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P54754 (EPHB3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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):
Developmental kinase 5
Short name=mDK-5
Tyrosine-protein kinase receptor SEK-4
Gene names
Name:Ephb3
Synonyms:Etk2, Mdk5, Sek4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length993 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.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10

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 Ref.8.

Tissue specificity

Expressed in cells of the retinal ganglion cell layer during retinal axon guidance to the optic disk. Expressed by Paneth and progenitor cells in the crypts of the intestinal epithelium (at protein level). Ref.6 Ref.7

Developmental stage

Expressed during development in yolk sacs and by embryonic endothelial cells. Expressed in the developing intestinal epithelium at the bottom of the intervillus pockets where undifferentiated cells are allocated (at protein level). Ref.5 Ref.7

Post-translational modification

Phosphorylated. Autophosphorylates upon ligand-binding. Autophosphorylation on Tyr-609 is required for interaction with SH2 domain-containing proteins By similarity.

Disruption phenotype

Mice are viable and fertile and show no obvious abnormal behavior. The corpus callosum, the main axon tract connecting the left and right cerebral hemispheres, is not formed in a significant fraction of newborns. This is associated with defects in guidance of callosal axons across the midline. Ref.4

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
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

axon guidance

Inferred from mutant phenotype PubMed 10839360Ref.4. Source: UniProtKB

axonal fasciculation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

cell migration

Inferred from mutant phenotype Ref.7. Source: UniProtKB

central nervous system projection neuron axonogenesis

Inferred from direct assay PubMed 12971893. Source: MGI

corpus callosum development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

dendritic spine development

Inferred from mutant phenotype Ref.8. Source: UniProtKB

dendritic spine morphogenesis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

digestive tract morphogenesis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

palate development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

positive regulation of synapse assembly

Inferred from mutant phenotype Ref.8. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Cdc42 GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of axonogenesis

Inferred from direct assay PubMed 17719550. Source: UniProtKB

regulation of cell-cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

retinal ganglion cell axon guidance

Inferred from direct assay PubMed 12971893. Source: MGI

substrate adhesion-dependent cell spreading

Inferred from sequence or structural similarity. Source: UniProtKB

thymus development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

urogenital system development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

   Cellular_componentdendrite

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

axon guidance receptor activity

Inferred from direct assay PubMed 11532925. Source: MGI

ephrin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane-ephrin receptor activity

Traceable author statement PubMed 11532925. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Chain30 – 993964Ephrin type-B receptor 3
PRO_0000016832

Regions

Topological domain30 – 554525Extracellular Potential
Transmembrane555 – 57521Helical; Potential
Topological domain576 – 993418Cytoplasmic Potential
Domain31 – 209179Eph LBD
Domain331 – 446116Fibronectin type-III 1
Domain447 – 54094Fibronectin type-III 2
Domain628 – 891264Protein kinase
Domain920 – 98465SAM
Nucleotide binding634 – 6429ATP By similarity
Motif991 – 9933PDZ-binding Potential
Compositional bias191 – 328138Cys-rich

Sites

Active site7531Proton acceptor By similarity
Binding site6601ATP By similarity

Amino acid modifications

Modified residue6091Phosphotyrosine; by autocatalysis By similarity
Glycosylation3431N-linked (GlcNAc...) Potential
Glycosylation4401N-linked (GlcNAc...) Potential
Disulfide bond73 ↔ 191 By similarity

Experimental info

Sequence conflict200 – 2012FY → GD in CAA88910. Ref.1
Sequence conflict3311V → E in CAA88910. Ref.1
Sequence conflict5671V → M in CAA88910. Ref.1
Sequence conflict7191R → Q in CAA53599. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P54754 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 07C6EF2AC98AE1B4

FASTA993109,662
        10         20         30         40         50         60 
MAGARPPPGL LPLLAPLLLP LLLPAGCWAL EETLMDTKWV TSELAWTSHP ESGWEEVSGY 

        70         80         90        100        110        120 
DEAMNPIRTY QVCNVRESSQ NNWLRTGFIW RREVQRVYVE LKFTVRDCNS IPNIPGSCKE 

       130        140        150        160        170        180 
TFNLFYYEAD SDVASASSPF WMENPYVKVD TIAPDESFSR LDAGRVNTKV RSFGPLSKAG 

       190        200        210        220        230        240 
FYLAFQDQGA CMSLISVRAF YKKCASTTAG FALFPETLTG AEPTSLVIAP GTCIANAVEV 

       250        260        270        280        290        300 
SVPLKLYCNG DGEWMVPVGA CTCATGHEPA AKESQCRACP PGSYKAKQGE GPCLPCPPNS 

       310        320        330        340        350        360 
RTTSPAASIC TCHNNFYRAD SDSADSACTT VPSPPRGVIS NVNETSLILE WSEPRDLGGR 

       370        380        390        400        410        420 
DDLLYNVICK KCRGSSGAGG PATCSRCDDN VEFVPRQLGL TERRVHISHL LAHTRYTFEV 

       430        440        450        460        470        480 
QAVNGVSGKS PLPPRYAAVN ITTNQAAPSE VPTLHLHSSS GSSLTLSWAP PERPNGVILD 

       490        500        510        520        530        540 
YEMKYFEKSK GIASTVTSQK NSVQLDGLQP DARYVVQVRA RTVAGYGQYS HPAEFETTSE 

       550        560        570        580        590        600 
RGSGAQQLQE QLPLIVGSTV AGFVFMVVVV VIALVCLRKQ RHGPDAEYTE KLQQYIAPGM 

       610        620        630        640        650        660 
KVYIDPFTYE DPNEAVREFA KEIDVSCVKI EEVIGAGEFG EVCRGRLKLP GRREVFVAIK 

       670        680        690        700        710        720 
TLKVGYTERQ RRDFLSEASI MGQFDHPNII RLEGVVTKSR PVMILTEFME NCALDSFLRL 

       730        740        750        760        770        780 
NDGQFTVIQL VGMLRGIAAG MKYLSEMNYV HRDLAARNIL VNSNLVCKVS DFGLSRFLED 

       790        800        810        820        830        840 
DPSDPTYTSS LGGKIPIRWT APEAIAYRKF TSASDVWSYG IVMWEVMSYG ERPYWDMSNQ 

       850        860        870        880        890        900 
DVINAVEQDY RLPPPMDCPT ALHQLMLDCW VRDRNLRPKF SQIVNTLDKL IRNAASLKVT 

       910        920        930        940        950        960 
ASAPSGMSQP LLDRTVPDYT TFTTVGDWLD AIKMGRYKES FVGAGFASFD LVAQMTAEDL 

       970        980        990 
LRIGVTLAGH QKKILCSIQD MRLQMNQTLP VQV 

« Hide

References

« Hide 'large scale' references
[1]"Cloning, characterization, and differential expression of MDK2 and MDK5, two novel receptor tyrosine kinases of the eck/eph family."
Ciossek T., Lerch M.M., Ullrich A.
Oncogene 11:2085-2095(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
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].
Strain: C57BL/6 and FVB/N.
Tissue: Brain and Mammary tumor.
[3]"Several receptor tyrosine kinase genes of the Eph family are segmentally expressed in the developing hindbrain."
Becker N., Seitanidou T., Murphy P., Mattei M.-G., Topilko P., Nieto A., Wilkinson D.G., Charnay P., Gilardi P.
Mech. Dev. 47:3-17(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 719-993.
Strain: BALB/c.
Tissue: Brain.
[4]"Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation."
Orioli D., Henkemeyer M., Lemke G., Klein R., Pawson T.
EMBO J. 15:6035-6049(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION IN AXON GUIDANCE, FUNCTION IN PALATE DEVELOPMENT.
[5]"Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis."
Adams R.H., Wilkinson G.A., Weiss C., Diella F., Gale N.W., Deutsch U., Risau W., Klein R.
Genes Dev. 13:295-306(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS, DEVELOPMENTAL STAGE.
[6]"Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons."
Imondi R., Wideman C., Kaprielian Z.
Development 127:1397-1410(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB."
Batlle E., Henderson J.T., Beghtel H., van den Born M.M., Sancho E., Huls G., Meeldijk J., Robertson J., van de Wetering M., Pawson T., Clevers H.
Cell 111:251-263(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INTESTINAL EPITHELIUM DIFFERENTIATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[8]"Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus."
Henkemeyer M., Itkis O.S., Ngo M., Hickmott P.W., Ethell I.M.
J. Cell Biol. 163:1313-1326(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DENDRITIC SPINE DEVELOPMENT, FUNCTION IN EXCITATORY SYNAPSE FORMATION, SUBCELLULAR LOCATION.
[9]"Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development."
Dravis C., Yokoyama N., Chumley M.J., Cowan C.A., Silvany R.E., Shay J., Baker L.A., Henkemeyer M.
Dev. Biol. 271:272-290(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN URORECTAL DEVELOPMENT.
[10]"On the role of Eph signalling in thymus histogenesis; EphB2/B3 and the organizing of the thymic epithelial network."
Garcia-Ceca J., Jimenez E., Alfaro D., Cejalvo T., Chumley M.J., Henkemeyer M., Munoz J.J., Zapata A.G.
Int. J. Dev. Biol. 53:971-982(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THYMUS DEVELOPMENT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z49086 mRNA. Translation: CAA88910.1.
BC014822 mRNA. Translation: AAH14822.1.
BC053085 mRNA. Translation: AAH53085.1.
X76012 mRNA. Translation: CAA53599.1.
CCDSCCDS28060.1.
PIRI48653.
I48761.
RefSeqNP_034273.1. NM_010143.1.
UniGeneMm.6972.

3D structure databases

ProteinModelPortalP54754.
SMRP54754. Positions 29-537, 543-899, 917-987.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199477. 1 interaction.

PTM databases

PhosphoSiteP54754.

Proteomic databases

MaxQBP54754.
PaxDbP54754.
PRIDEP54754.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000006112; ENSMUSP00000006112; ENSMUSG00000005958.
GeneID13845.
KEGGmmu:13845.
UCSCuc007yrg.1. mouse.

Organism-specific databases

CTD2049.
MGIMGI:104770. Ephb3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115081.
HOGENOMHOG000233856.
HOVERGENHBG062180.
InParanoidQ91YS9.
KOK05112.
OMANLRPKFA.
OrthoDBEOG7VTDM6.
TreeFamTF315608.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressP54754.
BgeeP54754.
CleanExMM_EPHB3.
GenevestigatorP54754.

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

NextBio284688.
PROP54754.
SOURCESearch...

Entry information

Entry nameEPHB3_MOUSE
AccessionPrimary (citable) accession number: P54754
Secondary accession number(s): Q62214, Q91YS9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot