Molecule Information

General Information of the Molecule (ID: Mol00063)

• Name: Ephrin type-A receptor 3 (EPHA3) ,Homo sapiens
• Synonyms: EPH-like kinase 4; EK4; hEK4; HEK; Human embryo kinase; Tyrosine-protein kinase TYRO4; Tyrosine-protein kinase receptor ETK1; Eph-like tyrosine kinase 1; ETK; ETK1; HEK; TYRO4
• Molecule Type: Protein
• Gene Name: EPHA3
• Gene ID: 2042
• Location: chr3:89107621-89482134[+]
• Sequence:
  MDCQLSILLLLSCSVLDSFGELIPQPSNEVNLLDSKTIQGELGWISYPSHGWEEISGVDE
  HYTPIRTYQVCNVMDHSQNNWLRTNWVPRNSAQKIYVELKFTLRDCNSIPLVLGTCKETF
  NLYYMESDDDHGVKFREHQFTKIDTIAADESFTQMDLGDRILKLNTEIREVGPVNKKGFY
  LAFQDVGACVALVSVRVYFKKCPFTVKNLAMFPDTVPMDSQSLVEVRGSCVNNSKEEDPP
  RMYCSTEGEWLVPIGKCSCNAGYEERGFMCQACRPGFYKALDGNMKCAKCPPHSSTQEDG
  SMNCRCENNYFRADKDPPSMACTRPPSSPRNVISNINETSVILDWSWPLDTGGRKDVTFN
  IICKKCGWNIKQCEPCSPNVRFLPRQFGLTNTTVTVTDLLAHTNYTFEIDAVNGVSELSS
  PPRQFAAVSITTNQAAPSPVLTIKKDRTSRNSISLSWQEPEHPNGIILDYEVKYYEKQEQ
  ETSYTILRARGTNVTISSLKPDTIYVFQIRARTAAGYGTNSRKFEFETSPDSFSISGESS
  QVVMIAISAAVAIILLTVVIYVLIGRFCGYKSKHGADEKRLHFGNGHLKLPGLRTYVDPH
  TYEDPTQAVHEFAKELDATNISIDKVVGAGEFGEVCSGRLKLPSKKEISVAIKTLKVGYT
  EKQRRDFLGEASIMGQFDHPNIIRLEGVVTKSKPVMIVTEYMENGSLDSFLRKHDAQFTV
  IQLVGMLRGIASGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT
  TRGGKIPIRWTSPEAIAYRKFTSASDVWSYGIVLWEVMSYGERPYWEMSNQDVIKAVDEG
  YRLPPPMDCPAALYQLMLDCWQKDRNNRPKFEQIVSILDKLIRNPGSLKIITSAAARPSN
  LLLDQSNVDITTFRTTGDWLNGVWTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVG
  PQKKIISSIKALETQSKNGPVPV
• 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.
• Uniprot ID: EPHA3_HUMAN
• Ensembl ID: ENSG00000044524
• HGNC ID: HGNC:3387

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Lung small cell carcinoma [1]

• Resistant Disease: Lung small cell carcinoma [ICD-11: 2C25.2]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: NCI-H69 cells; Lung; Homo sapiens (Human); CVCL_1579
• In Vitro Model: H69/AR cells; Lung; Homo sapiens (Human); CVCL_3513
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemical staining; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Cell scratch-wound healing assay; Flow cytometry assay
• Mechanism Description: miR495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Ectopic expression of Etk/BMX obviously rescued the miR495 elevation elevation-induced inhibition of drug resistance.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Lung small cell carcinoma [1]

• Resistant Disease: Lung small cell carcinoma [ICD-11: 2C25.2]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: NCI-H69 cells; Lung; Homo sapiens (Human); CVCL_1579
• In Vitro Model: H69/AR cells; Lung; Homo sapiens (Human); CVCL_3513
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemical staining; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Cell scratch-wound healing assay; Flow cytometry assay
• Mechanism Description: miR495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Ectopic expression of Etk/BMX obviously rescued the miR495 elevation elevation-induced inhibition of drug resistance.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Lung small cell carcinoma [1]

• Resistant Disease: Lung small cell carcinoma [ICD-11: 2C25.2]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: NCI-H69 cells; Lung; Homo sapiens (Human); CVCL_1579
• In Vitro Model: H69/AR cells; Lung; Homo sapiens (Human); CVCL_3513
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemical staining; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Cell scratch-wound healing assay; Flow cytometry assay
• Mechanism Description: miR495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Ectopic expression of Etk/BMX obviously rescued the miR495 elevation elevation-induced inhibition of drug resistance.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.64E-12; Fold-change: -2.91E-01; Z-score: -7.42E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.40E-10; Fold-change: -3.07E-01; Z-score: -7.02E-01

References

• Ref 1: miR-495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Am J Cancer Res. 2017 Mar 1;7(3):628-646. eCollection 2017.