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Protein

Ephrin type-A receptor 2

Gene

EPHA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (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.9 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei646ATPPROSITE-ProRule annotation1
Active sitei739Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi619 – 627ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • ephrin receptor activity Source: InterPro
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  • activation of GTPase activity Source: UniProtKB
  • axial mesoderm formation Source: Ensembl
  • blood vessel endothelial cell proliferation involved in sprouting angiogenesis Source: Ensembl
  • bone remodeling Source: UniProtKB
  • branching involved in mammary gland duct morphogenesis Source: UniProtKB
  • cAMP metabolic process Source: UniProtKB
  • cell chemotaxis Source: UniProtKB
  • cell migration Source: UniProtKB
  • cell motility Source: UniProtKB
  • defense response to Gram-positive bacterium Source: Ensembl
  • ephrin receptor signaling pathway Source: UniProtKB
  • inflammatory response Source: Ensembl
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  • keratinocyte differentiation Source: UniProtKB
  • lens fiber cell morphogenesis Source: UniProtKB
  • mammary gland epithelial cell proliferation Source: UniProtKB
  • multicellular organism development Source: ProtInc
  • negative regulation of angiogenesis Source: Ensembl
  • negative regulation of chemokine production Source: Ensembl
  • negative regulation of lymphangiogenesis Source: Ensembl
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • neural tube development Source: Ensembl
  • neuron differentiation Source: Ensembl
  • notochord cell development Source: Ensembl
  • notochord formation Source: Ensembl
  • osteoblast differentiation Source: UniProtKB
  • osteoclast differentiation Source: UniProtKB
  • pericyte cell differentiation Source: Ensembl
  • positive regulation of establishment of protein localization to plasma membrane Source: UniProtKB
  • post-anal tail morphogenesis Source: Ensembl
  • protein kinase B signaling Source: UniProtKB
  • regulation of angiogenesis Source: UniProtKB
  • regulation of blood vessel endothelial cell migration Source: UniProtKB
  • regulation of cell adhesion mediated by integrin Source: UniProtKB
  • regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • regulation of lamellipodium assembly Source: UniProtKB
  • response to growth factor Source: UniProtKB
  • skeletal system development Source: Ensembl
  • vasculogenesis Source: Ensembl
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis, Apoptosis, Cell adhesion, Differentiation, Host-virus interaction

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06946-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-2682334. EPH-Ephrin signaling.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
SignaLinkiP29317.
SIGNORiP29317.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 2 (EC:2.7.10.1)
Alternative name(s):
Epithelial cell kinase
Tyrosine-protein kinase receptor ECK
Gene namesi
Name:EPHA2
Synonyms:ECK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3386. EPHA2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 537ExtracellularSequence analysisAdd BLAST514
Transmembranei538 – 558HelicalSequence analysisAdd BLAST21
Topological domaini559 – 976CytoplasmicSequence analysisAdd BLAST418

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cell surface Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: GOC
  • lamellipodium Source: UniProtKB
  • lamellipodium membrane Source: UniProtKB-SubCell
  • leading edge membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • ruffle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Cataract 6, multiple types (CTRCT6)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age-related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision.
See also OMIM:116600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062532721R → Q in CTRCT6; retained in the cytoplasm and constitutively active it alters EPHA2 signaling. 1 PublicationCorresponds to variant rs116506614dbSNPEnsembl.1
Natural variantiVAR_058907940T → I in CTRCT6; reduced protein stability and reduced ability to stimulate cell migration in absence of its ephrin ligand. 2 PublicationsCorresponds to variant rs137853200dbSNPEnsembl.1
Natural variantiVAR_058908948G → W in CTRCT6; reduced protein stability and reduced ability to stimulate cell migration in absence of its ephrin ligand. 2 PublicationsCorresponds to variant rs137853199dbSNPEnsembl.1

Overexpressed in several cancer types and promotes malignancy.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi103R → E: Significantly reduced response to EFNA1. 1 Publication1
Mutagenesisi646K → M: Loss of kinase activity. 1 Publication1
Mutagenesisi739D → N: Increases serum-induced chemotaxis. Loss of EFNA1-dependent regulation of cell migration. 1 Publication1
Mutagenesisi897S → A or D: Loss of serum-induced phosphorylation by PKB. Loss of serum-induced chemotaxis. 1 Publication1

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

DisGeNETi1969.
MalaCardsiEPHA2.
MIMi116600. phenotype.
OpenTargetsiENSG00000142627.
Orphaneti98993. Posterior polar cataract.
98994. Total congenital cataract.
PharmGKBiPA27818.

Chemistry databases

ChEMBLiCHEMBL2068.
DrugBankiDB01254. Dasatinib.
DB08896. Regorafenib.
GuidetoPHARMACOLOGYi1822.

Polymorphism and mutation databases

BioMutaiEPHA2.
DMDMi229462861.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001680024 – 976Ephrin type-A receptor 2Add BLAST953

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi70 ↔ 188
Disulfide bondi105 ↔ 115
Glycosylationi407N-linked (GlcNAc...)Sequence analysis1
Glycosylationi435N-linked (GlcNAc...)1 Publication1
Modified residuei570PhosphoserineCombined sources1
Modified residuei575PhosphotyrosineCombined sources1
Modified residuei579PhosphoserineCombined sources1
Modified residuei588Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei594PhosphotyrosineBy similarity1
Modified residuei628PhosphotyrosineCombined sources1
Modified residuei647PhosphothreonineCombined sources1
Modified residuei735Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei772PhosphotyrosineBy similarity1
Modified residuei869PhosphoserineCombined sources1
Modified residuei892PhosphoserineCombined sources1
Modified residuei897Phosphoserine; by PKB/AKT1; RPS6KA1; RPS6KA3 AND PKACombined sources3 Publications1
Modified residuei901PhosphoserineCombined sources1 Publication1
Modified residuei921Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei930Phosphotyrosine1 Publication1

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. Phosphorylated at Ser-897 in response to TNF by RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Phosphorylated at Ser-897 by PKA; blocks cell retraction induced by EPHA2 kinase activity (PubMed:27385333). Dephosphorylated by ACP1.6 Publications
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

EPDiP29317.
MaxQBiP29317.
PaxDbiP29317.
PeptideAtlasiP29317.
PRIDEiP29317.

PTM databases

iPTMnetiP29317.
PhosphoSitePlusiP29317.
SwissPalmiP29317.
UniCarbKBiP29317.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

Up-regulated by UV irradiation via a TP53-independent, MAPK-dependent mechanism.1 Publication

Gene expression databases

BgeeiENSG00000142627.
CleanExiHS_EPHA2.
ExpressionAtlasiP29317. baseline and differential.
GenevisibleiP29317. HS.

Organism-specific databases

HPAiCAB010464.

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 (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.By similarity10 Publications
(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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
EFNA1P208277EBI-702104,EBI-715194
EPHA7Q153753EBI-702104,EBI-1383428
HSP90AB1P082382EBI-702104,EBI-352572
PTK2Q053973EBI-702104,EBI-702142

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

Protein-protein interaction databases

BioGridi108288. 67 interactors.
DIPiDIP-96N.
IntActiP29317. 30 interactors.
MINTiMINT-3972729.
STRINGi9606.ENSP00000351209.

Chemistry databases

BindingDBiP29317.

Structurei

Secondary structure

1976
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 33Combined sources6
Helixi34 – 36Combined sources3
Turni37 – 40Combined sources4
Beta strandi44 – 57Combined sources14
Beta strandi59 – 62Combined sources4
Beta strandi64 – 69Combined sources6
Beta strandi73 – 76Combined sources4
Beta strandi79 – 82Combined sources4
Beta strandi92 – 103Combined sources12
Helixi105 – 107Combined sources3
Beta strandi108 – 110Combined sources3
Turni112 – 114Combined sources3
Beta strandi119 – 128Combined sources10
Helixi136 – 138Combined sources3
Beta strandi139 – 145Combined sources7
Beta strandi148 – 151Combined sources4
Helixi153 – 157Combined sources5
Beta strandi161 – 170Combined sources10
Beta strandi175 – 187Combined sources13
Beta strandi189 – 199Combined sources11
Beta strandi204 – 206Combined sources3
Beta strandi209 – 211Combined sources3
Beta strandi218 – 221Combined sources4
Beta strandi224 – 227Combined sources4
Beta strandi238 – 240Combined sources3
Beta strandi244 – 247Combined sources4
Beta strandi253 – 257Combined sources5
Beta strandi266 – 269Combined sources4
Beta strandi272 – 275Combined sources4
Beta strandi286 – 288Combined sources3
Beta strandi295 – 298Combined sources4
Beta strandi335 – 338Combined sources4
Beta strandi343 – 348Combined sources6
Beta strandi361 – 369Combined sources9
Beta strandi376 – 378Combined sources3
Beta strandi384 – 387Combined sources4
Beta strandi389 – 392Combined sources4
Beta strandi394 – 400Combined sources7
Beta strandi407 – 415Combined sources9
Helixi419 – 421Combined sources3
Beta strandi427 – 433Combined sources7
Beta strandi441 – 446Combined sources6
Beta strandi453 – 457Combined sources5
Turni460 – 465Combined sources6
Beta strandi467 – 475Combined sources9
Beta strandi483 – 493Combined sources11
Beta strandi502 – 510Combined sources9
Beta strandi522 – 525Combined sources4
Helixi536 – 556Combined sources21
Beta strandi557 – 561Combined sources5
Helixi591 – 594Combined sources4
Helixi598 – 604Combined sources7
Helixi610 – 612Combined sources3
Beta strandi613 – 621Combined sources9
Beta strandi623 – 632Combined sources10
Beta strandi641 – 647Combined sources7
Helixi654 – 667Combined sources14
Beta strandi678 – 682Combined sources5
Beta strandi684 – 687Combined sources4
Beta strandi689 – 693Combined sources5
Helixi700 – 706Combined sources7
Turni707 – 709Combined sources3
Helixi713 – 732Combined sources20
Helixi742 – 744Combined sources3
Beta strandi745 – 747Combined sources3
Beta strandi753 – 755Combined sources3
Beta strandi776 – 779Combined sources4
Helixi781 – 783Combined sources3
Helixi786 – 791Combined sources6
Helixi796 – 811Combined sources16
Turni817 – 820Combined sources4
Helixi823 – 831Combined sources9
Helixi844 – 853Combined sources10
Helixi858 – 860Combined sources3
Helixi864 – 873Combined sources10
Helixi878 – 882Combined sources5
Helixi909 – 915Combined sources7
Helixi919 – 921Combined sources3
Helixi922 – 927Combined sources6
Helixi933 – 937Combined sources5
Helixi941 – 946Combined sources6
Helixi952 – 964Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MQBX-ray2.30A/B596-900[»]
2E8NNMR-A902-976[»]
2K9YNMR-A/B523-563[»]
2KSONMR-A908-972[»]
2X10X-ray3.00A27-534[»]
2X11X-ray4.83A27-534[»]
3C8XX-ray1.95A23-202[»]
3CZUX-ray2.65A23-202[»]
3FL7X-ray2.50A23-531[»]
3HEIX-ray2.00A/C/E/G/I/K/M/O28-201[»]
3HPNX-ray2.52A/B/C/D/E/F28-201[»]
3KKAX-ray2.40C/D/E903-971[»]
3MBWX-ray2.81A23-326[»]
3MX0X-ray3.51A/C27-435[»]
3SKJX-ray2.50E/F23-202[»]
4P2KX-ray1.50A590-876[»]
4PDOX-ray2.10A/B590-876[»]
4TRLX-ray2.45A590-876[»]
5EK7X-ray1.90A/B583-876[»]
ProteinModelPortaliP29317.
SMRiP29317.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29317.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 206Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini328 – 432Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST105
Domaini438 – 529Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST92
Domaini613 – 875Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini904 – 968SAMPROSITE-ProRule annotationAdd BLAST65

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 206Mediates interaction with CLDN41 PublicationAdd BLAST206
Regioni606 – 906Mediates interaction with ARHGEF16 and ELMO21 PublicationAdd BLAST301
Regioni886 – 976Negatively regulates interaction with ARHGEF161 PublicationAdd BLAST91

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi974 – 976PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi188 – 325Cys-richAdd BLAST138

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

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP29317.
KOiK05103.
OMAiCSPGFFK.
OrthoDBiEOG091G00W0.
PhylomeDBiP29317.
TreeFamiTF315608.

Family and domain databases

CDDicd00063. FN3. 2 hits.
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_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
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.
SM01411. Ephrin_rec_like. 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.
PROSITEiPS51550. 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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P29317-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELQAARACF ALLWGCALAA AAAAQGKEVV 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
CPELLQGLAH FPETIAGSDA PSLATVAGTC VDHAVVPPGG EEPRMHCAVD
260 270 280 290 300
GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEASESPC LECPEHTLPS
310 320 330 340 350
PEGATSCECE EGFFRAPQDP ASMPCTRPPS APHYLTAVGM GAKVELRWTP
360 370 380 390 400
PQDSGGREDI VYSVTCEQCW PESGECGPCE ASVRYSEPPH 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 GSGNLAVIGG VAVGVVLLLV
560 570 580 590 600
LAGVGFFIHR RRKNQRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA
610 620 630 640 650
VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG MLKTSSGKKE VPVAIKTLKA
660 670 680 690 700
GYTEKQRVDF LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEYMENGAL
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):108,266
Last modified:May 5, 2009 - v2
Checksum:i845D7E1BBCCAACCC
GO
Isoform 2 (identifier: P29317-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     477-497: GDSNSYNVRRTEGFSVTLDDL → VTPRGAGLALAGPTAGDRLVT
     498-976: Missing.

Show »
Length:497
Mass (Da):54,305
Checksum:iEB5CEB75AE01F814
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti94 – 99IFIELK → NNFELN in AAA53375 (PubMed:2174105).Curated6

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05598999K → N.Corresponds to variant rs1058372dbSNPEnsembl.1
Natural variantiVAR_042121391G → R.1 PublicationCorresponds to variant rs34192549dbSNPEnsembl.1
Natural variantiVAR_042122511T → M.1 PublicationCorresponds to variant rs55747232dbSNPEnsembl.1
Natural variantiVAR_042123568R → H.1 PublicationCorresponds to variant rs56198600dbSNPEnsembl.1
Natural variantiVAR_055990631M → T.Corresponds to variant rs34021505dbSNPEnsembl.1
Natural variantiVAR_062532721R → Q in CTRCT6; retained in the cytoplasm and constitutively active it alters EPHA2 signaling. 1 PublicationCorresponds to variant rs116506614dbSNPEnsembl.1
Natural variantiVAR_042124777G → S in a gastric adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042125876R → H.1 PublicationCorresponds to variant rs35903225dbSNPEnsembl.1
Natural variantiVAR_058907940T → I in CTRCT6; reduced protein stability and reduced ability to stimulate cell migration in absence of its ephrin ligand. 2 PublicationsCorresponds to variant rs137853200dbSNPEnsembl.1
Natural variantiVAR_058908948G → W in CTRCT6; reduced protein stability and reduced ability to stimulate cell migration in absence of its ephrin ligand. 2 PublicationsCorresponds to variant rs137853199dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056014477 – 497GDSNS…TLDDL → VTPRGAGLALAGPTAGDRLV T in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_056015498 – 976Missing in isoform 2. 1 PublicationAdd BLAST479

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59371 mRNA. Translation: AAA53375.1.
EU826606 mRNA. Translation: ACF47642.1.
AL451042 Genomic DNA. Translation: CAH71943.1.
CH471167 Genomic DNA. Translation: EAW51769.1.
BC037166 mRNA. Translation: AAH37166.1.
CCDSiCCDS169.1. [P29317-1]
PIRiA36355.
RefSeqiNP_004422.2. NM_004431.4. [P29317-1]
UniGeneiHs.171596.

Genome annotation databases

EnsembliENST00000358432; ENSP00000351209; ENSG00000142627. [P29317-1]
GeneIDi1969.
KEGGihsa:1969.
UCSCiuc001aya.2. human. [P29317-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59371 mRNA. Translation: AAA53375.1.
EU826606 mRNA. Translation: ACF47642.1.
AL451042 Genomic DNA. Translation: CAH71943.1.
CH471167 Genomic DNA. Translation: EAW51769.1.
BC037166 mRNA. Translation: AAH37166.1.
CCDSiCCDS169.1. [P29317-1]
PIRiA36355.
RefSeqiNP_004422.2. NM_004431.4. [P29317-1]
UniGeneiHs.171596.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MQBX-ray2.30A/B596-900[»]
2E8NNMR-A902-976[»]
2K9YNMR-A/B523-563[»]
2KSONMR-A908-972[»]
2X10X-ray3.00A27-534[»]
2X11X-ray4.83A27-534[»]
3C8XX-ray1.95A23-202[»]
3CZUX-ray2.65A23-202[»]
3FL7X-ray2.50A23-531[»]
3HEIX-ray2.00A/C/E/G/I/K/M/O28-201[»]
3HPNX-ray2.52A/B/C/D/E/F28-201[»]
3KKAX-ray2.40C/D/E903-971[»]
3MBWX-ray2.81A23-326[»]
3MX0X-ray3.51A/C27-435[»]
3SKJX-ray2.50E/F23-202[»]
4P2KX-ray1.50A590-876[»]
4PDOX-ray2.10A/B590-876[»]
4TRLX-ray2.45A590-876[»]
5EK7X-ray1.90A/B583-876[»]
ProteinModelPortaliP29317.
SMRiP29317.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108288. 67 interactors.
DIPiDIP-96N.
IntActiP29317. 30 interactors.
MINTiMINT-3972729.
STRINGi9606.ENSP00000351209.

Chemistry databases

BindingDBiP29317.
ChEMBLiCHEMBL2068.
DrugBankiDB01254. Dasatinib.
DB08896. Regorafenib.
GuidetoPHARMACOLOGYi1822.

PTM databases

iPTMnetiP29317.
PhosphoSitePlusiP29317.
SwissPalmiP29317.
UniCarbKBiP29317.

Polymorphism and mutation databases

BioMutaiEPHA2.
DMDMi229462861.

Proteomic databases

EPDiP29317.
MaxQBiP29317.
PaxDbiP29317.
PeptideAtlasiP29317.
PRIDEiP29317.

Protocols and materials databases

DNASUi1969.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358432; ENSP00000351209; ENSG00000142627. [P29317-1]
GeneIDi1969.
KEGGihsa:1969.
UCSCiuc001aya.2. human. [P29317-1]

Organism-specific databases

CTDi1969.
DisGeNETi1969.
GeneCardsiEPHA2.
HGNCiHGNC:3386. EPHA2.
HPAiCAB010464.
MalaCardsiEPHA2.
MIMi116600. phenotype.
176946. gene.
neXtProtiNX_P29317.
OpenTargetsiENSG00000142627.
Orphaneti98993. Posterior polar cataract.
98994. Total congenital cataract.
PharmGKBiPA27818.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP29317.
KOiK05103.
OMAiCSPGFFK.
OrthoDBiEOG091G00W0.
PhylomeDBiP29317.
TreeFamiTF315608.

Enzyme and pathway databases

BioCyciZFISH:HS06946-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-2682334. EPH-Ephrin signaling.
R-HSA-3928663. EPHA-mediated growth cone collapse.
R-HSA-3928665. EPH-ephrin mediated repulsion of cells.
SignaLinkiP29317.
SIGNORiP29317.

Miscellaneous databases

EvolutionaryTraceiP29317.
GeneWikiiEPH_receptor_A2.
GenomeRNAii1969.
PROiP29317.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142627.
CleanExiHS_EPHA2.
ExpressionAtlasiP29317. baseline and differential.
GenevisibleiP29317. HS.

Family and domain databases

CDDicd00063. FN3. 2 hits.
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_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
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.
SM01411. Ephrin_rec_like. 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.
PROSITEiPS51550. 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...

Entry informationi

Entry nameiEPHA2_HUMAN
AccessioniPrimary (citable) accession number: P29317
Secondary accession number(s): B5A968, Q8N3Z2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: May 5, 2009
Last modified: November 30, 2016
This is version 199 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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 one 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.