EPHA2

EPHA2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1MQB, 2E8N, 2K9Y, 2KSO, 2X10, 2X11, 3C8X, 3CZU, 3FL7, 3HEI, 3HPN, 3KKA, 3MBW, 3MX0, 3SKJ, 4P2K, 4PDO, 4TRL, 5EK7
Identifikatori
Aliasi	EPHA2
Vanjski ID-jevi	OMIM: 176946 MGI: 95278 HomoloGene: 20929 GeneCards: EPHA2
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	16,156,069 bp
Lokacija gena (miš)
Hrom.	Hromosom 4 (miš)
Kraj	141,056,695 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• nucleotide binding; • protein kinase activity; • aktivnost sa transferazom; • kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • protein tyrosine kinase activity; • ATP binding; • ephrin receptor activity; • transmembrane receptor protein tyrosine kinase activity; • cadherin binding; • virus receptor activity; • transmembrane-ephrin receptor activity;
Ćelijska komponenta	• integral component of membrane; • projekcija ćelije; • membrana; • ruffle membrane; • međućelijske veze; • lamellipodium membrane; • leading edge membrane; • focal adhesion; • integral component of plasma membrane; • intracellular anatomical structure; • ćelijska membrana; • lamellipodium; • cell surface; • neuron projection; • receptor complex; • tight junctions;
Biološki proces	• regulation of lamellipodium assembly; • skeletal system development; • negative regulation of protein kinase B signaling; • Ćelijska diferencijacija; • regulation of cell adhesion mediated by integrin; • protein kinase B signaling; • GO:0032861, GO:0032862, GO:0032856 activation of GTPase activity; • Fosforilacija; • transmembrane receptor protein tyrosine kinase signaling pathway; • keratinocyte differentiation; • Vaskulogeneza; • multicellular organism development; • protein phosphorylation; • Ćelijska adhezija; • blood vessel development; • notochord morphogenesis; • notochord cell development; • Angiogeneza; • intrinsic apoptotic signaling pathway in response to DNA damage; • neural tube development; • neuron differentiation; • Notohord; • regulation of ERK1 and ERK2 cascade; • cell chemotaxis; • post-anal tail morphogenesis; • axial mesoderm formation; • response to growth factor; • GO:0022415 viral process; • Ćelijska migracija; • GO:0097285 apoptoza; • peptidyl-tyrosine phosphorylation; • osteoclast differentiation; • osteoblast differentiation; • regulation of angiogenesis; • regulation of blood vessel endothelial cell migration; • ephrin receptor signaling pathway; • lens fiber cell morphogenesis; • mammary gland epithelial cell proliferation; • bone remodeling; • branching involved in mammary gland duct morphogenesis; • GO:0032697 negative regulation of cytokine production; • GO:0051637 defense response to Gram-positive bacterium; • negative regulation of lymphangiogenesis; • blood vessel endothelial cell proliferation involved in sprouting angiogenesis; • pericyte cell differentiation; • negative regulation of angiogenesis; • inflammatory response; • negative regulation of chemokine production; • blood vessel morphogenesis; • cAMP metabolic process; • cell motility; • viral entry into host cell; • positive regulation of protein localization to plasma membrane; • axon guidance; • protein localization to plasma membrane; • positive regulation of bicellular tight junction assembly;
	Izvori:Amigo / QuickGO
Ortolozi
	1969
	13836
	ENSG00000142627
	ENSMUSG00000006445
	P29317
	Q03145
	NM_004431; NM_001329090
	NM_010139
	NP_001316019; NP_004422
	NP_034269
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

EPH-receptor A2 (efrinski receptor 2 tip-A ) jest protein koji je kod ljudi kodiran genom EPHA2 sa hromosoma 1.^[5]^[6]

Amiokiselininska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 976 aminokiselina, a molekulska težina 108.266 Da.^[7]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

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

Funkcija[uredi | uredi izvor]

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]

Klinički značaj[uredi | uredi izvor]

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]

Interakcije[uredi | uredi izvor]

Pokazalo se da je EPH receptor A2 u interakciji sa:

Takođe je pokazano da je doksazosin mali molekulski agonist EPH receptora A2.^[14]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000142627 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000006445 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: EPHA2 EPH receptor A2".
^ "UniProt, P29317" (jezik: engleski). Pristupljeno 15. 11. 2021.
^ "Counteracting Drug Resistance in Melanoma". 2015. Arhivirano s originala, 4. 2. 2015. Pristupljeno 25. 11. 2021.
^ 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.
^ Himanen JP, Goldgur Y, Miao H, Myshkin E, Guo H, Buck M, Nguyen M, Rajashankar KR, Wang BC, Nikolov DB (juli 2009). "Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex". EMBO Rep. 10 (7): 722–8. doi:10.1038/embor.2009.91. PMC 2727437. PMID 19525919.
^ Kikawa KD, Vidale DR, Van Etten RL, Kinch MS (oktobar 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.
^ ^a ^b Pratt RL, Kinch MS (oktobar 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 (decembar 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.
^ 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.

Dopunska literatura[uredi | uredi izvor]

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.

Vanjski linkovi[uredi | uredi izvor]

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000142627 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000006445 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9119409-5] 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.

[entrez-6] "Entrez Gene: EPHA2 EPH receptor A2".

[UniProt-7] "UniProt, P29317" (jezik: engleski). Pristupljeno 15. 11. 2021.

[8] "Counteracting Drug Resistance in Melanoma". 2015. Arhivirano s originala, 4. 2. 2015. Pristupljeno 25. 11. 2021.

[9] 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.

[pmid19525919-10] Himanen JP, Goldgur Y, Miao H, Myshkin E, Guo H, Buck M, Nguyen M, Rajashankar KR, Wang BC, Nikolov DB (juli 2009). "Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex". EMBO Rep. 10 (7): 722–8. doi:10.1038/embor.2009.91. PMC 2727437. PMID 19525919.

[pmid12167657-11] Kikawa KD, Vidale DR, Van Etten RL, Kinch MS (oktobar 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.

[pmid12400011-12] Pratt RL, Kinch MS (oktobar 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.

[pmid7982920-13] Pandey A, Lazar DF, Saltiel AR, Dixit VM (decembar 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.

[pmid22916121-14] 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.

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p r u Enzimi
Teme	Aktivno mjesto Alosterna regulacija Difuzijski limitirani enzim EC broj Enzimska kataliza Inhibicija enzimskih reakcija Kinetika enzima Koenzim Kooperativnost Lineweaver–Burkov dijagram Michaelis–Mentenova kinetika Mjesto vezanja Spisak enzima
Tipovi	EC1 Oksidoreduktaze/spisak EC2 Transferaze/spisak EC3 Hidrolaze/spisak EC4 Lijaze/spisak EC5 Izomeraze/spisak EC6 Ligaze/spisak