Q03145 (EPHA2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin type-A receptor 2
EC=2.7.10.1

Alternative name(s):
Epithelial cell kinase
Tyrosine-protein kinase receptor ECK
Tyrosine-protein kinase receptor MPK-5
Tyrosine-protein kinase receptor SEK-2

Gene names

Name:	Epha2
Synonyms:	Eck, Myk2, Sek2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	977 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-A 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.1
Subunit structure	Homodimer. Interacts with INPPL1; regulates activated EPHA2 endocytosis and degradation. Interacts (inactivated form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16, DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4 and may regulate tight junctions. Interacts with ACP1 By similarity. Interacts with SLA. Interacts (phosphorylated form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3); critical for the EFNA1-induced activation of RAC1 which stimulates cell migration. Interacts with ANKS1A. Ref.9 Ref.13 Ref.14 Ref.21
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Cell projection › ruffle membrane; Single-pass type I membrane protein By similarity. Cell projection › lamellipodium membrane; Single-pass type I membrane protein By similarity. Cell junction › focal adhesion By similarity. Note: Present at regions of cell-cell contacts but also at the leading edge of migrating cells By similarity.
Tissue specificity	Expressed in the lung, intestine and liver. Ref.10
Developmental stage	First detected in gastrulation stage embryos (6.5-7.5 dpc) in ectodermal cells adjacent to the distal region of the primitive streak. By the neural plate stage (approximately 7.5 dpc), EPHA2 expression becomes restricted to the extreme distal end or node of the primitive streak. After the beginning of somitogenesis (approximately 8.0 dpc), expression persists in the node as this structure regresses toward the caudal end of the embryo. In addition, beginning at the mid head fold stage (approximately 7.75 dpc), we observe that EPHA2 exhibits a dynamic and spatially restricted expression pattern in the prospective hindbrain region. EPHA2 transcripts are initially detected in a 5-cell wide strip of mesodermal cells underlying prospective rhombomere 4 (R4). Subsequently at the beginning of somitogenesis, expression is observed in prospective R4. At the 4-8-somite stage, EPHA2 transcripts are observed in R4, mesenchymal cells underlying R4, and surface ectoderm in the vicinity of the developing second branchial arch. By the 10-somite stage, expression in these cells is down-regulated. Additionally, at the 5-8-somite stage, EPHA2 transcripts are detected initially in the lateral mesenchyme immediately underlying the surface ectoderm adjacent to R5 and R6, and subsequently in surface ectoderm overlying the developing third branchial arch. Ref.1 Ref.2 Ref.7 Ref.10
Post-translational modification	Autophosphorylates. Phosphorylated at Ser-898 by PKB; serum-induced phosphorylation which targets EPHA2 to the cell leading edge and stimulates cell migration. Phosphorylation by PKB is inhibited by EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal regulatory loop. Dephosphorylated by ACP1 By similarity. Phosphorylated on tyrosine upon binding and activation by EFNA1. Phosphorylated residues Tyr-589 and Tyr-595 are required for binding VAV2 and VAV3 while phosphorylated residues Tyr-736 and Tyr-931 are required for binding PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3). 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 cell migration By similarity. Ref.14 Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the HSP90 chaperone and regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation. Ref.21
Disruption phenotype	Mice are viable, fertile but exhibit aberrant development of tail vertebra and susceptibility to carcinogenesis. Ref.10 Ref.11 Ref.12
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	Angiogenesis Apoptosis Cell adhesion Differentiation
Cellular component	Cell junction Cell membrane Cell projection Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of Rac GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axial mesoderm formation Inferred from mutant phenotype Ref.10. Source: MGI bone remodeling Inferred from mutant phenotype Ref.16. Source: UniProtKB branching involved in mammary gland duct morphogenesis Inferred from mutant phenotype Ref.17. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB ephrin receptor signaling pathway Inferred from mutant phenotype Ref.15. Source: UniProtKB keratinocyte differentiation Inferred from electronic annotation. Source: Compara lens fiber cell morphogenesis Inferred from direct assay Ref.15. Source: UniProtKB mammary gland epithelial cell proliferation Inferred from mutant phenotype Ref.17. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB neural tube development Inferred from mutant phenotype Ref.10. Source: MGI neuron differentiation Inferred from direct assay PubMed 15145949. Source: MGI notochord cell development Inferred from mutant phenotype Ref.10. Source: MGI notochord formation Inferred from mutant phenotype Ref.10. Source: MGI osteoblast differentiation Inferred from mutant phenotype Ref.16. Source: UniProtKB osteoclast differentiation Inferred from direct assay Ref.16. Source: UniProtKB positive regulation of establishment of protein localization to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB post-anal tail morphogenesis Inferred from mutant phenotype Ref.10. Source: MGI protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara regulation of angiogenesis Inferred from direct assay Ref.13. Source: UniProtKB regulation of blood vessel endothelial cell migration Inferred from direct assay Ref.13. Source: UniProtKB regulation of cell adhesion mediated by integrin Inferred from sequence or structural similarity. Source: UniProtKB regulation of lamellipodium assembly Inferred from sequence or structural similarity. Source: UniProtKB response to growth factor stimulus Inferred from sequence or structural similarity. Source: UniProtKB skeletal system development Inferred from mutant phenotype Ref.10. Source: MGI vasculogenesis Inferred from mutant phenotype Ref.10. Source: MGI
Cellular_component	focal adhesion Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell leading edge membrane Inferred from sequence or structural similarity. Source: UniProtKB ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ephrin receptor activity Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 977	952	Ephrin type-A receptor 2		PRO_0000016801
Regions
	Topological domain	26 – 538	513	Extracellular Potential
	Transmembrane	539 – 559	21	Helical; Potential
	Topological domain	560 – 977	418	Cytoplasmic Potential
	Domain	27 – 205	179	Eph LBD
	Domain	329 – 430	102	Fibronectin type-III 1
	Domain	436 – 527	92	Fibronectin type-III 2
	Domain	614 – 876	263	Protein kinase
	Domain	905 – 969	65	SAM
	Nucleotide binding	620 – 628	9	ATP By similarity
	Region	1 – 205	205	Mediates interaction with CLDN4 By similarity
	Region	607 – 907	301	Mediates interaction with ARHGEF16 By similarity
	Region	887 – 977	91	Negatively regulates interaction with ARHGEF16 By similarity
	Motif	975 – 977	3	PDZ-binding Potential
	Compositional bias	187 – 326	140	Cys-rich
Sites
	Active site	740	1	Proton acceptor By similarity
	Binding site	647	1	ATP By similarity
Amino acid modifications
	Modified residue	152	1	Phosphoserine By similarity
	Modified residue	374	1	Phosphoserine By similarity
	Modified residue	571	1	Phosphoserine By similarity
	Modified residue	580	1	Phosphoserine By similarity
	Modified residue	588	1	Phosphothreonine By similarity
	Modified residue	589	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	594	1	Phosphothreonine By similarity
	Modified residue	595	1	Phosphotyrosine; by autocatalysis Ref.14 Ref.19
	Modified residue	629	1	Phosphotyrosine By similarity
	Modified residue	648	1	Phosphothreonine By similarity
	Modified residue	736	1	Phosphotyrosine; by autocatalysis Ref.14
	Modified residue	772	1	Phosphothreonine By similarity
	Modified residue	773	1	Phosphotyrosine; by autocatalysis Ref.14 Ref.19
	Modified residue	791	1	Phosphoserine By similarity
	Modified residue	792	1	Phosphotyrosine By similarity
	Modified residue	870	1	Phosphoserine By similarity
	Modified residue	881	1	Phosphoserine By similarity
	Modified residue	893	1	Phosphoserine By similarity
	Modified residue	898	1	Phosphoserine By similarity
	Modified residue	899	1	Phosphothreonine By similarity
	Modified residue	900	1	Phosphoserine By similarity
	Modified residue	902	1	Phosphoserine By similarity
	Modified residue	911	1	Phosphoserine By similarity
	Modified residue	922	1	Phosphotyrosine; by autocatalysis Potential
	Modified residue	931	1	Phosphotyrosine By similarity
	Modified residue	961	1	Phosphotyrosine By similarity
	Glycosylation	408	1	N-linked (GlcNAc...) Ref.18 Ref.20
	Glycosylation	436	1	N-linked (GlcNAc...) Ref.18 Ref.20
	Disulfide bond	69 ↔ 187		By similarity
	Disulfide bond	104 ↔ 114		By similarity
Experimental info
	Mutagenesis	589	1	Y → E: No significant effect on kinase activity and loss of binding to VAV2 and VAV3. Inhibits EFNA1-induced vascular assembly and RAC1 activation in endothelial cells, no significant effect on kinase activity, significant reduction in phosphorylation and binding to VAV3; when associated with E-595. Ref.13 Ref.14
	Mutagenesis	589	1	Y → F: Inhibits EFNA1-induced vascular assembly and kinase activity. Ref.13 Ref.14
	Mutagenesis	595	1	Y → E: No significant effect on kinase activity and loss of binding to VAV2 and VAV3. Inhibits EFNA1-induced vascular assembly and RAC1 activation in endothelial cells, no significant effect on kinase activity, significant reduction in phosphorylation and binding to VAV3; when associated with E-589. Ref.13 Ref.14
	Mutagenesis	595	1	Y → F: Inhibits EFNA1-induced vascular assembly and abolishes kinase activity. Ref.13 Ref.14
	Mutagenesis	736	1	Y → F: Inhibits EFNA1-induced vascular assembly and RAC1 activation in endothelial cells. No significant effect on kinase activity. Loss of binding to PI3-kinase p85 subunit. Ref.14
	Mutagenesis	740	1	D → N: Loss of kinase activity and binding to VAV3. Ref.13
	Mutagenesis	773	1	Y → F: No significant effect on kinase activity. Significant reduction in phosphorylation. Ref.14
	Mutagenesis	931	1	Y → F: Inhibits EFNA1-induced vascular assembly and RAC1 activation in endothelial cells. Inhibits kinase activity. Loss of binding to VAV3 and PI3-kinase p85 subunit. Ref.14
	Sequence conflict	5	1	A → T in CAA55135. Ref.1
	Sequence conflict	112 – 113	2	SS → HA in AAA82113. Ref.2
	Sequence conflict	189	1	A → R in AAA82113. Ref.2
	Sequence conflict	209	1	R → C in AAA82113. Ref.2
	Sequence conflict	244	1	P → A in AAA82113. Ref.2
	Sequence conflict	258 – 260	3	IGQ → SE in AAA82113. Ref.2
	Sequence conflict	291	1	C → S in AAA82113. Ref.2
	Sequence conflict	339 – 340	2	IG → C in AAA82113. Ref.2
	Sequence conflict	371 – 372	2	WP → CA in AAA82113. Ref.2
	Sequence conflict	383	1	S → T in AAA82113. Ref.2
	Sequence conflict	457	1	W → R in AAA82113. Ref.2
	Sequence conflict	485	1	V → G in AAA82113. Ref.2
	Sequence conflict	511	1	L → W in AAA82113. Ref.2
	Sequence conflict	534	1	A → R in AAA82113. Ref.2
	Sequence conflict	678	1	R → P in CAA55135. Ref.1
	Sequence conflict	681	1	G → A in AAA82113. Ref.2
	Sequence conflict	819 – 820	2	YW → LL in AAA82113. Ref.2
	Sequence conflict	878	1	A → R in AAA82113. Ref.2
	Sequence conflict	919 – 920	2	MQ → IE in AAA82113. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q03145 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 66338CE7EF2DEE02	FASTA	977	108,852
	10 20 30 40 50 60 MELRAVGFCL ALLWGCALAA AAAQGKEVVL LDFAAMKGEL GWLTHPYGKG WDLMQNIMDD 70 80 90 100 110 120 MPIYMYSVCN VVSGDQDNWL RTNWVYREEA ERIFIELKFT VRDCNSFPGG ASSCKETFNL 130 140 150 160 170 180 YYAESDVDYG TNFQKRQFTK IDTIAPDEIT VSSDFEARNV KLNVEERMVG PLTRKGFYLA 190 200 210 220 230 240 FQDIGACVAL LSVRVYYKKC PEMLQSLARF PETIAVAVSD TQPLATVAGT CVDHAVVPYG 250 260 270 280 290 300 GEGPLMHCTV DGEWLVPIGQ CLCQEGYEKV EDACRACSPG FFKSEASESP CLECPEHTLP 310 320 330 340 350 360 STEGATSCQC EEGYFRAPED PLSMSCTRPP SAPNYLTAIG MGAKVELRWT APKDTGGRQD 370 380 390 400 410 420 IVYSVTCEQC WPESGECGPC EASVRYSEPP HALTRTSVTV SDLEPHMNYT FAVEARNGVS 430 440 450 460 470 480 GLVTSRSFRT ASVSINQTEP PKVRLEDRST TSLSVTWSIP VSQQSRVWKY EVTYRKKGDA 490 500 510 520 530 540 NSYNVRRTEG FSVTLDDLAP DTTYLVQVQA LTQEGQGAGS KVHEFQTLST EGSANMAVIG 550 560 570 580 590 600 GVAVGVVLLL VLAGVGLFIH RRRRNLRARQ SSEDVRFSKS EQLKPLKTYV DPHTYEDPNQ 610 620 630 640 650 660 AVLKFTTEIH PSCVARQKVI GAGEFGEVYK GTLKASSGKK EIPVAIKTLK AGYTEKQRVD 670 680 690 700 710 720 FLSEASIMGQ FSHHNIIRLE GVVSKYKPMM IITEYMENGA LDKFLREKDG EFSVLQLVGM 730 740 750 760 770 780 LRGIASGMKY LANMNYVHRD LAARNILVNS NLVCKVSDFG LSRVLEDDPE ATYTTSGGKI 790 800 810 820 830 840 PIRWTAPEAI SYRKFTSASD VWSYGIVMWE VMTYGERPYW ELSNHEVMKA INDGFRLPTP 850 860 870 880 890 900 MDCPSAIYQL MMQCWQQERS RRPKFADIVS ILDKLIRAPD SLKTLADFDP RVSIRLPSTS 910 920 930 940 950 960 GSEGVPFRTV SEWLESIKMQ QYTEHFMVAG YTAIEKVVQM SNEDIKRIGV RLPGHQKRIA 970 YSLLGLKDQV NTVGIPI

References

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[1]	"The Eck receptor tyrosine kinase is implicated in pattern formation during gastrulation, hindbrain segmentation and limb development." Ganju P., Shigemoto K., Brennan J., Entwistle A., Reith A.D. Oncogene 9:1613-1624(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE.
[2]	"The expression of the receptor-protein tyrosine kinase gene, eck, is highly restricted during early mouse development." Ruiz J.C., Robertson E.J. Mech. Dev. 46:87-100(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Bone marrow and Vagina.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Several receptor tyrosine kinase genes of the Eph family are segmentally expressed in the developing hindbrain." Becker N., Seitanidou T., Murphy P., Mattei M.-G., Topilko P., Nieto A., Wilkinson D.G., Charnay P., Gilardi P. Mech. Dev. 47:3-17(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 552-977, DEVELOPMENTAL STAGE. Strain: C57BL/6. Tissue: Embryo.
[8]	"An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain." Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P. Oncogene 7:2499-2506(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 742-799. Tissue: Embryonic brain.
[9]	"Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase." Pandey A., Duan H., Dixit V.M. J. Biol. Chem. 270:19201-19204(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLA. Tissue: Embryonic brain.
[10]	"Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1." Naruse-Nakajima C., Asano M., Iwakura Y. Mech. Dev. 102:95-105(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[11]	"EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation." Brantley-Sieders D.M., Caughron J., Hicks D., Pozzi A., Ruiz J.C., Chen J. J. Cell Sci. 117:2037-2049(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ANGIOGENESIS, DISRUPTION PHENOTYPE.
[12]	"Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin." Guo H., Miao H., Gerber L., Singh J., Denning M.F., Gilliam A.C., Wang B. Cancer Res. 66:7050-7058(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, DISRUPTION PHENOTYPE.
[13]	"Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis." Hunter S.G., Zhuang G., Brantley-Sieders D.M., Swat W., Cowan C.W., Chen J. Mol. Cell. Biol. 26:4830-4842(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ANGIOGENESIS, INTERACTION WITH VAV2 AND VAV3, MUTAGENESIS OF TYR-589; TYR-595 AND ASP-740.
[14]	"Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase." Fang W.B., Brantley-Sieders D.M., Hwang Y., Ham A.-J.L., Chen J. J. Biol. Chem. 283:16017-16026(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH VAV2; VAV3 AND PI3-KINASE P85 SUBUNIT, PHOSPHORYLATION AT TYR-589; TYR-595; TYR-736 AND TYR-773, MUTAGENESIS OF TYR-589; TYR-595; TYR-736; TYR-773 AND TYR-931.
[15]	"Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract." Cooper M.A., Son A.I., Komlos D., Sun Y., Kleiman N.J., Zhou R. Proc. Natl. Acad. Sci. U.S.A. 105:16620-16625(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LENS FIBER CELLS MORPHOGENESIS.
[16]	"Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis." Irie N., Takada Y., Watanabe Y., Matsuzaki Y., Naruse C., Asano M., Iwakura Y., Suda T., Matsuo K. J. Biol. Chem. 284:14637-14644(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN BONE IN REMODELING.
[17]	"Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase." Vaught D., Chen J., Brantley-Sieders D.M. Mol. Biol. Cell 20:2572-2581(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MAMMARY GLAND DEVELOPMENT.
[18]	"The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation." Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B. Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436, MASS SPECTROMETRY. Tissue: Myoblast.
[19]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-595 AND TYR-773, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[20]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-408 AND ASN-436, MASS SPECTROMETRY.
[21]	"The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors." Kim J., Lee H., Kim Y., Yoo S., Park E., Park S. Mol. Cell. Biol. 30:1582-1592(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH ANKS1A.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X78339 mRNA. Translation: CAA55135.1. U07634 mRNA. Translation: AAA82113.1. AK137704 mRNA. Translation: BAE23470.1. AK144202 mRNA. Translation: BAE25765.1. AL607087, AL670285 Genomic DNA. Translation: CAM17000.1. AL670285, AL607087 Genomic DNA. Translation: CAM20402.1. CH466615 Genomic DNA. Translation: EDL13361.1. BC140960 mRNA. Translation: AAI40961.1. X76010 mRNA. Translation: CAA53597.1. X57243 mRNA. Translation: CAA40519.1.
IPI	IPI00129220.
PIR	I48759. I48974. S49004.
RefSeq	NP_034269.2. NM_010139.3.
UniGene	Mm.2581.
3D structure databases
ProteinModelPortal	Q03145.
SMR	Q03145. Positions 24-529, 603-971.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-829N.
IntAct	Q03145. 3 interactions.
MINT	MINT-3388286.
PTM databases
PhosphoSite	Q03145.
Proteomic databases
PaxDb	Q03145.
PRIDE	Q03145.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000006614; ENSMUSP00000006614; ENSMUSG00000006445.
GeneID	13836.
KEGG	mmu:13836.
Organism-specific databases
CTD	1969.
MGI	MGI:95278. Epha2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104300.
HOGENOM	HOG000233856.
HOVERGEN	HBG062180.
InParanoid	Q3UNI2.
KO	K05103.
OMA	LVPIGQC.
OrthoDB	EOG4Q84WS.
Enzyme and pathway databases
BRENDA	2.7.10.1. 3474.
Gene expression databases
Bgee	Q03145.
CleanEx	MM_EPHA2.
Genevestigator	Q03145.
GermOnline	ENSMUSG00000006445. Mus musculus.
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. IPR009030. Growth_fac_rcpt. IPR013783. Ig-like_fold. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001660. SAM. IPR013761. SAM/pointed. IPR021129. SAM_type1. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. 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. PF07714. Pkinase_Tyr. 1 hit. PF00536. SAM_1. 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. SSF57184. Grow_fac_recept. 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
NextBio	284656.
SOURCE	Search...

Entry information

Entry name

EPHA2_MOUSE

Accession

Primary (citable) accession number: Q03145
Secondary accession number(s): Q3UNI2, Q60633, Q62212

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 141 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program