InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EPHA2

Summary

InnateDB Protein

IDBP-91411.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EPHA2

Protein Name

EPH receptor A2

Synonyms

ARCC2; CTPA; CTPP1; CTRCT6; ECK;

Species

Homo sapiens

Ensembl Protein

ENSP00000351209

InnateDB Gene

IDBG-91407 (EPHA2)

Protein Structure

UniProt Annotation

Function

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand- independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269PubMed:10655584, ECO:0000269PubMed:16236711, ECO:0000269PubMed:18339848, ECO:0000269PubMed:19573808, ECO:0000269PubMed:20679435, ECO:0000269PubMed:20861311, ECO:0000269PubMed:23358419}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Cell projection, ruffle membrane; Single-pass type I membrane protein. Cell projection, lamellipodium membrane; Single- pass type I membrane protein. Cell junction, focal adhesion. Note=Present at regions of cell-cell contacts but also at the leading edge of migrating cells.

Disease Associations

Cataract 6, multiple types (CTRCT6) [MIM:116600]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age- related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision. {ECO:0000269PubMed:19005574, ECO:0000269PubMed:19306328, ECO:0000269PubMed:19649315}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Overexpressed in several cancer types and promotes malignancy. {ECO:0000269PubMed:19573808}.

Tissue Specificity

Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g. skin, intestine, lung, and ovary. {ECO:0000269PubMed:17332925}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 49 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	49 [view]
Protein-Protein	47 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005003	ephrin receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0001501	skeletal system development
GO:0001525	angiogenesis
GO:0001568	blood vessel development
GO:0001570	vasculogenesis
GO:0001649	osteoblast differentiation
GO:0006468	protein phosphorylation
GO:0007155	cell adhesion
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007275	multicellular organismal development
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010591	regulation of lamellipodium assembly
GO:0014028	notochord formation
GO:0016032	viral process
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0021915	neural tube development
GO:0030182	neuron differentiation
GO:0030216	keratinocyte differentiation
GO:0030316	osteoclast differentiation
GO:0032863	activation of Rac GTPase activity
GO:0033598	mammary gland epithelial cell proliferation
GO:0033628	regulation of cell adhesion mediated by integrin
GO:0036342	post-anal tail morphogenesis
GO:0043491	protein kinase B signaling
GO:0043535	regulation of blood vessel endothelial cell migration
GO:0045765	regulation of angiogenesis
GO:0046849	bone remodeling
GO:0048013	ephrin receptor signaling pathway
GO:0048320	axial mesoderm formation
GO:0048570	notochord morphogenesis
GO:0051898	negative regulation of protein kinase B signaling
GO:0060035	notochord cell development
GO:0060326	cell chemotaxis
GO:0060444	branching involved in mammary gland duct morphogenesis
GO:0070309	lens fiber cell morphogenesis
GO:0070372	regulation of ERK1 and ERK2 cascade
GO:0070848	response to growth factor
GO:0090004	positive regulation of establishment of protein localization to plasma membrane

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005925	focal adhesion
GO:0031256	leading edge membrane
GO:0031258	lamellipodium membrane
GO:0032587	ruffle membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001090 Ephrin receptor ligand binding domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001660 Sterile alpha motif domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003961 Fibronectin, type III
IPR008979 Galactose-binding domain-like
IPR009030 Insulin-like growth factor binding protein, N-terminal
IPR011009 Protein kinase-like domain
IPR011510 Sterile alpha motif, type 2
IPR013761 Sterile alpha motif/pointed domain
IPR015373 Interferon alpha/beta receptor, beta chain
IPR016257 Ephrin receptor type-A /type-B
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR021129 Sterile alpha motif, type 1

PFAM