EPHA3

EPHA3

A gene on chromosome 3p11.2 that encodes a member of the ephrin-A receptor subfamily of receptor tyrosine kinases, which promiscuously bind membrane-bound ephrin-A family ligands residing on adajcent cells, leading to contact-dependent bidirectional signalling into neighbouring cells. EPHA3 mediates developmental events, especially in the nervous system—once activated by EFNA5, it regulates cell–cell adhesion, cytoskeletal organisation and cell migration. It plays a role in cardiac cell migration and differentiation, and it regulates formation of the atrioventricular canal and septum during development. It is involved in the retinotectal mapping of neurons and may control the segregation—but not the guidance—of motor and sensory axons during neuromuscular circuit development.
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Ifabotuzumab, which targets the Eph type-A receptor 3 (EphA3), is being explored as a potential treatment for a range of solid tumors, as well as a backbone for a novel CAR-T construct, and a bispecific antibody platform.
Gene name Gene Conserved 8-mer 7-mer symbol sites Chemokine Z (C-X-C motif) CXC 12 1 1 ligand 12 NOTCH-regulated ankyrin NRARP 1 1 repeat protein Astrotactin-1 ASTN1 1 1 Nasal embryonic LHRH NELF 1 1 factor K(Lysine) acetyl KAT6B 1 1 transferase 6B Protein kinase C, alpha PRKCA 1 1 EF-hand domain family, EFHD2 1 1 member D2 Mitogen-activated protein MAP2K4 1 1 kinase kinase 4 Zinc finger protein 219 ZNF219 1 1 Ring finger protein 165 RNF165 1 1 Protocadherin 7 PCDH7 1 1 EPH receptor A3 EPHA3 1 1 Insulin receptor IRS1 1 1 substrate 1 POU class 2 homeobox 1 POU2F1 1 1
Los genes involucrados se asocian a diferentes etapas del proceso de carcinogenesis, como la regulacion del ciclo celular y la apoptosis (p15, p16, Rb1, p27, p73), la reparacion del ADN (MgMTdApK), la migracion y metastasis tumoral (E-cadherin, RAE[beta]), los factores de crecimiento (ER, EphA3), la diferenciacion celular y la respuesta inmune (C/EBPs), (SOCS-1), entre otros.
In our prediction list, five genes can be classified in such subfamily: EPHA3, EPHA4, EPHA5, EPHA7, and EPHB2.
The protein, (http://www.ncbi.nlm.nih.gov/pubmed/23410976) EphA3 , was discovered more than 20 years ago by QIMR Berghofer Medical Research Institute's professor, Andrew Boyd.
Symbol Entrez gene name WNT16 Wingless-type MMTV integration site family, member 16 PLCD4 Phospholipase C, delta 4 ADAM29 ADAM metallopeptidase domain 29 MMP8 Matrix metallopeptidase 8 (neutrophil collagenase) EPHA6 EPH receptor A6 PAK7 p21 protein (Cdc42/Rac)-activated kinase 7 EPHA7 EPH receptor A7 EPHA3 EPH receptor A3 SEMA6D Serna domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D ADAM30 ADAM metallopeptidase domain 30 UNC5D Unc-5 homolog D (C.
Cruz-Orengo et al., "Upregulation of EphA3 receptor after spinal cord injury," Journal of Neurotrauma, vol.
KaloBios Pharmaceuticals, a biopharmaceutical company, has received a notice of allowance for a composition of matter patent covering certain antibodies targeting EphA3, including KaloBios' experimental anti-cancer monoclonal antibody (mAb), KB004, with the US Patent and Trademark Office.
Among neural-derived cells, integrated mRNA-miRNA functional analyses of mature neurons (MNs), neural progenitor cells (NPCs), and neuroblastoma cells (NBCs) revealed that several very highly expressed genes (e.g., Robo1, Nrp1, Epha3, Unc5c, Dcc, Pak3, and Limk4) and a few underexpressed miRNAs (e.g., miR-152, miR-146b, and miR-339-5p) in MNs are associated with one important cellular process-axon guidance; some very highly expressed mitogenic pathway genes (e.g., Map2k1, Igf1r, Rara, and Runx1) and underexpressed miRNAs (e.g., miR-370, miR-9, and miR-672) in NBCs are associated with cancer pathways [23].
These mutations were associated with 12 core signaling pathways.7 Based on the frequency of genetically affected genes in pancreatic cancers, a genetic "topographic map" of the pancreatic cancers can be generated in which the most frequent mutations are represented as 4 "mountains" (high-frequency driver genes) involving KRAS2, CDKN2A/p16, SMAD4/DPC4, and TP53, with numerous "hills" (low-frequency driver genes) involving SMARC4A, CDH1, EPHA3, FBXW7, EGFR, IDH1, and NF1.
It is targeted towards EphA3 expressing hematologic malignancies, which are believed to account for about 50 percent of acute leukaemias as well as a number of other human cancers, including a significant proportion of malignant melanomas, brain tumours and lung cancers.
It's still early days but there are reports that EphA3, A4, A7 and B3 all reappear following injury.