Affinage

HOXA3

Homeobox protein Hox-A3 · UniProt O43365

Length
443 aa
Mass
46.4 kDa
Annotated
2026-06-10
56 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXA3 is a homeodomain transcription factor that controls cell-fate decisions during pharyngeal organ development and hematovascular differentiation by directly regulating downstream target genes (PMID:7635047, PMID:21170035, PMID:39740793). In the third pharyngeal pouch it acts cell-autonomously in endoderm to initiate the thymus program and to drive parathyroid differentiation, and non-cell-autonomously in neural crest cells for organ morphogenesis, with combined loss in both lineages reproducing the null athymic phenotype (PMID:25249461, PMID:27178667); mechanistically it maintains Pax1 expression and operates in a Hoxa3–Pax1 genetic pathway governing epithelial proliferation, survival, and differentiation marked by Gcm2 and Foxn1 (PMID:7635047, PMID:10820253, PMID:11476574), and is required for carotid body formation through maintenance of the third arch artery (PMID:12074562). Its early hindbrain expression in rhombomeres 5/6 is initiated by direct binding of the Maf factor Krml1 (kreisler) to a single high-affinity enhancer site and subsequently maintained through auto- and cross-regulatory Hox/Pbx feedback loops (PMID:9895323, PMID:11566863). HOXA3 is an apical regulator of the endothelial-to-hematopoietic transition, restraining hematopoietic commitment by downregulating Runx1 and other key hematopoietic transcription factors and by inducing Jagged1-mediated cis-inhibition of Notch signaling (PMID:21170035, PMID:29073173). In wound healing it promotes endothelial migration and angiogenesis through uPAR-dependent induction of MMP-14 and uPAR, mobilizes endothelial progenitor cells, and steers myeloid cells toward proangiogenic, M2-polarized states via Pu.1/Spi1, Stat6, Runx1, and NF-κB modulation (PMID:15914537, PMID:19544454, PMID:20974673, PMID:27342843, PMID:31626638). HOXA3 additionally functions as a direct transcriptional regulator in disease contexts, activating USP15 to suppress autophagy via SQSTM1 deubiquitination (PMID:39740793) and repressing NLRP3 and HO-1 to modulate inflammasome and interferon responses (PMID:33100331, PMID:34851144). Its own expression is post-transcriptionally constrained by a 5'UTR uORF-based Translation Inhibitory Element that requires the non-canonical factor eIF2D for cap-dependent inhibition (PMID:34076576).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1994 High

    Established that Hoxa3 acts in dosage-dependent synergy with Hoxd3 to control axial skeletal precursor cell behavior rather than acting alone in simple positional identity.

    Evidence Genetic epistasis with Hoxa3/Hoxd3 double knockout mice and skeletal analysis

    PMID:7913519

    Open questions at the time
    • Molecular target genes mediating the proliferation effect not identified
    • Direct DNA-binding evidence absent
  2. 1995 High

    Defined the core developmental phenotype, showing Hoxa3 loss causes athymia and thyroid hypoplasia through effects on differentiation, not neural crest migration, and maintains Pax1 in third-pouch neural crest.

    Evidence Knockout mouse with carbocyanine dye tracing, molecular markers, and in situ hybridization

    PMID:7635047

    Open questions at the time
    • Whether Pax1 regulation is direct not established
    • Cell-autonomy not yet resolved
  3. 1999 High

    Identified the upstream initiator of Hoxa3 hindbrain expression, showing Krml1/kreisler directly binds a defined enhancer to drive r5/r6 expression.

    Evidence Transgenic enhancer analysis, EMSA binding-site mapping, and kreisler mutant embryos

    PMID:9895323

    Open questions at the time
    • Maintenance phase of expression not explained by this element
    • Downstream hindbrain targets unknown
  4. 2001 High

    Resolved the Hoxa3-Pax1 pathway in thymus/parathyroid organogenesis, localizing the defect to radio-resistant epithelial stroma and linking it to epithelial death, proliferation, and Gcm2/Foxn1 marker expression.

    Evidence Compound mutant mice, fetal liver adoptive transfer, flow cytometry, and organ-specific in situ markers

    PMID:10820253 PMID:11476574

    Open questions at the time
    • Direct transcriptional targets of Hoxa3 in epithelium not identified
    • Mechanism of apoptosis induction unknown
  5. 2001 High

    Showed that sustained r5/r6 expression is maintained independently of kreisler by conserved bipartite Hox/Pbx sites mediating auto/cross-regulatory feedback.

    Evidence Transgenic mouse and chick analysis with deletion and Hox/Pbx site mutagenesis across species

    PMID:11566863

    Open questions at the time
    • Identity of the specific Hox/Pbx partners binding in vivo not defined
  6. 2002 High

    Extended the developmental role to vascular structures, showing Hoxa3 is required for carotid body formation via maintenance of the third arch artery.

    Evidence Knockout mouse histology and immunohistochemistry with complete penetrance

    PMID:12074562

    Open questions at the time
    • Molecular effectors of arch artery maintenance unknown
    • Cell type executing the requirement not pinpointed
  7. 2003 Medium

    Demonstrated Hoxa3 is not only necessary but sufficient to specify somatic motoneurone identity, acting upstream of the patterning gene Irx3.

    Evidence Rhombomere transplantation and targeted gain-of-function with Irx3 in situ readout

    PMID:12756180

    Open questions at the time
    • Single study
    • Whether Irx3 repression is direct not tested
  8. 2004 Medium

    Localized the parathyroid requirement cell-autonomously to pouch endoderm, separating it from neural crest migration.

    Evidence Knockout mouse with SP-1/chromogranin A immunohistochemistry and connexin43-lacZ crest tracing

    PMID:15100241

    Open questions at the time
    • Single lab
    • Endoderm-intrinsic target genes not identified
  9. 2005 High

    Identified an angiogenic effector function, showing HOXA3 drives endothelial and keratinocyte migration and wound angiogenesis via uPAR-dependent induction of MMP-14 and uPAR.

    Evidence In vitro migration assays, in vivo gene transfer into diabetic wounds, and uPAR blocking

    PMID:15914537

    Open questions at the time
    • Whether MMP-14/uPAR are direct transcriptional targets not shown
    • Connection to developmental role unclear
  10. 2009 Medium

    Showed HOXA3 reshapes the wound cellular environment by recruiting endothelial progenitors and suppressing pro-inflammatory NF-κB pathway members.

    Evidence GFP bone marrow chimeras, in vivo gene transfer, flow cytometry, and microarray

    PMID:19544454

    Open questions at the time
    • Directness of MyD88/TOLLIP repression untested
    • Single lab
  11. 2010 High

    Established HOXA3 as an apical regulator of the endothelial-to-hematopoietic transition by repressing Runx1 and other hematopoietic factors, and showed it promotes proangiogenic myeloid differentiation that rescues the diabetic phenotype.

    Evidence Reciprocal loss/gain-of-function with epistasis, expression profiling, and ex vivo/in vivo functional rescue

    PMID:20974673 PMID:21170035

    Open questions at the time
    • Whether Runx1 repression is direct binding not shown in this work
    • Mechanism of myeloid reprogramming undefined
  12. 2010 High

    Mapped functional divergence between orthologs to the protein C-terminal domain, indicating tissue-specific activity resides outside the homeodomain.

    Evidence Knock-in of zebrafish hoxa3a at the mouse locus and chimeric protein allele with tissue rescue analysis

    PMID:20498049

    Open questions at the time
    • Biochemical basis of C-terminal specificity unknown
    • Cofactor differences not identified
  13. 2014 High

    Dissected cell-autonomous versus non-autonomous roles, showing endoderm-intrinsic function in thymus/parathyroid and crest-based morphogenetic function, with combined deletion phenocopying the null.

    Evidence Tissue-specific and double conditional knockouts with Hoxa3-Cre lineage tracing

    PMID:25249461 PMID:27178667

    Open questions at the time
    • Lineage-specific direct targets not enumerated
    • Temporal target switching unresolved
  14. 2016 Medium

    Showed HOXA3 controls macrophage polarization, suppressing M1 and promoting M2 states via Pu.1/Spi1 and Stat6 in a DNA-binding-independent manner.

    Evidence Protein transduction in vitro, in vivo gene transfer, Western blot, and immunofluorescence of polarization markers

    PMID:27342843

    Open questions at the time
    • Non-DNA-binding mechanism not molecularly defined
    • Single lab
  15. 2017 Medium

    Defined the HoxA3-Notch link, showing it induces Jagged1 to cis-inhibit Notch and render hemogenic endothelium non-responsive, a prerequisite step preceding EHT.

    Evidence Gain-of-function with Notch activation/inhibition, Jag1 knockdown, and expression/phenotype assays

    PMID:29073173

    Open questions at the time
    • Whether Jag1 is a direct transcriptional target not confirmed
    • Single lab
  16. 2019 Medium

    Connected HOXA3 to inflammatory and chromatin regulation, rescuing diabetic human macrophage defects through Runx1 upregulation and modulation of NF-κB and TNF promoter acetylation.

    Evidence Protein transduction, Western blot, HAT/HDAC activity assay, and ChIP of TNF promoter acetylation in primary human cells

    PMID:31626638

    Open questions at the time
    • Direct versus indirect Runx1 regulation unresolved (contrasts with hematopoietic repression)
    • Single lab
  17. 2020 Medium

    Placed HOXA3 in a GDF11/Smad2/3 axis as a direct transcriptional repressor of NLRP3 that limits cardiomyocyte pyroptosis.

    Evidence ChIP assay, AAV9 in vivo overexpression, and Smad pathway Western blot

    PMID:33100331

    Open questions at the time
    • Generalizability beyond cardiomyocytes unknown
    • Single lab
  18. 2021 Medium

    Identified an antiviral-suppressive role in which HOXA3 represses HO-1 transcription, weakening HO-1-IRF3 interaction and dampening type I interferon production.

    Evidence Luciferase reporter, knockdown/overexpression, Co-IP, and IRF3 phosphorylation/translocation assays during PRRSV infection

    PMID:34851144

    Open questions at the time
    • Direct HOXA3 binding to HO-1 promoter via ChIP not shown
    • Single lab
  19. 2021 High

    Revealed translational control of HOXA3 itself through a 5'UTR uORF-based Translation Inhibitory Element requiring eIF2D, with an IRES enabling cap-independent translation.

    Evidence In vitro translation, uORF mutagenesis, eIF2D requirement, and reporter assays

    PMID:34076576

    Open questions at the time
    • Physiological contexts engaging the TIE versus IRES unknown
    • In vivo relevance not established
  20. 2021 Low

    Reported that HOXA2 and HOXA3 can heterodimerize, raising the possibility of combinatorial control of HOX binding specificity.

    Evidence ChIP-seq, in vitro binding assays, and protein-protein interaction assay

    PMID:34940502

    Open questions at the time
    • Functional consequences of heterodimerization not directly tested
    • Single method for the interaction
    • In vivo relevance unverified
  21. 2024 Medium

    Established a HOXA3/USP15/SQSTM1 axis in which HOXA3 directly activates USP15 to suppress autophagy and promote M2 polarization and tumor growth in renal cell carcinoma.

    Evidence ChIP, EMSA, dual-luciferase, Co-IP, ubiquitination assay, autophagy imaging, and xenograft

    PMID:39740793

    Open questions at the time
    • Generality across tumor types untested
    • Single lab
  22. 2024 Medium

    Extended the developmental role to a human model, showing HOXA3 controls third pharyngeal pouch endoderm commitment via Wnt signaling through transcriptional activation of EPHB2.

    Evidence hESC differentiation with HOXA3 knockdown, Wnt reporter, and proliferation/migration assays

    PMID:38259452

    Open questions at the time
    • Direct EPHB2 binding not fully resolved
    • In vivo human relevance not established
  23. 2024 Medium

    Positioned HOXA3 as a downstream effector of isoform-specific WT1, mediating G1 arrest and cytarabine resistance in AML.

    Evidence RNA-seq, HOXA3 overexpression, cell-cycle/CD71 flow cytometry, and chemoresistance assays

    PMID:38867543

    Open questions at the time
    • HOXA3 transcriptional targets driving resistance not identified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying biochemical question — what cofactors and direct genome-wide target sets allow one homeodomain factor to switch between developmental patterning, hematovascular fate, and inflammatory/tumor programs — remains unresolved.
  • No comprehensive genome-wide HOXA3 binding map across cell types
  • C-terminal specificity determinants not mechanistically explained
  • Reconciliation of context-dependent Runx1 repression versus activation unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
HOXA2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Targeted disruption of Hoxa3 results in athymia and thyroid hypoplasia; analysis with carbocyanine dye and molecular markers showed neural crest migration was not grossly affected, indicating Hoxa3 affects the intrinsic capacity of neural crest cells to differentiate and/or induce proper differentiation of surrounding pharyngeal tissues. Hoxa3 loss causes a marked reduction in Pax1 expression in neural crest cells of the 3rd pharyngeal pouch, suggesting Hoxa3 is required to maintain Pax1 expression as part of the athymic phenotype. Gene targeting (knockout mouse), carbocyanine dye injection, molecular marker analysis, in situ hybridization Development High 7635047
1994 Hoxa3 and Hoxd3 show synergistic, dosage-dependent interactions: double mutants show deletion of the entire atlas rather than simple homeotic transformation seen in single Hoxd3 mutants, interpreted as differential regulation of proliferation rates of precursor cells. Genetic epistasis (double knockout mice), skeletal analysis Nature High 7913519
1999 Hoxa3 expression in rhombomeres 5 and 6 of the hindbrain is directly regulated by the Maf bZIP transcription factor Krml1 (kreisler): a single high-affinity Krml1 binding site in a 600 bp enhancer in the Hoxa3/Hoxa4 intergenic region is necessary and sufficient for r5/r6 expression, and this activity depends on endogenous kreisler. Transgenic enhancer analysis, deletion mapping, electrophoretic mobility shift assay (binding site identification), ectopic kreisler expression, kreisler mutant analysis Development High 9895323
2001 Hoxa3 and Pax1 act synergistically in a genetic pathway required for thymic epithelial cell development: Hoxa3(+/-)Pax1(-/-) compound mutants show defective MHC class II+ epithelial cells, reduced thymocyte maturation with a block at CD4-8- to CD4+8+ transition, and increased apoptosis of CD4+8+ thymocytes. Fetal liver adoptive transfer showed the defect resides in radio-resistant stromal (epithelial) cells, not hematopoietic cells. Compound mutant mice (genetic epistasis), fetal liver adoptive transfer, flow cytometry, immunohistochemistry Journal of Immunology High 10820253
2001 Maintenance of Hoxa3 expression in r5 and r6 during late hindbrain development is controlled by a conserved cis-element containing two bipartite Hox/Pbx-binding sites that mediate auto- and cross-regulatory feedback loops, independently of kreisler. This element is conserved in human and horn shark Hoxa3 loci. Transgenic analysis in mouse and chick embryos, deletion analysis of cis-regulatory elements, site-directed mutagenesis of Hox/Pbx binding sites Development High 11566863
2001 Hoxa3 and Pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis: compound mutants show increased apoptosis in the forming primordium, and Gcm2 (parathyroid marker) expression is progressively lost while thymus-specific Foxn1 initiates normally but thymic epithelial cells die. The Hoxa3-Pax1 pathway is required for both epithelial cell growth and differentiation. Compound mutant mice, immunohistochemistry, in situ hybridization for organ-specific markers (Gcm2, Foxn1), apoptosis assays Developmental Biology High 11476574
2002 Hoxa3 is essential for formation of the carotid body; in null mutants, the third arch artery degenerates bilaterally beginning at E10.5, leading to malformation of the carotid artery system and absence of carotid body. Neural crest cell migration to the third arch was not affected. Knockout mouse analysis, histology, immunohistochemistry Developmental Biology High 12074562
2003 Targeted overexpression of Hoxa3 in the rostral hindbrain (r1-4) leads to generation of ectopic somatic motoneurones and repression of the dorsoventral patterning gene Irx3, demonstrating Hoxa3 is sufficient to specify somatic motoneurone identity and acts upstream of Irx3. Heterotopic rhombomere transplantation, targeted overexpression (gain-of-function), in situ hybridization for Irx3 Development Medium 12756180
2004 Hoxa3 null mutation prevents differentiation of the third pharyngeal pouch into the parathyroid rudiment (absence of SP-1/chromogranin A immunoreactivity at E11.5), while neural crest cell migration to surround the third pouch epithelium is unaffected, indicating Hoxa3 acts cell-autonomously in pouch endoderm for parathyroid initiation. Knockout mouse, immunohistochemistry (SP-1/chromogranin A), connexin43-lacZ transgene for neural crest cell visualization Journal of Histochemistry and Cytochemistry Medium 15100241
2005 HOXA3 promotes endothelial cell migration and angiogenesis in vivo, and increases expression of MMP-14 and uPAR genes in endothelial cells in culture and in vivo during wound healing. HOXA3-induced migration of endothelial cells and keratinocytes is uPAR-dependent. Gene transfer of HOXA3 into diabetic mouse wounds improves angiogenesis and wound closure. Gene transfer (in vivo), endothelial cell migration assay, angiogenesis assay in vivo, gene expression analysis (MMP-14, uPAR), uPAR blocking experiments Journal of Cell Science High 15914537
2005 Hoxa3 is required for proliferation and differentiation of the third pharyngeal arch mesenchyme: null mutants show delayed fusion of the third pharyngeal arch with the second and fourth arches, reduced number of proliferating cells in the third arch, and regression of the third arch artery at E11.5. Neural crest cell migration to the third arch is not affected. Knockout mouse with connexin43-lacZ neural crest reporter, BrdU proliferation assay, whole-mount X-gal staining, immunohistochemistry Cell and Tissue Research Medium 15714286
2009 HOXA3 expression in diabetic mouse wounds significantly increases mobilization and recruitment of endothelial progenitor cells (bone marrow-derived) while reducing inflammatory cell recruitment. HOXA3 locally suppresses expression of pro-inflammatory NF-κB pathway members (MyD88, TOLLIP) as identified by microarray. GFP bone marrow chimeras, gene transfer (in vivo), flow cytometry, microarray gene expression analysis Stem Cells Medium 19544454
2010 HoxA3 restrains haematopoietic differentiation of hemogenic endothelium by downregulating key haematopoietic transcription factors including Runx1, Gata1, Gfi1B, Ikaros, and PU.1. Loss-of-function and gain-of-function epistasis experiments showed that Runx1 is uniquely able to erase the endothelial program set up by HoxA3, establishing HoxA3 as an apical regulator of the endothelial-to-hematopoietic transition. Loss-of-function and gain-of-function experiments, epistasis analysis, gene expression profiling, cell fate assays (CD41 marker) Nature Cell Biology High 21170035
2010 Hoxa3 promotes differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells; sustained Hoxa3 expression in diabetic-derived Gr-1+CD11b+ cells reverses their diabetic phenotype (restoring proliferation, chemotaxis, adhesion, and differentiation) and stimulates neovascularization in vivo. Gene transfer (ex vivo and in vivo), flow cytometry, proliferation/chemotaxis/adhesion assays, in vivo angiogenesis assay Blood Medium 20974673
2010 Mouse and zebrafish Hoxa3a proteins have nonequivalent in vivo function: zebrafish hoxa3a expressed from the mouse Hoxa3 locus can substitute for mouse Hoxa3 in some tissues but not others, and the functional difference maps primarily to the C-terminal domain of the protein, as shown by a chimeric protein allele. Knock-in mouse (zebrafish hoxa3a expressed from mouse locus), chimeric protein allele, tissue-specific phenotypic rescue analysis PNAS High 20498049
2014 Tissue-specific deletion experiments show Hoxa3 has distinct cell-autonomous roles: in endoderm, it temporally regulates initiation of the thymus program and is required cell-autonomously for parathyroid differentiation; in neural crest cells, it is primarily required for morphogenesis (organ migration). Expression in either tissue alone is sufficient for organ survival, while simultaneous deletion in both endoderm and NCC leads to athymia similar to the null. Tissue-specific conditional knockout (endoderm-Cre, NCC-Cre, double Cre), lineage analysis with Hoxa3-Cre, marker expression analysis Development High 25249461
2016 Hoxa3 protein transduction in macrophages enhances macrophage maturation, inhibits M1 (classical) polarization, and promotes M2 (alternative) polarization, in part via regulation of Pu.1/Spi1 and Stat6. In vivo, sustained Hoxa3 expression reduces Nos2+ (M1-like) macrophages and increases Arg1+/VEGF+ (M2-like) macrophages in diabetic wounds. This phenotypic switching occurs in a DNA-binding independent manner. Protein transduction in vitro, in vivo gene transfer, flow cytometry, Western blot (Pu.1, Stat6), immunofluorescence (Nos2, Arg1, VEGF) Journal of Immunology Medium 27342843
2016 Comprehensive temporal/spatial analysis shows HOXA3 functions in both cell-autonomous and non-cell-autonomous manners: cell-autonomously in tracheal epithelium, thymus, and parathyroid endodermal cells for differentiation; non-cell-autonomously in NCCs for structures that are Hoxa3-lineage-negative. These defects reflect roles in differentiation and morphogenesis programs rather than positional identity. Temporal conditional knockout (tamoxifen-inducible Cre), tissue-specific Cre, Hoxa3-Cre lineage tracing, marker expression analysis Developmental Biology High 27178667
2017 HoxA3 inhibits the Notch pathway in hemogenic endothelium by inducing upregulation of the Jagged1 (Jag1) ligand, which causes cis-inhibition of Notch signaling, rendering hemogenic endothelial cells non-responsive to Notch signals. Notch activation or Jag1 downregulation is required to downregulate endothelial markers as a prerequisite for endothelial-to-hematopoietic transition (EHT). Gain-of-function (HoxA3 overexpression), Notch pathway activation/inhibition, Jag1 knockdown, gene expression analysis, cell phenotype assays PLoS One Medium 29073173
2019 Diabetic-derived human macrophages show maturation defects associated with reduced RUNX1 expression. Protein transduction of Hoxa3 rescues inflammation and maturation defects in diabetic human macrophages via upregulation of Runx1, and also modulates p65/NF-κB levels, histone acetyltransferase/deacetylase activity, and inhibits acetylation of the TNF promoter. Protein transduction, Western blot (RUNX1, p65/NF-κB), histone acetyltransferase/deacetylase activity assay, chromatin immunoprecipitation (TNF promoter acetylation), flow cytometry PLoS One Medium 31626638
2020 GDF11 promotes HOXA3 expression via Smad2/3 pathway activation, and HOXA3 negatively regulates NLRP3 inflammasome expression; HOXA3 was confirmed as a transcriptional regulator of NLRP3 by ChIP assay, forming a GDF11/Smad2/3/HOXA3/NLRP3 signaling pathway that inhibits cardiomyocyte pyroptosis. ChIP assay, AAV9-mediated gene overexpression in vivo, Western blot (Smad2/3 pathway), gene knockdown/overexpression Cell Death & Disease Medium 33100331
2021 HOXA3 negatively regulates transcription of the HO-1 (heme oxygenase-1) gene; PRRSV induces HOXA3 upregulation, which suppresses HO-1 transcription, thereby weakening HO-1-IRF3 interaction, reducing IRF3 phosphorylation and nuclear translocation, and suppressing type I interferon (IFN-β and ISG) production. Luciferase reporter assay (HO-1 promoter), gene knockdown/overexpression, co-immunoprecipitation (HO-1-IRF3), Western blot (IRF3 phosphorylation, nuclear translocation), viral infection assay Journal of Virology Medium 34851144
2021 The Hoxa3 5'UTR contains an upstream ORF (uORF) that is critical for inhibiting cap-dependent translation of Hoxa3 mRNA, forming a Translation Inhibitory Element (TIE). The non-canonical initiation factor eIF2D is required for this uORF-mediated cap-dependent translation inhibition, while an IRES in the same 5'UTR enables cap-independent translation. In vitro translation assay, uORF mutagenesis, eIF2D requirement experiments, reporter assays eLife High 34076576
2021 HOXA2 and HOXA3 can heterodimerise, which may have functional consequences for HOX patterning in vivo. In vitro binding characterization showed that the highest enriched motif in HOXA2 chromatin peaks is not recognized by HOXA2 in vitro, highlighting the importance of in vivo context for HOX binding specificity. ChIP-seq (in vivo binding), in vitro binding assay (EMSA or equivalent), protein-protein interaction assay for heterodimerization Journal of Developmental Biology Low 34940502
2024 HOXA3 transcriptionally activates USP15 expression (confirmed by ChIP, EMSA, and dual-luciferase reporter assays), and USP15 then deubiquitinates SQSTM1. This HOXA3/USP15/SQSTM1 axis suppresses autophagy (inhibiting autolysosome fusion) and promotes M2-type macrophage polarization in renal cell carcinoma through stimulation of CCL2 secretion. ChIP assay, EMSA, dual-luciferase reporter assay, Co-immunoprecipitation (USP15-SQSTM1 interaction), ubiquitination assay, immunofluorescence (LC3/LAMP2), in vivo xenograft experiment, Western blot American Journal of Physiology Cell Physiology Medium 39740793
2024 HOXA3 regulates the differentiation, proliferation, and migration of third pharyngeal pouch endoderm (3PPE) derived from hESCs, and controls 3PPE commitment through the Wnt signaling pathway by transcriptionally activating EPHB2. hESC differentiation, HOXA3 knockdown, gene expression analysis, Wnt pathway reporter/assay, cell proliferation and migration assays Frontiers in Immunology Medium 38259452
2024 Short WT1 transcripts (sWT1+/-) specifically upregulate HOXA3, and overexpression of HOXA3 alone reproduces the effects of sWT1+/- in AML cells: decreased cell growth, G1 arrest, reduced CD71 expression, and cytarabine resistance, demonstrating HOXA3 as a downstream effector of isoform-specific WT1 in mediating chemotherapy resistance. RNA-seq differential expression, HOXA3 overexpression, flow cytometry (cell cycle, CD71), cytarabine resistance assay British Journal of Haematology Medium 38867543

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The role of Hoxa-3 in mouse thymus and thyroid development. Development (Cambridge, England) 355 7635047
1994 Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Nature 226 7913519
2001 Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Developmental biology 114 11476574
2005 HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair. Journal of cell science 108 15914537
1999 Conserved and distinct roles of kreisler in regulation of the paralogous Hoxa3 and Hoxb3 genes. Development (Cambridge, England) 103 9895323
2001 Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms. Development (Cambridge, England) 85 11566863
2010 HoxA3 is an apical regulator of haemogenic endothelium. Nature cell biology 68 21170035
2020 GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3. Cell death & disease 66 33100331
2019 LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells. Oncogenesis 62 31615976
2000 Hoxa3 and pax1 transcription factors regulate the ability of fetal thymic epithelial cells to promote thymocyte development. Journal of immunology (Baltimore, Md. : 1950) 61 10820253
2019 LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis. Human gene therapy 59 30375256
1998 Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1. Teratology 54 9894676
1996 Rhombomere of origin determines autonomous versus environmentally regulated expression of Hoxa-3 in the avian embryo. Development (Cambridge, England) 54 8631267
2002 Homeobox gene hoxa3 is essential for the formation of the carotid body in the mouse embryos. Developmental biology 53 12074562
2017 HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway. Journal of cellular biochemistry 47 29073728
2003 Somatic motoneurone specification in the hindbrain: the influence of somite-derived signals, retinoic acid and Hoxa3. Development (Cambridge, England) 45 12756180
2014 Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development (Cambridge, England) 38 25249461
2005 Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice. Cell and tissue research 38 15714286
2009 HOXA3 modulates injury-induced mobilization and recruitment of bone marrow-derived cells. Stem cells (Dayton, Ohio) 36 19544454
2010 Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells. Blood 35 20974673
2009 Hoxa3 and signaling molecules involved in aortic arch patterning and remodeling. Cell and tissue research 35 19290546
2003 Disruption of the Hoxa3 homeobox gene results in anomalies of the carotid artery system and the arterial baroreceptors. Cell and tissue research 33 12658442
2018 TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEK/ERK pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 30551418
2018 Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis. International journal of oncology 29 30066858
2004 The role of Hoxa3 gene in parathyroid gland organogenesis of the mouse. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 29 15100241
2016 Enforced Expression of Hoxa3 Inhibits Classical and Promotes Alternative Activation of Macrophages In Vitro and In Vivo. Journal of immunology (Baltimore, Md. : 1950) 28 27342843
2010 Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function. Proceedings of the National Academy of Sciences of the United States of America 28 20498049
2011 A retinoic acid responsive Hoxa3 transgene expressed in embryonic pharyngeal endoderm, cardiac neural crest and a subdomain of the second heart field. PloS one 27 22110697
2021 Induction of HOXA3 by Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Response through Negative Regulation of HO-1 Transcription. Journal of virology 26 34851144
2001 Hoxa3 regulates integration of glossopharyngeal nerve precursor cells. Developmental biology 26 11784044
2019 miR-10b suppresses cell invasion and metastasis through targeting HOXA3 regulated by FAK/YAP signaling pathway in clear-cell renal cell carcinoma. BMC nephrology 23 30975094
2016 Temporal and spatial requirements for Hoxa3 in mouse embryonic development. Developmental biology 20 27178667
2021 ARID1B/SUB1-activated lncRNA HOXA-AS2 drives the malignant behaviour of hepatoblastoma through regulation of HOXA3. Journal of cellular and molecular medicine 18 33683826
2019 Dysregulation of macrophage development and phenotype in diabetic human macrophages can be rescued by Hoxa3 protein transduction. PloS one 18 31626638
2018 Hox genes in the pharyngeal region: how Hoxa3 controls early embryonic development of the pharyngeal organs. The International journal of developmental biology 18 30604847
2020 LINC00689 induces gastric cancer progression via modulating the miR-338-3p/HOXA3 axis. The journal of gene medicine 16 32926751
2016 Chicken gga-miR-130a targets HOXA3 and MDFIC and inhibits Marek's disease lymphoma cell proliferation and migration. Molecular biology reports 16 27178573
2002 Stage-specific changes in fetal thymocyte proliferation during the CD4-8- to CD4+8+ transition in wild type, Rag1-/-, and Hoxa3,Pax1 mutant mice. BMC immunology 11 12241558
2021 Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition. eLife 10 34076576
2007 Expression of homeotic genes Hoxa3, Hoxb3, Hoxd3 and Hoxc4 is decreased in the lungs but not in the hearts of adriamycin-exposed mice. Pediatric surgery international 10 17211587
2011 Chicken HOXA3 gene: its expression pattern and role in branchial nerve precursor cell migration. International journal of biological sciences 9 21278919
2024 HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway. Frontiers in immunology 8 38259452
2019 miR‑338‑3p suppresses the malignancy of T‑cell lymphoblastic lymphoma by downregulating HOXA3. Molecular medicine reports 7 31322185
2023 HOXA3 accelerates wound healing in diabetic and aged non-diabetic mammals. Scientific reports 6 37337031
2014 Secreted HoxA3 Promotes Epidermal Proliferation and Angiogenesis in Genetically Modified Three-Dimensional Composite Skin Constructs. Advances in wound care 6 25302136
2023 ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia. The Malaysian journal of pathology 5 37119247
2024 Epigenetic regulation of HOXA3 and its impact on oral squamous cell carcinoma progression. Oral surgery, oral medicine, oral pathology and oral radiology 4 39658479
2017 Notch activation is required for downregulation of HoxA3-dependent endothelial cell phenotype during blood formation. PloS one 4 29073173
2025 High expression and regulatory mechanisms of ANGPT1 and HOXA3 in acute myeloid leukemia. Bulletin du cancer 3 40107921
2024 Upregulation of HOXA3 by isoform-specific Wilms tumour 1 drives chemotherapy resistance in acute myeloid leukaemia. British journal of haematology 3 38867543
2021 Molecular Characterization of HOXA2 and HOXA3 Binding Properties. Journal of developmental biology 3 34940502
2017 Escapees from Rhombomeric Lineage Restriction: Extensive Migration Rostral to the r4/r5 Border of Hox-a3 Expression. Anatomical record (Hoboken, N.J. : 2007) 3 28667681
2014 The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis. Journal of pediatric endocrinology & metabolism : JPEM 3 24127533
2024 Expression profiling by high-throughput sequencing reveals GADD45, SMAD7, EGR-1 and HOXA3 activation in Myostatin (MSTN) and GDF11 treated myoblasts. Genetics and molecular biology 2 39012095
2026 Acute myeloid leukemia (AML)-derived bone mesenchymal stem cell exosomal METTL14 promotes AML cell growth and glycolysis by HOXA3/WNT7B axis. Cell biology and toxicology 0 41609866
2024 HOXA3 activates USP15 to suppress autophagy and promote M2-type macrophage polarization in renal cell carcinoma via facilitating the deubiquitination of SQSTM1. American journal of physiology. Cell physiology 0 39740793

Missed literature

Know a paper Affinage missed for HOXA3? Flag it for the maintainers and the community.

No submissions yet.