EPH receptor A2 (ephrin type-A receptor 2) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''EPHA2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
This gene belongs to the
ephrin
Ephrins (also known as ephrin ligands or Eph family receptor interacting proteins) are a family of proteins that serve as the ligands of the Eph receptor. Eph receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinas ...
receptor subfamily of the protein-
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a
Cys-rich domain and 2
fibronectin
Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...
type III repeats. The ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s. This gene encodes a protein that binds ephrin-A ligands.
Clinical significance
It may be implicated in
BRAF mutated
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
s becoming resistant to BRAF-inhibitors and
MEK inhibitor A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2.
They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical sign ...
s. It is also the receptor by which
Kaposi sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvirus ...
(KSHV) enters host cells; small molecule inhibitors of EphA2 have shown some ability to block KSHV entry into human cells.
Interactions
EPH receptor A2 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
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Ephrin_A1
Ephrin A1 is a protein that in humans is encoded by the ''EFNA1'' gene.
This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been ...
*
ACP1
Low molecular weight phosphotyrosine protein phosphatase is an enzyme that in humans is encoded by the ''ACP1'' gene.
The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phospha ...
*
Grb2,
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PIK3R1
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the ''PIK3R1'' gene.
Function
Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The e ...
,
and
*
SHC1
SHC-transforming protein 1 is a protein that in humans is encoded by the ''SHC1'' gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
SCOP classifies the 3D structure as belonging to th ...
.
[
It was also shown that ]Doxazosin
Doxazosin, sold under the brand names Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate) and hypertension (high blood pressure). For high blood pressure, it is a less preferred option. ...
is a small molecule agonist of EPH receptor A2.
References
Further reading
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External links
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Tyrosine kinase receptors
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