UniProt functional annotation for P54762



	UniProt functional annotation for P54762

UniProt code: P54762.

Organism: Homo sapiens (Human).

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

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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}.

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. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts with EPHB6; transphosphorylates EPHB6 to form an active signaling complex. Interacts with PICK1 (By similarity). Interacts (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade to regulate cell adhesion (By similarity). The ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The ligand-activated form interacts (residues within the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell migration. Interacts with CBL; regulates receptor degradation through ubiquitination. Interacts with ACP1. {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:11713248, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:8798570, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:18034775}; Single-pass type I membrane protein {ECO:0000269|PubMed:18034775}. Early endosome membrane {ECO:0000269|PubMed:18034775}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q8CBF3}.

Tissue specificity: Preferentially expressed in brain.

Ptm: Phosphorylated. Autophosphorylation is stimulated by the ligand EFNB1. Required for interaction with SH2 domain-containing interactors, for activation of the MAPK/ERK and JUN signaling cascades and for ubiquitination by CBL. {ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:8798570}.

Ptm: Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi- ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation. {ECO:0000269|PubMed:18034775}.

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

Sequence caution: Sequence=AAB94627.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305}; Sequence=AAB94628.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305}; Sequence=AAD02031.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};

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:		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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250\|UniProtKB:Q8CBF3, ECO:0000269\|PubMed:12223469, ECO:0000269\|PubMed:12925710, ECO:0000269\|PubMed:18034775, ECO:0000269\|PubMed:9430661, ECO:0000269\|PubMed:9499402}.


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. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts with EPHB6; transphosphorylates EPHB6 to form an active signaling complex. Interacts with PICK1 (By similarity). Interacts (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade to regulate cell adhesion (By similarity). The ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The ligand-activated form interacts (residues within the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell migration. Interacts with CBL; regulates receptor degradation through ubiquitination. Interacts with ACP1. {ECO:0000250\|UniProtKB:Q8CBF3, ECO:0000269\|PubMed:11713248, ECO:0000269\|PubMed:12223469, ECO:0000269\|PubMed:12925710, ECO:0000269\|PubMed:18034775, ECO:0000269\|PubMed:8798570, ECO:0000269\|PubMed:9430661, ECO:0000269\|PubMed:9499402}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:18034775}; Single-pass type I membrane protein {ECO:0000269\|PubMed:18034775}. Early endosome membrane {ECO:0000269\|PubMed:18034775}. Cell projection, dendrite {ECO:0000250\|UniProtKB:Q8CBF3}.
Tissue specificity:		Preferentially expressed in brain.
Ptm:		Phosphorylated. Autophosphorylation is stimulated by the ligand EFNB1. Required for interaction with SH2 domain-containing interactors, for activation of the MAPK/ERK and JUN signaling cascades and for ubiquitination by CBL. {ECO:0000269\|PubMed:12223469, ECO:0000269\|PubMed:18034775, ECO:0000269\|PubMed:8798570}.
Ptm:		Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi- ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation. {ECO:0000269\|PubMed:18034775}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Sequence caution:		Sequence=AAB94627.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305}; Sequence=AAB94628.1; Type=Miscellaneous discrepancy; Note=wrong intron-exon boundaries.; Evidence={ECO:0000305}; Sequence=AAD02031.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};