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Protein

Ephrin type-B receptor 3

Gene

Ephb3

Organism
Mus musculus (Mouse)
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.6 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei660ATPPROSITE-ProRule annotation1
Active sitei753Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi634 – 642ATPPROSITE-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 3474
ReactomeiR-MMU-2682334 EPH-Ephrin signaling
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-3928664 Ephrin signaling
R-MMU-3928665 EPH-ephrin mediated repulsion of cells

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Ephb3
Synonyms:Etk2, Mdk5, Sek4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:104770 Ephb3

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 domaini30 – 554ExtracellularSequence analysisAdd BLAST525
Transmembranei555 – 575HelicalSequence analysisAdd BLAST21
Topological domaini576 – 993CytoplasmicSequence analysisAdd BLAST418

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Chemistry databases

GuidetoPHARMACOLOGYi1832

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000001683230 – 993Ephrin type-B receptor 3Add BLAST964

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi73 ↔ 191By similarity
Glycosylationi343N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi440N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei609Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP54754
PaxDbiP54754
PeptideAtlasiP54754
PRIDEiP54754

PTM databases

iPTMnetiP54754
PhosphoSitePlusiP54754

Expressioni

Tissue specificityi

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). Expressed in myogenic progenitor cells (PubMed:27446912).3 Publications

Developmental stagei

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). In myogenic progenitor cells, highly expressed during early development (E11.5) and progressively repressed as developments proceeds (PubMed:27446912).3 Publications

Gene expression databases

BgeeiENSMUSG00000005958 Expressed in 260 organ(s), highest expression level in membranous labyrinth
CleanExiMM_EPHB3
ExpressionAtlasiP54754 baseline and differential
GenevisibleiP54754 MM

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

BioGridi199477, 4 interactors
STRINGi10090.ENSMUSP00000006112

Structurei

3D structure databases

ProteinModelPortaliP54754
SMRiP54754
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 209Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini331 – 446Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST116
Domaini447 – 540Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST94
Domaini628 – 891Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini920 – 984SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi991 – 993PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi191 – 328Cys-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
InParanoidiP54754
KOiK05112
OMAiKKCSVER
OrthoDBiEOG091G00W0
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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P54754-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGARPPPGL LPLLAPLLLP LLLPAGCWAL EETLMDTKWV TSELAWTSHP
60 70 80 90 100
ESGWEEVSGY DEAMNPIRTY QVCNVRESSQ NNWLRTGFIW RREVQRVYVE
110 120 130 140 150
LKFTVRDCNS IPNIPGSCKE TFNLFYYEAD SDVASASSPF WMENPYVKVD
160 170 180 190 200
TIAPDESFSR LDAGRVNTKV RSFGPLSKAG FYLAFQDQGA CMSLISVRAF
210 220 230 240 250
YKKCASTTAG FALFPETLTG AEPTSLVIAP GTCIANAVEV SVPLKLYCNG
260 270 280 290 300
DGEWMVPVGA CTCATGHEPA AKESQCRACP PGSYKAKQGE GPCLPCPPNS
310 320 330 340 350
RTTSPAASIC TCHNNFYRAD SDSADSACTT VPSPPRGVIS NVNETSLILE
360 370 380 390 400
WSEPRDLGGR DDLLYNVICK KCRGSSGAGG PATCSRCDDN VEFVPRQLGL
410 420 430 440 450
TERRVHISHL LAHTRYTFEV QAVNGVSGKS PLPPRYAAVN ITTNQAAPSE
460 470 480 490 500
VPTLHLHSSS GSSLTLSWAP PERPNGVILD YEMKYFEKSK GIASTVTSQK
510 520 530 540 550
NSVQLDGLQP DARYVVQVRA RTVAGYGQYS HPAEFETTSE RGSGAQQLQE
560 570 580 590 600
QLPLIVGSTV AGFVFMVVVV VIALVCLRKQ RHGPDAEYTE KLQQYIAPGM
610 620 630 640 650
KVYIDPFTYE DPNEAVREFA KEIDVSCVKI EEVIGAGEFG EVCRGRLKLP
660 670 680 690 700
GRREVFVAIK TLKVGYTERQ RRDFLSEASI MGQFDHPNII RLEGVVTKSR
710 720 730 740 750
PVMILTEFME NCALDSFLRL NDGQFTVIQL VGMLRGIAAG MKYLSEMNYV
760 770 780 790 800
HRDLAARNIL VNSNLVCKVS DFGLSRFLED DPSDPTYTSS LGGKIPIRWT
810 820 830 840 850
APEAIAYRKF TSASDVWSYG IVMWEVMSYG ERPYWDMSNQ DVINAVEQDY
860 870 880 890 900
RLPPPMDCPT ALHQLMLDCW VRDRNLRPKF SQIVNTLDKL IRNAASLKVT
910 920 930 940 950
ASAPSGMSQP LLDRTVPDYT TFTTVGDWLD AIKMGRYKES FVGAGFASFD
960 970 980 990
LVAQMTAEDL LRIGVTLAGH QKKILCSIQD MRLQMNQTLP VQV
Length:993
Mass (Da):109,662
Last modified:July 27, 2011 - v2
Checksum:i07C6EF2AC98AE1B4
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E0CYA3E0CYA3_MOUSE
Ephrin type-B receptor 3
Ephb3
739Annotation score:
A0A338P6E0A0A338P6E0_MOUSE
Ephrin type-B receptor 3
Ephb3
191Annotation score:
A0A338P6F1A0A338P6F1_MOUSE
Ephrin type-B receptor 3
Ephb3
79Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti200 – 201FY → GD in CAA88910 (PubMed:7478528).Curated2
Sequence conflicti331V → E in CAA88910 (PubMed:7478528).Curated1
Sequence conflicti567V → M in CAA88910 (PubMed:7478528).Curated1
Sequence conflicti719R → Q in CAA53599 (PubMed:7947319).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49086 mRNA Translation: CAA88910.1
BC014822 mRNA Translation: AAH14822.1
BC053085 mRNA Translation: AAH53085.1
X76012 mRNA Translation: CAA53599.1
CCDSiCCDS28060.1
PIRiI48653
I48761
RefSeqiNP_034273.1, NM_010143.1
UniGeneiMm.6972

Genome annotation databases

EnsembliENSMUST00000006112; ENSMUSP00000006112; ENSMUSG00000005958
GeneIDi13845
KEGGimmu:13845
UCSCiuc007yrg.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49086 mRNA Translation: CAA88910.1
BC014822 mRNA Translation: AAH14822.1
BC053085 mRNA Translation: AAH53085.1
X76012 mRNA Translation: CAA53599.1
CCDSiCCDS28060.1
PIRiI48653
I48761
RefSeqiNP_034273.1, NM_010143.1
UniGeneiMm.6972

3D structure databases

ProteinModelPortaliP54754
SMRiP54754
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199477, 4 interactors
STRINGi10090.ENSMUSP00000006112

Chemistry databases

GuidetoPHARMACOLOGYi1832

PTM databases

iPTMnetiP54754
PhosphoSitePlusiP54754

Proteomic databases

MaxQBiP54754
PaxDbiP54754
PeptideAtlasiP54754
PRIDEiP54754

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006112; ENSMUSP00000006112; ENSMUSG00000005958
GeneIDi13845
KEGGimmu:13845
UCSCiuc007yrg.1 mouse

Organism-specific databases

CTDi2049
MGIiMGI:104770 Ephb3

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP54754
KOiK05112
OMAiKKCSVER
OrthoDBiEOG091G00W0
TreeFamiTF315608

Enzyme and pathway databases

BRENDAi2.7.10.1 3474
ReactomeiR-MMU-2682334 EPH-Ephrin signaling
R-MMU-3928662 EPHB-mediated forward signaling
R-MMU-3928664 Ephrin signaling
R-MMU-3928665 EPH-ephrin mediated repulsion of cells

Miscellaneous databases

ChiTaRSiEphb3 mouse
PROiPR:P54754
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005958 Expressed in 260 organ(s), highest expression level in membranous labyrinth
CleanExiMM_EPHB3
ExpressionAtlasiP54754 baseline and differential
GenevisibleiP54754 MM

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
ProtoNetiSearch...

Entry informationi

Entry nameiEPHB3_MOUSE
AccessioniPrimary (citable) accession number: P54754
Secondary accession number(s): Q62214, Q91YS9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 174 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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