EPH-receptor A2 (efrinski receptor 2 tip-A ) jest protein koji je kod ljudi kodiran genom EPHA2 sa hromosoma 1.[5][6]
Kratke činjenice Dostupne strukture, PDB ...
EPHA2 |
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Dostupne strukture |
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PDB | Pretraga ortologa: PDBe RCSB |
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Spisak PDB ID kodova |
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1MQB, 2E8N, 2K9Y, 2KSO, 2X10, 2X11, 3C8X, 3CZU, 3FL7, 3HEI, 3HPN, 3KKA, 3MBW, 3MX0, 3SKJ, 4P2K, 4PDO, 4TRL, 5EK7 |
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Identifikatori |
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Aliasi | EPHA2 |
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Vanjski ID-jevi | OMIM: 176946 MGI: 95278 HomoloGene: 20929 GeneCards: EPHA2 |
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Ortolozi |
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Vrste | Čovjek | Miš |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNK) | | |
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RefSeq (bjelančevina) | | |
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Lokacija (UCSC) | Chr 1: 16.12 – 16.16 Mb | Chr 4: 141.03 – 141.06 Mb |
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PubMed pretraga | [3] | [4] |
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Wikipodaci |
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Zatvori
Dužina polipeptidnog lanca je 976 aminokiselina, a molekulska težina 108.266 Da.[7]
10 | | 20 | | 30 | | 40 | | 50 |
MELQAARACF | | ALLWGCALAA | | AAAAQGKEVV | | LLDFAAAGGE | | LGWLTHPYGK |
GWDLMQNIMN | | DMPIYMYSVC | | NVMSGDQDNW | | LRTNWVYRGE | | AERIFIELKF |
TVRDCNSFPG | | GASSCKETFN | | LYYAESDLDY | | GTNFQKRLFT | | KIDTIAPDEI |
TVSSDFEARH | | VKLNVEERSV | | GPLTRKGFYL | | AFQDIGACVA | | LLSVRVYYKK |
CPELLQGLAH | | FPETIAGSDA | | PSLATVAGTC | | VDHAVVPPGG | | EEPRMHCAVD |
GEWLVPIGQC | | LCQAGYEKVE | | DACQACSPGF | | FKFEASESPC | | LECPEHTLPS |
PEGATSCECE | | EGFFRAPQDP | | ASMPCTRPPS | | APHYLTAVGM | | GAKVELRWTP |
PQDSGGREDI | | VYSVTCEQCW | | PESGECGPCE | | ASVRYSEPPH | | GLTRTSVTVS |
DLEPHMNYTF | | TVEARNGVSG | | LVTSRSFRTA | | SVSINQTEPP | | KVRLEGRSTT |
SLSVSWSIPP | | PQQSRVWKYE | | VTYRKKGDSN | | SYNVRRTEGF | | SVTLDDLAPD |
TTYLVQVQAL | | TQEGQGAGSK | | VHEFQTLSPE | | GSGNLAVIGG | | VAVGVVLLLV |
LAGVGFFIHR | | RRKNQRARQS | | PEDVYFSKSE | | QLKPLKTYVD | | PHTYEDPNQA |
VLKFTTEIHP | | SCVTRQKVIG | | AGEFGEVYKG | | MLKTSSGKKE | | VPVAIKTLKA |
GYTEKQRVDF | | LGEAGIMGQF | | SHHNIIRLEG | | VISKYKPMMI | | ITEYMENGAL |
DKFLREKDGE | | FSVLQLVGML | | RGIAAGMKYL | | ANMNYVHRDL | | AARNILVNSN |
LVCKVSDFGL | | SRVLEDDPEA | | TYTTSGGKIP | | IRWTAPEAIS | | YRKFTSASDV |
WSFGIVMWEV | | MTYGERPYWE | | LSNHEVMKAI | | NDGFRLPTPM | | DCPSAIYQLM |
MQCWQQERAR | | RPKFADIVSI | | LDKLIRAPDS | | LKTLADFDPR | | VSIRLPSTSG |
SEGVPFRTVS | | EWLESIKMQQ | | YTEHFMAAGY | | TAIEKVVQMT | | NDDIKRIGVR |
LPGHQKRIAY | | SLLGLKDQVN | | TVGIPI |
Ovaj gen pripada potporodici receptora efrinske porodice proteina tirozin-kinaza. EPH i receptori povezani sa EPH su uključeni u posredovanje razvojnih događaja, posebno u nervnom sistemu. Receptori u potporodici EPH tipski imaju jedan domen kinaze i vanćelijsku regiju koja sadrži Cys bogat domen i dva fibronektinska ponavljanja tipa III. Efrinski receptori su podijeljeni u dvije grupe, na osnovu sličnosti njihovih vanćelijskih domenskih sekvenci i njihovih afiniteta za vezivanje liganda efrina-A i efrina-B. Ovaj gen kodira protein koji veže ligande za efrin-A.[6]
Može biti upleten u BRAF mutirani melanom koji postaje otporan na BRAF inhibitore i MEK inhibitor.[8] Također je receptor putem kojeg Kaposi sarkomu-pridruženi herpesvirus (KSHV) ulazi u ćelije domaćina; mala molekula inhibitora EphA2 pokazuje izvjesnu sposobnost blokiranja ulaska KSHV u ljudske ćelije.[9]
Pokazalo se da je EPH receptor A2 u interakciji sa:
Takođe je pokazano da je doksazosin mali molekulski agonist EPH receptora A2.[14]
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. 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. Petty A, Myshkin E, Qin H, Guo H, Miao H, Tochtrop GP, Hsieh JT, Page P, Liu L, Lindner DJ, Acharya C, MacKerell AD, Ficker E, Song J, Wang BC (august 2012). "A small molecule agonist of EphA2 receptor tyrosine kinase inhibits tumor cell migration in vitro and prostate cancer metastasis in vivo". PLOS ONE. 7 (8): e42120. doi:10.1371/journal.pone.0042120. PMC 3419725. PMID 22916121.
- 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. S2CID 1278600.
- 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. doi:10.1242/dev.126.10.2033. PMID 10207129.
- Wilkinson DG (2000). "Eph receptors and ephrins: regulators of guidance and assembly". Int. Rev. Cytol. International Review of Cytology. 196: 177–244. doi:10.1016/S0074-7696(00)96005-4. ISBN 9780123646002. 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. S2CID 205014301.
- 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. S2CID 2472961.
- 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. doi:10.1128/mcb.10.12.6316. 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. Bibcode:1995Sci...268..567P. 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. S2CID 21419336.
- 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. Bibcode:1994Sci...266..816D. 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. doi:10.1016/S0021-9258(18)43790-8. 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. S2CID 1075856.
- 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. S2CID 26773768.