Reviewed, UniProtKB/Swiss-Prot P29317 (EPHA2_HUMAN)

Names and origin

Protein names

Recommended name:
    Ephrin type-A receptor 2
    EC=2.7.10.1
Alternative name(s):
    Tyrosine-protein kinase receptor ECK
    Epithelial cell kinase

Gene names

Name:	EPHA2
Synonyms:	ECK

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	976 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for members of the ephrin-A family. Binds to ephrin-A1, -A3, -A4 and -A5. Plays an important role in angiogenesis and tumor neovascularization. The recruitement of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly By similarity. Induces apoptosis in a TP53/p53-independent, caspase-8-dependent manner. Ref.10
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Monomer at low protein concentrations (around 10 µM) and forms homodimers at higher concentrations. Forms heterodimers with EFNA1. Interacts with SLA. The phosphorylated form interacts with VAV2, VAV3 and PI3-kinase p85 subunit By similarity. Interacts with INPPL1/SHIP2. Ref.8 Ref.19
Subcellular location	Membrane; Single-pass type I membrane protein Ref.11.
Tissue specificity	Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g., skin, intestine, lung, and ovary. Ref.7
Induction	By ultraviolet radiation (UV) via a TP53/p53-independent, but MAPK-dependent, mechanism. Ref.10
Post-translational modification	Activated by EFNA1 via tyrosine phosphorylation. Phosphorylated residues Tyr-588 and Tyr-594 are required for binding VAV2 and VAV3 while phosphorylated residues Tyr-735 and Tyr-930 are required for binding PI3-kinase p85 subunit. These phosphorylated residues are critical for recruitment of VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream signaling to activate RAC1 GTPase and endothelial cell migration. They also play a critical role in transducing EPHA2 signaling in vascular endothelial cells during tumor angiogenesis By similarity. Ref.11 Ref.5 Ref.6 Ref.9 Ref.12 Ref.13 Ref.15
Involvement in disease	Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:613020]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision. Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:116600]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. Contains 2 fibronectin type-III domains. Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Angiogenesis Apoptosis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW apoptosis Ref.10 Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of blood vessel endothelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ephrin receptor activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Chain

25 – 976

952

Ephrin type-A receptor 2

PRO_0000016800

Regions

Topological domain

25 – 534

510

Extracellular Potential

Transmembrane

535 – 558

24

Potential

Topological domain

559 – 976

418

Cytoplasmic Potential

Domain

328 – 429

102

Fibronectin type-III 1

Domain

435 – 526

92

Fibronectin type-III 2

Domain

613 – 875

263

Protein kinase

Domain

904 – 968

65

SAM

Nucleotide binding

619 – 627

9

ATP By similarity

Motif

974 – 976

3

PDZ-binding Potential

Compositional bias

188 – 325

138

Cys-rich

Sites

Active site

739

1

Proton acceptor By similarity

Binding site

646

1

ATP By similarity

Amino acid modifications

Modified residue

153

1

Phosphoserine

Modified residue

373

1

Phosphoserine

Modified residue

570

1

Phosphoserine Ref.9 Ref.12 Ref.13

Modified residue

575

1

Phosphotyrosine Ref.6 Ref.12 Ref.15

Modified residue

579

1

Phosphoserine Ref.12

Modified residue

587

1

Phosphothreonine

Modified residue

588

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

593

1

Phosphothreonine

Modified residue

594

1

Phosphotyrosine; by autocatalysis Ref.5 Ref.6 Ref.9 Ref.12 Ref.15

Modified residue

628

1

Phosphotyrosine Ref.12

Modified residue

647

1

Phosphothreonine Ref.12

Modified residue

735

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

771

1

Phosphothreonine

Modified residue

772

1

Phosphotyrosine; by autocatalysis Ref.5 Ref.6 Ref.9 Ref.12 Ref.15

Modified residue

790

1

Phosphoserine

Modified residue

791

1

Phosphotyrosine

Modified residue

869

1

Phosphoserine

Modified residue

880

1

Phosphoserine

Modified residue

892

1

Phosphoserine Ref.13

Modified residue

897

1

Phosphoserine Ref.9 Ref.12

Modified residue

898

1

Phosphothreonine Ref.9 Ref.12

Modified residue

899

1

Phosphoserine Ref.12

Modified residue

901

1

Phosphoserine Ref.9 Ref.12 Ref.13

Modified residue

910

1

Phosphoserine

Modified residue

921

1

Phosphotyrosine; by autocatalysis Potential

Modified residue

930

1

Phosphotyrosine Ref.5

Modified residue

960

1

Phosphotyrosine Ref.15

Glycosylation

407

1

N-linked (GlcNAc...) Potential

Glycosylation

435

1

N-linked (GlcNAc...) Ref.14

Disulfide bond

70 ↔ 188

Ref.19

Disulfide bond

105 ↔ 115

Ref.19

Natural variations

Natural variant

99

1

K → N: dbSNP rs1058372.

VAR_055989

Natural variant

391

1

G → R: dbSNP rs34192549. Ref.22

VAR_042121

Natural variant

511

1

T → M: dbSNP rs55747232. Ref.22

VAR_042122

Natural variant

568

1

R → H: dbSNP rs56198600. Ref.22

VAR_042123

Natural variant

631

1

M → T: dbSNP rs34021505.

VAR_055990

Natural variant

721

1

R → Q in ARCC2; alters EPHA2 signaling.

VAR_062532

Natural variant

777

1

G → S in a gastric adenocarcinoma sample; somatic mutation. Ref.22

VAR_042124

Natural variant

876

1

R → H: dbSNP rs35903225. Ref.22

VAR_042125

Natural variant

940

1

T → I in CTPP1.

VAR_058907

Natural variant

948

1

G → W in CTPP1.

VAR_058908

Experimental info

Mutagenesis

103

1

R → E: Significantly reduced response to EFNA1. Ref.19

Sequence conflict

94 – 99

6

IFIELK → NNFELN in AAA53375. Ref.1

Secondary structure

1

.

.

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976

Helix Strand Turn

Details...

Turn

610 – 612

3

Beta strand

613 – 621

9

Beta strand

623 – 633

11

Beta strand

640 – 648

9

Helix

654 – 668

15

Beta strand

678 – 682

5

Beta strand

684 – 693

10

Helix

700 – 706

7

Turn

707 – 709

3

Helix

713 – 732

20

Helix

742 – 744

3

Beta strand

745 – 747

3

Beta strand

753 – 755

3

Helix

781 – 783

3

Helix

786 – 790

5

Helix

796 – 811

16

Turn

817 – 820

4

Helix

823 – 831

9

Helix

844 – 853

10

Turn

858 – 860

3

Helix

864 – 876

13

Helix

878 – 882

5

Helix

909 – 915

7

Helix

919 – 921

3

Helix

922 – 928

7

Helix

933 – 936

4

Helix

943 – 946

4

Helix

952 – 970

19

Sequences

	Sequence		Length	Mass (Da)
	P29317-1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 845D7E1BBCCAACCC	FASTA	976	108,266
	10 20 30 40 50 60 MELQAARACF ALLWGCALAA AAAAQGKEVV LLDFAAAGGE LGWLTHPYGK GWDLMQNIMN 70 80 90 100 110 120 DMPIYMYSVC NVMSGDQDNW LRTNWVYRGE AERIFIELKF TVRDCNSFPG GASSCKETFN 130 140 150 160 170 180 LYYAESDLDY GTNFQKRLFT KIDTIAPDEI TVSSDFEARH VKLNVEERSV GPLTRKGFYL 190 200 210 220 230 240 AFQDIGACVA LLSVRVYYKK CPELLQGLAH FPETIAGSDA PSLATVAGTC VDHAVVPPGG 250 260 270 280 290 300 EEPRMHCAVD GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEASESPC LECPEHTLPS 310 320 330 340 350 360 PEGATSCECE EGFFRAPQDP ASMPCTRPPS APHYLTAVGM GAKVELRWTP PQDSGGREDI 370 380 390 400 410 420 VYSVTCEQCW PESGECGPCE ASVRYSEPPH GLTRTSVTVS DLEPHMNYTF TVEARNGVSG 430 440 450 460 470 480 LVTSRSFRTA SVSINQTEPP KVRLEGRSTT SLSVSWSIPP PQQSRVWKYE VTYRKKGDSN 490 500 510 520 530 540 SYNVRRTEGF SVTLDDLAPD TTYLVQVQAL TQEGQGAGSK VHEFQTLSPE GSGNLAVIGG 550 560 570 580 590 600 VAVGVVLLLV LAGVGFFIHR RRKNQRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA 610 620 630 640 650 660 VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG MLKTSSGKKE VPVAIKTLKA GYTEKQRVDF 670 680 690 700 710 720 LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEYMENGAL DKFLREKDGE FSVLQLVGML 730 740 750 760 770 780 RGIAAGMKYL ANMNYVHRDL AARNILVNSN LVCKVSDFGL SRVLEDDPEA TYTTSGGKIP 790 800 810 820 830 840 IRWTAPEAIS YRKFTSASDV WSFGIVMWEV MTYGERPYWE LSNHEVMKAI NDGFRLPTPM 850 860 870 880 890 900 DCPSAIYQLM MQCWQQERAR RPKFADIVSI LDKLIRAPDS LKTLADFDPR VSIRLPSTSG 910 920 930 940 950 960 SEGVPFRTVS EWLESIKMQQ YTEHFMAAGY TAIEKVVQMT NDDIKRIGVR LPGHQKRIAY 970 SLLGLKDQVN TVGIPI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases." Lindberg R.A., Hunter T. Mol. Cell. Biol. 10:6316-6324(1990) [PubMed: 2174105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epithelium.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[5]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-588; TYR-594; TYR-772; TYR-921 AND TYR-930, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-575; TYR-588; TYR-594 AND TYR-772, MASS SPECTROMETRY.
[7]	"Ephrin-A1 is a negative regulator in glioma through down-regulation of EphA2 and FAK." Liu D.-P., Wang Y., Koeffler H.P., Xie D. Int. J. Oncol. 30:865-871(2007) [PubMed: 17332925] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation." Zhuang G., Hunter S., Hwang Y., Chen J. J. Biol. Chem. 282:2683-2694(2007) [PubMed: 17135240] [Abstract] Cited for: INTERACTION WITH INPPL1.
[9]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; TYR-594; TYR-772; SER-897; THR-898 AND SER-901, MASS SPECTROMETRY.
[10]	"EphA2 is an essential mediator of UV radiation-induced apoptosis." Zhang G., Njauw C.-N., Park J.M., Naruse C., Asano M., Tsao H. Cancer Res. 68:1691-1696(2008) [PubMed: 18339848] [Abstract] Cited for: FUNCTION, INDUCTION.
[11]	"Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor." Wykosky J., Palma E., Gibo D.M., Ringler S., Turner C.P., Debinski W. Oncogene 27:7260-7273(2008) [PubMed: 18794797] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; TYR-575; SER-579; TYR-594; TYR-628; THR-647; TYR-772; SER-897; THR-898; SER-899 AND SER-901, MASS SPECTROMETRY.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; SER-892 AND SER-901, MASS SPECTROMETRY.
[14]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-435, MASS SPECTROMETRY. Tissue: Liver.
[15]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-575; TYR-588; TYR-594; TYR-772 AND TYR-960, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[16]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-373; SER-570; TYR-575; THR-587; TYR-588; THR-593; TYR-594; TYR-628; THR-647; THR-771; TYR-772; SER-790; TYR-791; SER-869; SER-880; SER-897; THR-898; SER-899; SER-901; SER-910 AND TYR-960, MASS SPECTROMETRY.
[17]	"Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography." Nowakowski J., Cronin C.N., McRee D.E., Knuth M.W., Nelson C.G., Pavletich N.P., Rogers J., Sang B.C., Scheibe D.N., Swanson R.V., Thompson D.A. Structure 10:1659-1667(2002) [PubMed: 12467573] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 596-900.
[18]	"Solution structure of the C-terminal SAM-domain of EPHAA2: ephrin type-A receptor 2 precursor (EC 2.7.10.1)." RIKEN structural genomics initiative (RSGI) Submitted (JAN-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 902-976.
[19]	"Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex." Himanen J.P., Goldgur Y., Miao H., Myshkin E., Guo H., Buck M., Nguyen M., Rajashankar K.R., Wang B., Nikolov D.B. EMBO Rep. 10:722-728(2009) [PubMed: 19525919] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 28-201, X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 28-201 IN COMPLEX WITH EFNA1, SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF ARG-103.
[20]	"Ephrin A1 bound to the ligand binding domain of the human ephrin A2 (epha2) receptor protein kinase." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 25-202, DISULFIDE BOND.
[21]	"Left-handed dimer of EPHA2 transmembrane domain helix packing diversity among receptor tyrosine kinases." Mayzel M.L., Bocharov E.V., Volynsky P.E., Arseniev A.S. Submitted (AUG-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 523-563.
[22]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-391; MET-511; HIS-568; SER-777 AND HIS-876.
[23]	"The EPHA2 gene is associated with cataracts linked to chromosome 1p." Shiels A., Bennett T.M., Knopf H.L.S., Maraini G., Li A., Jiao X., Hejtmancik J.F. Mol. Vis. 14:2042-2055(2008) [PubMed: 19005574] [Abstract] Cited for: VARIANT CTPP1 TRP-948, INVOLVEMENT IN AGE-RELATED CATARACTS.
[24]	"Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract." Zhang T., Hua R., Xiao W., Burdon K.P., Bhattacharya S.S., Craig J.E., Shang D., Zhao X., Mackey D.A., Moore A.T., Luo Y., Zhang J., Zhang X. Hum. Mutat. 30:E603-E611(2009) [PubMed: 19306328] [Abstract] Cited for: VARIANT CTPP1 ILE-940.
[25]	"EPHA2 is associated with age-related cortical cataract in mice and humans." Jun G., Guo H., Klein B.E., Klein R., Wang J.J., Mitchell P., Miao H., Lee K.E., Joshi T., Buck M., Chugha P., Bardenstein D., Klein A.P., Bailey-Wilson J.E., Gong X., Spector T.D., Andrew T., Hammond C.J. , Elston R.C., Iyengar S.K., Wang B. PLoS Genet. 5:E1000584-E1000584(2009) [PubMed: 19649315] [Abstract] Cited for: VARIANT ARCC2 GLN-721, CHARACTERIZATION OF VARIANT ARCC2 GLN-721.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M59371 mRNA. Translation: AAA53375.1.
AL451042 Genomic DNA. Translation: CAH71943.1.
CH471167 Genomic DNA. Translation: EAW51769.1.
BC037166 mRNA. Translation: AAH37166.1.

IPI

IPI00021267.

PIR

A36355.

RefSeq

NP_004422.2.

UniGene

Hs.171596

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MQB	X-ray	2.30	A/B	596-900	[»]
2E8N	NMR	-	A	902-976	[»]
2K9Y	NMR	-	A/B	523-563	[»]
3C8X	X-ray	1.95	A	23-202	[»]
3CZU	X-ray	2.65	A	23-202	[»]
3FL7	X-ray	2.50	A	23-531	[»]
3HEI	X-ray	2.00	A/C/E/G/I/K/M/O	28-201	[»]
3HPN	X-ray	2.52	A/B/C/D/E/F	28-201	[»]
3KKA	X-ray	2.40	C/D/E	903-971	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-96N.

STRING

P29317.

PTM databases

PhosphoSite

P29317.

Proteomic databases

PRIDE

P29317.

Genome annotation databases

Ensembl

ENST00000358432; ENSP00000351209; ENSG00000142627; Homo sapiens. [Genome view]
ENST00000407976; ENSP00000384858; ENSG00000142627; Homo sapiens. [Genome view]

GeneID

1969.

KEGG

hsa:1969.

Organism-specific databases

CTD

1969.

GeneCards

GC01M016323.

HGNC

HGNC:3386. EPHA2.

HPA

CAB010464.

MIM

116600. phenotype.
176946. gene.
613020. phenotype.

Orphanet

98993. Cataract, posterior polar.

PharmGKB

PA27818.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08660.

HOGENOM

HBG755340.

HOVERGEN

P29317.

InParanoid

P29317.

OMA

VHEFQTL.

OrthoDB

EOG9JDKSD.

PhylomeDB

P29317.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
epha2_fwdpathway. EPHA2 forward signaling.
ephrina_ephapathway. EphrinA-EPHA pathway.

Gene expression databases

ArrayExpress

P29317.

Bgee

P29317.

CleanEx

HS_EPHA2.

Genevestigator

P29317.

GermOnline

ENSG00000142627. Homo sapiens.

Family and domain databases

InterPro

IPR001090. Ephrin_rcpt_lig-bd.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR010993. SAM_homology.
IPR013761. SAM_type.
IPR021129. SAM_type1.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR016257. Tyr_prot_kinase_ephrin_rcpt.
IPR001426. Tyr_prot_kinase_rcpt_V_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 1 hit.
G3DSA:1.10.150.50. SAM_type. 1 hit.

PANTHER

PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF00536. SAM_1. 1 hit.
[Graphical view]

PIRSF

PIRSF000666. TyrPK_ephrin_receptor. 1 hit.

SMART

SM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS50853. FN3. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00790. RECEPTOR_TYR_KIN_V_1. 1 hit.
PS00791. RECEPTOR_TYR_KIN_V_2. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01254. Dasatinib.

NextBio

7983.

SOURCE

Search...

Entry information

Entry name

EPHA2_HUMAN

Accession

Primary (citable) accession number: P29317
Secondary accession number(s): Q8N3Z2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	May 5, 2009
Last modified:	February 9, 2010
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.