Ephrin type-A receptor 3

Details

Name
Ephrin type-A receptor 3
Synonyms
  • 2.7.10.1
  • EK4
  • EPH-like kinase 4
  • Eph-like tyrosine kinase 1
  • ETK
  • ETK1
  • HEK
  • hEK4
  • Human embryo kinase
  • TYRO4
  • Tyrosine-protein kinase receptor ETK1
  • Tyrosine-protein kinase TYRO4
Gene Name
EPHA3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051752|Ephrin type-A receptor 3
MDCQLSILLLLSCSVLDSFGELIPQPSNEVNLLDSKTIQGELGWISYPSHGWEEISGVDE
HYTPIRTYQVCNVMDHSQNNWLRTNWVPRNSAQKIYVELKFTLRDCNSIPLVLGTCKETF
NLYYMESDDDHGVKFREHQFTKIDTIAADESFTQMDLGDRILKLNTEIREVGPVNKKGFY
LAFQDVGACVALVSVRVYFKKCPFTVKNLAMFPDTVPMDSQSLVEVRGSCVNNSKEEDPP
RMYCSTEGEWLVPIGKCSCNAGYEERGFMCQACRPGFYKALDGNMKCAKCPPHSSTQEDG
SMNCRCENNYFRADKDPPSMACTRPPSSPRNVISNINETSVILDWSWPLDTGGRKDVTFN
IICKKCGWNIKQCEPCSPNVRFLPRQFGLTNTTVTVTDLLAHTNYTFEIDAVNGVSELSS
PPRQFAAVSITTNQAAPSPVLTIKKDRTSRNSISLSWQEPEHPNGIILDYEVKYYEKQEQ
ETSYTILRARGTNVTISSLKPDTIYVFQIRARTAAGYGTNSRKFEFETSPDSFSISGESS
QVVMIAISAAVAIILLTVVIYVLIGRFCGYKSKHGADEKRLHFGNGHLKLPGLRTYVDPH
TYEDPTQAVHEFAKELDATNISIDKVVGAGEFGEVCSGRLKLPSKKEISVAIKTLKVGYT
EKQRRDFLGEASIMGQFDHPNIIRLEGVVTKSKPVMIVTEYMENGSLDSFLRKHDAQFTV
IQLVGMLRGIASGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYT
TRGGKIPIRWTSPEAIAYRKFTSASDVWSYGIVLWEVMSYGERPYWEMSNQDVIKAVDEG
YRLPPPMDCPAALYQLMLDCWQKDRNNRPKFEQIVSILDKLIRNPGSLKIITSAAARPSN
LLLDQSNVDITTFRTTGDWLNGVWTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVG
PQKKIISSIKALETQSKNGPVPV
Number of residues
983
Molecular Weight
110129.68
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / GPI-linked ephrin receptor activity
Processes
cell adhesion / cell migration / cellular response to retinoic acid / ephrin receptor signaling pathway / fasciculation of motor neuron axon / fasciculation of sensory neuron axon / negative regulation of endocytosis / peptidyl-tyrosine phosphorylation / positive regulation of neuron projection development / positive regulation of protein localization to plasma membrane / regulation of actin cytoskeleton organization / regulation of epithelial to mesenchymal transition / regulation of focal adhesion assembly / regulation of GTPase activity / regulation of microtubule cytoskeleton organization
Components
early endosome / extracellular region / integral component of plasma membrane / plasma membrane
General 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.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
542-565
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0051753|Ephrin type-A receptor 3 (EPHA3)
ATGGATTGTCAGCTCTCCATCCTCCTCCTTCTCAGCTGCTCTGTTCTCGACAGCTTCGGG
GAACTGATTCCGCAGCCTTCCAATGAAGTCAATCTACTGGATTCAAAAACAATTCAAGGG
GAGCTGGGCTGGATCTCTTATCCATCACATGGGTGGGAAGAGATCAGTGGTGTGGATGAA
CATTACACACCCATCAGGACTTACCAGGTGTGCAATGTCATGGACCACAGTCAAAACAAT
TGGCTGAGAACAAACTGGGTCCCCAGGAACTCAGCTCAGAAGATTTATGTGGAGCTCAAG
TTCACTCTACGAGACTGCAATAGCATTCCATTGGTTTTAGGAACTTGCAAGGAGACATTC
AACCTGTACTACATGGAGTCTGATGATGATCATGGGGTGAAATTTCGAGAGCATCAGTTT
ACAAAGATTGACACCATTGCAGCTGATGAAAGTTTCACTCAAATGGATCTTGGGGACCGT
ATTCTGAAGCTCAACACTGAGATTAGAGAAGTAGGTCCTGTCAACAAGAAGGGATTTTAT
TTGGCATTTCAAGATGTTGGTGCTTGTGTTGCCTTGGTGTCTGTGAGAGTATACTTCAAA
AAGTGCCCATTTACAGTGAAGAATCTGGCTATGTTTCCAGACACGGTACCCATGGACTCC
CAGTCCCTGGTGGAGGTTAGAGGGTCTTGTGTCAACAATTCTAAGGAGGAAGATCCTCCA
AGGATGTACTGCAGTACAGAAGGCGAATGGCTTGTACCCATTGGCAAGTGTTCCTGCAAT
GCTGGCTATGAAGAAAGAGGTTTTATGTGCCAAGCTTGTCGACCAGGTTTCTACAAGGCA
TTGGATGGTAATATGAAGTGTGCTAAGTGCCCGCCTCACAGTTCTACTCAGGAAGATGGT
TCAATGAACTGCAGGTGTGAGAATAATTACTTCCGGGCAGACAAAGACCCTCCATCCATG
GCTTGTACCCGACCTCCATCTTCACCAAGAAATGTTATCTCTAATATAAACGAGACCTCA
GTTATCCTGGACTGGAGTTGGCCCCTGGACACAGGAGGCCGGAAAGATGTTACCTTCAAC
ATCATATGTAAAAAATGTGGGTGGAATATAAAACAGTGTGAGCCATGCAGCCCAAATGTC
CGCTTCCTCCCTCGACAGTTTGGACTCACCAACACCACGGTGACAGTGACAGACCTTCTG
GCACATACTAACTACACCTTTGAGATTGATGCCGTTAATGGGGTGTCAGAGCTGAGCTCC
CCACCAAGACAGTTTGCTGCGGTCAGCATCACAACTAATCAGGCTGCTCCATCACCTGTC
CTGACGATTAAGAAAGATCGGACCTCCAGAAATAGCATCTCTTTGTCCTGGCAAGAACCT
GAACATCCTAATGGGATCATATTGGACTACGAGGTCAAATACTATGAAAAGCAGGAACAA
GAAACAAGTTATACCATTCTGAGGGCAAGAGGCACAAATGTTACCATCAGTAGCCTCAAG
CCTGACACTATATACGTATTCCAAATCCGAGCCCGAACAGCCGCTGGATATGGGACGAAC
AGCCGCAAGTTTGAGTTTGAAACTAGTCCAGACTCTTTCTCCATCTCTGGTGAAAGTAGC
CAAGTGGTCATGATCGCCATTTCAGCGGCAGTAGCAATTATTCTCCTCACTGTTGTCATC
TATGTTTTGATTGGGAGGTTCTGTGGCTATAAGTCAAAACATGGGGCAGATGAAAAAAGA
CTTCATTTTGGCAATGGGCATTTAAAACTTCCAGGTCTCAGGACTTATGTTGACCCACAT
ACATATGAAGACCCTACCCAAGCTGTTCATGAGTTTGCCAAGGAATTGGATGCCACCAAC
ATATCCATTGATAAAGTTGTTGGAGCAGGTGAATTTGGAGAGGTGTGCAGTGGTCGCTTA
AAACTTCCTTCAAAAAAAGAGATTTCAGTGGCCATTAAGACCCTGAAAGTTGGCTACACA
GAAAAGCAGAGGAGAGACTTCCTGGGAGAAGCAAGCATTATGGGACAGTTTGACCACCCC
AATATCATTCGACTGGAAGGAGTTGTTACCAAAAGTAAGCCAGTTATGATTGTCACAGAA
TACATGGAGAATGGTTCCTTGGATAGTTTCCTACGTAAACACGATGCCCAGTTTACTGTC
ATTCAGCTAGTGGGGATGCTTCGAGGGATAGCATCTGGCATGAAGTACCTGTCAGACATG
GGCTATGTTCACCGAGACCTCGCTGCTCGGAACATCTTGATCAACAGTAACTTGGTGTGT
AAGGTTTCTGATTTCGGACTTTCGCGTGTCCTGGAGGATGACCCAGAAGCTGCTTATACA
ACAAGAGGAGGGAAGATCCCAATCAGGTGGACATCACCAGAAGCTATAGCCTACCGCAAG
TTCACGTCAGCCAGCGATGTATGGAGTTATGGGATTGTTCTCTGGGAGGTGATGTCTTAT
GGAGAGAGACCATACTGGGAGATGTCCAATCAGGATGTAATTAAAGCTGTAGATGAGGGC
TATCGACTGCCACCCCCCATGGACTGCCCAGCTGCCTTGTATCAGCTGATGCTGGACTGC
TGGCAGAAAGACAGGAACAACAGACCCAAGTTTGAGCAGATTGTTAGTATTCTGGACAAG
CTTATCCGGAATCCCGGCAGCCTGAAGATCATCACCAGTGCAGCCGCAAGGCCATCAAAC
CTTCTTCTGGACCAAAGCAATGTGGATATCACTACCTTCCGCACAACAGGTGACTGGCTT
AATGGTGTCTGGACAGCACACTGCAAGGAAATCTTCACGGGTGTGGAGTACAGTTCTTGT
GACACAATAGCCAAGATTTCCACAGATGACATGAAAAAGGTTGGTGTCACCGTGGTTGGG
CCACAGAAGAAGATCATCAGTAGCATTAAAGCTCTAGAAACGCAATCAAAGAATGGCCCA
GTTCCCGTGTAA
Chromosome Location
3
Locus
3p11.1
External Identifiers
ResourceLink
UniProtKB IDP29320
UniProtKB Entry NameEPHA3_HUMAN
HGNC IDHGNC:3387
General References
  1. Wicks IP, Wilkinson D, Salvaris E, Boyd AW: Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1611-5. [Article]
  2. Chiari R, Hames G, Stroobant V, Texier C, Maillere B, Boon T, Coulie PG: Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules. Cancer Res. 2000 Sep 1;60(17):4855-63. [Article]
  3. Boyd AW, Ward LD, Wicks IP, Simpson RJ, Salvaris E, Wilks A, Welch K, Loudovaris M, Rockman S, Busmanis I: Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. J Biol Chem. 1992 Feb 15;267(5):3262-7. [Article]
  4. Authors unspecified: Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell. 1997 Aug 8;90(3):403-4. [Article]
  5. Lawrenson ID, Wimmer-Kleikamp SH, Lock P, Schoenwaelder SM, Down M, Boyd AW, Alewood PF, Lackmann M: Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 2002 Mar 1;115(Pt 5):1059-72. [Article]
  6. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE: Mutational analysis of the tyrosine kinome in colorectal cancers. Science. 2003 May 9;300(5621):949. [Article]
  7. Smith FM, Vearing C, Lackmann M, Treutlein H, Himanen J, Chen K, Saul A, Nikolov D, Boyd AW: Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen. J Biol Chem. 2004 Mar 5;279(10):9522-31. Epub 2003 Dec 2. [Article]
  8. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB: Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell. 2005 Oct 21;123(2):291-304. [Article]
  9. Day B, To C, Himanen JP, Smith FM, Nikolov DB, Boyd AW, Lackmann M: Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3. J Biol Chem. 2005 Jul 15;280(28):26526-32. Epub 2005 May 18. [Article]
  10. Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M: PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010 Dec 6. [Article]
  11. Davis TL, Walker JR, Loppnau P, Butler-Cole C, Allali-Hassani A, Dhe-Paganon S: Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure. 2008 Jun;16(6):873-84. doi: 10.1016/j.str.2008.03.008. [Article]
  12. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]
  13. Wood LD, Calhoun ES, Silliman N, Ptak J, Szabo S, Powell SM, Riggins GJ, Wang TL, Yan H, Gazdar A, Kern SE, Pennacchio L, Kinzler KW, Vogelstein B, Velculescu VE: Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat. 2006 Oct;27(10):1060-1. [Article]
  14. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
  15. Corbo V, Ritelli R, Barbi S, Funel N, Campani D, Bardelli A, Scarpa A: Mutational profiling of kinases in human tumours of pancreatic origin identifies candidate cancer genes in ductal and ampulla of vater carcinomas. PLoS One. 2010 Sep 8;5(9):e12653. doi: 10.1371/journal.pone.0012653. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails