The reference OMIM entry for this protein is 600011

Ephrin receptor ephb4; ephb4
Hepatoma transmembrane kinase; htk
Myk, mouse, homolog of; myk1
Tyro11

CLONING

See 179610 for background on Eph receptors and their ligands, the ephrins. In CD34+ human bone marrow cells and a human hepatocellular carcinoma cell line, Bennett et al. (1994) identified a novel transmembrane tyrosine kinase, which they called hepatoma transmembrane kinase, or HTK. They reported that the predicted 987-amino acid sequence of HTK includes a transmembrane region and signal sequence. The predicted extracellular domain contains a cysteine-rich region and tandem fibronectin type III repeats, while the intracellular domain contains the catalytic domain. Northern blot analysis demonstrated a single HTK transcript abundantly expressed in placenta and in a range of primary tissues and malignant cell lines. It is expressed in fetal, but not adult, brain, and in primitive and myeloid, but not lymphoid, hematopoietic cells. The protein shared amino acid similarity with the Eph subfamily of tyrosine kinases.

GENE FUNCTION

Berclaz et al. (1996) examined the expression of HTK in normal and malignant breast tissue. They found that in normal breast, expression is confined to secretory luminal epithelial cells. They found elevated expression of HTK in several human breast carcinoma cell lines as well as in primary ductal carcinomas of the breast. The authors suggested that HTK may have a role in the differentiation or maintenance of secretory epithelia. Blood vessels form de novo (vasculogenesis) or upon sprouting of capillaries from preexisting blood vessels (angiogenesis). Using high-resolution imaging of zebrafish vascular development, Herbert et al. (2009) uncovered a third mode of blood vessel formation whereby the first embryonic artery and vein, 2 unconnected blood vessels, arise from a common precursor vessel. The first embryonic vein formed by selective sprouting of progenitor cells from the precursor vessel, followed by vessel segregation. Herbert et al. (2009) found that these processes were regulated by the ligand ephrin B2 (600527) and its receptor EphB4, which are expressed in arterial-fated and venous-fated progenitors, respectively, and interact to orient the direction of progenitor migration. Thus, Herbert et al. (2009) concluded that directional control of progenitor migration drives arterial-venous segregation and generation of separate parallel vessels from a single precursor vessel, a process essential for vascular development.

MAPPING

Using 2 independent sets of primers specific for human HTK to amplify DNA from a panel of human-hamster hybrid cell lines, Bennett et al. (1994) demonstrated that the human EPHB4 gene is located on chromosome 7.

ANIMAL MODEL

Gerety et al. (1999) generated mice with a targeted disruption of EphB4 by introducing a tau-lacZ marker into the gene. Unlike the broadly expressed ephrin B2 gene (EFNB2; 600527), EphB4 is uniquely expressed in vascular endothelial and endocardial cells. The authors' analysis also confirmed that EphB4 is preferentially expressed on veins. Remarkably, the phenotype of homozygous EphB4 mutants was virtually symmetric to that of EfnB2 mutants. These data identified EphB4 as the major essential interaction partner of EFNB2 in angiogenesis and further indicated that the requisite function of this receptor is intrinsic to the circulatory system. In addition, these data indicated that EFNB2 and EphB4 mediate reciprocal interactions between arteries and veins that are essential for proper angiogenic remodeling of the ca ... More on the omim web site

Subscribe to this protein entry history

June 7, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 600011 was added.