Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Electronic Gene Ontology annotations created by ARBA machine learning models
Impact of cytosine methylation on DNA binding specificities of human transcription factors.
The homeoprotein Alx3 expressed in pancreatic beta-cells regulates insulin gene transcription by interacting with the basic helix-loop-helix protein E47.
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Mouse Alx3 occupies insulin-promoter chromatin and activates a defined regulatory element with E47; these experiments support the conserved transcriptional mechanism without assigning a measured human target promoter.
"Alx3 transactivates the insulin
promoter by acting on the E2A3/4 enhancer"
Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by recessive mutations in the ALX3 homeobox gene.
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Seven families with homozygous ALX3 variants establish a human craniofacial disease association. The reported loss of function is predicted from the variant classes, not a direct DNA-binding assay in this study.
"In total, we identified seven different homozygous
pathogenic mutations in seven families."
Alx3-deficient mice exhibit folic acid-resistant craniofacial midline and neural tube closure defects.
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Alx3 loss affects cranial neural-tube closure and survival of head-region cells in mice. These outcomes do not by themselves identify a neuron-maturation step.
"Alx3-deficient mice exhibit increased failure of cranial neural tube closure and
increased cell death in the craniofacial region"
DNA binding analysis of rare variants in homeodomains reveals homeodomain specificity-determining residues.
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Human ALX3 homeodomain protein-binding microarray measurements detect reduced DNA affinity for L168V. The assay uses an isolated GST-fusion DNA-binding domain and does not measure full-length occupancy in human cells.
"ALX3 L168V shows reduced affinity across all significantly bound 8-mers."
Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.
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The adult constitutive mouse-knockout study links Alx3 to metabolic regulation and identifies arcuate-neuron expression; neuron-specific causal attribution remains to be established.
"the use of a constitutive knock out model represents a limitation"