Protein: Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) (P29320)
Organism: Homo sapiens (Human)
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.
Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:11870224}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000269|PubMed:21135139}.
Sequence: MDCQLSILLLLSCSVLDSFGELIPQPSNEVNLLDSKTIQGELGWISYPSHGWEEISGVDEHYTPIRTYQVCNVMDHSQNNWLRTNWVPRNSAQKIYVELKFTLRDCNSIPLVLGTCKETFNLYYMESDDDHGVKFREHQFTKIDTIAADESFTQMDLGDRILKLNTEIREVGPVNKKGFYLAFQDVGACVALVSVRVYFKKCPFTVKNLAMFPDTVPMDSQSLVEVRGSCVNNSKEEDPPRMYCSTEGEWLVPIGKCSCNAGYEERGFMCQACRPGFYKALDGNMKCAKCPPHSSTQEDGSMNCRCENNYFRADKDPPSMACTRPPSSPRNVISNINETSVILDWSWPLDTGGRKDVTFNIICKKCGWNIKQCEPCSPNVRFLPRQFGLTNTTVTVTDLLAHTNYTFEIDAVNGVSELSSPPRQFAAVSITTNQAAPSPVLTIKKDRTSRNSISLSWQEPEHPNGIILDYEVKYYEKQEQETSYTILRARGTNVTISSLKPDTIYVFQIRARTAAGYGTNSRKFEFETSPDSFSISGESSQVVMIAISAAVAIILLTVVIYVLIGRFCGYKSKHGADEKRLHFGNGHLKLPGLRTYVDPHTYEDPTQAVHEFAKELDATNISIDKVVGAGEFGEVCSGRLKLPSKKEISVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIRLEGVVTKSKPVMIVTEYMENGSLDSFLRKHDAQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPIRWTSPEAIAYRKFTSASDVWSYGIVLWEVMSYGERPYWEMSNQDVIKAVDEGYRLPPPMDCPAALYQLMLDCWQKDRNNRPKFEQIVSILDKLIRNPGSLKIITSAAARPSNLLLDQSNVDITTFRTTGDWLNGVWTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVGPQKKIISSIKALETQSKNGPVPV
InterPro domains: - IPR036116: Fibronectin type III superfamily (homologous_superfamily) [325-530]
- IPR050449: Ephrin receptor tyrosine kinases (family) [22-976]
- IPR001426: Tyrosine-protein kinase, receptor class V, conserved site (conserved_site) [183-264]
- IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [621-878]
- IPR034266: Ephrin type-A receptor 3, ligand binding domain (domain) [29-201]
- IPR016257: Ephrin receptor type-A /type-B (family) [1-982]
- IPR001660: Sterile alpha motif domain (domain) [908-975]
- IPR027936: Ephrin receptor, transmembrane domain (domain) [545-618]
- IPR013783: Immunoglobulin-like fold (homologous_superfamily) [326-534]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [622-878]
- IPR001090: Ephrin receptor ligand binding domain (domain) [29-207]
- IPR000719: Protein kinase domain (domain) [621-882]
- 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) [614-915]
- IPR003961: Fibronectin type III (domain) [325-531]
- IPR013761: Sterile alpha motif/pointed domain superfamily (homologous_superfamily) [903-980]
- IPR017441: Protein kinase, ATP binding site (binding_site) [627-653]
- IPR011641: Tyrosine-protein kinase ephrin type A/B receptor-like (domain) [269-303]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [742-754]
Interaction partners: - Ephrin-A5
- Ephrin-B2
- Ephrin-A2
- Ephrin-A1
- Ephrin-A3
- Ephrin-A4
- Tyrosine-protein kinase ABL1
- Ephrin-B3
- Ephexin-1
- Ephrin type-A receptor 7
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0040011 (locomotion), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0051641 (cellular localization), GO:0023057 (negative regulation of signaling), GO:0048870 (cell motility), GO:0042221 (response to chemical), GO:0042330 (taxis), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0033036 (macromolecule localization), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0008219 (cell death), GO:0040017 (positive regulation of locomotion), 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:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0040012 (regulation of locomotion), GO:0048522 (positive regulation of cellular process), GO:0050790 (regulation of catalytic activity), GO:0009968 (negative regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:1903829 (positive regulation of protein localization), GO:0012501 (programmed cell death), GO:0044093 (positive regulation of molecular function), GO:1901564 (organonitrogen compound metabolic process), GO:2000145 (regulation of cell motility), GO:0035556 (intracellular signal transduction), GO:0030154 (cell differentiation), GO:0046483 (heterocycle metabolic process), GO:0060341 (regulation of cellular localization), GO:0019637 (organophosphate metabolic process), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0030155 (regulation of cell adhesion), GO:0051130 (positive regulation of cellular component organization), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0051668 (localization within membrane), GO:0044089 (positive regulation of cellular component biogenesis), GO:2000147 (positive regulation of cell motility), GO:1901135 (carbohydrate derivative metabolic process), GO:0044087 (regulation of cellular component biogenesis), GO:0006793 (phosphorus metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0009888 (tissue development), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0055086 (nucleobase-containing small molecule metabolic process), GO:0097190 (apoptotic signaling pathway), GO:0070727 (cellular macromolecule localization), GO:0007166 (cell surface receptor signaling pathway), GO:0051128 (regulation of cellular component organization), GO:0006935 (chemotaxis), GO:0016477 (cell migration), GO:1901890 (positive regulation of cell junction assembly), GO:0043491 (protein kinase B signaling), GO:0006753 (nucleoside phosphate metabolic process), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:1904377 (positive regulation of protein localization to cell periphery), GO:0031344 (regulation of cell projection organization), GO:0006974 (cellular response to DNA damage stimulus), GO:0051336 (regulation of hydrolase activity), GO:1901888 (regulation of cell junction assembly), GO:0006796 (phosphate-containing compound metabolic process), GO:0032880 (regulation of protein localization), GO:1902532 (negative regulation of intracellular signal transduction), GO:0043588 (skin development), GO:0030334 (regulation of cell migration), GO:0072521 (purine-containing compound metabolic process), GO:1905477 (positive regulation of protein localization to membrane), GO:0060491 (regulation of cell projection assembly), GO:0030855 (epithelial cell differentiation), GO:0060326 (cell chemotaxis), GO:0072657 (protein localization to membrane), GO:0008544 (epidermis development), GO:0019693 (ribose phosphate metabolic process), GO:0006915 (apoptotic process), GO:0030335 (positive regulation of cell migration), GO:0097193 (intrinsic apoptotic signaling pathway), GO:0033628 (regulation of cell adhesion mediated by integrin), GO:0008104 (protein localization), GO:0043085 (positive regulation of catalytic activity), GO:0060429 (epithelium development), GO:1902531 (regulation of intracellular signal transduction), GO:0043408 (regulation of MAPK cascade), GO:0120032 (regulation of plasma membrane bounded cell projection assembly), GO:1905475 (regulation of protein localization to membrane), GO:0009117 (nucleotide metabolic process), GO:0120035 (regulation of plasma membrane bounded cell projection organization), GO:1990778 (protein localization to cell periphery), GO:0009259 (ribonucleotide metabolic process), GO:0051898 (negative regulation of protein kinase B signaling), GO:0043087 (regulation of GTPase activity), GO:0008630 (intrinsic apoptotic signaling pathway in response to DNA damage), GO:0051896 (regulation of protein kinase B signaling), GO:0030216 (keratinocyte differentiation), GO:0007169 (transmembrane receptor protein tyrosine kinase signaling pathway), GO:2000810 (regulation of bicellular tight junction assembly), GO:0072659 (protein localization to plasma membrane), GO:0006163 (purine nucleotide metabolic process), GO:0051345 (positive regulation of hydrolase activity), GO:0009913 (epidermal cell differentiation), GO:1904375 (regulation of protein localization to cell periphery), GO:1903078 (positive regulation of protein localization to plasma membrane), GO:1903076 (regulation of protein localization to plasma membrane), GO:0009150 (purine ribonucleotide metabolic process), GO:0009187 (cyclic nucleotide metabolic process), GO:0043547 (positive regulation of GTPase activity), GO:1902743 (regulation of lamellipodium organization), GO:0010591 (regulation of lamellipodium assembly), GO:0052652 (cyclic purine nucleotide metabolic process), GO:0048013 (ephrin receptor signaling pathway), GO:0070372 (regulation of ERK1 and ERK2 cascade), GO:0090630 (activation of GTPase activity), GO:0046058 (cAMP metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0012505 (endomembrane system), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031975 (envelope), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0005654 (nucleoplasm), GO:0031090 (organelle membrane), GO:0031967 (organelle envelope), GO:0043233 (organelle lumen), GO:0005635 (nuclear envelope), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043228 (non-membrane-bounded organelle), GO:0031965 (nuclear membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0005856 (cytoskeleton), GO:0031981 (nuclear lumen), GO:0005634 (nucleus), GO:0015629 (actin cytoskeleton)