| Tclin | Ephrin type-A receptor 2 |
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]
Comments
| Disease | Target Count |
|---|---|
| CATARACT, POSTERIOR POLAR, 1 | 1 |
| Congenital total cataract | 8 |
| Disease Progression | 125 |
| LEOPARD Syndrome | 20 |
| Noonan Syndrome | 33 |
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6685 | 1.82258089791818E-54 |
| Breast cancer | 3099 | 3.35252013868005E-22 |
| lung carcinoma | 2844 | 2.55687660151414E-10 |
| nasopharyngeal carcinoma | 1056 | 1.74207779701986E-7 |
| ulcerative colitis | 2087 | 1.96605003176522E-6 |
| adrenocortical carcinoma | 1427 | 3.57470959945034E-6 |
| ovarian cancer | 8492 | 8.28958765118741E-6 |
| pancreatic cancer | 2300 | 2.16557166959651E-5 |
| Atopic dermatitis | 944 | 1.79978402088402E-4 |
| intraductal papillary-mucinous neoplasm (IPMN) | 3289 | 0.00360834763670924 |
| pancreatic ductal adenocarcinoma liver metastasis | 1795 | 0.00742144034630417 |
| atypical teratoid / rhabdoid tumor | 4369 | 0.00900837331762278 |
| group 3 medulloblastoma | 2254 | 0.0295105341583509 |
| sarcoidosis | 368 | 0.0368544734784704 |
| chronic rhinosinusitis | 512 | 0.0370475747611765 |
| spina bifida | 1064 | 0.0475261269221921 |
| Disease | Target Count |
|---|---|
| Cataract 6, multiple types | 1 |
| Disease | log2 FC | p |
|---|---|---|
| psoriasis | 1.600 | 0.000 |
| atypical teratoid / rhabdoid tumor | 1.100 | 0.009 |
| Atopic dermatitis | 1.100 | 0.000 |
| adrenocortical carcinoma | -1.053 | 0.000 |
| pancreatic ductal adenocarcinoma liver m... | 1.795 | 0.007 |
| intraductal papillary-mucinous neoplasm ... | 2.100 | 0.004 |
| sarcoidosis | -1.100 | 0.037 |
| pancreatic cancer | 1.400 | 0.000 |
| group 3 medulloblastoma | 1.400 | 0.030 |
| nasopharyngeal carcinoma | -1.200 | 0.000 |
| lung carcinoma | -1.200 | 0.000 |
| spina bifida | -1.840 | 0.048 |
| Breast cancer | -1.600 | 0.000 |
| ulcerative colitis | 2.000 | 0.000 |
| ovarian cancer | 1.600 | 0.000 |
| chronic rhinosinusitis | -1.171 | 0.037 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Platypus | OMA EggNOG Inparanoid |
| Xenopus | OMA Inparanoid |
CHEMBL3577124
pIC50 7.70
CHEMBL1688860
pIC50 7.75
CHEMBL3426225
pIC50 7.80
CHEMBL2029988
pKd 7.85
CHEMBL478629
pIC50 7.96
CHEMBL1688861
pIC50 7.96
CHEMBL249097
pKd 8.10
CHEMBL386051
pKd 8.42
CHEMBL1230609
pKd 8.44
CHEMBL566515
pIC50 8.64
CHEMBL1784637
pIC50 9.22
| PMID | Text |
|---|---|
| 26900323 | Mis-localization of two of the mutant proteins in epithelial cells suggests that some disease-causing mutations in EPHA2 likely affect lens epithelial cell homeostasis and contribute to cataract. |
| 26843134 | These data suggest that miR-26b enhances the radiosensitivity of 97H hepatocellular cancer cells by targeting EphA2 protein. |
| 26744526 | Role for EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI-resistant tumors. |
| 26722543 | EphA2 protein may be used as a new marker for the prognosis of clear cell renal cell carcinoma. |
| 26565750 | Based on these findings we propose that EphA2 promotes cell adhesion by an unknown signaling pathway that largely depends on the extracellular region of EphA2 and the activation of outside-in integrin signaling |
| 26363067 | EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. |
| 26283684 | EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer |
| 26191168 | Overexpression of miR-26b dramatically inhibited the proliferation, invasion, and migration of hepatocellular carcinoma cells by targeting EphA2. |
| 26177500 | EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of renal cell carcinoma |
| 26130649 | Data show that ligand-binding domain of receptor tyrosine kinase EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP. |
| More... |
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMNDMPIYMYSVC 1 - 70 NVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFNLYYAESDLDYGTNFQKRLFT 71 - 140 KIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYLAFQDIGACVALLSVRVYYKKCPELLQGLAH 141 - 210 FPETIAGSDAPSLATVAGTCVDHAVVPPGGEEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGF 211 - 280 FKFEASESPCLECPEHTLPSPEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTP 281 - 350 PQDSGGREDIVYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSG 351 - 420 LVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSNSYNVRRTEGF 421 - 490 SVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGGVAVGVVLLLVLAGVGFFIHR 491 - 560 RRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQAVLKFTTEIHPSCVTRQKVIGAGEFGEVYKG 561 - 630 MLKTSSGKKEVPVAIKTLKAGYTEKQRVDFLGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGAL 631 - 700 DKFLREKDGEFSVLQLVGMLRGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEA 701 - 770 TYTTSGGKIPIRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPM 771 - 840 DCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSGSEGVPFRTVS 841 - 910 EWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAYSLLGLKDQVNTVGIPI 911 - 976 //
| PMID | Year | Title |
|---|---|---|
| 27385333 | 2016 | Protein kinase A can block EphA2 receptor-mediated cell repulsion by increasing EphA2 S897 phosphorylation. |
| 26900323 | 2016 | EPHA2 MUTATIONS CONTRIBUTE TO CONGENITAL CATARACT THROUGH DIVERSE MECHANISMS. |
| 26843134 | 2016 | MicroRNA-26b Enhances the Radiosensitivity of Hepatocellular Carcinoma Cells by Targeting EphA2. |
| 26744526 | 2016 | EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer. |
| 26722543 | 2015 | Expression of EphA2 protein is positively associated with age, tumor size and Fuhrman nuclear grade in clear cell renal cell carcinomas. |
| 26565750 | 2015 | EphA2 promotes cell adhesion and spreading of monocyte and monocyte/macrophage cell lines on integrin ligand-coated surfaces. |
| 26363067 | 2015 | EphA2 Receptor Unliganded Dimers Suppress EphA2 Pro-tumorigenic Signaling. |
| 26283684 | 2016 | EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer. |
| 26191168 | 2015 | MiR-26b inhibits hepatocellular carcinoma cell proliferation, migration, and invasion by targeting EphA2. |
| 26177500 | 2015 | EphA2 Is a Potential Player of Malignant Cellular Behavior in Non-Metastatic Renal Cell Carcinoma Cells but Not in Metastatic Renal Cell Carcinoma Cells. |
| More... |
