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Protein

Ephrin type-B receptor 3

Gene

EPHB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei665ATPPROSITE-ProRule annotation1
Active sitei758Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi639 – 647ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processAngiogenesis, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-2682334 EPH-Ephrin signaling
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-3928664 Ephrin signaling
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
SignaLinkiP54753
SIGNORiP54753

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-B receptor 3 (EC:2.7.10.1)
Alternative name(s):
EPH-like tyrosine kinase 2
Short name:
EPH-like kinase 2
Embryonic kinase 2
Short name:
EK2
Short name:
hEK2
Tyrosine-protein kinase TYRO6
Gene namesi
Name:EPHB3
Synonyms:ETK2, HEK2, TYRO6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000182580.2
HGNCiHGNC:3394 EPHB3
MIMi601839 gene
neXtProtiNX_P54753

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini34 – 559ExtracellularSequence analysisAdd BLAST526
Transmembranei560 – 580HelicalSequence analysisAdd BLAST21
Topological domaini581 – 998CytoplasmicSequence analysisAdd BLAST418

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi614Y → F: Partial loss of phosphorylation and loss of interaction with SH2-containing proteins. 1 Publication1
Mutagenesisi665K → R: Kinase-dead. Loss of autophosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi2049
OpenTargetsiENSG00000182580
PharmGKBiPA27826

Chemistry databases

ChEMBLiCHEMBL4901
GuidetoPHARMACOLOGYi1832

Polymorphism and mutation databases

BioMutaiEPHB3
DMDMi76803655

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000001683134 – 998Ephrin type-B receptor 3Add BLAST965

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi81 ↔ 1991 Publication
Glycosylationi351N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi445N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei614Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Phosphorylated. Autophosphorylates upon ligand-binding. Autophosphorylation on Tyr-614 is required for interaction with SH2 domain-containing proteins.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP54753
MaxQBiP54753
PaxDbiP54753
PeptideAtlasiP54753
PRIDEiP54753

PTM databases

iPTMnetiP54753
PhosphoSitePlusiP54753

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000182580
CleanExiHS_EPHB3
GenevisibleiP54753 HS

Organism-specific databases

HPAiCAB034350
HPA007698
HPA008184

Interactioni

Subunit structurei

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi108363, 12 interactors
IntActiP54753, 5 interactors
MINTiP54753
STRINGi9606.ENSP00000332118

Chemistry databases

BindingDBiP54753

Structurei

Secondary structure

1998
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 44Combined sources6
Helixi45 – 47Combined sources3
Beta strandi55 – 58Combined sources4
Beta strandi63 – 68Combined sources6
Beta strandi74 – 80Combined sources7
Beta strandi85 – 87Combined sources3
Beta strandi90 – 93Combined sources4
Beta strandi103 – 114Combined sources12
Helixi116 – 118Combined sources3
Beta strandi130 – 139Combined sources10
Beta strandi155 – 160Combined sources6
Beta strandi175 – 181Combined sources7
Beta strandi186 – 198Combined sources13
Beta strandi200 – 210Combined sources11
Beta strandi633 – 640Combined sources8
Beta strandi646 – 652Combined sources7
Beta strandi655 – 657Combined sources3
Beta strandi660 – 666Combined sources7
Helixi673 – 687Combined sources15
Beta strandi697 – 701Combined sources5
Beta strandi703 – 706Combined sources4
Beta strandi708 – 712Combined sources5
Helixi719 – 725Combined sources7
Turni726 – 728Combined sources3
Helixi732 – 751Combined sources20
Helixi761 – 763Combined sources3
Beta strandi764 – 766Combined sources3
Beta strandi772 – 774Combined sources3
Beta strandi791 – 793Combined sources3
Beta strandi796 – 798Combined sources3
Helixi802 – 804Combined sources3
Helixi807 – 812Combined sources6
Helixi817 – 832Combined sources16
Turni838 – 841Combined sources4
Helixi844 – 852Combined sources9
Helixi865 – 874Combined sources10
Turni879 – 881Combined sources3
Helixi885 – 897Combined sources13
Helixi899 – 902Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P1IX-ray2.10A/B/C39-211[»]
3ZFYX-ray2.20A/B616-910[»]
5L6OX-ray1.88A616-910[»]
5L6PX-ray2.26A616-910[»]
ProteinModelPortaliP54753
SMRiP54753
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54753

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 217Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini339 – 451Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST113
Domaini452 – 545Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST94
Domaini633 – 896Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini925 – 989SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi996 – 998PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi199 – 336Cys-richAdd BLAST138

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP54753
KOiK05112
OMAiELAWTAH
OrthoDBiEOG091G00W0
PhylomeDBiP54753
TreeFamiTF315608

Family and domain databases

CDDicd10478 EphR_LBD_B3, 1 hit
cd00063 FN3, 2 hits
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034245 EphB3_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001660 SAM
IPR013761 SAM/pointed_sf
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
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF07699 Ephrin_rec_like, 1 hit
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

Sequencei

Sequence statusi: Complete.

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

P54753-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARARPPPPP SPPPGLLPLL PPLLLLPLLL LPAGCRALEE TLMDTKWVTS
60 70 80 90 100
ELAWTSHPES GWEEVSGYDE AMNPIRTYQV CNVRESSQNN WLRTGFIWRR
110 120 130 140 150
DVQRVYVELK FTVRDCNSIP NIPGSCKETF NLFYYEADSD VASASSPFWM
160 170 180 190 200
ENPYVKVDTI APDESFSRLD AGRVNTKVRS FGPLSKAGFY LAFQDQGACM
210 220 230 240 250
SLISVRAFYK KCASTTAGFA LFPETLTGAE PTSLVIAPGT CIPNAVEVSV
260 270 280 290 300
PLKLYCNGDG EWMVPVGACT CATGHEPAAK ESQCRPCPPG SYKAKQGEGP
310 320 330 340 350
CLPCPPNSRT TSPAASICTC HNNFYRADSD SADSACTTVP SPPRGVISNV
360 370 380 390 400
NETSLILEWS EPRDLGGRDD LLYNVICKKC HGAGGASACS RCDDNVEFVP
410 420 430 440 450
RQLGLTERRV HISHLLAHTR YTFEVQAVNG VSGKSPLPPR YAAVNITTNQ
460 470 480 490 500
AAPSEVPTLR LHSSSGSSLT LSWAPPERPN GVILDYEMKY FEKSEGIAST
510 520 530 540 550
VTSQMNSVQL DGLRPDARYV VQVRARTVAG YGQYSRPAEF ETTSERGSGA
560 570 580 590 600
QQLQEQLPLI VGSATAGLVF VVAVVVIAIV CLRKQRHGSD SEYTEKLQQY
610 620 630 640 650
IAPGMKVYID PFTYEDPNEA VREFAKEIDV SCVKIEEVIG AGEFGEVCRG
660 670 680 690 700
RLKQPGRREV FVAIKTLKVG YTERQRRDFL SEASIMGQFD HPNIIRLEGV
710 720 730 740 750
VTKSRPVMIL TEFMENCALD SFLRLNDGQF TVIQLVGMLR GIAAGMKYLS
760 770 780 790 800
EMNYVHRDLA ARNILVNSNL VCKVSDFGLS RFLEDDPSDP TYTSSLGGKI
810 820 830 840 850
PIRWTAPEAI AYRKFTSASD VWSYGIVMWE VMSYGERPYW DMSNQDVINA
860 870 880 890 900
VEQDYRLPPP MDCPTALHQL MLDCWVRDRN LRPKFSQIVN TLDKLIRNAA
910 920 930 940 950
SLKVIASAQS GMSQPLLDRT VPDYTTFTTV GDWLDAIKMG RYKESFVSAG
960 970 980 990
FASFDLVAQM TAEDLLRIGV TLAGHQKKIL SSIQDMRLQM NQTLPVQV
Length:998
Mass (Da):110,330
Last modified:September 27, 2005 - v2
Checksum:i9B65A4EF58B27407
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti367G → V in CAA53021 (PubMed:8397371).Curated1
Sequence conflicti406 – 408TER → SEP in CAA53021 (PubMed:8397371).Curated3
Sequence conflicti412I → T in CAA53021 (PubMed:8397371).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042176168R → L in a lung small cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042177440R → C1 PublicationCorresponds to variant dbSNP:rs56029711Ensembl.1
Natural variantiVAR_042178579I → V1 PublicationCorresponds to variant dbSNP:rs56103851Ensembl.1
Natural variantiVAR_042179601I → L1 PublicationCorresponds to variant dbSNP:rs56129875Ensembl.1
Natural variantiVAR_042180724R → W in a lung neuroendocrine carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs371378866Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75208 mRNA Translation: CAA53021.1
BC052968 mRNA Translation: AAH52968.1
CCDSiCCDS3268.1
PIRiS37627
RefSeqiNP_004434.2, NM_004443.3
UniGeneiHs.2913

Genome annotation databases

EnsembliENST00000330394; ENSP00000332118; ENSG00000182580
GeneIDi2049
KEGGihsa:2049
UCSCiuc003foz.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEPHB3_HUMAN
AccessioniPrimary (citable) accession number: P54753
Secondary accession number(s): Q7Z740
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 27, 2005
Last modified: May 23, 2018
This is version 179 of the entry and version 2 of the sequence. See 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 3
    Human chromosome 3: 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

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