UniProt functional annotation for P20827



	UniProt functional annotation for P20827

UniProt code: P20827.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Plays an important role in angiogenesis and tumor neovascularization. The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Exerts anti-oncogenic effects in tumor cells through activation and down- regulation of EPHA2. Activates EPHA2 by inducing tyrosine phosphorylation which leads to its internalization and degradation. Acts as a negative regulator in the tumorigenesis of gliomas by down- regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal growth cone and regulates dendritic spine morphogenesis. {ECO:0000269|PubMed:17332925, ECO:0000269|PubMed:18794797}.

Subunit: Monomer. Homodimer. Forms heterodimers with EPHA2. Binds to the receptor tyrosine kinases EPHA2, EPHA3, EPHA4, EPHA5, EPHA6 and EPHA7. Also binds with low affinity to EPHA1. {ECO:0000269|PubMed:18794797, ECO:0000269|PubMed:19525919, ECO:0000269|PubMed:20505120}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:18794797}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:18794797}.

Subcellular location: [Ephrin-A1, secreted form]: Secreted {ECO:0000269|PubMed:18794797}.

Tissue specificity: Brain. Down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells (at protein level). {ECO:0000269|PubMed:17332925}.

Induction: By TNF and IL1B/interleukin-1 beta.

Ptm: Undergoes proteolysis by a metalloprotease to give rise to a soluble monomeric form.

Ptm: N-Glycosylation is required for binding to EPHA2 receptor and inducing its internalization. {ECO:0000269|PubMed:23661698}.

Similarity: Belongs to the ephrin family. {ECO:0000255|PROSITE- ProRule:PRU00884}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Plays an important role in angiogenesis and tumor neovascularization. The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Exerts anti-oncogenic effects in tumor cells through activation and down- regulation of EPHA2. Activates EPHA2 by inducing tyrosine phosphorylation which leads to its internalization and degradation. Acts as a negative regulator in the tumorigenesis of gliomas by down- regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal growth cone and regulates dendritic spine morphogenesis. {ECO:0000269\|PubMed:17332925, ECO:0000269\|PubMed:18794797}.


Subunit:		Monomer. Homodimer. Forms heterodimers with EPHA2. Binds to the receptor tyrosine kinases EPHA2, EPHA3, EPHA4, EPHA5, EPHA6 and EPHA7. Also binds with low affinity to EPHA1. {ECO:0000269\|PubMed:18794797, ECO:0000269\|PubMed:19525919, ECO:0000269\|PubMed:20505120}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:18794797}; Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:18794797}.
Subcellular location:		[Ephrin-A1, secreted form]: Secreted {ECO:0000269\|PubMed:18794797}.
Tissue specificity:		Brain. Down-regulated in primary glioma tissues compared to the normal tissues. The soluble monomeric form is expressed in the glioblastoma multiforme (GBM) and breast cancer cells (at protein level). {ECO:0000269\|PubMed:17332925}.
Induction:		By TNF and IL1B/interleukin-1 beta.
Ptm:		Undergoes proteolysis by a metalloprotease to give rise to a soluble monomeric form.
Ptm:		N-Glycosylation is required for binding to EPHA2 receptor and inducing its internalization. {ECO:0000269\|PubMed:23661698}.
Similarity:		Belongs to the ephrin family. {ECO:0000255\|PROSITE- ProRule:PRU00884}.