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Protein

Ephrin type-A receptor 2

Gene

EPHA2

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei646 – 6461ATPPROSITE-ProRule annotation
Active sitei739 – 7391Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi619 – 6279ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis, Apoptosis, Cell adhesion, Differentiation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 2 (EC:2.7.10.1)
Gene namesi
Name:EPHA2
OrganismiMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Taxonomic identifieri9541 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 537513ExtracellularSequence AnalysisAdd
BLAST
Transmembranei538 – 55821HelicalSequence AnalysisAdd
BLAST
Topological domaini559 – 976418CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 976953Ephrin type-A receptor 2PRO_0000260316Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi70 ↔ 188By similarity
Disulfide bondi105 ↔ 115By similarity
Glycosylationi407 – 4071N-linked (GlcNAc...)Sequence Analysis
Glycosylationi435 – 4351N-linked (GlcNAc...)Sequence Analysis
Modified residuei570 – 5701PhosphoserineBy similarity
Modified residuei579 – 5791PhosphoserineBy similarity
Modified residuei588 – 5881Phosphotyrosine; by autocatalysisBy similarity
Modified residuei628 – 6281PhosphotyrosineBy similarity
Modified residuei647 – 6471PhosphothreonineBy similarity
Modified residuei735 – 7351Phosphotyrosine; by autocatalysisBy similarity
Modified residuei869 – 8691PhosphoserineBy similarity
Modified residuei892 – 8921PhosphoserineBy similarity
Modified residuei897 – 8971PhosphoserineBy similarity
Modified residuei901 – 9011PhosphoserineBy similarity
Modified residuei921 – 9211Phosphotyrosine; by autocatalysisSequence Analysis
Modified residuei930 – 9301PhosphotyrosineBy similarity

Post-translational modificationi

Autophosphorylates. Phosphorylated on tyrosine upon binding and activation by EFNA1. 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 (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. Dephosphorylation of Tyr-930 by PTPRF prevents the interaction of EPHA2 with NCK1. Phosphorylated at Ser-897 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).By similarity
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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ1KL86.

Interactioni

Subunit structurei

Homodimer. 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 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. Interacts with ANKS1A. Interacts with CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell migration and adhesion (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ1KL86.
SMRiQ1KL86. Positions 27-201, 602-883, 904-976.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 206179Eph LBDPROSITE-ProRule annotationAdd
BLAST
Domaini328 – 432105Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini438 – 52992Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini613 – 875263Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini904 – 96865SAMPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 206206Mediates interaction with CLDN4By similarityAdd
BLAST
Regioni606 – 906301Mediates interaction with ARHGEF16By similarityAdd
BLAST
Regioni886 – 97691Negatively regulates interaction with ARHGEF16By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi974 – 9763PDZ-bindingSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi188 – 325138Cys-richAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
Contains 1 Eph LBD (Eph ligand-binding) domain.PROSITE-ProRule annotation
Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG062180.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS01186. EGF_2. 1 hit.
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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q1KL86-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELWAARACF VLLWGCALAP ATAAQGKEVV LLDFAAAGGE LGWLTHPYGK
60 70 80 90 100
GWDLMQNIMN DMPIYMYSVC NVMSGDQDNW LRTNWVYRGE AERIFIELKF
110 120 130 140 150
TVRDCNSFPG GASSCKETFN LYYAESDLDY GTNFQKRLFT KIDTIAPDEI
160 170 180 190 200
TVSSDFEARH VKLNVEERSV GPLTRKGFYL AFQDIGACVA LLSVRVYYKK
210 220 230 240 250
CPELLQSLAR FPETIAGSDA PSLATVAGTC VDHAVVPPGG EEPRMHCAVD
260 270 280 290 300
GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEVSESPC LECPEHTLPS
310 320 330 340 350
PEGATSCECE EGFFRAPQDP MSMPCTRPPS APHYLTAVGM GAKVELRWTP
360 370 380 390 400
PQDSGGREDI VYSVTCEQCW PESGECGPCE SSVRYSEPPH GLTRTSVTVS
410 420 430 440 450
DLEPHMNYTF TVEARNGVSG LVTSRSFRTA SVSINQTEPP KVRLEGRSTT
460 470 480 490 500
SLSVSWSIPP PQQSRVWKYE VTYRKKGDSN SYNVRRTEGF SVTLDDLAPD
510 520 530 540 550
TTYLVQVQAL TQEGQGAGSK VHEFQTLSPE GSGSLAVIGG VAVCVVLLLL
560 570 580 590 600
LAGAGFFIHR RRKNLRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA
610 620 630 640 650
VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG TLKTSSGKKE VPVAIKTLKA
660 670 680 690 700
GYTEKQRVDF LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEFMENGAL
710 720 730 740 750
DKFLREKDGE FSVLQLVGML RGIAAGMKYL ANMNYVHRDL AARNILVNSN
760 770 780 790 800
LVCKVSDFGL SRVLEDDPEA TYTTSGGKIP IRWTAPEAIS YRKFTSASDV
810 820 830 840 850
WSFGIVMWEV MTYGERPYWE LSNHEVMKAI NDGFRLPTPM DCPSAIYQLM
860 870 880 890 900
MQCWQQERAR RPKFADIVSI LDKLIRAPDS LKTLADFDPR VSIRLPSTSG
910 920 930 940 950
SEGVPFRTVS EWLESIKMQQ YTEHFMAAGY TAIEKVVQMT NDDIKRIGVR
960 970
LPGHQKRIAY SLLGLKDQVN TVGIPI
Length:976
Mass (Da):108,506
Last modified:May 30, 2006 - v1
Checksum:i244DD74D78F14EFB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ478608 mRNA. Translation: ABE96827.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ478608 mRNA. Translation: ABE96827.1.

3D structure databases

ProteinModelPortaliQ1KL86.
SMRiQ1KL86. Positions 27-201, 602-883, 904-976.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiQ1KL86.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG062180.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS01186. EGF_2. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

  1. "Macaca fascicularis EPH receptor A2 (EPHA2)."
    Walsh W.D., Bruckheimer E.M.
    Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skin.

Entry informationi

Entry nameiEPHA2_MACFA
AccessioniPrimary (citable) accession number: Q1KL86
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: May 30, 2006
Last modified: June 24, 2015
This is version 72 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.