility to kainate-induced seizures, and activates MAP kinase in dendritic regions of hippocampal neurons in vivo, establishing DBP as a transcriptional link between GLP-1R activation and hippocampal neuroplasticity. rAAV-mediated gene delivery, microarray analysis, behavioral testing (water maze), kainate seizure model, in vivo MAP kinase immunostaining Molecular and cellular neurosciences Medium 16257226
2006 Circadian Dbp transcription is driven by rhythmic binding of BMAL1 and CLOCK to multiple extra- and intragenic E-box motifs. This binding is accompanied by marked daily chromatin transitions: the transcriptionally active phase shows acetylation of H3K9, trimethylation of H3K4, and reduced histone density, while the repressive phase shows dimethylation of H3K9, binding of heterochromatin protein 1α (HP1α), and increased histone density. The rhythmic conversion between permissive chromatin and facultative heterochromatin requires functional BMAL1-CLOCK binding sites. ChIP assays (BMAL1, CLOCK, histone modifications, HP1α) across circadian time-points, E-box mutant analysis Nature genetics High 16474407
2006 PAR bZIP proteins DBP, TEF, and HLF control expression of many enzymes involved in xenobiotic detoxification and drug metabolism in liver and kidney, including cytochrome P450 enzymes, carboxylesterases, and constitutive androstane receptor (CAR). Triple knockout mice (Dbp/Tef/Hlf -/-) are hypersensitive to xenobiotic compounds, and the deficiency in detoxification contributes to their early aging and premature death phenotype. Triple knockout mouse generation and analysis, liver/kidney transcriptome comparison, xenobiotic challenge experiments Cell metabolism High 16814730
2010 Triple PAR bZIP knockout mice (Dbp/Tef/Hlf -/-) develop cardiac hypertrophy and left ventricular dysfunction associated with low blood pressure and abnormally low aldosterone levels, demonstrating that PAR bZIP transcription factors (including DBP) are required for normal circadian regulation of cardiovascular function. Echocardiography, blood pressure measurement, aldosterone assays in triple PAR bZIP knockout mice American journal of physiology. Regulatory, integrative and comparative physiology Medium 20686175
2011 Cell-autonomous siRNA knockdown of DBP in Rat-1 fibroblasts produces a short-period circadian phenotype, while DBP overexpression produces a long-period rhythm in Per1 and Per2 promoter-driven bioluminescence reporters. Conversely, knockdown/overexpression of E4BP4 (the D-box repressor) has the opposite effect. This establishes that DBP (D-box activator) and E4BP4 (D-box repressor) are critical cell-autonomous determinants of circadian period length. siRNA knockdown, cDNA overexpression, bioluminescent circadian reporter assays in Rat-1 fibroblasts FEBS letters Medium 21635892
2011 DBP binds to a D-box element in the Kiss1 promoter in the anteroventral periventricular nucleus (AVPV) and triggers Kiss1 transcription; this effect is synergistic with estrogen receptor α (ERα) and estrogen. Dbp mRNA accumulates with a robust diurnal rhythm in the AVPV specifically on proestrus (but not diestrus), and some AVPV cells co-express DBP and ERα. This establishes DBP as a circadian transcriptional regulator linking the clock to the GnRH/LH surge through Kiss1. Reporter gene/cotransfection assays with D-box mutations, in situ hybridization, immunohistochemistry of AVPV Molecular and cellular endocrinology Medium 21458520
2012 BMAL1-CLOCK associations with Dbp chromatin are extremely unstable, showing stochastic, proteasome-dependent fluctuations monitored in real time by fluorescent BMAL1 at tandem Dbp repeat arrays. Proteasome inhibition prolongs BMAL1-CLOCK residence time but immediately attenuates Dbp transcription by decreasing both the frequency and size of transcriptional bursts. This reveals that BMAL1 and CLOCK act as 'Kamikaze activators' that must be rapidly degraded after binding to sustain transcriptional cycling. Live-cell fluorescence time-lapse microscopy of BMAL1-GFP at Dbp locus arrays, proteasome inhibition, single-copy Dbp-luciferase reporter analysis of transcriptional bursting Molecular cell High 22981862
2016 PI3K signaling is required for BMAL1/CLOCK-mediated circadian transcription from the Dbp promoter. Pharmacological inhibition or shRNA knockdown of PI3K blocked serum-shock-induced upregulation of Dbp mRNA and reduced Dbp promoter activity. PI3K inhibition decreased recruitment of BMAL1/CLOCK to the E-box in the Dbp promoter and blocked BMAL1-CLOCK heterodimerization, establishing PI3K as an upstream modulator of the circadian transcriptional complex at Dbp. Pharmacological PI3K inhibition, shRNA knockdown, RT-PCR, luciferase reporter assays, ChIP assay (BMAL1 at E-box), co-immunoprecipitation of BMAL1-CLOCK Bioscience, biotechnology, and biochemistry Medium 27022680

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocrine reviews 1274 15583024
2010 Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet (London, England) 1249 20541252
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2005 Vitamin D. American journal of physiology. Renal physiology 1008 15951480
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2013 Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PloS one 609 23359474
2010 Genome-wide association study of circulating vitamin D levels. Human molecular genetics 607 20418485
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2006 Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nature genetics 467 16474407
2006 The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell metabolism 400 16814730
1990 DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell 385 2331750
2000 CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP. Genes & development 343 10733528
2013 Vitamin D and DBP: the free hormone hypothesis revisited. The Journal of steroid biochemistry and molecular biology 322 24095930
2011 Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 295 21416506
1993 Circadian transcription of the cholesterol 7 alpha hydroxylase gene may involve the liver-enriched bZIP protein DBP. Genes & development 275 8405996
2001 Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). Proceedings of the National Academy of Sciences of the United States of America 238 11717447
1997 The DBP gene is expressed according to a circadian rhythm in the suprachiasmatic nucleus and influences circadian behavior. The EMBO journal 238 9362490
1990 Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. Cell 212 2261643
2008 Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans. The Journal of clinical endocrinology and metabolism 210 18593774
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2000 Role of DBP in the circadian oscillatory mechanism. Molecular and cellular biology 203 10848603
2010 Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. American journal of human genetics 199 20673864
2014 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. The Journal of clinical endocrinology and metabolism 191 24885631
2008 Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. The American journal of clinical nutrition 191 19116321
2010 A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations. The Journal of steroid biochemistry and molecular biology 177 20363324
1985 Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. The Journal of clinical investigation 167 2416779
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2009 Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation. Clinical biochemistry 158 19302999
1985 Human group-specific component (Gc) is a member of the albumin family. Proceedings of the National Academy of Sciences of the United States of America 154 2415977
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
1999 Circadian expression of the steroid 15 alpha-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP. Molecular and cellular biology 135 10490589
2010 First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia. Hypertension (Dallas, Tex. : 1979) 133 20733087
2012 Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. PLoS genetics 132 22916037
2009 Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk. Carcinogenesis 132 19255064
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2002 Crystal structures of the vitamin D-binding protein and its complex with actin: structural basis of the actin-scavenger system. Proceedings of the National Academy of Sciences of the United States of America 120 12048248
2010 Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects. Human genetics 119 20809279
1992 Molecular analysis of the gene for the human vitamin-D-binding protein (group-specific component): allelic differences of the common genetic GC types. Human genetics 118 1352271
2011 Dimerization of Plasmodium vivax DBP is induced upon receptor binding and drives recognition of DARC. Nature structural & molecular biology 116 21743458
2003 Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice. Neoplasia (New York, N.Y.) 104 12659668
2000 The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 102 10632591
2020 Effect of polystyrene on di-butyl phthalate (DBP) bioavailability and DBP-induced phytotoxicity in lettuce. Environmental pollution (Barking, Essex : 1987) 93 33120154
2012 Circadian Dbp transcription relies on highly dynamic BMAL1-CLOCK interaction with E boxes and requires the proteasome. Molecular cell 93 22981862
2014 Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC. PLoS pathogens 90 24415938
1991 Chicken vitellogenin gene-binding protein, a leucine zipper transcription factor that binds to an important control element in the chicken vitellogenin II promoter, is related to rat DBP. Molecular and cellular biology 90 1922023
1992 Regulated expression of alpha 2,6-sialyltransferase by the liver-enriched transcription factors HNF-1, DBP, and LAP. The Journal of biological chemistry 75 1737800
2017 Biodegradation of di-n-butyl phthalate (DBP) by a novel endophytic Bacillus megaterium strain YJB3. The Science of the total environment 72 29112835
2004 Pure estrogenic effect of benzophenone-2 (BP2) but not of bisphenol A (BPA) and dibutylphtalate (DBP) in uterus, vagina and bone. Toxicology 60 15458795
2004 Neonatal exposure to di(n-butyl) phthalate (DBP) alters male reproductive-tract development. Journal of toxicology and environmental health. Part A 60 15513902
2017 Role of PI3K/AKT/mTOR signaling pathway in DBP-induced apoptosis of testicular sertoli cells in vitro. Environmental toxicology and pharmacology 59 28578144
2015 Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice. Reproductive toxicology (Elmsford, N.Y.) 59 25765776
2011 Cellular DBP and E4BP4 proteins are critical for determining the period length of the circadian oscillator. FEBS letters 58 21635892
2004 Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP. Genes to cells : devoted to molecular & cellular mechanisms 58 15066123
2010 Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF. American journal of physiology. Regulatory, integrative and comparative physiology 56 20686175
2020 Complete biodegradation of di-n-butyl phthalate (DBP) by a novel Pseudomonas sp. YJB6. The Science of the total environment 55 33162130
2018 Exposure to DBP induces the toxicity in early development and adverse effects on cardiac development in zebrafish (Danio rerio). Chemosphere 55 30469006
2020 The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate. Journal of medical virology 53 32770768
2014 The causal effect of vitamin D binding protein (DBP) levels on calcemic and cardiometabolic diseases: a Mendelian randomization study. PLoS medicine 53 25350643
1993 Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation. Nature genetics 52 8499951
2019 Structural basis for neutralization of Plasmodium vivax by naturally acquired human antibodies that target DBP. Nature microbiology 50 31133752
2017 Oxidative Damage and Genetic Toxicity Induced by DBP in Earthworms (Eisenia fetida). Archives of environmental contamination and toxicology 49 28913550
2008 Alteration of DBP levels in CSF of patients with MS by proteomics analysis. Cellular and molecular neurobiology 48 18807170
1999 Effect of cis-, trans-diamminedichloroplatinum(II) and DBP on human serum albumin. Journal of inorganic biochemistry 48 10643655
2013 Short-term neonatal/prepubertal exposure of dibutyl phthalate (DBP) advanced pubertal timing and affected hypothalamic kisspeptin/GPR54 expression differently in female rats. Toxicology 47 24056307
2023 Unravelling High-Molecular-Weight DBP Toxicity Drivers in Chlorinated and Chloraminated Drinking Water: Effect-Directed Analysis of Molecular Weight Fractions. Environmental science & technology 46 37418586
2019 Role of JNK and ERK1/2 MAPK signaling pathway in testicular injury of rats induced by di-N-butyl-phthalate (DBP). Biological research 45 31387634
2009 Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: proliferative and inflammatory disorders and a possible role of androgens. Toxicology 45 19549552
1992 Role of the liver-enriched transcription factor DBP in expression of the cytochrome P450 CYP2C6 gene. Molecular and cellular biology 45 1588973
2014 Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population. PloS one 44 25541958
1995 Pharmacokinetic studies of vitamin D analogues: relationship to vitamin D binding protein (DBP). Endocrine 44 21153172
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