Protein: Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (rEK4) (Tyrosine-protein kinase TYRO4) (O08680)
Organism: Rattus norvegicus (Rat)
Function: Receptor tyrosine kinase which binds promiscuously 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 for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development (By similarity).
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P29320}; Single-pass type I membrane protein {ECO:0000255}.
Sequence: MDCHLSILILFGCCVLSCSRELSPQPSNEVNLLDSKTIQGELGWISYPSHGWEEISGVDEHYTPIRTYQVCNVMDHSQNNWLRTNWVPRNSAQKIYVELKFTLRDCNSIPLVLGTCKETFNLYYMESDDDHGVKFLEHQFTKIDTIAADESFTQMDLGDRILKLNTEIREVGPVNKKGFYLAFQDVGACVALVSVRVYFKKCPFTVKNLAMFPDTVPMDSQSLVEVRGSCVNNSKEEDPPRMYCSTEGEWLVPIGKCTCNAGYEERGFICQACRPGFYKALDGVAKCTKCPPHSSTQEDGSMNCRCENNYFRAEKDPPSMACTRPPSAPRNVISNINETSVILDWSWPLDTGGRKDITFNIICKKCGWNVRQCEPCSPNVRFLPRQLGLTNTTVTVTDLLAHTNYTFEIDAINGVSELSSPPRQFAAVSITTNQAAPSPVMTIKKDRTSRNSISLSWQEPEHPNGIILDYEVKYYEKQEQETSYTILRARGTNVTISSLKPDTTYVFQIRARTAAGYGTNSRKFEFENSPDSFSISGENSHVVMIAISAAVAIIVLTVVTYVLVGRFCGYHKSKHSSDEKRLHFGNGHLRLPGLRTYVDPHTYEDPTQAVHEFAKELDATNIAIDKVVGAGEFGEVCSGRLKLPSKKEISVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIRLEGVVTKSKPVMIVTEYMENGSLDSFLRKHDAQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPVRWTSPEATAYRKFTSASDVWSYGIVLWEVMSYGERPYWEMSNQDVIKAVDEGYRLPLPMDCPAALYQLMLDCWQKDRNNRPKFEQIVSILDKLIRNPGSLKIITSAAARPSNLLLDQSNVDIATFHTTGDWLNGMRTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVGPQKKIISSIKALETQSKNGPVPV
InterPro domains: - IPR036116: Fibronectin type III superfamily (homologous_superfamily) [325-526]
- IPR050449: Ephrin receptor tyrosine kinases (family) [20-977]
- IPR001426: Tyrosine-protein kinase, receptor class V, conserved site (conserved_site) [183-264]
- IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [622-879]
- IPR034266: Ephrin type-A receptor 3, ligand binding domain (domain) [29-201]
- IPR016257: Ephrin receptor type-A /type-B (family) [1-983]
- IPR001660: Sterile alpha motif domain (domain) [909-976]
- IPR027936: Ephrin receptor, transmembrane domain (domain) [544-619]
- IPR013783: Immunoglobulin-like fold (homologous_superfamily) [326-533]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [623-879]
- IPR001090: Ephrin receptor ligand binding domain (domain) [29-207]
- IPR000719: Protein kinase domain (domain) [622-883]
- IPR009030: Growth factor receptor cysteine-rich domain superfamily (homologous_superfamily) [253-379]
- IPR008979: Galactose-binding-like domain superfamily (homologous_superfamily) [29-201]
- IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [615-913]
- IPR003961: Fibronectin type III (domain) [325-532]
- IPR013761: Sterile alpha motif/pointed domain superfamily (homologous_superfamily) [904-981]
- IPR017441: Protein kinase, ATP binding site (binding_site) [628-654]
- IPR011641: Tyrosine-protein kinase ephrin type A/B receptor-like (domain) [270-303]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [743-755]
Interaction partners: - Ephrin-A5
- Ephrin A2
- Ephrin-A1
- Ephrin-A3
- Tyrosine-protein kinase
- Ephrin-A4
- Ephrin B2
- Ephexin-1
- Ras GTPase-activating protein 1
- Tyrosine-protein kinase.
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0044877 (protein-containing complex binding)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0048856 (anatomical structure development), GO:0048870 (cell motility), GO:0042221 (response to chemical), GO:0051240 (positive regulation of multicellular organismal process), GO:0071840 (cellular component organization or biogenesis), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0065008 (regulation of biological quality), GO:0010496 (intercellular transport), GO:0009607 (response to biotic stimulus), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051707 (response to other organism), GO:0007275 (multicellular organism development), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0051234 (establishment of localization), GO:0002682 (regulation of immune system process), GO:0051094 (positive regulation of developmental process), GO:0048522 (positive regulation of cellular process), GO:0044085 (cellular component biogenesis), GO:0043207 (response to external biotic stimulus), GO:0080134 (regulation of response to stress), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0050803 (regulation of synapse structure or activity), GO:0001817 (regulation of cytokine production), GO:0044089 (positive regulation of cellular component biogenesis), GO:0044087 (regulation of cellular component biogenesis), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0060999 (positive regulation of dendritic spine development), GO:0045595 (regulation of cell differentiation), GO:0016043 (cellular component organization), GO:0051128 (regulation of cellular component organization), GO:0051962 (positive regulation of nervous system development), GO:0016477 (cell migration), GO:0060998 (regulation of dendritic spine development), GO:0050773 (regulation of dendrite development), GO:0045597 (positive regulation of cell differentiation), GO:1903829 (positive regulation of protein localization), GO:0060341 (regulation of cellular localization), GO:0030902 (hindbrain development), GO:1901700 (response to oxygen-containing compound), GO:0051130 (positive regulation of cellular component organization), GO:0071216 (cellular response to biotic stimulus), GO:0010033 (response to organic substance), GO:2000026 (regulation of multicellular organismal development), GO:0050776 (regulation of immune response), GO:1901698 (response to nitrogen compound), GO:0060322 (head development), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0009617 (response to bacterium), GO:0006810 (transport), GO:0001818 (negative regulation of cytokine production), GO:0050795 (regulation of behavior), GO:1901652 (response to peptide), GO:0031347 (regulation of defense response), GO:0061003 (positive regulation of dendritic spine morphogenesis), GO:0050807 (regulation of synapse organization), GO:0002237 (response to molecule of bacterial origin), GO:0050769 (positive regulation of neurogenesis), GO:2000010 (positive regulation of protein localization to cell surface), GO:1904892 (regulation of receptor signaling pathway via STAT), GO:0010468 (regulation of gene expression), GO:0060491 (regulation of cell projection assembly), GO:0022607 (cellular component assembly), GO:0007420 (brain development), GO:0007399 (nervous system development), GO:0007417 (central nervous system development), GO:1901701 (cellular response to oxygen-containing compound), GO:0010629 (negative regulation of gene expression), GO:0002819 (regulation of adaptive immune response), GO:0061024 (membrane organization), GO:1901890 (positive regulation of cell junction assembly), GO:0071417 (cellular response to organonitrogen compound), GO:0022604 (regulation of cell morphogenesis), GO:0071219 (cellular response to molecule of bacterial origin), GO:0032496 (response to lipopolysaccharide), GO:0031344 (regulation of cell projection organization), GO:0071310 (cellular response to organic substance), GO:1901888 (regulation of cell junction assembly), GO:0060284 (regulation of cell development), GO:0010720 (positive regulation of cell development), GO:1901699 (cellular response to nitrogen compound), GO:1900015 (regulation of cytokine production involved in inflammatory response), GO:0021535 (cell migration in hindbrain), GO:0048814 (regulation of dendrite morphogenesis), GO:0032880 (regulation of protein localization), GO:0051960 (regulation of nervous system development), GO:1900016 (negative regulation of cytokine production involved in inflammatory response), GO:0061001 (regulation of dendritic spine morphogenesis), GO:0010243 (response to organonitrogen compound), GO:0051965 (positive regulation of synapse assembly), GO:0031346 (positive regulation of cell projection organization), GO:0033993 (response to lipid), GO:0044091 (membrane biogenesis), GO:0016192 (vesicle-mediated transport), GO:0099173 (postsynapse organization), GO:0034330 (cell junction organization), GO:0007416 (synapse assembly), GO:0071222 (cellular response to lipopolysaccharide), GO:0120032 (regulation of plasma membrane bounded cell projection assembly), GO:0099068 (postsynapse assembly), GO:0002822 (regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains), GO:0046425 (regulation of receptor signaling pathway via JAK-STAT), GO:0034329 (cell junction assembly), GO:0051963 (regulation of synapse assembly), GO:0071709 (membrane assembly), GO:0050767 (regulation of neurogenesis), GO:0010770 (positive regulation of cell morphogenesis involved in differentiation), GO:0099175 (regulation of postsynapse organization), GO:0120035 (regulation of plasma membrane bounded cell projection organization), GO:0001941 (postsynaptic membrane organization), GO:0010976 (positive regulation of neuron projection development), GO:0071396 (cellular response to lipid), GO:0010769 (regulation of cell morphogenesis involved in differentiation), GO:1901653 (cellular response to peptide), GO:1904645 (response to amyloid-beta), GO:0050808 (synapse organization), GO:0050775 (positive regulation of dendrite morphogenesis), GO:2000008 (regulation of protein localization to cell surface), GO:0045216 (cell-cell junction organization), GO:1904646 (cellular response to amyloid-beta), GO:0120193 (tight junction organization), GO:0010975 (regulation of neuron projection development), GO:0007043 (cell-cell junction assembly), GO:0051489 (regulation of filopodium assembly), GO:2000316 (regulation of T-helper 17 type immune response), GO:0120192 (tight junction assembly)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0042995 (cell projection), GO:0098794 (postsynapse), GO:0044297 (cell body), GO:0009986 (cell surface), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0030054 (cell junction), GO:0043025 (neuronal cell body), GO:0005794 (Golgi apparatus), GO:0043197 (dendritic spine), GO:0120025 (plasma membrane bounded cell projection), GO:0097447 (dendritic tree), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0043227 (membrane-bounded organelle), GO:0043005 (neuron projection), GO:0043231 (intracellular membrane-bounded organelle), GO:0098978 (glutamatergic synapse), GO:0030425 (dendrite), GO:0044309 (neuron spine)