Affinage

HOXB5

Homeobox protein Hox-B5 · UniProt P09067

Length
269 aa
Mass
29.4 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXB5 is a homeodomain transcription factor that directs cell fate specification and tissue morphogenesis across multiple developmental and adult contexts, including axial patterning, neural crest survival and migration, vascular endothelial differentiation, lung branching morphogenesis, and hematopoietic stem cell identity. It binds DNA cooperatively at tandem sites through a homeodomain-adjacent N-terminal domain, with cooperativity regulated by a redox-sensitive cysteine between homeodomain helices 2 and 3 (PMID:8101633); direct transcriptional targets include FLK1/VEGFR2 (PMID:12897140), RET (synergistically with NKX2-1) (PMID:21677782, PMID:24794774), SOX9 (PMID:24141719), FOXD3 (PMID:25220476), CTNNB1 (PMID:26467157), EGFR (PMID:30115380), ANGPT2 (PMID:19403561), IL6 (PMID:33858489), and CXCR4 (PMID:33456563). In vivo, Hoxb5 knockout causes rostral homeotic shifts of the shoulder girdle and, in compound mutants with Hoxa5, lethal lung branching defects (PMID:7828847, PMID:23585229); Hoxb5 marks long-term hematopoietic stem cells in a perivascular bone marrow niche and can reprogram B-lineage cells into functional T lymphocytes (PMID:26863982, PMID:29434353). Nuclear translocation of HOXB5 is regulated post-translationally by CARD9 SUMOylation-dependent inhibition of O-GlcNAc glycosylation (PMID:39496070).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Identifying HOXB5 as a transcriptional activator of specific downstream genes established that individual HOX proteins regulate distinct adhesion-molecule targets, not just axial identity.

    Evidence Cotransfection reporter assay showing HOXB5 transactivates N-CAM promoter through a specific binding site, antagonized by HOXB4, in NIH 3T3 cells

    PMID:1347944

    Open questions at the time
    • Endogenous chromatin context not tested
    • N-CAM regulation not validated in vivo
    • Mechanism of HOXB4 antagonism undefined
  2. 1993 High

    Demonstrating cooperative DNA binding regulated by a redox-sensitive cysteine revealed a distinctive biochemical property that distinguishes HOXB5 from most other homeodomain proteins and from Fos/Jun-type transcription factors.

    Evidence In vitro DNA binding with mutagenesis showing cooperative binding at tandem sites requires N-terminal domain and is enhanced by oxidation of Cys in helix 2-3 turn

    PMID:8101633

    Open questions at the time
    • In vivo relevance of redox regulation untested
    • Structural basis of oxidation-enhanced cooperativity unknown
    • Identity of physiological redox signals unclear
  3. 1995 High

    Knockout mice established that HOXB5 specifies axial position of the shoulder girdle and cooperates with HOXB6 in cervicothoracic vertebral identity, resolving its developmental patterning role.

    Evidence Gene targeting in mice producing rostral shoulder girdle shift; HOXB5/HOXB6 transheterozygotes show homeotic vertebral transformation

    PMID:7828847

    Open questions at the time
    • Downstream transcriptional targets mediating skeletal phenotype unknown
    • Single versus redundant function with paralogous group 5 Hox genes not fully resolved
  4. 2000 Medium

    Ex vivo lung culture experiments showed that HOXB5 protein levels, regulated by retinoic acid, quantitatively control airway branching morphogenesis, extending its role beyond skeletal patterning.

    Evidence Antisense knockdown and RA treatment in embryonic mouse lung explants with morphometric analysis

    PMID:10913834

    Open questions at the time
    • Antisense approach lacks genetic specificity
    • Direct transcriptional targets in lung not identified
    • Interaction with RA signaling pathway not molecularly defined
  5. 2003 High

    Identification of FLK1/VEGFR2 as a direct HOXB5 target linked HOXB5 to vascular endothelial specification, explaining how a HOX transcription factor can instruct angioblast fate.

    Evidence Yeast one-hybrid identification of intronic HOXB5-binding element, reporter assays, and embryoid body overexpression expanding flk1+ angioblasts

    PMID:12897140

    Open questions at the time
    • Loss-of-function in endothelial lineage not performed
    • Sufficiency versus necessity not distinguished in vivo
  6. 2008 High

    Demonstrating that HOXB5 directly activates RET in vagal neural crest cells, with dominant-negative HOXB5 causing hypoganglionosis, established a transcriptional hierarchy controlling enteric nervous system colonization.

    Evidence Dominant-negative transgenic mice with reduced Ret, impaired NCC migration, and gut hypoganglionosis; Ret reporter activation in neuroblastoma cells

    PMID:18395091

    Open questions at the time
    • Full knockout of HOXB5 in NCC lineage not reported at this time
    • Relationship to Hirschsprung disease causation in humans not established
  7. 2009 High

    Showing HOXB5 transcriptionally activates angiopoietin-2 and that Tie-2 blockade abolishes HOXB5-driven sprouting angiogenesis defined the downstream effector pathway for HOXB5 in vascular remodeling.

    Evidence HUVEC spheroid sprouting, CAM assay, Ang2 promoter reporter, and soluble Tie-2 functional blockade

    PMID:19403561

    Open questions at the time
    • Endogenous HOXB5 loss-of-function in endothelium not tested
    • Relative contribution of Ang2 versus FLK1 to HOXB5 angiogenic function unclear
  8. 2011 High

    ChIP and co-immunoprecipitation revealed that HOXB5 and NKX2-1 form a protein complex that synergistically activates RET, and that Hirschsprung-associated SNPs at the NKX2-1 site abolish this synergism, providing a molecular mechanism for disease-associated regulatory variation.

    Evidence ChIP, co-IP, and luciferase reporter with SNP analysis in RET promoter

    PMID:21677782

    Open questions at the time
    • Crystal structure of HOXB5–NKX2-1 complex unavailable
    • Functional consequence of SNP on enteric NCC development not shown in vivo
  9. 2013 High

    Identification of SOX9 and FOXD3 as direct HOXB5 transcriptional targets in neural crest cells, with genetic epistasis showing rescue of apoptosis, built a HOXB5→SOX9/FOXD3 survival circuit governing NCC fate.

    Evidence ChIP, reporter assays, in ovo gain/loss-of-function, and compound mutant mouse analysis for SOX9 (2013) and FOXD3 (2014)

    PMID:24141719 PMID:25220476

    Open questions at the time
    • Whether SOX9 and FOXD3 are independent or epistatic downstream of HOXB5 is unclear
    • NCC-specific HOXB5 conditional knockout not reported
  10. 2013 High

    Compound Hoxa5;Hoxb5 knockout mice revealed functional redundancy in lung morphogenesis, with lethality demonstrating that HOXB5 contributes non-redundantly to branching, goblet cell specification, and postnatal lung structure.

    Evidence Compound knockout mouse genetics with histological and morphological phenotyping

    PMID:23585229

    Open questions at the time
    • Direct transcriptional targets mediating lung phenotype not identified
    • Cell-type-specific contributions of HOXB5 in lung epithelium versus mesenchyme unknown
  11. 2016 High

    An endogenous knock-in reporter demonstrated that Hoxb5 expression exclusively marks long-term HSCs in bone marrow, with >94% residing in a perivascular niche, redefining the HSC identity marker landscape.

    Evidence Tri-mCherry knock-in reporter at Hoxb5 locus, prospective isolation, serial transplantation, in situ imaging

    PMID:26863982

    Open questions at the time
    • Whether HOXB5 is functionally required for HSC self-renewal is unknown
    • Mechanism by which HOXB5 expression is restricted to LT-HSCs not defined
  12. 2018 High

    HOXB5 overexpression was shown to reprogram pro-pre-B cells into functional T lymphocytes by repressing B-cell genes and activating T-cell regulators, revealing an unexpected lineage-reprogramming capacity.

    Evidence Retroviral HOXB5 overexpression, transplantation, transcriptome analysis, and functional immunological assays in mice

    PMID:29434353

    Open questions at the time
    • Direct chromatin targets mediating B-to-T reprogramming not comprehensively mapped
    • Whether endogenous HOXB5 levels influence normal lymphoid lineage decisions is untested
  13. 2015 High

    Identifying CTNNB1 and EGFR as direct HOXB5 targets in cancer cells linked HOXB5 transcriptional activity to oncogenic signaling through Wnt/β-catenin and EGFR pathways, extending its role beyond development.

    Evidence ChIP and reporter assays in gastric cancer (CTNNB1) and breast/HNSCC (EGFR) cells with knockdown rescue

    PMID:26467157 PMID:30115380 PMID:31864826

    Open questions at the time
    • Whether HOXB5 activates these targets in normal adult tissues is unknown
    • Genome-wide target landscape in cancer not defined by unbiased approaches
  14. 2021 High

    Discovery of HOXB5-driven positive feedback loops (CXCL12→HOXB5→CXCR4 in colorectal cancer; circATP5B→miR-185-5p→HOXB5 in glioma) revealed that HOXB5 expression is itself amplified through feed-forward circuits in malignancy.

    Evidence ChIP, reporter assays, RNA pulldown, RIP, and in vivo metastasis models with pharmacological inhibition (AMD3100)

    PMID:33456563 PMID:33858489

    Open questions at the time
    • Relevance of these feedback loops in non-cancer contexts unknown
    • Therapeutic targeting of HOXB5 itself not explored
  15. 2024 Medium

    A novel post-translational regulatory mechanism was uncovered in which CARD9 SUMOylation inhibits HOXB5 O-GlcNAc glycosylation and nuclear translocation, linking innate immune adaptor signaling to HOXB5 transcriptional activity.

    Evidence Co-IP, SUMOylation and O-GlcNAc assays, nuclear fractionation, Parkin reporter, in cardiomyocyte ischemia-reperfusion model

    PMID:39496070

    Open questions at the time
    • Single-lab finding not independently replicated
    • Sites of O-GlcNAc modification on HOXB5 not mapped
    • Generality beyond cardiomyocyte I/R context unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include whether HOXB5 is functionally required for LT-HSC self-renewal, the genome-wide direct target landscape by unbiased ChIP-seq, the structural basis of redox-regulated cooperative DNA binding, and the physiological significance of CARD9-mediated post-translational regulation of HOXB5 nuclear entry.
  • No conditional knockout in HSCs reported
  • No genome-wide binding profile (ChIP-seq) published
  • No structural model of HOXB5 homeodomain cooperativity
  • CARD9–HOXB5 axis awaits independent confirmation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 11 GO:0140110 transcription regulator activity 10
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 2
Partners
CARD9HOXA5HOXB6NKX2-1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The human HoxB5 protein binds DNA in a sequence-specific manner; cooperative DNA binding to tandem sites is stabilized by at least 100-fold relative to a single site and requires a small domain adjacent to the homeodomain on the amino-terminal side. Cooperative binding is under redox regulation: a cysteine residue in the turn between homeodomain helices 2 and 3 is necessary for cooperativity, and oxidation of HoxB5 enhances (rather than inhibits) cooperative DNA binding, opposite to the redox regulation of Fos, Jun, and other transcription factors. In vitro DNA binding assays, mutational analysis of cysteine residues, domain deletion experiments Molecular and cellular biology High 8101633
1992 HoxB5 (Hox-2.5) transactivates the mouse N-CAM gene promoter through a specific homeodomain binding site (site II) in cotransfection assays; the adjacent HoxB4 (Hox-2.4) protein antagonizes this activation, demonstrating that two adjacent Hox gene products can differentially regulate a downstream cell adhesion molecule gene. Cotransfection/reporter gene assay (CAT) in NIH 3T3 cells, mutational analysis of homeodomain binding sites Proceedings of the National Academy of Sciences of the United States of America High 1347944
2003 HoxB5 acts as an upstream transcriptional activator of flk1 (VEGFR2/KDR) in endothelial precursor differentiation. A cis-acting element in the first intron of flk1 (HoxB5-binding element, HBE) is required for endothelium-dependent expression; HoxB5 binds this element (identified by yeast one-hybrid), transactivates the flk1 promoter in an HBE-dependent fashion, and overexpression of HoxB5 expands flk1+ angioblasts and increases PECAM+ primitive blood vessels in embryoid bodies. Yeast one-hybrid screen, transient transfection reporter assay, overexpression in embryoid bodies, transgenic reporter assay Molecular and cellular biology High 12897140
2009 HoxB5 promotes endothelial cell sprouting in vitro and modifies intussusceptive angiogenesis in vivo; HoxB5 overexpression upregulates angiopoietin-2 (Ang2) transcriptionally, and the HoxB5-induced sprouting effect is abolished by soluble Tie-2 (angiopoietin antagonist), placing Ang2 as a functional downstream mediator. HUVEC spheroid sprouting assay, chick chorioallantoic membrane assay, luciferase reporter assay for Ang2 promoter, soluble Tie-2 functional blockade Cardiovascular research High 19403561
2008 Hoxb5 acts as a transcriptional activator upstream of Ret in vagal neural crest cells; a dominant-negative Hoxb5 (enb5, fused to Engrailed repressor domain) in vagal NCCs reduces Ret expression, impairs NCC migration to distal intestine, and causes hypoganglionosis. Hoxb5 directly induces Ret transcription in neuroblastoma cells. Transgenic dominant-negative expression in mice, in vitro Ret reporter assay in neuroblastoma cells, histological analysis of ganglia Gastroenterology High 18395091
2011 HOXB5 directly binds the promoter region upstream of the NKX2-1 binding site in the RET gene and transactivates RET expression. HOXB5 and NKX2-1 form a protein complex and synergistically activate RET transcription; HSCR-associated SNPs at the NKX2-1 binding site abolish this synergism. HOXB5 cooperates additively (not synergistically) with SOX10, PAX3, and PHOX2B in RET transactivation. Chromatin immunoprecipitation, luciferase reporter assay, co-immunoprecipitation (protein complex), promoter deletion analysis PloS one High 21677782
2014 HOXB5 binds to a multi-species conserved sequence (MCS+9.7) in the first intron of the RET gene and enhances RET transcription in an MCS+9.7-dependent manner. HOXB5 binding to MCS+9.7 alters chromatin conformation and induces histone H3K4 trimethylation at RET locus chromatin, facilitating transcription complex formation and RET expression. ChIP, RET mini-gene reporter system, deletion of HOXB5 binding site, histone modification analysis, TBP co-precipitation assay, in ovo chick embryo reporter The international journal of biochemistry & cell biology High 24794774
2013 Perturbation of Hoxb5 signaling in trunk and vagal neural crest cells causes Sox9 downregulation, NCC apoptosis, and multiple neurocristopathies. Hoxb5 directly binds and transactivates the Sox9 promoter in vitro and in vivo; Sox9 expression in ovo alleviates apoptosis induced by perturbed Hoxb5 signaling; ectopic Hoxb5 induces ectopic Sox9 in chick neural tube. Transgenic dominant-negative expression, Sox9 promoter ChIP and reporter assay in neuroblastoma cells, in ovo gain/loss-of-function, genetic epistasis with NCC-specific Sox9 deletion mice Cell death and differentiation High 24141719
2014 Hoxb5 directly binds and transactivates the Foxd3 promoter in neural crest-derived neuroblastoma cells. In vivo, Wnt1-Cre-mediated perturbation of Hoxb5 signaling causes Foxd3 downregulation in mouse embryos. In ovo, Hoxb5 induces ectopic Foxd3 in chick neural tube, and Foxd3 alleviates apoptosis induced by perturbed Hoxb5 signaling. Luciferase reporter assay, ChIP in brain/neural tube, in ovo gain/loss-of-function, mouse conditional perturbation The international journal of biochemistry & cell biology High 25220476
2015 HOXB5 directly binds the CTNNB1 (β-catenin) promoter and transcriptionally activates β-catenin expression in human gastric cancer cells, leading to upregulation of downstream targets cyclin D1 and c-Myc, and promoting invasion and migration. HOXB5 knockdown reduces β-catenin levels and invasive capacity. ChIP, luciferase reporter assay, siRNA knockdown, correlation analysis in patient tissues The Biochemical journal High 26467157
2018 Hoxb5 reprograms pro-pre-B cells into functional T lymphocytes in vivo by repressing B cell master genes, activating T cell regulators, and modulating chromatin modifiers. Reprogramming begins in bone marrow and completes in thymus, generating T cells with normal transcriptomes, tissue distribution, and immunological function. Retroviral overexpression in pro-pre-B cells, transplantation into mice, transcriptome analysis, functional immunological assays Nature immunology High 29434353
2018 HOXB5 directly binds the EGFR promoter and transcriptionally activates EGFR expression in ER-positive breast cancer cells; HOXB5 promotes phosphorylation of EGFR and its downstream effectors; EGFR knockdown reverses HOXB5-induced invasion. ChIP, luciferase reporter assay, EGFR knockdown rescue experiment, western blot for phosphorylation Biochemical and biophysical research communications High 30115380
2019 HOXB5 directly binds the EGFR promoter and activates EGFR transcription in head and neck squamous cell carcinoma cells, consequently regulating the Akt/Wnt/β-catenin signaling axis; HOXB5 knockdown reduces proliferation, tumor growth, and EMT-associated protein expression in vitro and in vivo. ChIP, luciferase reporter assay, HOXB5 knockdown in cell lines and xenograft, western blot for pathway components European journal of surgical oncology High 31864826
2021 HOXB5 transcriptionally activates CXCR4 and ITGB3 to promote colorectal cancer metastasis. CXCL12 upregulates HOXB5 through the ERK/ETS1 pathway, creating a positive feedback loop (CXCL12-HOXB5-CXCR4). AMD3100 (CXCR4 inhibitor) suppresses HOXB5-mediated metastasis. ChIP, luciferase reporter assay, siRNA knockdown, in vivo lung/liver metastasis models, pharmacological inhibition Theranostics High 33456563
2021 HOXB5 transcriptionally regulates IL6 expression in glioma stem cells, promoting GSC proliferation via JAK2/STAT3 signaling. HOXB5 also transcriptionally activates SRSF1, which promotes circATP5B biogenesis; circATP5B sponges miR-185-5p to upregulate HOXB5, forming a positive feedback loop. ChIP, luciferase reporter assay, RNA-binding protein immunoprecipitation, RNA pulldown, neurosphere/limiting dilution assay Journal of experimental & clinical cancer research High 33858489
2019 In Tmem67 knockout mouse cerebella, HOXB5 protein levels are elevated and HOXB5 occupancy at the β-catenin promoter is significantly increased upon activation of canonical Wnt signaling; increased canonical Wnt signaling following loss of TMEM67 is dependent on HOXB5, linking HOXB5 to ciliary Wnt/β-catenin pathway regulation in cerebellar development. ChIP, western blot, Tmem67 knockout mouse model, transcriptome profiling Scientific reports Medium 30931988
2013 HoxB5 overexpression in endothelial cells increases expression of MCP-1 and IL-6 in vitro and in vivo; HoxB5-induced monocyte migration is antagonized by MCP-1 blocking antibody, indicating that HoxB5-driven vascular remodeling is mediated partly through MCP-1 and IL-6 upregulation and leucocyte infiltration. Adenoviral overexpression in mice (femoral artery ligation), proteome profiler array, MCP-1 blocking antibody experiment, immunohistochemistry Cardiovascular research Medium 24189625
2016 Hoxb5 expression marks long-term hematopoietic stem cells (LT-HSCs) specifically in mouse bone marrow; only Hoxb5+ HSCs exhibit long-term multi-lineage reconstitution in primary and secondary transplant recipients; in situ imaging shows >94% of Hoxb5+ (LT-HSCs) are directly attached to VE-cadherin+ (perivascular) cells, establishing a near-homogeneous perivascular niche. Endogenous reporter knock-in (tri-mCherry), prospective isolation, serial transplantation, in situ bone marrow imaging Nature High 26863982
1997 A HoxB5 epitope-specific antibody was used to immunopurify chromatin from mouse CNS; a 910 bp genomic fragment containing a consensus Antennapedia-like binding site was recovered, identified as the promoter of the SPI3 gene (serine protease inhibitor); SPI3 and HoxB5 show overlapping expression in CNS of E15 mouse embryos, suggesting SPI3 is a candidate direct target of HoxB5. Immunoaffinity chromatin purification, gel mobility shift assay, in situ hybridization Brain research. Developmental brain research Low 9174240
2000 Hoxb5 protein levels in developing mouse lung are regulated by retinoic acid (upregulation) and antisense oligonucleotide knockdown; RA increases branching with elongated primary branches, while Hoxb5 antisense decreases both primary and secondary branching, demonstrating that regional and quantitative Hoxb5 expression controls early airway morphogenesis. Antisense oligonucleotide knockdown, RA treatment of embryonic lung cultures, immunohistochemistry, western blot, morphometric branching analysis Biochimica et biophysica acta Medium 10913834
2013 Hoxa5 and Hoxb5 display partial functional redundancy during mouse lung morphogenesis; Hoxa5;Hoxb5 compound mutants carrying four mutated alleles exhibit aggravated lung phenotype (death at birth) compared to single mutants, with Hoxb5 contributing to branching morphogenesis, goblet cell specification, and postnatal air space structure. Compound knockout mouse genetics, morphological and histological phenotyping, genetic complementation analysis American journal of physiology. Lung cellular and molecular physiology High 23585229
1995 Targeted disruption of hoxb-5 in mice causes a rostral shift of the shoulder girdle (analogous to human Sprengel anomaly), establishing a role for hoxb-5 in specifying limb position along the anteroposterior axis. hoxb-5/hoxb-6 transheterozygotes exhibit anteriorizing homeotic transformation of cervicothoracic vertebrae (C6–T1), demonstrating nonallelic noncomplementation and that hoxb-5 and hoxb-6 function together to specify this region. Gene targeting (knockout) in mice, skeletal phenotype analysis, genetic complementation test (transheterozygotes) Genes & development High 7828847
2022 HOXB5 directly transcriptionally activates ANGPT2 (angiopoietin-2) in esophageal cancer cells; HOXB5-activated ANGPT2 promotes proliferation, migration, invasion, and angiogenesis via the ERK/AKT signaling pathway; HOXB5 overexpression reverses the effects of ANGPT2 silencing. ChIP, luciferase reporter assay, siRNA knockdown, HOXB5 overexpression rescue, tube formation assay, western blot for ERK/AKT pathway Experimental and therapeutic medicine Medium 35949323
2024 SUMOylation of CARD9 (mediated by PIAS3) promotes CARD9 binding to HOXB5 and inhibits HOXB5 O-GlcNAc glycosylation, which is required for HOXB5 nuclear translocation. Dissociation of CARD9 from HOXB5 (via PIAS3 knockdown) allows O-GlcNAc glycosylation of HOXB5 and subsequent nuclear translocation, where HOXB5 transcriptionally activates Parkin to promote mitophagy and attenuate myocardial I/R injury. Co-immunoprecipitation, PIAS3 knockdown, CARD9 SUMOylation assay, O-GlcNAc modification assay, nuclear fractionation, luciferase reporter for Parkin Journal of cellular and molecular medicine Medium 39496070

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature 515 2571936
1990 Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 474 1975088
1992 Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development (Cambridge, England) 442 1363087
1993 The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation. Cell 291 8093858
1990 Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development (Cambridge, England) 287 1983472
1991 Introduction of a subtle mutation into the Hox-2.6 locus in embryonic stem cells. Nature 282 1672446
2016 Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature 262 26863982
1995 Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation. Genes & development 233 7828847
1992 Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4. Proceedings of the National Academy of Sciences of the United States of America 221 1347944
1991 Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. The EMBO journal 219 1915273
1990 Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and larvae. Cell 163 1979525
1992 Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions. Nature 151 1545869
1988 Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene. Genes & development 143 2463210
1989 Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic acids research 130 2564662
1992 Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions in the nervous system and the potential for shared regulatory regions. The EMBO journal 118 1582411
2007 DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets. Molecular cancer 117 17623056
1990 Hox-2.3 upstream sequences mediate lacZ expression in intermediate mesoderm derivatives of transgenic mice. Development (Cambridge, England) 105 1977573
1991 The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development. Development (Cambridge, England) 100 1685115
1991 The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays a collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos. Nucleic acids research 99 1682879
1993 Conditional immortalization of mouse myelomonocytic, megakaryocytic and mast cell progenitors by the Hox-2.4 homeobox gene. The EMBO journal 97 8104786
2003 HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts. Developmental dynamics : an official publication of the American Association of Anatomists 77 12950074
2003 Expression of Hoxb-5 during human lung development and in congenital lung malformations. Birth defects research. Part A, Clinical and molecular teratology 73 14632303
1987 Sequence analysis of the murine Hox-2.2, -2.3, and -2.4 homeo boxes: evolutionary and structural comparisons. Genomics 72 2891608
1991 The oncogenic potential of an activated Hox-2.4 homeobox gene in mouse fibroblasts. Molecular and cellular biology 68 1670897
2003 HoxB5 is an upstream transcriptional switch for differentiation of the vascular endothelium from precursor cells. Molecular and cellular biology 67 12897140
1989 Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system. Differentiation; research in biological diversity 64 2570724
1989 The developmental expression pattern of a new murine homeo box gene: Hox-2.5. Developmental biology 61 2567250
1990 Expression of the murine homeobox-containing gene Hox-2.3 suggests multiple time-dependent and tissue-specific roles during development. Development (Cambridge, England) 60 1983116
2021 CXCL12-mediated HOXB5 overexpression facilitates Colorectal Cancer metastasis through transactivating CXCR4 and ITGB3. Theranostics 54 33456563
1997 Hoxb-5 expression in the developing mouse lung suggests a role in branching morphogenesis and epithelial cell fate. Histochemistry and cell biology 54 9450632
1992 Ectopic expression of Hox-2.3 induces craniofacial and skeletal malformations in transgenic mice. Mechanisms of development 54 1362649
2017 Knockdown of Homeobox B5 (HOXB5) Inhibits Cell Proliferation, Migration, and Invasion in Non-Small Cell Lung Cancer Cells Through Inactivation of the Wnt/β-Catenin Pathway. Oncology research 53 28337958
2001 Additional hox clusters in the zebrafish: divergent expression patterns belie equivalent activities of duplicate hoxB5 genes. Evolution & development 53 11440248
1993 Colinearity in the Xenopus laevis Hox-2 complex. Mechanisms of development 53 8095151
2003 Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development. Gene 51 12527197
1993 Cooperative DNA binding of the human HoxB5 (Hox-2.1) protein is under redox regulation in vitro. Molecular and cellular biology 51 8101633
1988 Structure and expression of Hox-2.2, a murine homeobox-containing gene. Proceedings of the National Academy of Sciences of the United States of America 51 2899893
2013 Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis. American journal of physiology. Lung cellular and molecular physiology 50 23585229
1993 Proximal cis-acting elements cooperate to set Hoxb-7 (Hox-2.3) expression boundaries in transgenic mice. Development (Cambridge, England) 50 8104144
2021 The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway. Journal of experimental & clinical cancer research : CR 48 33858489
2015 HOXB5 Promotes the Proliferation and Invasion of Breast Cancer Cells. International journal of biological sciences 48 25999793
1990 The zebrafish homeobox gene hox-2.2: transcription unit, potential regulatory regions and in situ localization of transcripts. The EMBO journal 47 1968004
2015 HOXB5 induces invasion and migration through direct transcriptional up-regulation of β-catenin in human gastric carcinoma. The Biochemical journal 45 26467157
1990 A yeast artificial chromosome containing the mouse homeobox cluster Hox-2. Proceedings of the National Academy of Sciences of the United States of America 45 1972280
2008 Perturbation of hoxb5 signaling in vagal neural crests down-regulates ret leading to intestinal hypoganglionosis in mice. Gastroenterology 43 18395091
1992 Xenopus Hox-2 genes are expressed sequentially after the onset of gastrulation and are differentially inducible by retinoic acid. Development (Cambridge, England) 43 1363722
1992 Dominant mutation of the murine Hox-2.2 gene results in developmental abnormalities. The Journal of experimental zoology 41 1358998
1992 Inhibition of specific pathways of myeloid cell differentiation by an activated Hox-2.4 homeobox gene. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 41 1359901
2018 Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes. Nature immunology 39 29434353
2009 HoxB5 induces endothelial sprouting in vitro and modifies intussusceptive angiogenesis in vivo involving angiopoietin-2. Cardiovascular research 39 19403561
1997 Lineage-specific regulation of hematopoiesis by HOX-B8 (HOX-2.4): inhibition of granulocytic differentiation and potentiation of monocytic differentiation. Blood 38 9292516
2019 Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America 37 31754028
2000 Hoxb-5 control of early airway formation during branching morphogenesis in the developing mouse lung. Biochimica et biophysica acta 35 10913834
1992 Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes. Blood 35 1351762
2014 Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 and OLFM4 genes with obesity-related traits among Portuguese children. Journal of human genetics 34 24670271
1991 Expression of the HOX-2.3 homeobox gene in human lymphocytes and lymphoid tissues. Blood 33 1676919
1986 The murine Hox-2 cluster of homeo box containing genes maps distal on chromosome 11 near the tail-short (Ts) locus. Cytogenetics and cell genetics 32 2875852
2015 Roles of Hoxb5 in the development of vagal and trunk neural crest cells. Development, growth & differentiation 30 25703667
1992 DNA sequence polymorphism within hominoid species exceeds the number of phylogenetically informative characters for a HOX2 locus. Molecular biology and evolution 30 1352841
2018 HOXB5 promotes retinoblastoma cell migration and invasion via ERK1/2 pathway-mediated MMPs production. American journal of translational research 28 30018711
2018 Transcriptional activation of EGFR by HOXB5 and its role in breast cancer cell invasion. Biochemical and biophysical research communications 28 30115380
2011 HOXB5 expression in oral squamous cell carcinoma. Journal of applied oral science : revista FOB 26 21552713
2019 HOXB5 acts as an oncogenic driver in head and neck squamous cell carcinoma via EGFR/Akt/Wnt/β-catenin signaling axis. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 25 31864826
2011 HOXB5 cooperates with NKX2-1 in the transcription of human RET. PloS one 25 21677782
1988 A zebrafish homologue of the murine Hox-2.1 gene. FEBS letters 25 2895022
1987 The mouse Hox2.3 homeobox-containing gene: regulation in differentiating pluripotent stem cells and expression pattern in embryos. Differentiation; research in biological diversity 25 2892751
1988 In situ hybridization patterns of zebrafish homeobox genes homologous to Hox-2.1 and En-2 of mouse. Biochemical and biophysical research communications 24 2904810
1998 Growth factors and dexamethasone regulate Hoxb5 protein in cultured murine fetal lungs. The American journal of physiology 23 9575880
2016 MicroRNA-1275 suppresses cell growth, and retards G1/S transition in human nasopharyngeal carcinoma by down-regulation of HOXB5. Journal of cell communication and signaling 22 27644407
1991 Characterization of the murine Hox-2.3 promoter: involvement of the transcription factor USF (MLTF). Mechanisms of development 22 1677811
2013 The transcription factor HoxB5 stimulates vascular remodelling in a cytokine-dependent manner. Cardiovascular research 20 24189625
2019 The ciliary Frizzled-like receptor Tmem67 regulates canonical Wnt/β-catenin signalling in the developing cerebellum via Hoxb5. Scientific reports 19 30931988
2014 HOXB5 binds to multi-species conserved sequence (MCS+9.7) of RET gene and regulates RET expression. The international journal of biochemistry & cell biology 18 24794774
2013 Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice. Cell death and differentiation 18 24141719
2008 Functional resolution of duplicated hoxb5 genes in teleosts. Development (Cambridge, England) 18 18832391
1988 The Hox-2 homeo box gene complex on mouse chromosome 11 is closely linked to Re. Genetics 18 2896141
2000 Association of bronchopulmonary sequestration with expression of the homeobox protein Hoxb-5. Journal of pediatric surgery 17 11101743
1991 A deletion and a rearrangement distinguish between the intracisternal A-particle of Hox-2.4 and that of interleukin-3 in the same leukemic cells. Virology 17 1673811
1991 Possible role of DNA topoisomerase II on transcription of the homeobox gene Hox-2.1 in F9 embryonal carcinoma cells. Nucleic acids research 17 1683482
2021 LncRNA DCST1-AS1 Promotes Endometrial Cancer Progression by Modulating the MiR-665/HOXB5 and MiR-873-5p/CADM1 Pathways. Frontiers in oncology 15 34497766
2020 HOXB5 promotes the progression of breast cancer through wnt/beta-catenin pathway. Pathology, research and practice 15 34118725
2021 Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment. Biochemical and biophysical research communications 14 33418191
1993 Induction of HOX-2 genes in P19 embryocarcinoma cells is dependent on retinoic acid receptor alpha. Experimental cell research 13 8097725
2022 Circ_0020123 enhances the cisplatin resistance in non-small cell lung cancer cells partly by sponging miR-140-3p to regulate homeobox B5 (HOXB5). Bioengineered 12 35170372
2020 HOXB5 promotes proliferation, migration, and invasion of pancreatic cancer cell through the activation of the GSK3β/β-catenin pathway. Anti-cancer drugs 11 32796404
1992 The murine Hox-2.4 promoter contains a functional octamer motif. Nucleic acids research 11 1349742
2019 MicroRNA-625 inhibits the progression of non‑small cell lung cancer by directly targeting HOXB5 and deactivating the Wnt/β-catenin pathway. International journal of molecular medicine 10 31115501
2005 Ets identified as a trans-regulatory factor of amphioxus Hox2 by transgenic analysis using ascidian embryos. Developmental biology 10 16051213
1988 Restriction fragment length polymorphism and chromosome mapping of a mouse homeo box gene, Hox-2.1. Biochemical genetics 10 2907403
2022 miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR. Frontiers in oncology 9 35847904
2019 HOXB5 promotes malignant progression in pancreatic cancer via the miR-6732 pathway. Cell cycle (Georgetown, Tex.) 9 31876226
2013 Regulatory interactions between androgens, Hoxb5, and TGF β signaling in murine lung development. BioMed research international 9 24078914
2006 Developmental methylation of the regulatory region of HoxB5 gene in mouse correlates with its tissue-specific expression. Gene 9 16870358
1997 A target of the HoxB5 gene from the mouse nervous system. Brain research. Developmental brain research 8 9174240
2024 CARD9 protein SUMOylation regulates HOXB5 nuclear translocation and Parkin-mediated mitophagy in myocardial I/R injury. Journal of cellular and molecular medicine 7 39496070
2020 Long non‑coding RNA PRNCR1 exerts oncogenic effects in tongue squamous cell carcinoma in vitro and in vivo by sponging microRNA‑944 and thereby increasing HOXB5 expression. International journal of molecular medicine 7 32319550
2014 Homeobox b5 (Hoxb5) regulates the expression of Forkhead box D3 gene (Foxd3) in neural crest. The international journal of biochemistry & cell biology 7 25220476
2011 Overexpression of HOXB5, cyclin D1 and PCNA in congenital cystic adenomatoid malformation. Fetal diagnosis and therapy 7 21228548
2022 HOXB5-activated ANGPT2 promotes the proliferation, migration, invasion and angiogenic effect of esophageal cancer cells via activating ERK/AKT signaling pathway. Experimental and therapeutic medicine 6 35949323
1994 The 5'-sequence of the murine Hox-b3 (Hox-2.7) gene and its intron contain multiple transcription-regulatory elements. The International journal of biochemistry 6 7890121