InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Epha4

Summary

InnateDB Protein

IDBP-172042.6

Last Modified

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

Gene Symbol

Epha4

Protein Name

Eph receptor A4

Synonyms

2900005C20Rik; AI385584; Cek8; Hek8; rb; Sek; Sek1; Tyro1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000027451

InnateDB Gene

IDBG-172040 (Epha4)

Protein Structure

UniProt Annotation

Function

Receptor tyrosine kinase which binds membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. {ECO:0000269PubMed:15537875, ECO:0000269PubMed:16802330, ECO:0000269PubMed:16818734, ECO:0000269PubMed:17143272, ECO:0000269PubMed:17719550, ECO:0000269PubMed:17785183, ECO:0000269PubMed:18094260, ECO:0000269PubMed:18403711, ECO:0000269PubMed:9789074}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:17143272}; Single-pass type I membrane protein {ECO:0000269PubMed:17143272}. Cell projection, axon {ECO:0000269PubMed:17143272}. Cell projection, dendrite {ECO:0000269PubMed:17143272}. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density {ECO:0000250}. Early endosome {ECO:0000269PubMed:17143272}. Note=Clustered upon activation and targeted to early endosome.

Disease Associations

Tissue Specificity

Highest expression in the adult brain and retina and also detectable in kidney, lung, skeletal muscle and thymus. Not detected in heart and liver.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 21 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	21 [view]
Protein-Protein	18 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005003	ephrin receptor activity
GO:0005004	GPI-linked ephrin receptor activity
GO:0005005	transmembrane-ephrin receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042731	PH domain binding
GO:0042802	identical protein binding
GO:0046875	ephrin receptor binding
GO:0097161	DH domain binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007155	cell adhesion
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007411	axon guidance
GO:0007628	adult walking behavior
GO:0008045	motor neuron axon guidance
GO:0008347	glial cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0021957	corticospinal tract morphogenesis
GO:0032314	regulation of Rac GTPase activity
GO:0032317	regulation of Rap GTPase activity
GO:0032319	regulation of Rho GTPase activity
GO:0043507	positive regulation of JUN kinase activity
GO:0046777	protein autophosphorylation
GO:0048013	ephrin receptor signaling pathway
GO:0048681	negative regulation of axon regeneration
GO:0048710	regulation of astrocyte differentiation
GO:0050770	regulation of axonogenesis
GO:0050775	positive regulation of dendrite morphogenesis
GO:0061001	regulation of dendritic spine morphogenesis
GO:0097155	fasciculation of sensory neuron axon
GO:0097156	fasciculation of motor neuron axon
GO:2001108	positive regulation of Rho guanyl-nucleotide exchange factor activity

Cellular Component

GO:0005737	cytoplasm
GO:0005741	mitochondrial outer membrane
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0014069	postsynaptic density
GO:0030054	cell junction
GO:0030175	filopodium
GO:0030424	axon
GO:0030425	dendrite
GO:0031594	neuromuscular junction
GO:0031901	early endosome membrane
GO:0042995	cell projection
GO:0043197	dendritic spine
GO:0043204	perikaryon
GO:0043679	axon terminus
GO:0044295	axonal growth cone
GO:0044297	cell body
GO:0045211	postsynaptic membrane

Protein Structure and Domains

PDB ID

MGI:98277

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
IPR016257 Ephrin receptor type-A /type-B
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR021129 Sterile alpha motif, type 1

PFAM