Homeobox protein engrailed-2 is a protein that in humans is encoded by the EN2 gene. [5] It is a member of the engrailed gene family.
Homeobox-containing genes are thought to have a role in controlling development. In Drosophila , the 'engrailed' (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system. [5]
The Engrailed-2 gene encodes for the Engrailed-2 homeobox transcription factor. The signaling molecule, fibroblast growth factor 8 (FGF8), controls the expression of the En2 gene. The isthmus organizer expresses varying concentrations of FGF8 that influence the En2 transcription factor. En2 transcription factor is involved in patterning the midbrain of the central nervous system during embryonic development. Specifically, it is required for proper positioning of folia in the developing hemispheres. It continues to regulate foliation throughout nervous system development. En2 patterns cerebellum foliation in the mediolateral axis. Several birth defects can arise from inadequate or abnormal En2 expression. Scientists use a mice model to study the effects of En2 knockout alleles on development. When the En2 gene is knocked out, vermis foliation patterning becomes extremely altered. Along with decreased cerebellum foliation complexity, mutations in the En2 gene result in a depleted vermis or an overly simplified foliation pattern. The Engrailed genes are essential to proper neural circuit development.
A method for diagnosing prostate cancer by detection of EN2 in urine has been developed. The results of a clinical trial of 288 men suggest that EN2 could be a marker for prostate cancer which might prove more reliable than current methods that use prostate-specific antigen (PSA). If effective, a urine test is considered easier and less embarrassing for the patient than blood tests or rectal examinations and, therefore, less likely to discourage early diagnosis. At the time of the report, it was not clear whether or not the EN2 test could distinguish between aggressive tumours that would require intervention and relatively benign ones that would not. [6]
The EN2 test for prostate cancer has been licensed to Zeus Scientific, as they reported in March 2013. In that announcement they said they expected the test to be submitted to the US-FDA in a year, [7] and available worldwide in 2 years. [8]
However, an independent study published in 2020 questioned the value of EN2 as a urinary marker for prostate cancer. [9] In a comparison between 90 PC patients and 30 healthy subjects, their results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice. Despite their announcement of new clinical trial in 2018, [10] the developers of the urinary EN2 test at the University of Surrey never registered such a trial at ClinicalTrials.gov or published any results of it. [11] Also, Randox Ltd, the diagnostic company which was to commercialize the urinary EN2, does not offer it any more in their product portfolio.
T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.
Homeobox protein MSX-1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and is responsive to thyroid hormone. MSX1 is also expressed in highly differentiated pituitary cells which until recently was thought to be expressed exclusively during embryogenesis. There is a highly conserved structural organization of the members of the MSX family of genes and their abundant expression at sites of inductive cell–cell interactions in the embryo suggest that they have a pivotal role during early development.
Homeobox protein Nkx-3.1, also known as NKX3-1, NKX3, BAPX2, NKX3A and NKX3.1 is a protein that in humans is encoded by the NKX3-1 gene located on chromosome 8p. NKX3-1 is a prostatic tumor suppressor gene.
Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.
Homeobox protein Hox-A1 is a protein that in humans is encoded by the HOXA1 gene.
Homeobox D10, also known as HOXD10, is a protein which in humans is encoded by the HOXD10 gene.
Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.
Homeobox protein Hox-A11 is a protein that in humans is encoded by the HOXA11 gene.
Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene and also known as Proline Rich Homeodomain protein PRH.
Homeobox protein Hox-C8 is a protein that in humans is encoded by the HOXC8 gene.
Homeobox protein Hox-A13 is a protein that in humans is encoded by the HOXA13 gene.
Homeobox protein Hox-B9 is a protein that in humans is encoded by the HOXB9 gene.
Paired-like homeodomain 1 is a protein that in humans is encoded by the PITX1 gene.
Homeobox protein Hox-B13 is a protein that in humans is encoded by the HOXB13 gene.
Homeobox protein Hox-C6 is a protein that in humans is encoded by the HOXC6 gene. Hox-C6 expression is highest in the fallopian tube and ovary. HoxC6 has been highly expressed in many types of cancers including prostate, breast, and esophageal squamous cell cancer.
Homeobox protein Emx2 is a protein that in humans is encoded by the EMX2 gene.
Homeobox protein engrailed-1 is a protein that in humans is encoded by the EN1 gene.
Homeobox protein goosecoid(GSC) is a homeobox protein that is encoded in humans by the GSC gene. Like other homeobox proteins, goosecoid functions as a transcription factor involved in morphogenesis. In Xenopus, GSC is thought to play a crucial role in the phenomenon of the Spemann-Mangold organizer. Through lineage tracing and timelapse microscopy, the effects of GSC on neighboring cell fates could be observed. In an experiment that injected cells with GSC and observed the effects of uninjected cells, GSC recruited neighboring uninjected cells in the dorsal blastopore lip of the Xenopus gastrula to form a twinned dorsal axis, suggesting that the goosecoid protein plays a role in the regulation and migration of cells during gastrulation.
Homeobox protein GBX-2 is a protein that in humans is encoded by the GBX2 gene.
Iroquois-class homeodomain protein IRX-5, also known as Iroquois homeobox protein 5, is a protein that in humans is encoded by the IRX5 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.