EPH receptor A2

PDB rendering based on 1mqb.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1MQB, 2E8N, 2K9Y, 2KSO, 2X10, 2X11, 3C8X, 3CZU, 3FL7, 3HEI, 3HPN, 3KKA, 3MBW, 3MX0, 3SKJ, 4P2K, 4PDO, 4TRL

Identifiers

Symbols

EPHA2 ; ARCC2; CTPA; CTPP1; CTRCT6; ECK

External IDs

OMIM: 176946 MGI: 95278 HomoloGene: 20929 ChEMBL: 2068 GeneCards: EPHA2 Gene

EC number

2.7.10.1

Gene ontology
Molecular function	• transmembrane receptor protein tyrosine kinase activity • ephrin receptor activity • protein binding • ATP binding
Cellular component	• intracellular • plasma membrane • integral component of plasma membrane • focal adhesion • cell surface • leading edge membrane • lamellipodium membrane • ruffle membrane
Biological process	• skeletal system development • angiogenesis • vasculogenesis • osteoblast differentiation • cell adhesion • multicellular organismal development • axon guidance • intrinsic apoptotic signaling pathway in response to DNA damage • regulation of lamellipodium assembly • notochord formation • viral process • cell migration • peptidyl-tyrosine phosphorylation • neural tube development • keratinocyte differentiation • osteoclast differentiation • mammary gland epithelial cell proliferation • regulation of cell adhesion mediated by integrin • post-anal tail morphogenesis • protein kinase B signaling • regulation of blood vessel endothelial cell migration • regulation of angiogenesis • bone remodeling • ephrin receptor signaling pathway • axial mesoderm formation • negative regulation of protein kinase B signaling • notochord cell development • cell chemotaxis • branching involved in mammary gland duct morphogenesis • lens fiber cell morphogenesis • regulation of ERK1 and ERK2 cascade • response to growth factor • positive regulation of establishment of protein localization to plasma membrane • activation of GTPase activity
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
16.12 – 16.16 Mb

Chr 4:
141.3 – 141.33 Mb

PubMed search

EPH receptor A2 (ephrin type-A receptor 2) is a protein that in humans is encoded by the EPHA2 gene.^[1]^[2]

Function

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.^[2]

Clinical significance

It may be implicated in BRAF mutated melanomas becoming resistant to BRAF-inhibitors and MEK inhibitors.^[3] It also the receptor by which Kaposi sarcoma-associated herpesvirus (KSHV) enters host cells and small molecule inhibitors of EphA2 have shown some ability to block KSHV entry into human cells.^[4]

Interactions

EPH receptor A2 has been shown to interact with:

References

↑ Sulman EP, Tang XX, Allen C, Biegel JA, Pleasure DE, Brodeur GM, Ikegaki N (April 1997). "ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers". Genomics 40 (2): 371–4. doi:10.1006/geno.1996.4569. PMID 9119409.
1 2 "Entrez Gene: EPHA2 EPH receptor A2".
↑ "Counteracting Drug Resistance in Melanoma". 2015.
↑ Hahn AS, Kaufmann JK, Wies E, Naschberger E, Panteleev-Ivlev J, Schmidt K, Holzer A, Schmidt M, Chen J, König S, Ensser A, Myoung J, Brockmeyer NH, Stürzl M, Fleckenstein B, Neipel F (2012). "The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's sarcoma–associated herpesvirus". Nat. Med. 18 (6): 961–6. doi:10.1038/nm.2805. PMC 3645317. PMID 22635007.
↑ Kikawa KD, Vidale DR, Van Etten RL, Kinch MS (October 2002). "Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation". J. Biol. Chem. 277 (42): 39274–9. doi:10.1074/jbc.M207127200. PMID 12167657.
1 2 Pratt RL, Kinch MS (October 2002). "Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade". Oncogene 21 (50): 7690–9. doi:10.1038/sj.onc.1205758. PMID 12400011.
↑ Pandey A, Lazar DF, Saltiel AR, Dixit VM (December 1994). "Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". J. Biol. Chem. 269 (48): 30154–7. PMID 7982920.

Flanagan JG, Vanderhaeghen P (1998). "The ephrins and Eph receptors in neural development". Annu. Rev. Neurosci. 21: 309–45. doi:10.1146/annurev.neuro.21.1.309. PMID 9530499.
Zhou R (1998). "The Eph family receptors and ligands". Pharmacol. Ther. 77 (3): 151–81. doi:10.1016/S0163-7258(97)00112-5. PMID 9576626.
Holder N, Klein R (1999). "Eph receptors and ephrins: effectors of morphogenesis". Development 126 (10): 2033–44. PMID 10207129.
Wilkinson DG (2000). "Eph receptors and ephrins: regulators of guidance and assembly". Int. Rev. Cytol. 196: 177–244. doi:10.1016/S0074-7696(00)96005-4. PMID 10730216.
Xu Q, Mellitzer G, Wilkinson DG (2000). "Roles of Eph receptors and ephrins in segmental patterning". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 355 (1399): 993–1002. doi:10.1098/rstb.2000.0635. PMC 1692797. PMID 11128993.
Wilkinson DG (2001). "Multiple roles of EPH receptors and ephrins in neural development". Nat. Rev. Neurosci. 2 (3): 155–64. doi:10.1038/35058515. PMID 11256076.
Kinch MS, Carles-Kinch K (2003). "Overexpression and functional alterations of the EphA2 tyrosine kinase in cancer". Clin. Exp. Metastasis 20 (1): 59–68. doi:10.1023/A:1022546620495. PMID 12650608.
Walker-Daniels J, Hess AR, Hendrix MJ, Kinch MS (2003). "Differential regulation of EphA2 in normal and malignant cells". Am. J. Pathol. 162 (4): 1037–42. doi:10.1016/S0002-9440(10)63899-0. PMC 1851246. PMID 12651595.
Lindberg RA, Hunter T (1990). "cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases". Mol. Cell. Biol. 10 (12): 6316–24. PMC 362907. PMID 2174105.
Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM (1995). "Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis". Science 268 (5210): 567–9. doi:10.1126/science.7536959. PMID 7536959.
Pandey A, Duan H, Dixit VM (1995). "Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase". J. Biol. Chem. 270 (33): 19201–4. doi:10.1074/jbc.270.33.19201. PMID 7543898.
Ruiz JC, Robertson EJ (1994). "The expression of the receptor-protein tyrosine kinase gene, eck, is highly restricted during early mouse development". Mech. Dev. 46 (2): 87–100. doi:10.1016/0925-4773(94)90078-7. PMID 7918100.
Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD (1994). "Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity". Science 266 (5186): 816–9. doi:10.1126/science.7973638. PMID 7973638.
Pandey A, Lazar DF, Saltiel AR, Dixit VM (1994). "Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". J. Biol. Chem. 269 (48): 30154–7. PMID 7982920.
Ganju P, Shigemoto K, Brennan J, Entwistle A, Reith AD (1994). "The Eck receptor tyrosine kinase is implicated in pattern formation during gastrulation, hindbrain segmentation and limb development". Oncogene 9 (6): 1613–24. PMID 8183555.
Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE, Henkemeyer M, Strebhardt K, Hirai H, Wilkinson DG, Pawson T, Davis S, Yancopoulos GD (1996). "Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis". Neuron 17 (1): 9–19. doi:10.1016/S0896-6273(00)80276-7. PMID 8755474.
Kozlosky CJ, VandenBos T, Park L, Cerretti DP, Carpenter MK (1997). "LERK-7: a ligand of the Eph-related kinases is developmentally regulated in the brain". Cytokine 9 (8): 540–9. doi:10.1006/cyto.1997.0199. PMID 9245480.
Ephnomenclaturecommittee (1997). "Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee". Cell 90 (3): 403–4. doi:10.1016/S0092-8674(00)80500-0. PMID 9267020.

PDB gallery

1mqb: Crystal Structure of Ephrin A2 (ephA2) Receptor Protein Kinase

Protein kinases: tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4

Insulin receptor family	IGF1R INSR INSRR

PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)

FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4

VEGF receptors family	VEGFR1 VEGFR2 VEGFR3

HGF receptor family	MET RON

Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

ROR1
ROR2

DDR receptor family

DDR1
DDR2

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AATYK
AATYK2

AXL receptor family

RET receptor family

uncatagorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG

ACK family	ACK1 TNK1

CSK family	CSK MATK

FAK family	FAK PYK2

FES family	FES FER

FRK family	FRK BRK SRMS

JAK family	JAK1 JAK2 JAK3 TYK2

SRC-A family	SRC FGR FYN YES1

SRC-B family	BLK HCK LCK LYN

TEC family	TEC BMX BTK ITK TXK

SYK family	SYK ZAP70

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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EPH receptor A2

Function

Clinical significance

Interactions

References

Further reading