UniProt functional annotation for P54763



	UniProt functional annotation for P54763

UniProt code: P54763.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (By similarity). {ECO:0000250|UniProtKB:P29323, ECO:0000269|PubMed:10839360, ECO:0000269|PubMed:14691139, ECO:0000269|PubMed:15223334, ECO:0000269|PubMed:21029865, ECO:0000269|PubMed:8689685, ECO:0000269|PubMed:8947026, ECO:0000269|PubMed:9990854}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};

Subunit: Heterotetramer upon binding of the ligand (PubMed:11780069). The heterotetramer is composed of an ephrin dimer and a receptor dimer (PubMed:11780069). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (PubMed:9883737). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome (PubMed:21029865). Interacts with AQP1; involved in endolymph production in the inner ear (PubMed:10839360). Interacts with EFNA5 (PubMed:15107857). Interacts with SPSB1 (By similarity). Interacts with SPSB4 (PubMed:28931592). Interacts with SH2D3C (PubMed:10542222). {ECO:0000250|UniProtKB:P29323, ECO:0000269|PubMed:10542222, ECO:0000269|PubMed:10839360, ECO:0000269|PubMed:11780069, ECO:0000269|PubMed:15107857, ECO:0000269|PubMed:21029865, ECO:0000269|PubMed:28931592, ECO:0000269|PubMed:9883737}.

Subcellular location: Cell membrane; Single-pass type I membrane protein. Cell projection, axon. Cell projection, dendrite.

Tissue specificity: Expressed in the epithelial dark cells of the inner ear. Expressed in the region of the proximal tubules of the kidney nephron. Expressed in myogenic progenitor cells (PubMed:27446912). {ECO:0000269|PubMed:10839360, ECO:0000269|PubMed:27446912}.

Developmental stage: Highly expressed in ventral cells of the neural tube and within axons of the peripheral nervous system during development. Expressed in the vestibulo-acoustic system and hindbrain as early as 11.5 dpc. Detected in the spinal cord at 12 dpc. Expressed in cells of the developing outer retina. Also expressed in mesenchyme adjacent to vessels. In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912). {ECO:0000269|PubMed:10704386, ECO:0000269|PubMed:10839360, ECO:0000269|PubMed:27446912, ECO:0000269|PubMed:8689685, ECO:0000269|PubMed:9990854}.

Ptm: Autophosphorylated; ligand binding stimulates autophosphorylation on tyrosine residues. {ECO:0000269|PubMed:17428795}.

Ptm: Polyubiquitinated; ligand binding stimulates ubiquitination. {ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:28931592}.

Ptm: Ligand binding induces cleavage by matrix metalloproteinases (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved by MMPs, producing EphB2/CTF1 which is further cleaved by the PS1/gamma-secretase producing EphB2/CTF2. {ECO:0000269|PubMed:17428795}.

Disruption phenotype: Mice are long-lived and fertile. They display strain-specific circling behavior, are hyperactive and exhibit rapid head bobbing and twirled excessively when picked-up by the tail. This is probably due to abnormal vestibular function. {ECO:0000269|PubMed:10839360, ECO:0000269|PubMed:8689685}.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.

Sequence caution: Sequence=AAA72411.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH62924.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (By similarity). {ECO:0000250\|UniProtKB:P29323, ECO:0000269\|PubMed:10839360, ECO:0000269\|PubMed:14691139, ECO:0000269\|PubMed:15223334, ECO:0000269\|PubMed:21029865, ECO:0000269\|PubMed:8689685, ECO:0000269\|PubMed:8947026, ECO:0000269\|PubMed:9990854}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028};
Subunit:		Heterotetramer upon binding of the ligand (PubMed:11780069). The heterotetramer is composed of an ephrin dimer and a receptor dimer (PubMed:11780069). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (PubMed:9883737). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome (PubMed:21029865). Interacts with AQP1; involved in endolymph production in the inner ear (PubMed:10839360). Interacts with EFNA5 (PubMed:15107857). Interacts with SPSB1 (By similarity). Interacts with SPSB4 (PubMed:28931592). Interacts with SH2D3C (PubMed:10542222). {ECO:0000250\|UniProtKB:P29323, ECO:0000269\|PubMed:10542222, ECO:0000269\|PubMed:10839360, ECO:0000269\|PubMed:11780069, ECO:0000269\|PubMed:15107857, ECO:0000269\|PubMed:21029865, ECO:0000269\|PubMed:28931592, ECO:0000269\|PubMed:9883737}.
Subcellular location:		Cell membrane; Single-pass type I membrane protein. Cell projection, axon. Cell projection, dendrite.
Tissue specificity:		Expressed in the epithelial dark cells of the inner ear. Expressed in the region of the proximal tubules of the kidney nephron. Expressed in myogenic progenitor cells (PubMed:27446912). {ECO:0000269\|PubMed:10839360, ECO:0000269\|PubMed:27446912}.
Developmental stage:		Highly expressed in ventral cells of the neural tube and within axons of the peripheral nervous system during development. Expressed in the vestibulo-acoustic system and hindbrain as early as 11.5 dpc. Detected in the spinal cord at 12 dpc. Expressed in cells of the developing outer retina. Also expressed in mesenchyme adjacent to vessels. In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912). {ECO:0000269\|PubMed:10704386, ECO:0000269\|PubMed:10839360, ECO:0000269\|PubMed:27446912, ECO:0000269\|PubMed:8689685, ECO:0000269\|PubMed:9990854}.
Ptm:		Autophosphorylated; ligand binding stimulates autophosphorylation on tyrosine residues. {ECO:0000269\|PubMed:17428795}.
Ptm:		Polyubiquitinated; ligand binding stimulates ubiquitination. {ECO:0000269\|PubMed:17428795, ECO:0000269\|PubMed:28931592}.
Ptm:		Ligand binding induces cleavage by matrix metalloproteinases (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved by MMPs, producing EphB2/CTF1 which is further cleaved by the PS1/gamma-secretase producing EphB2/CTF2. {ECO:0000269\|PubMed:17428795}.
Disruption phenotype:		Mice are long-lived and fertile. They display strain-specific circling behavior, are hyperactive and exhibit rapid head bobbing and twirled excessively when picked-up by the tail. This is probably due to abnormal vestibular function. {ECO:0000269\|PubMed:10839360, ECO:0000269\|PubMed:8689685}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Sequence caution:		Sequence=AAA72411.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH62924.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};