P29320 (EPHA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-A receptor 3
EC=2.7.10.1

Alternative name(s):
EPH-like kinase 4
Short name=EK4
Short name=hEK4
HEK
Short name=Human embryo kinase
Tyrosine-protein kinase TYRO4
Tyrosine-protein kinase receptor ETK1
Short name=Eph-like tyrosine kinase 1

Gene names

Name:	EPHA3
Synonyms:	ETK, ETK1, HEK, TYRO4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	983 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 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. Ref.5
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling By similarity. Interacts (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Ref.5 Ref.6 Ref.7 Ref.9
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.5 Ref.9. Isoform 2: Secreted Ref.5 Ref.9.
Tissue specificity	Widely expressed. Highest level in placenta.
Post-translational modification	Autophosphorylates upon activation by EFNA5. Phosphorylation on Tyr-602 mediates interaction with NCK1. Dephosphorylated by PTPN1. Ref.9 Ref.10
Involvement in disease	Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note: The gene represented in this entry may be involved in disease pathogenesis.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. Contains 1 Eph LBD (Eph ligand-binding) domain. Contains 2 fibronectin type-III domains. Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell migration Inferred from sequence or structural similarity. Source: UniProtKB cellular response to retinoic acid Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL fasciculation of motor neuron axon Inferred from sequence or structural similarity. Source: UniProtKB fasciculation of sensory neuron axon Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron projection development Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL regulation of Rho GTPase activity Inferred from direct assay Ref.5. Source: UniProtKB regulation of actin cytoskeleton organization Inferred from direct assay Ref.5. Source: UniProtKB regulation of epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB regulation of focal adhesion assembly Inferred from direct assay Ref.5. Source: UniProtKB regulation of microtubule cytoskeleton organization Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	early endosome Inferred from direct assay Ref.9. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from direct assay Ref.5Ref.9. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GPI-linked ephrin receptor activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P29320-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P29320-2)

The sequence of this isoform differs from the canonical sequence as follows:
     532-539: SFSISGES → CMYYFNAV
     540-983: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Ref.3

Chain

21 – 983

963

Ephrin type-A receptor 3

PRO_0000016802

Regions

Topological domain

21 – 541

521

Extracellular Potential

Transmembrane

542 – 565

24

Helical; Potential

Topological domain

566 – 983

418

Cytoplasmic Potential

Domain

29 – 207

179

Eph LBD

Domain

325 – 429

105

Fibronectin type-III 1

Domain

437 – 528

92

Fibronectin type-III 2

Domain

621 – 882

262

Protein kinase

Domain

911 – 975

65

SAM

Nucleotide binding

628 – 633

6

ATP

Nucleotide binding

700 – 706

7

ATP

Nucleotide binding

750 – 751

2

ATP

Motif

981 – 983

3

PDZ-binding Potential

Compositional bias

189 – 322

134

Cys-rich

Sites

Active site

746

1

Proton acceptor By similarity

Binding site

653

1

ATP

Amino acid modifications

Modified residue

596

1

Phosphotyrosine; by autocatalysis Ref.10

Modified residue

602

1

Phosphotyrosine; by autocatalysis Ref.10

Modified residue

701

1

Phosphotyrosine; by autocatalysis Ref.10

Modified residue

779

1

Phosphotyrosine; by autocatalysis

Modified residue

937

1

Phosphotyrosine By similarity

Glycosylation

232

1

N-linked (GlcNAc...) Potential

Glycosylation

337

1

N-linked (GlcNAc...) Potential

Glycosylation

391

1

N-linked (GlcNAc...) Potential

Glycosylation

404

1

N-linked (GlcNAc...) Potential

Glycosylation

493

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

532 – 539

8

SFSISGES → CMYYFNAV in isoform 2.

VSP_002995

Alternative sequence

540 – 983

444

Missing in isoform 2.

VSP_002996

Natural variant

37

1

T → K in a colorectal cancer sample; somatic mutation. Ref.11

VAR_036086

Natural variant

85

1

N → S in a colorectal cancer sample; somatic mutation. Ref.11

VAR_036087

Natural variant

207

1

K → N in a pancreatic ductal adenocarcinoma sample; somatic mutation. Ref.14

VAR_068853

Natural variant

229

1

S → Y in a lung large cell carcinoma sample; somatic mutation. Ref.13

VAR_042126

Natural variant

449

1

S → F in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.13

VAR_042127

Natural variant

518

1

G → L in a lung squamous cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions. Ref.13

VAR_042128

Natural variant

564

1

I → V. Ref.13
Corresponds to variant rs55712516 [ dbSNP | Ensembl ].

VAR_042129

Natural variant

568

1

C → S. Ref.13
Corresponds to variant rs56077781 [ dbSNP | Ensembl ].

VAR_042130

Natural variant

590

1

L → P. Ref.13
Corresponds to variant rs56081642 [ dbSNP | Ensembl ].

VAR_042131

Natural variant

621

1

I → L in a colorectal cancer sample; somatic mutation. Ref.11

VAR_036088

Natural variant

660

1

T → K in a lung carcinoma sample; somatic mutation. Ref.12

VAR_065831

Natural variant

766

1

G → E in a lung adenocarcinoma sample; somatic mutation. Ref.13

VAR_042132

Natural variant

777

1

A → G. Ref.13
Corresponds to variant rs34437982 [ dbSNP | Ensembl ].

VAR_042133

Natural variant

806

1

D → N in a colorectal cancer sample; somatic mutation. Ref.11

VAR_036089

Natural variant

914

1

R → H. Ref.13
Corresponds to variant rs17801309 [ dbSNP | Ensembl ].

VAR_027919

Natural variant

924

1

W → R. Ref.1 Ref.13
Corresponds to variant rs35124509 [ dbSNP | Ensembl ].

VAR_042134

Natural variant

933

1

T → M in a lung carcinoma sample; somatic mutation. Ref.12

VAR_065832

Experimental info

Mutagenesis

133

1

V → E: Loss of EFNA5-binding ability and function. Ref.6

Mutagenesis

152

1

F → L: Loss of EFNA5-binding ability and function. Ref.6

Mutagenesis

596

1

Y → F: 10-fold suppression of kinase activity; when associated with F-602. Full kinase activity; when associated with F-602 and F-742. Full kinase activity; when associated with F-602 and A-768. Ref.10

Mutagenesis

602

1

Y → F: 10-fold suppression of kinase activity; when associated with F-596. Full kinase activity; when associated with F-596 and F-742. Full kinase activity; when associated with F-596 and A-768. Ref.10

Mutagenesis

742

1

Y → F: Full kinase activity; when associated with F-596 and F-602. Ref.10

Mutagenesis

768

1

S → A: Full kinase activity; when associated with F-596 and F-602. Ref.10

Sequence conflict

911

1

T → S in AAA58633. Ref.1

Secondary structure

1

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983

Helix Strand Turn

Details...

Turn

610 – 612

3

Helix

618 – 620

3

Beta strand

621 – 629

9

Beta strand

631 – 641

11

Beta strand

647 – 654

8

Helix

661 – 674

14

Beta strand

685 – 689

5

Beta strand

691 – 694

4

Beta strand

696 – 700

5

Helix

707 – 712

6

Turn

713 – 716

4

Helix

720 – 739

20

Helix

749 – 751

3

Beta strand

752 – 754

3

Beta strand

760 – 762

3

Helix

765 – 767

3

Helix

788 – 790

3

Helix

793 – 798

6

Helix

803 – 818

16

Turn

819 – 821

3

Turn

824 – 827

4

Helix

830 – 838

9

Helix

851 – 860

10

Helix

865 – 867

3

Helix

871 – 883

13

Helix

885 – 889

5

Beta strand

890 – 892

3

Beta strand

898 – 903

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: BE04DBF958245424	FASTA	983	110,131
	10 20 30 40 50 60 MDCQLSILLL LSCSVLDSFG ELIPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE 70 80 90 100 110 120 HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF 130 140 150 160 170 180 NLYYMESDDD HGVKFREHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY 190 200 210 220 230 240 LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP 250 260 270 280 290 300 RMYCSTEGEW LVPIGKCSCN AGYEERGFMC QACRPGFYKA LDGNMKCAKC PPHSSTQEDG 310 320 330 340 350 360 SMNCRCENNY FRADKDPPSM ACTRPPSSPR NVISNINETS VILDWSWPLD TGGRKDVTFN 370 380 390 400 410 420 IICKKCGWNI KQCEPCSPNV RFLPRQFGLT NTTVTVTDLL AHTNYTFEID AVNGVSELSS 430 440 450 460 470 480 PPRQFAAVSI TTNQAAPSPV LTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ 490 500 510 520 530 540 ETSYTILRAR GTNVTISSLK PDTIYVFQIR ARTAAGYGTN SRKFEFETSP DSFSISGESS 550 560 570 580 590 600 QVVMIAISAA VAIILLTVVI YVLIGRFCGY KSKHGADEKR LHFGNGHLKL PGLRTYVDPH 610 620 630 640 650 660 TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKVGYT 670 680 690 700 710 720 EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPVMIVTE YMENGSLDSF LRKHDAQFTV 730 740 750 760 770 780 IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT 790 800 810 820 830 840 TRGGKIPIRW TSPEAIAYRK FTSASDVWSY GIVLWEVMSY GERPYWEMSN QDVIKAVDEG 850 860 870 880 890 900 YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN 910 920 930 940 950 960 LLLDQSNVDI TTFRTTGDWL NGVWTAHCKE IFTGVEYSSC DTIAKISTDD MKKVGVTVVG 970 980 PQKKIISSIK ALETQSKNGP VPV
	Isoform 2 [UniParc]. Checksum: 14736950EF1153F1	FASTA	539	60,946
	10 20 30 40 50 60 MDCQLSILLL LSCSVLDSFG ELIPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE 70 80 90 100 110 120 HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF 130 140 150 160 170 180 NLYYMESDDD HGVKFREHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY 190 200 210 220 230 240 LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP 250 260 270 280 290 300 RMYCSTEGEW LVPIGKCSCN AGYEERGFMC QACRPGFYKA LDGNMKCAKC PPHSSTQEDG 310 320 330 340 350 360 SMNCRCENNY FRADKDPPSM ACTRPPSSPR NVISNINETS VILDWSWPLD TGGRKDVTFN 370 380 390 400 410 420 IICKKCGWNI KQCEPCSPNV RFLPRQFGLT NTTVTVTDLL AHTNYTFEID AVNGVSELSS 430 440 450 460 470 480 PPRQFAAVSI TTNQAAPSPV LTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ 490 500 510 520 530 ETSYTILRAR GTNVTISSLK PDTIYVFQIR ARTAAGYGTN SRKFEFETSP DCMYYFNAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines." Wicks I.P., Wilkinson D., Salvaris E., Boyd A.W. Proc. Natl. Acad. Sci. U.S.A. 89:1611-1615(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-924.
[2]	"Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules." Chiari R., Hames G., Stroobant V., Texier C., Maillere B., Boon T., Coulie P.G. Cancer Res. 60:4855-4863(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Melanoma.
[3]	"Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line." Boyd A.W., Ward L.D., Wicks I.P., Simpson R.J., Salvaris E., Wilks A., Welch K., Loudovaris M., Rockman S., Busmanis I. J. Biol. Chem. 267:3262-3267(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-29 AND 840-860, CHARACTERIZATION.
[4]	"Unified nomenclature for Eph family receptors and their ligands, the ephrins." Eph nomenclature committee Cell 90:403-404(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NOMENCLATURE.
[5]	"Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling." Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M., Boyd A.W., Alewood P.F., Lackmann M. J. Cell Sci. 115:1059-1072(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL-CELL ADHESION, EFNA5-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH CRK.
[6]	"Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen." Smith F.M., Vearing C., Lackmann M., Treutlein H., Himanen J., Chen K., Saul A., Nikolov D., Boyd A.W. J. Biol. Chem. 279:9522-9531(2004) [PubMed] [Europe PMC] [Abstract] Cited for: EPHRIN LIGAND-BINDING, OLIGOMERIZATION, MUTAGENESIS OF VAL-133 AND PHE-152, INTERACTION WITH CRK.
[7]	"Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans." Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B. Cell 123:291-304(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH ADAM10 AND EFNA5.
[8]	"Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3." Day B., To C., Himanen J.P., Smith F.M., Nikolov D.B., Boyd A.W., Lackmann M. J. Biol. Chem. 280:26526-26532(2005) [PubMed] [Europe PMC] [Abstract] Cited for: EFNA5 LIGAND-BINDING.
[9]	"PTP1B regulates Eph receptor function and trafficking." Nievergall E., Janes P.W., Stegmayer C., Vail M.E., Haj F.G., Teng S.W., Neel B.G., Bastiaens P.I., Lackmann M. J. Cell Biol. 191:1189-1203(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPN1, PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN1, SUBCELLULAR LOCATION.
[10]	"Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3)." Davis T.L., Walker J.R., Loppnau P., Butler-Cole C., Allali-Hassani A., Dhe-Paganon S. Structure 16:873-884(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.07 ANGSTROMS) OF 577-947 IN COMPLEX WITH ATP ANALOG, IDENTIFICATION BY MASS SPECTROMETRY, AUTOPHOSPHORYLATION AT TYR-596; TYR-602 AND TYR-701, MUTAGENESIS OF TYR-596; TYR-602; TYR-742 AND SER-768.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-37; SER-85; LEU-621 AND ASN-806.
[12]	"Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers." Wood L.D., Calhoun E.S., Silliman N., Ptak J., Szabo S., Powell S.M., Riggins G.J., Wang T.L., Yan H., Gazdar A., Kern S.E., Pennacchio L., Kinzler K.W., Vogelstein B., Velculescu V.E. Hum. Mutat. 27:1060-1061(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-660 AND MET-933.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-229; PHE-449; LEU-518; VAL-564; SER-568; PRO-590; GLU-766; GLY-777; HIS-914 AND ARG-924.
[14]	"Mutational profiling of kinases in human tumours of pancreatic origin identifies candidate cancer genes in ductal and ampulla of vater carcinomas." Corbo V., Ritelli R., Barbi S., Funel N., Campani D., Bardelli A., Scarpa A. PLoS ONE 5:E12653-E12653(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASN-207.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M83941 mRNA. Translation: AAA58633.1.
AF213459 mRNA. Translation: AAG43576.1.
AF213460 mRNA. Translation: AAG43577.1.

IPI

IPI00219172.
IPI00298105.

PIR

A38224.

RefSeq

NP_005224.2. NM_005233.5.
NP_872585.1. NM_182644.2.

UniGene

Hs.123642.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GSF	X-ray	1.77	A	577-947	[»]
2QO2	X-ray	1.60	A	577-947	[»]
2QO7	X-ray	1.60	A	577-947	[»]
2QO9	X-ray	1.55	A	577-947	[»]
2QOB	X-ray	1.65	A	606-947	[»]
2QOC	X-ray	1.25	A	606-947	[»]
2QOD	X-ray	1.15	A	577-947	[»]
2QOF	X-ray	1.20	A	577-947	[»]
2QOI	X-ray	1.25	A	577-947	[»]
2QOK	X-ray	1.20	A	577-947	[»]
2QOL	X-ray	1.07	A	577-947	[»]
2QON	X-ray	1.79	A	577-947	[»]
2QOO	X-ray	1.25	A	577-947	[»]
2QOQ	X-ray	1.60	A	577-947	[»]
3DZQ	X-ray	1.75	A	606-947	[»]
3FXX	X-ray	1.70	A	577-947	[»]
3FY2	X-ray	1.80	A	577-947	[»]
4G2F	X-ray	1.70	A	606-947	[»]
4GK2	X-ray	2.20	A	606-947	[»]
4GK3	X-ray	1.90	A	606-947	[»]
4GK4	X-ray	2.10	A	606-947	[»]

ProteinModelPortal

P29320.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-40307N.

IntAct

P29320. 3 interactions.

STRING

9606.ENSP00000337451.

PTM databases

PhosphoSite

P29320.

Polymorphism databases

DMDM

116241351.

Proteomic databases

PaxDb

P29320.

PRIDE

P29320.

Protocols and materials databases

DNASU

2042.

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000336596; ENSP00000337451; ENSG00000044524.
ENST00000452448; ENSP00000399926; ENSG00000044524.

GeneID

2042.

KEGG

hsa:2042.

UCSC

uc003dqx.1. human.
uc003dqy.3. human.

Organism-specific databases

CTD

2042.

GeneCards

GC03P089239.

HGNC

HGNC:3387. EPHA3.

HPA

CAB010462.

MIM

114500. phenotype.
179611. gene.

neXtProt

NX_P29320.

PharmGKB

PA27819.

GenAtlas

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Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233856.

HOVERGEN

HBG062180.

InParanoid

P29320.

KO

K05104.

OMA

DMKKVGV.

OrthoDB

EOG4SXNBR.

PhylomeDB

P29320.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Pathway_Interaction_DB

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

Gene expression databases

ArrayExpress

P29320.

Bgee

P29320.

CleanEx

HS_EPHA3.

Genevestigator

P29320.

GermOnline

ENSG00000044524. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.
2.60.40.10. 2 hits.

InterPro

IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. Fibronectin_type3.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016257. Tyr_kinase_ephrin_rcpt.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]

Pfam

PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07699. GCC2_GCC3. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]

PIRSF

PIRSF000666. TyrPK_ephrin_receptor. 1 hit.

PRINTS

PR00109. TYRKINASE.

SMART

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

SUPFAM

SSF49265. FN_III-like. 2 hits.
SSF49785. Gal_bind_like. 1 hit.
SSF56112. Kinase_like. 1 hit.
SSF47769. SAM_homology. 1 hit.

PROSITE

PS01186. EGF_2. 1 hit. Uncertain.
PS51550. EPH_LBD. 1 hit.
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

BindingDB

P29320.

ChEMBL

CHEMBL4954.

EvolutionaryTrace

P29320.

GenomeRNAi

2042.

NextBio

8295.

SOURCE

Search...

Entry information

Entry name

EPHA3_HUMAN

Accession

Primary (citable) accession number: P29320
Secondary accession number(s): Q9H2V3, Q9H2V4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 151 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.