Product: Phospho-EPHA2/3/4 (Tyr588/Tyr596) Antibody
Catalog: AF0028
Description: Rabbit polyclonal antibody to Phospho-EPHA2/3/4 (Tyr588/Tyr596)
Application: WB IHC IF/ICC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Xenopus
Mol.Wt.: 130kDa; 108kD,110kD(Calculated).
Uniprot: P29317 | P29320 | P54764
RRID: AB_2833511

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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IF/ICC 1:100-1:500, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Xenopus(100%)
Clonality:
Polyclonal
Specificity:
Phospho-EPHA2/3/4 (Tyr588/Tyr596) Antibody detects endogenous levels of EPHA2/3/4 only when phosphorylated at Tyrosine 588 and 596.
RRID:
AB_2833511
Cite Format: Affinity Biosciences Cat# AF0028, RRID:AB_2833511.
Conjugate:
Unconjugated.
Purification:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

ARCC2; AW545284; CTPA; CTPP1; CTRCT6; EC 2.7.10.1; Eck; Eph receptor A2; EPHA2; EPHA2_HUMAN; Ephrin receptor; Ephrin receptor EphA2; Ephrin type A receptor 2; Ephrin type-A receptor 2; Epithelial cell kinase; Epithelial cell receptor protein tyrosine kinase; Myk 2; Myk2; Sek 2; Sek2; Soluble EPHA2 variant 1; Tyrosine protein kinase receptor ECK; Tyrosine-protein kinase receptor ECK; Tyrosine-protein kinase receptor MPK-5; Tyrosine-protein kinase receptor SEK-2; AW492086; Cek4; EC 2.7.10.1; EK4; End3; Eph receptor A3; EPH-like kinase 4; EPH-like tyrosine kinase 1; EPHA3; EPHA3_HUMAN; Ephrin receptor EphA3; Ephrin type-A receptor 3; ETK 1; ETK; ETK1; HEK 4; HEK; HEK4; Human embryo kinase 1; Human embryo kinase; Mek4; MGC109882; Receptor tyrosine kinase HEK; Testicular tissue protein Li 64; Tyro 4; Tyro4; TYRO4 protein tyrosine kinase; Tyrosine protein kinase receptor ETK 1; Tyrosine-protein kinase receptor ETK1; Tyrosine-protein kinase TYRO4; Cek 8; CEK8; EK8; eph receptor a4; EPH-like kinase 8; EPHA4; EPHA4_HUMAN; Ephrin type-A receptor 4; HEK 8; hEK8; Receptor protein-tyrosine kinase HEK8; Sek 1; SEK; TYRO 1 protein tyrosine kinase; TYRO1; Tyrosine-protein kinase receptor SEK; Tyrosine-protein kinase TYRO1;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
P29317 EPHA2_HUMAN:

Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g. skin, intestine, lung, and ovary.

P29320 EPHA3_HUMAN:

Widely expressed. Highest level in placenta.

P54764 EPHA4_HUMAN:

Ubiquitous.

Description:
EphA2 a receptor tyrosine kinase. Receptor for members of the ephrin-A family. Binds to ephrin-A1, -A3, -A4 AND -A5. The Eph receptor tyrosine kinase family, the largest in the tyrosine kinase group, has fourteen members. They bind membrane-anchored ligands, ephrins, at sites of cell-cell contact, regulating the repulsion and adhesion of cells that underlie the establishment, maintenance, and remodeling of patterns of cellular organization. Eph signals are particularly important in regulating cell adhesion and cell migration during development, axon guidance, homeostasis and disease.
Sequence:
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMNDMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFNLYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYLAFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGGEEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPSPEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDIVYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSGLVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSNSYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGGVAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQAVLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDFLGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGMLRGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIPIRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPMDCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSGSEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAYSLLGLKDQVNTVGIPI

MDCQLSILLLLSCSVLDSFGELIPQPSNEVNLLDSKTIQGELGWISYPSHGWEEISGVDEHYTPIRTYQVCNVMDHSQNNWLRTNWVPRNSAQKIYVELKFTLRDCNSIPLVLGTCKETFNLYYMESDDDHGVKFREHQFTKIDTIAADESFTQMDLGDRILKLNTEIREVGPVNKKGFYLAFQDVGACVALVSVRVYFKKCPFTVKNLAMFPDTVPMDSQSLVEVRGSCVNNSKEEDPPRMYCSTEGEWLVPIGKCSCNAGYEERGFMCQACRPGFYKALDGNMKCAKCPPHSSTQEDGSMNCRCENNYFRADKDPPSMACTRPPSSPRNVISNINETSVILDWSWPLDTGGRKDVTFNIICKKCGWNIKQCEPCSPNVRFLPRQFGLTNTTVTVTDLLAHTNYTFEIDAVNGVSELSSPPRQFAAVSITTNQAAPSPVLTIKKDRTSRNSISLSWQEPEHPNGIILDYEVKYYEKQEQETSYTILRARGTNVTISSLKPDTIYVFQIRARTAAGYGTNSRKFEFETSPDSFSISGESSQVVMIAISAAVAIILLTVVIYVLIGRFCGYKSKHGADEKRLHFGNGHLKLPGLRTYVDPHTYEDPTQAVHEFAKELDATNISIDKVVGAGEFGEVCSGRLKLPSKKEISVAIKTLKVGYTEKQRRDFLGEASIMGQFDHPNIIRLEGVVTKSKPVMIVTEYMENGSLDSFLRKHDAQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKIPIRWTSPEAIAYRKFTSASDVWSYGIVLWEVMSYGERPYWEMSNQDVIKAVDEGYRLPPPMDCPAALYQLMLDCWQKDRNNRPKFEQIVSILDKLIRNPGSLKIITSAAARPSNLLLDQSNVDITTFRTTGDWLNGVWTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVGPQKKIISSIKALETQSKNGPVPV

MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWITREGAQRVYIEIKFTLRDCNSLPGVMGTCKETFNLYYYESDNDKERFIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEIRDVGPLSKKGFYLAFQDVGACIALVSVRVFYKKCPLTVRNLAQFPDTITGADTSSLVEVRGSCVNNSEEKDVPKMYCGADGEWLVPIGNCLCNAGHEERSGECQACKIGYYKALSTDATCAKCPPHSYSVWEGATSCTCDRGFFRADNDAASMPCTRPPSAPLNLISNVNETSVNLEWSSPQNTGGRQDISYNVVCKKCGAGDPSKCRPCGSGVHYTPQQNGLKTTKVSITDLLAHTNYTFEIWAVNGVSKYNPNPDQSVSVTVTTNQAAPSSIALVQAKEVTRYSVALAWLEPDRPNGVILEYEVKYYEKDQNERSYRIVRTAARNTDIKGLNPLTSYVFHVRARTAAGYGDFSEPLEVTTNTVPSRIIGDGANSTVLLVSVSGSVVLVVILIAAFVISRRRSKYSKAKQEADEEKHLNQGVRTYVDPFTYEDPNQAVREFAKEIDASCIKIEKVIGVGEFGEVCSGRLKVPGKREICVAIKTLKAGYTDKQRRDFLSEASIMGQFDHPNIIHLEGVVTKCKPVMIITEYMENGSLDAFLRKNDGRFTVIQLVGMLRGIGSGMKYLSDMSYVHRDLAARNILVNSNLVCKVSDFGMSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPPPMDCPIALHQLMLDCWQKERSDRPKFGQIVNMLDKLIRNPNSLKRTGTESSRPNTALLDPSSPEFSAVVSVGDWLQAIKMDRYKDNFTAAGYTTLEAVVHVNQEDLARIGITAITHQNKILSSVQAMRTQMQQMHGRMVPV

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Horse
100
Bovine
100
Sheep
100
Dog
100
Xenopus
100
Rabbit
100
Zebrafish
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P29317/P29320/P54764 As Substrate

Site PTM Type Enzyme
Y67 Phosphorylation
K136 Ubiquitination
K141 Ubiquitination
S153 Phosphorylation
S154 Phosphorylation
K162 Ubiquitination
S373 Phosphorylation
S426 Phosphorylation
S433 Phosphorylation
N435 N-Glycosylation
T437 Phosphorylation
S570 Phosphorylation
Y575 Phosphorylation P29317 (EPHA2)
S577 Phosphorylation
K578 Ubiquitination
S579 Phosphorylation
K583 Ubiquitination
K586 Ubiquitination
T587 Phosphorylation
Y588 Phosphorylation P29317 (EPHA2)
T593 Phosphorylation
Y594 Phosphorylation P12931 (SRC) , P29317 (EPHA2)
K603 Ubiquitination
C612 S-Nitrosylation
K617 Ubiquitination
Y628 Phosphorylation P29317 (EPHA2)
K629 Ubiquitination
K639 Ubiquitination
K646 Ubiquitination
T647 Phosphorylation
K649 Ubiquitination
K655 Ubiquitination
Y685 Phosphorylation
K686 Ubiquitination
T692 Phosphorylation
Y694 Phosphorylation P29317 (EPHA2)
S712 Phosphorylation
K728 Ubiquitination
Y735 Phosphorylation P29317 (EPHA2)
S749 Phosphorylation
S756 Phosphorylation
S761 Phosphorylation
T771 Phosphorylation
Y772 Phosphorylation P29317 (EPHA2)
T773 Phosphorylation
T774 Phosphorylation
S775 Phosphorylation
K778 Ubiquitination
S790 Phosphorylation
Y791 Phosphorylation
K828 Sumoylation
S869 Phosphorylation
K873 Ubiquitination
S880 Phosphorylation
K882 Ubiquitination
T883 Phosphorylation
S892 Phosphorylation
S897 Phosphorylation P51812 (RPS6KA3) , P31749 (AKT1) , Q15418 (RPS6KA1)
T898 Phosphorylation
S899 Phosphorylation
S901 Phosphorylation
S910 Phosphorylation
Y921 Phosphorylation P29317 (EPHA2)
T922 Phosphorylation
Y930 Phosphorylation
K935 Ubiquitination
T940 Phosphorylation
K945 Ubiquitination
Y960 Phosphorylation P29317 (EPHA2)
S961 Phosphorylation
Site PTM Type Enzyme
S294 Phosphorylation
T432 Phosphorylation
T442 Phosphorylation
T485 Phosphorylation
S497 Phosphorylation
S498 Phosphorylation
Y561 Phosphorylation
Y570 Phosphorylation
T595 Phosphorylation
Y596 Phosphorylation P29320 (EPHA3)
T601 Phosphorylation
Y602 Phosphorylation P29320 (EPHA3)
K625 Ubiquitination
T654 Phosphorylation
K656 Ubiquitination
Y659 Phosphorylation
Y701 Phosphorylation P29320 (EPHA3)
Y736 Phosphorylation
Y742 Phosphorylation
S768 Phosphorylation
Y779 Phosphorylation P29320 (EPHA3)
T781 Phosphorylation
Y937 Phosphorylation
T974 Phosphorylation
S976 Phosphorylation
Site PTM Type Enzyme
T117 Phosphorylation
T168 Phosphorylation
S349 Phosphorylation
S350 Phosphorylation
T354 Phosphorylation
T595 Phosphorylation
Y596 Phosphorylation P54764 (EPHA4)
T601 Phosphorylation
Y602 Phosphorylation P54764 (EPHA4)
S637 Phosphorylation
K693 Acetylation
K735 Ubiquitination
S741 Phosphorylation
Y779 Phosphorylation
T781 Phosphorylation
Y798 Phosphorylation
S887 Phosphorylation
T957 Phosphorylation

PTMs - P29317/P29320/P54764 As Enzyme

Substrate Site Source
O14493 (CLDN4) Y208 Uniprot
P29317-1 (EPHA2) S570 Uniprot
P29317 (EPHA2) Y575 Uniprot
P29317 (EPHA2) Y588 Uniprot
P29317 (EPHA2) Y594 Uniprot
P29317 (EPHA2) Y628 Uniprot
P29317 (EPHA2) Y694 Uniprot
P29317 (EPHA2) Y735 Uniprot
P29317 (EPHA2) Y772 Uniprot
P29317-1 (EPHA2) S897 Uniprot
P29317-1 (EPHA2) T898 Uniprot
P29317-1 (EPHA2) S899 Uniprot
P29317-1 (EPHA2) S901 Uniprot
P29317 (EPHA2) Y921 Uniprot
P29317 (EPHA2) Y960 Uniprot
Substrate Site Source
P29320 (EPHA3) Y596 Uniprot
P29320 (EPHA3) Y602 Uniprot
P29320 (EPHA3) Y701 Uniprot
P29320 (EPHA3) Y779 Uniprot
P40763-1 (STAT3) Y705 Uniprot
Substrate Site Source
P19174 (PLCG1) Y783 Uniprot
P54764-1 (EPHA4) Y596 Uniprot
P54764 (EPHA4) Y602 Uniprot
Q00535 (CDK5) Y15 Uniprot

Research Backgrounds

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 (MAPK3/MAPK1, respectively) 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.

(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.

PTMs:

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. Phosphorylated at Ser-897 in response to TNF by RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell migration. Phosphorylated at Ser-897 by PKA; blocks cell retraction induced by EPHA2 kinase activity. Dephosphorylated by ACP1.

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).

Subcellular Location:

Cell membrane>Single-pass type I membrane protein. Cell projection>Ruffle membrane>Single-pass type I membrane protein. Cell projection>Lamellipodium membrane>Single-pass type I membrane protein. Cell junction>Focal adhesion.
Note: Present at regions of cell-cell contacts but also at the leading edge of migrating cells (PubMed:19573808, PubMed:20861311). Relocates from the plasma membrane to the cytoplasmic and perinuclear regions in cancer cells (PubMed:18794797).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g. skin, intestine, lung, and ovary.

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

(Microbial infection) Interacts with human herpes virus 8/HHV-8 glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction triggers EPHA2 phosphorylation and endocytosis, allowing virus entry.

(Microbial infection) Interacts with Epstein-Barr virus/HHV-4 glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction facilitates virus internalization and fusion.

Family&Domains:

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

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.

PTMs:

Autophosphorylates upon activation by EFNA5. Phosphorylation on Tyr-602 mediates interaction with NCK1. Dephosphorylated by PTPN1.

Subcellular Location:

Cell membrane>Single-pass type I membrane protein.

Secreted.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Widely expressed. Highest level in placenta.

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.

Family&Domains:

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Function:

Receptor tyrosine kinase which binds 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, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity).

Subcellular Location:

Cell membrane>Single-pass type I membrane protein. Cell projection>Axon. Cell projection>Dendrite. Cell junction>Synapse>Postsynaptic density membrane. Early endosome. Cell junction>Adherens junction.
Note: Clustered upon activation and targeted to early endosome.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Ubiquitous.

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. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation (By similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases. Forms a ternary complex composed of ADAM10, CADH1 and EPHA4; within the complex, CADH1 is cleaved by ADAM10 which disrupts adherens junctions (By similarity).

Family&Domains:

The protein kinase domain mediates interaction with NGEF.

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Research Fields

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Ras signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Rap1 signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Organismal Systems > Development > Axon guidance.   (View pathway)

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