Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q1KL86

- EPHA2_MACFA

UniProt

Q1KL86 - EPHA2_MACFA

Protein

Ephrin type-A receptor 2

Gene

EPHA2

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 67 (01 Oct 2014)
      Sequence version 1 (30 May 2006)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    1. ATP binding Source: UniProtKB-KW
    2. ephrin receptor activity Source: InterPro
    3. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. activation of Rac GTPase activity Source: UniProtKB
    2. angiogenesis Source: UniProtKB-KW
    3. apoptotic process Source: UniProtKB-KW
    4. bone remodeling Source: UniProtKB
    5. branching involved in mammary gland duct morphogenesis Source: UniProtKB
    6. cell adhesion Source: UniProtKB-KW
    7. cell chemotaxis Source: UniProtKB
    8. cell migration Source: UniProtKB
    9. ephrin receptor signaling pathway Source: UniProtKB
    10. lens fiber cell morphogenesis Source: UniProtKB
    11. mammary gland epithelial cell proliferation Source: UniProtKB
    12. negative regulation of protein kinase B signaling Source: UniProtKB
    13. osteoblast differentiation Source: UniProtKB
    14. osteoclast differentiation Source: UniProtKB
    15. peptidyl-tyrosine phosphorylation Source: GOC
    16. positive regulation of establishment of protein localization to plasma membrane Source: UniProtKB
    17. protein kinase B signaling Source: UniProtKB
    18. regulation of angiogenesis Source: UniProtKB
    19. regulation of cell adhesion mediated by integrin Source: UniProtKB
    20. regulation of lamellipodium assembly Source: UniProtKB
    21. response to growth factor Source: UniProtKB

    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

    Cell membrane By similarity; Single-pass type I membrane protein By similarity. Cell projectionruffle membrane By similarity; Single-pass type I membrane protein By similarity. Cell projectionlamellipodium membrane By similarity; 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

    GO - Cellular componenti

    1. focal adhesion Source: UniProtKB
    2. integral component of plasma membrane Source: UniProtKB
    3. lamellipodium membrane Source: UniProtKB-SubCell
    4. leading edge membrane Source: UniProtKB
    5. ruffle membrane Source: UniProtKB-SubCell

    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
    Modified residuei153 – 1531PhosphoserineBy similarity
    Modified residuei373 – 3731PhosphoserineBy similarity
    Glycosylationi407 – 4071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi435 – 4351N-linked (GlcNAc...)Sequence Analysis
    Modified residuei570 – 5701PhosphoserineBy similarity
    Modified residuei575 – 5751PhosphotyrosineBy similarity
    Modified residuei579 – 5791PhosphoserineBy similarity
    Modified residuei587 – 5871PhosphothreonineBy similarity
    Modified residuei588 – 5881Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei593 – 5931PhosphothreonineBy similarity
    Modified residuei594 – 5941Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei628 – 6281PhosphotyrosineBy similarity
    Modified residuei647 – 6471PhosphothreonineBy similarity
    Modified residuei735 – 7351Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei771 – 7711PhosphothreonineBy similarity
    Modified residuei772 – 7721Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei790 – 7901PhosphoserineBy similarity
    Modified residuei791 – 7911PhosphotyrosineBy similarity
    Modified residuei869 – 8691PhosphoserineBy similarity
    Modified residuei880 – 8801PhosphoserineBy similarity
    Modified residuei892 – 8921PhosphoserineBy similarity
    Modified residuei897 – 8971PhosphoserineBy similarity
    Modified residuei898 – 8981PhosphothreonineBy similarity
    Modified residuei899 – 8991PhosphoserineBy similarity
    Modified residuei901 – 9011PhosphoserineBy similarity
    Modified residuei910 – 9101PhosphoserineBy similarity
    Modified residuei921 – 9211Phosphotyrosine; by autocatalysisSequence Analysis
    Modified residuei930 – 9301PhosphotyrosineBy similarity
    Modified residuei960 – 9601PhosphotyrosineBy 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...

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei538 – 55821HelicalSequence AnalysisAdd
    BLAST

    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. 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]
    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

    MELWAARACF VLLWGCALAP ATAAQGKEVV LLDFAAAGGE LGWLTHPYGK    50
    GWDLMQNIMN DMPIYMYSVC NVMSGDQDNW LRTNWVYRGE AERIFIELKF 100
    TVRDCNSFPG GASSCKETFN LYYAESDLDY GTNFQKRLFT KIDTIAPDEI 150
    TVSSDFEARH VKLNVEERSV GPLTRKGFYL AFQDIGACVA LLSVRVYYKK 200
    CPELLQSLAR FPETIAGSDA PSLATVAGTC VDHAVVPPGG EEPRMHCAVD 250
    GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEVSESPC LECPEHTLPS 300
    PEGATSCECE EGFFRAPQDP MSMPCTRPPS APHYLTAVGM GAKVELRWTP 350
    PQDSGGREDI VYSVTCEQCW PESGECGPCE SSVRYSEPPH GLTRTSVTVS 400
    DLEPHMNYTF TVEARNGVSG LVTSRSFRTA SVSINQTEPP KVRLEGRSTT 450
    SLSVSWSIPP PQQSRVWKYE VTYRKKGDSN SYNVRRTEGF SVTLDDLAPD 500
    TTYLVQVQAL TQEGQGAGSK VHEFQTLSPE GSGSLAVIGG VAVCVVLLLL 550
    LAGAGFFIHR RRKNLRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA 600
    VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG TLKTSSGKKE VPVAIKTLKA 650
    GYTEKQRVDF LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEFMENGAL 700
    DKFLREKDGE FSVLQLVGML RGIAAGMKYL ANMNYVHRDL AARNILVNSN 750
    LVCKVSDFGL SRVLEDDPEA TYTTSGGKIP IRWTAPEAIS YRKFTSASDV 800
    WSFGIVMWEV MTYGERPYWE LSNHEVMKAI NDGFRLPTPM DCPSAIYQLM 850
    MQCWQQERAR RPKFADIVSI LDKLIRAPDS LKTLADFDPR VSIRLPSTSG 900
    SEGVPFRTVS EWLESIKMQQ YTEHFMAAGY TAIEKVVQMT NDDIKRIGVR 950
    LPGHQKRIAY SLLGLKDQVN TVGIPI 976
    Length:976
    Mass (Da):108,506
    Last modified:May 30, 2006 - v1
    Checksum:i244DD74D78F14EFB
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DQ478608 mRNA. Translation: ABE96827.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DQ478608 mRNA. Translation: ABE96827.1 .

    3D structure databases

    ProteinModelPortali Q1KL86.
    SMRi Q1KL86. Positions 27-201, 602-883, 904-976.
    ModBasei Search...
    MobiDBi Search...

    Proteomic databases

    PRIDEi Q1KL86.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    HOVERGENi HBG062180.

    Family and domain databases

    Gene3Di 1.10.150.50. 1 hit.
    2.60.120.260. 1 hit.
    2.60.40.10. 2 hits.
    InterProi IPR027936. 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 ]
    Pfami PF14575. 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 ]
    PIRSFi PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00615. EPH_lbd. 1 hit.
    SM00060. FN3. 2 hits.
    SM00454. SAM. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47769. SSF47769. 1 hit.
    SSF49265. SSF49265. 1 hit.
    SSF49785. SSF49785. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 2 hits.
    PROSITEi PS01186. 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 ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 67 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