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P54753 (EPHB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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 namesRecommended 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 names
Name:EPHB3
Synonyms:ETK2, HEK2, TYRO6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length998 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Beside 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. Ref.5

Catalytic activity

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

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 By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein. Cell projectiondendrite By similarity Ref.5.

Tissue specificity

Ubiquitous.

Post-translational modification

Phosphorylated. Autophosphorylates upon ligand-binding. Autophosphorylation on Tyr-614 is required for interaction with SH2 domain-containing proteins. Ref.1 Ref.4 Ref.5

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
Neurogenesis
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

axonal fasciculation

Inferred from sequence or structural similarity. Source: UniProtKB

cell migration

Inferred from direct assay Ref.5. Source: UniProtKB

central nervous system projection neuron axonogenesis

Inferred from electronic annotation. Source: Ensembl

corpus callosum development

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine development

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

digestive tract morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from direct assay Ref.5Ref.1. Source: UniProtKB

palate development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of synapse assembly

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.5Ref.1. Source: UniProtKB

regulation of Cdc42 GTPase activity

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell-cell adhesion

Inferred from direct assay Ref.1. Source: UniProtKB

retinal ganglion cell axon guidance

Inferred from electronic annotation. Source: Ensembl

substrate adhesion-dependent cell spreading

Inferred from direct assay Ref.5. Source: UniProtKB

thymus development

Inferred from sequence or structural similarity. Source: UniProtKB

urogenital system development

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentdendrite

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay Ref.5Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

axon guidance receptor activity

Inferred from electronic annotation. Source: Ensembl

ephrin receptor activity

Inferred from direct assay Ref.5Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Chain34 – 998965Ephrin type-B receptor 3
PRO_0000016831

Regions

Topological domain34 – 559526Extracellular Potential
Transmembrane560 – 58021Helical; Potential
Topological domain581 – 998418Cytoplasmic Potential
Domain39 – 217179Eph LBD
Domain339 – 451113Fibronectin type-III 1
Domain452 – 54594Fibronectin type-III 2
Domain633 – 896264Protein kinase
Domain925 – 98965SAM
Nucleotide binding639 – 6479ATP By similarity
Motif996 – 9983PDZ-binding Potential
Compositional bias199 – 336138Cys-rich

Sites

Active site7581Proton acceptor By similarity
Binding site6651ATP By similarity

Amino acid modifications

Modified residue6141Phosphotyrosine; by autocatalysis Ref.4
Glycosylation3511N-linked (GlcNAc...) Potential
Glycosylation4451N-linked (GlcNAc...) Potential
Disulfide bond81 ↔ 199 Ref.7

Natural variations

Natural variant1681R → L in a lung small cell carcinoma sample; somatic mutation. Ref.8
VAR_042176
Natural variant4401R → C. Ref.8
Corresponds to variant rs56029711 [ dbSNP | Ensembl ].
VAR_042177
Natural variant5791I → V. Ref.8
Corresponds to variant rs56103851 [ dbSNP | Ensembl ].
VAR_042178
Natural variant6011I → L. Ref.8
Corresponds to variant rs56129875 [ dbSNP | Ensembl ].
VAR_042179
Natural variant7241R → W in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.8
VAR_042180

Experimental info

Mutagenesis6141Y → F: Partial loss of phosphorylation and loss of interaction with SH2-containing proteins. Ref.4
Mutagenesis6651K → R: Kinase-dead. Loss of autophosphorylation. Ref.4
Sequence conflict3671G → V in CAA53021. Ref.1
Sequence conflict406 – 4083TER → SEP in CAA53021. Ref.1
Sequence conflict4121I → T in CAA53021. Ref.1

Secondary structure

...................................................................... 998
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P54753 [UniParc].

Last modified September 27, 2005. Version 2.
Checksum: 9B65A4EF58B27407

FASTA998110,330
        10         20         30         40         50         60 
MARARPPPPP SPPPGLLPLL PPLLLLPLLL LPAGCRALEE TLMDTKWVTS ELAWTSHPES 

        70         80         90        100        110        120 
GWEEVSGYDE AMNPIRTYQV CNVRESSQNN WLRTGFIWRR DVQRVYVELK FTVRDCNSIP 

       130        140        150        160        170        180 
NIPGSCKETF NLFYYEADSD VASASSPFWM ENPYVKVDTI APDESFSRLD AGRVNTKVRS 

       190        200        210        220        230        240 
FGPLSKAGFY LAFQDQGACM SLISVRAFYK KCASTTAGFA LFPETLTGAE PTSLVIAPGT 

       250        260        270        280        290        300 
CIPNAVEVSV PLKLYCNGDG EWMVPVGACT CATGHEPAAK ESQCRPCPPG SYKAKQGEGP 

       310        320        330        340        350        360 
CLPCPPNSRT TSPAASICTC HNNFYRADSD SADSACTTVP SPPRGVISNV NETSLILEWS 

       370        380        390        400        410        420 
EPRDLGGRDD LLYNVICKKC HGAGGASACS RCDDNVEFVP RQLGLTERRV HISHLLAHTR 

       430        440        450        460        470        480 
YTFEVQAVNG VSGKSPLPPR YAAVNITTNQ AAPSEVPTLR LHSSSGSSLT LSWAPPERPN 

       490        500        510        520        530        540 
GVILDYEMKY FEKSEGIAST VTSQMNSVQL DGLRPDARYV VQVRARTVAG YGQYSRPAEF 

       550        560        570        580        590        600 
ETTSERGSGA QQLQEQLPLI VGSATAGLVF VVAVVVIAIV CLRKQRHGSD SEYTEKLQQY 

       610        620        630        640        650        660 
IAPGMKVYID PFTYEDPNEA VREFAKEIDV SCVKIEEVIG AGEFGEVCRG RLKQPGRREV 

       670        680        690        700        710        720 
FVAIKTLKVG YTERQRRDFL SEASIMGQFD HPNIIRLEGV VTKSRPVMIL TEFMENCALD 

       730        740        750        760        770        780 
SFLRLNDGQF TVIQLVGMLR GIAAGMKYLS EMNYVHRDLA ARNILVNSNL VCKVSDFGLS 

       790        800        810        820        830        840 
RFLEDDPSDP TYTSSLGGKI PIRWTAPEAI AYRKFTSASD VWSYGIVMWE VMSYGERPYW 

       850        860        870        880        890        900 
DMSNQDVINA VEQDYRLPPP MDCPTALHQL MLDCWVRDRN LRPKFSQIVN TLDKLIRNAA 

       910        920        930        940        950        960 
SLKVIASAQS GMSQPLLDRT VPDYTTFTTV GDWLDAIKMG RYKESFVSAG FASFDLVAQM 

       970        980        990 
TAEDLLRIGV TLAGHQKKIL SSIQDMRLQM NQTLPVQV 

« Hide

References

« Hide 'large scale' references
[1]"PCR mediated detection of a new human receptor-tyrosine-kinase, HEK 2."
Boehme B., Holtrich U., Wolf G., Luzius H., Grzeschik K.-H., Strebhardt K., Ruebsamen-Waigmann H.
Oncogene 8:2857-2862(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF EFNB1 AND EFNB2 AS LIGANDS, AUTOPHOSPHORYLATION.
Tissue: Embryo.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[3]"Unified nomenclature for Eph family receptors and their ligands, the ephrins."
Eph nomenclature committee
Cell 90:403-404(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NOMENCLATURE.
[4]"Tyrosine-614, the major autophosphorylation site of the receptor tyrosine kinase HEK2, functions as multi-docking site for SH2-domain mediated interactions."
Hock B., Boehme B., Karn T., Feller S., Ruebsamen-Waigmann H., Strebhardt K.
Oncogene 17:255-260(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-614, MUTAGENESIS OF TYR-614 AND LYS-665.
[5]"Inhibition of integrin-mediated cell adhesion but not directional cell migration requires catalytic activity of EphB3 receptor tyrosine kinase. Role of Rho family small GTPases."
Miao H., Strebhardt K., Pasquale E.B., Shen T.L., Guan J.L., Wang B.
J. Biol. Chem. 280:923-932(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION, FUNCTION IN CELL ADHESION, FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION.
[6]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Ligand binding domain of human EPHB3."
Structural genomics consortium (SGC)
Submitted (JAN-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 39-211, DISULFIDE BOND.
[8]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-168; CYS-440; VAL-579; LEU-601 AND TRP-724.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X75208 mRNA. Translation: CAA53021.1.
BC052968 mRNA. Translation: AAH52968.1.
CCDSCCDS3268.1.
PIRS37627.
RefSeqNP_004434.2. NM_004443.3.
UniGeneHs.2913.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3P1IX-ray2.10A/B/C39-211[»]
3ZFYX-ray2.20A/B616-910[»]
ProteinModelPortalP54753.
SMRP54753. Positions 37-905, 922-992.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108363. 10 interactions.
IntActP54753. 3 interactions.
MINTMINT-1538099.
STRING9606.ENSP00000332118.

Chemistry

BindingDBP54753.
ChEMBLCHEMBL2363043.
GuidetoPHARMACOLOGY1832.

PTM databases

PhosphoSiteP54753.

Polymorphism databases

DMDM76803655.

Proteomic databases

MaxQBP54753.
PaxDbP54753.
PRIDEP54753.

Protocols and materials databases

DNASU2049.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330394; ENSP00000332118; ENSG00000182580.
GeneID2049.
KEGGhsa:2049.
UCSCuc003foz.3. human.

Organism-specific databases

CTD2049.
GeneCardsGC03P184279.
HGNCHGNC:3394. EPHB3.
HPAHPA007698.
HPA008184.
MIM601839. gene.
neXtProtNX_P54753.
PharmGKBPA27826.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233856.
HOVERGENHBG062180.
InParanoidP54753.
KOK05112.
OMANLRPKFA.
OrthoDBEOG7VTDM6.
PhylomeDBP54753.
TreeFamTF315608.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
SignaLinkP54753.

Gene expression databases

ArrayExpressP54753.
BgeeP54753.
CleanExHS_EPHB3.
GenevestigatorP54753.

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.
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.
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]
PfamPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07699. GCC2_GCC3. 1 hit.
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.
PROSITEPS51550. 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...

Other

EvolutionaryTraceP54753.
GeneWikiEPHB3.
GenomeRNAi2049.
NextBio8331.
PROP54753.
SOURCESearch...

Entry information

Entry nameEPHB3_HUMAN
AccessionPrimary (citable) accession number: P54753
Secondary accession number(s): Q7Z740
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 27, 2005
Last modified: July 9, 2014
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM