| 68926 | HoxA2 Symbol and Name Change | Dracheva, S., LocusLink Nomenclature Update. October 2001 | We have all reasons to believe that locus locus 24452 (RGD id 2813, RATMAP id 34054) for Hoxa11 must be renamed Hoxa2 (please see message below). Blast of the sequence M91802 gives best alignment with mouse Hoxa2 and Human HOXA2 sequences.
The LL page is called rat Hoxa11 (LocusID: 24452), and my curator says it
should be called rat Hoxa2. This protein is, in sequence and in function,
homologous to human (LocusID: 3199) and mouse (LocusID: 15399) Hoxa2.
There are three papers describing this rat protein, none of which call it
Hoxa11, all call it either Hoxa2 or the alternate name for Hoxa2 which is
Hox1.11. These are:
BioTechniques 16 (5), 856-858, 1994 (LL cloning paper)
J. Biol. Chem. 267 (36), 26085-26090 (1992) (Unigene cloning paper)
Dev Dyn 1996 Sep;207(1):47-59 (found by curator) | | 2001-10-01 |
| 11055832 | Molecular Analysis of the HOXA2-Dependent Degradation of RCHY1. | Bridoux L, etal., PLoS One. 2015 Oct 23;10(10):e0141347. doi: 10.1371/journal.pone.0141347. eCollection 2015. | The homeodomain transcription factor Hoxa2 interacts with the RING-finger type E3 ubiquitin ligase RCHY1 and induces its proteasomal degradation. In this work, we dissected this non-transcriptional activity of Hoxa2 at the molecular level. The Hoxa2-mediated decay of RCHY1 involves both the 19S and 20S proteasome complexes. It relies on both the Hoxa2 homeodomain and C-terminal moiety although no single deletion in the Hoxa2 sequence could disrupt the RCHY1 interaction. That the Hoxa2 homeodomain alone could mediate RCHY1 binding is consistent with the shared ability all the Hox proteins we tested to interact with RCHY1. Nonetheless, the ability to induce RCHY1 degradation although critically relying on the homeodomain is not common to all Hox proteins. This identifies the homeodomain as necessary but not sufficient for what appears to be an almost generic Hox protein activity. Finally we provide evidence that the Hoxa2-induced degradation of RCHY1 is evolutionarily conserved among vertebrates. These data therefore support the hypothesis that the molecular and functional interaction between Hox proteins and RCHY1 is an ancestral Hox property. | 26496426 | 1000-04-01 |
| 11344157 | KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity. | Bridoux L, etal., Biochim Biophys Acta. 2015 Oct;1849(10):1298-311. doi: 10.1016/j.bbagrm.2015.08.006. Epub 2015 Aug 21. | Regulation of transcription factor activity relies on molecular interactions or enzymatic modifications which influence their interaction with DNA cis-regulatory sequences, their transcriptional activation or repression, and stability or intracellular distribution of these proteins. Regarding the we ll-conserved Hox protein family, a restricted number of activity regulators have been highlighted thus far. In the framework of a proteome-wide screening aiming at identifying proteins interacting with Hoxa2, KPC2, an adapter protein constitutive of the KPC ubiquitin-ligase complex, was identified. In this work, KPC2 was confirmed as being a genuine interactor of Hoxa2 by co-precipitation and bimolecular fluorescence complementation assays. At functional level, KPC2 diminishes the transcriptional activity and induces the nuclear exit of Hoxa2. Gene expression analyses revealed that Kpc2 is active in restricted areas of the developing mouse embryo which overlap with the Hoxa2 expression domain. Together, our data support that KPC2 regulates Hoxa2 by promoting its relocation to the cytoplasm. | 26303204 | 2015-07-01 |
| 11553827 | A mutation in HOXA2 is responsible for autosomal-recessive microtia in an Iranian family. | Alasti F, etal., Am J Hum Genet. 2008 Apr;82(4):982-91. doi: 10.1016/j.ajhg.2008.02.015. | Microtia, a congenital deformity manifesting as an abnormally shaped or absent external ear, occurs in one out of 8,000-10,000 births. We ascertained a consanguineous Iranian family segregating with autosomal-recessive bilateral microtia, mixed symmetrical severe to profound hearing impairment, and partial cleft palate. Genome-wide linkage analysis localized the responsible gene to chromosome 7p14.3-p15.3 with a maximum multi-point LOD score of 4.17. In this region, homeobox genes from the HOXA cluster were the most interesting candidates. Subsequent DNA sequence analysis of the HOXA1 and HOXA2 homeobox genes from the candidate region identified an interesting HOXA2 homeodomain variant: a change in a highly conserved amino acid (p.Q186K). The variant was not found in 231 Iranian and 109 Belgian control samples. The critical contribution of HoxA2 for auditory-system development has already been shown in mouse models. We built a homology model to predict the effect of this mutation on the structure and DNA-binding activity of the homeodomain by using the program Modeler 8v2. In the model of the mutant homeodomain, the position of the mutant lysine side chain is consistently farther away from a nearby phosphate group; this altered position results in the loss of a hydrogen bond and affects the DNA-binding activity. | 18394579 | 2008-10-01 |
| 598118358 | Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non-syndromic microtia and distinctive ear morphology. | Piceci F, etal., Clin Genet. 2017 May;91(5):774-779. doi: 10.1111/cge.12845. Epub 2016 Sep 13. | Microtia is a congenital defect affecting external ears, which appear smaller and sometimes malformed. Here we describe a five-generation family with isolated bilateral microtia segregating as an autosomal dominant trait. Similar features have been previously observed in an autosomal dominant family with non-syndromic microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2 biallelic mutations were also described in an inbreed family with autosomal recessive microtia, hearing impairment and incomplete cleft palate. In our family, sequence analysis detected a heterozygous protein truncating nonsense variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and absent in public databases. This study confirms the role of HOXA2 gene in dominant isolated microtia and contribute to further define the dysmorphogenetic effect of this gene on ear development. | 27503514 | 2017-05-01 |
