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Q1KL86 (EPHA2_MACFA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 64. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein attributes

Sequence length976 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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 By similarity.

Catalytic activity

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

Subunit structure

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 By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cell projectionruffle membrane; Single-pass type I membrane protein By similarity. Cell projectionlamellipodium membrane; Single-pass type I membrane protein By similarity. Cell junctionfocal adhesion By similarity. Note: Present at regions of cell-cell contacts but also at the leading edge of migrating cells By similarity.

Post-translational modification

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 By similarity. 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.

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.

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 processAngiogenesis
Apoptosis
Cell adhesion
Differentiation
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
Gene Ontology (GO)
   Biological_processactivation 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

bone remodeling

Inferred from sequence or structural similarity. Source: UniProtKB

branching involved in mammary gland duct morphogenesis

Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB

lens fiber cell morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

mammary gland epithelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

osteoclast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

positive regulation of establishment of protein localization to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of angiogenesis

Inferred from sequence or structural similarity. 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

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentfocal adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of 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_functionATP 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 976953Ephrin type-A receptor 2
PRO_0000260316

Regions

Topological domain25 – 537513Extracellular Potential
Transmembrane538 – 55821Helical; Potential
Topological domain559 – 976418Cytoplasmic Potential
Domain28 – 206179Eph LBD
Domain328 – 432105Fibronectin type-III 1
Domain438 – 52992Fibronectin type-III 2
Domain613 – 875263Protein kinase
Domain904 – 96865SAM
Nucleotide binding619 – 6279ATP By similarity
Region1 – 206206Mediates interaction with CLDN4 By similarity
Region606 – 906301Mediates interaction with ARHGEF16 By similarity
Region886 – 97691Negatively regulates interaction with ARHGEF16 By similarity
Motif974 – 9763PDZ-binding Potential
Compositional bias188 – 325138Cys-rich

Sites

Active site7391Proton acceptor By similarity
Binding site6461ATP By similarity

Amino acid modifications

Modified residue1531Phosphoserine By similarity
Modified residue3731Phosphoserine By similarity
Modified residue5701Phosphoserine By similarity
Modified residue5751Phosphotyrosine By similarity
Modified residue5791Phosphoserine By similarity
Modified residue5871Phosphothreonine By similarity
Modified residue5881Phosphotyrosine; by autocatalysis By similarity
Modified residue5931Phosphothreonine By similarity
Modified residue5941Phosphotyrosine; by autocatalysis By similarity
Modified residue6281Phosphotyrosine By similarity
Modified residue6471Phosphothreonine By similarity
Modified residue7351Phosphotyrosine; by autocatalysis By similarity
Modified residue7711Phosphothreonine By similarity
Modified residue7721Phosphotyrosine; by autocatalysis By similarity
Modified residue7901Phosphoserine By similarity
Modified residue7911Phosphotyrosine By similarity
Modified residue8691Phosphoserine By similarity
Modified residue8801Phosphoserine By similarity
Modified residue8921Phosphoserine By similarity
Modified residue8971Phosphoserine By similarity
Modified residue8981Phosphothreonine By similarity
Modified residue8991Phosphoserine By similarity
Modified residue9011Phosphoserine By similarity
Modified residue9101Phosphoserine By similarity
Modified residue9211Phosphotyrosine; by autocatalysis Potential
Modified residue9301Phosphotyrosine By similarity
Modified residue9601Phosphotyrosine By similarity
Glycosylation4071N-linked (GlcNAc...) Potential
Glycosylation4351N-linked (GlcNAc...) Potential
Disulfide bond70 ↔ 188 By similarity
Disulfide bond105 ↔ 115 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q1KL86 [UniParc].

Last modified May 30, 2006. Version 1.
Checksum: 244DD74D78F14EFB

FASTA976108,506
        10         20         30         40         50         60 
MELWAARACF VLLWGCALAP ATAAQGKEVV 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 CPELLQSLAR FPETIAGSDA PSLATVAGTC VDHAVVPPGG 

       250        260        270        280        290        300 
EEPRMHCAVD GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEVSESPC LECPEHTLPS 

       310        320        330        340        350        360 
PEGATSCECE EGFFRAPQDP MSMPCTRPPS APHYLTAVGM GAKVELRWTP PQDSGGREDI 

       370        380        390        400        410        420 
VYSVTCEQCW PESGECGPCE SSVRYSEPPH 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 GSGSLAVIGG 

       550        560        570        580        590        600 
VAVCVVLLLL LAGAGFFIHR RRKNLRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA 

       610        620        630        640        650        660 
VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG TLKTSSGKKE VPVAIKTLKA GYTEKQRVDF 

       670        680        690        700        710        720 
LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEFMENGAL 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 

« Hide

References

[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ478608 mRNA. Translation: ABE96827.1.

3D structure databases

ProteinModelPortalQ1KL86.
SMRQ1KL86. Positions 27-201, 602-883, 904-976.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ1KL86.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG062180.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. Fibronectin_type3.
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]
PfamPF14575. 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]
PIRSFPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEPS01186. 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]
ProtoNetSearch...

Entry information

Entry nameEPHA2_MACFA
AccessionPrimary (citable) accession number: Q1KL86
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: May 30, 2006
Last modified: April 16, 2014
This is version 64 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families