UniProtKB - P54754 (EPHB3_MOUSE)
Protein
Ephrin type-B receptor 3
Gene
Ephb3
Organism
Mus musculus (Mouse)
Status
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
- EC:2.7.10.1PROSITE-ProRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 660 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 753 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 634 – 642 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- axon guidance receptor activity Source: MGI
- ephrin receptor activity Source: UniProtKB
- transmembrane-ephrin receptor activity Source: GO_Central
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- angiogenesis Source: UniProtKB
- axonal fasciculation Source: UniProtKB
- axon guidance Source: MGI
- cell migration Source: UniProtKB
- central nervous system projection neuron axonogenesis Source: MGI
- corpus callosum development Source: UniProtKB
- dendritic spine development Source: UniProtKB
- dendritic spine morphogenesis Source: UniProtKB
- digestive tract morphogenesis Source: UniProtKB
- ephrin receptor signaling pathway Source: UniProtKB
- multicellular organism development Source: GO_Central
- positive regulation of kinase activity Source: GO_Central
- positive regulation of synapse assembly Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- regulation of axonogenesis Source: UniProtKB
- regulation of cell-cell adhesion Source: UniProtKB
- regulation of GTPase activity Source: UniProtKB
- retinal ganglion cell axon guidance Source: MGI
- roof of mouth development Source: UniProtKB
- substrate adhesion-dependent cell spreading Source: UniProtKB
- thymus development Source: UniProtKB
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- urogenital system development Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Biological process | Angiogenesis, Neurogenesis |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 3474 |
Reactomei | R-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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104770, Ephb3 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication
Other locations
- dendrite 1 Publication
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
Other locations
- dendrite Source: UniProtKB-SubCell
- neuron projection Source: GO_Central
- receptor complex Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 30 – 554 | ExtracellularSequence analysisAdd BLAST | 525 | |
Transmembranei | 555 – 575 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 576 – 993 | CytoplasmicSequence analysisAdd BLAST | 418 |
Keywords - Cellular componenti
Cell membrane, Cell projection, MembranePathology & 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
GuidetoPHARMACOLOGYi | 1832 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 29 | Sequence analysisAdd BLAST | 29 | |
ChainiPRO_0000016832 | 30 – 993 | Ephrin type-B receptor 3Add BLAST | 964 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 73 ↔ 191 | By similarity | ||
Glycosylationi | 343 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 440 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 609 | Phosphotyrosine; by autocatalysisBy similarity | 1 |
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, PhosphoproteinProteomic databases
MaxQBi | P54754 |
PaxDbi | P54754 |
PeptideAtlasi | P54754 |
PRIDEi | P54754 |
ProteomicsDBi | 275627 |
PTM databases
GlyGeni | P54754, 2 sites |
iPTMneti | P54754 |
PhosphoSitePlusi | P54754 |
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 (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912).3 Publications
Gene expression databases
Bgeei | ENSMUSG00000005958, Expressed in membranous labyrinth and 277 other tissues |
ExpressionAtlasi | P54754, baseline and differential |
Genevisiblei | P54754, 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 similarityProtein-protein interaction databases
BioGRIDi | 199477, 12 interactors |
STRINGi | 10090.ENSMUSP00000006112 |
Miscellaneous databases
RNActi | P54754, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 31 – 209 | Eph LBDPROSITE-ProRule annotationAdd BLAST | 179 | |
Domaini | 331 – 446 | Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST | 116 | |
Domaini | 447 – 540 | Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST | 94 | |
Domaini | 628 – 891 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 264 | |
Domaini | 920 – 984 | SAMPROSITE-ProRule annotationAdd BLAST | 65 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 991 – 993 | PDZ-bindingSequence analysis | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 191 – 328 | Cys-richAdd BLAST | 138 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0196, Eukaryota |
GeneTreei | ENSGT00940000158024 |
HOGENOMi | CLU_000288_141_0_1 |
InParanoidi | P54754 |
OMAi | AGICTCH |
OrthoDBi | 933071at2759 |
TreeFami | TF315608 |
Family and domain databases
CDDi | cd10478, EphR_LBD_B3, 1 hit cd00063, FN3, 2 hits |
Gene3Di | 1.10.150.50, 1 hit 2.60.120.260, 1 hit 2.60.40.10, 2 hits |
InterProi | View 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 |
Pfami | View protein in Pfam PF14575, EphA2_TM, 1 hit PF01404, Ephrin_lbd, 1 hit PF07699, Ephrin_rec_like, 1 hit PF00041, fn3, 2 hits PF07714, PK_Tyr_Ser-Thr, 1 hit PF00536, SAM_1, 1 hit |
PIRSFi | PIRSF000666, TyrPK_ephrin_receptor, 1 hit |
PRINTSi | PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00615, EPH_lbd, 1 hit SM00060, FN3, 2 hits SM00454, SAM, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF47769, SSF47769, 1 hit SSF49265, SSF49265, 1 hit SSF49785, SSF49785, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
P54754-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE0CYA3 | E0CYA3_MOUSE | Receptor protein-tyrosine kinase | Ephb3 | 739 | Annotation score: | ||
A0A338P6E0 | A0A338P6E0_MOUSE | Ephrin type-B receptor 3 | Ephb3 | 191 | Annotation score: | ||
A0A338P6F1 | A0A338P6F1_MOUSE | Ephrin type-B receptor 3 | Ephb3 | 79 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 200 – 201 | FY → GD in CAA88910 (PubMed:7478528).Curated | 2 | |
Sequence conflicti | 331 | V → E in CAA88910 (PubMed:7478528).Curated | 1 | |
Sequence conflicti | 567 | V → M in CAA88910 (PubMed:7478528).Curated | 1 | |
Sequence conflicti | 719 | R → Q in CAA53599 (PubMed:7947319).Curated | 1 |
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 |
CCDSi | CCDS28060.1 |
PIRi | I48653 I48761 |
RefSeqi | NP_034273.1, NM_010143.1 |
Genome annotation databases
Ensembli | ENSMUST00000006112; ENSMUSP00000006112; ENSMUSG00000005958 |
GeneIDi | 13845 |
KEGGi | mmu:13845 |
UCSCi | uc007yrg.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 |
CCDSi | CCDS28060.1 |
PIRi | I48653 I48761 |
RefSeqi | NP_034273.1, NM_010143.1 |
3D structure databases
SMRi | P54754 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 199477, 12 interactors |
STRINGi | 10090.ENSMUSP00000006112 |
Chemistry databases
GuidetoPHARMACOLOGYi | 1832 |
PTM databases
GlyGeni | P54754, 2 sites |
iPTMneti | P54754 |
PhosphoSitePlusi | P54754 |
Proteomic databases
MaxQBi | P54754 |
PaxDbi | P54754 |
PeptideAtlasi | P54754 |
PRIDEi | P54754 |
ProteomicsDBi | 275627 |
Protocols and materials databases
Antibodypediai | 2107, 593 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000006112; ENSMUSP00000006112; ENSMUSG00000005958 |
GeneIDi | 13845 |
KEGGi | mmu:13845 |
UCSCi | uc007yrg.1, mouse |
Organism-specific databases
CTDi | 2049 |
MGIi | MGI:104770, Ephb3 |
Phylogenomic databases
eggNOGi | KOG0196, Eukaryota |
GeneTreei | ENSGT00940000158024 |
HOGENOMi | CLU_000288_141_0_1 |
InParanoidi | P54754 |
OMAi | AGICTCH |
OrthoDBi | 933071at2759 |
TreeFami | TF315608 |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 3474 |
Reactomei | R-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
BioGRID-ORCSi | 13845, 0 hits in 52 CRISPR screens |
ChiTaRSi | Ephb3, mouse |
PROi | PR:P54754 |
RNActi | P54754, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000005958, Expressed in membranous labyrinth and 277 other tissues |
ExpressionAtlasi | P54754, baseline and differential |
Genevisiblei | P54754, MM |
Family and domain databases
CDDi | cd10478, EphR_LBD_B3, 1 hit cd00063, FN3, 2 hits |
Gene3Di | 1.10.150.50, 1 hit 2.60.120.260, 1 hit 2.60.40.10, 2 hits |
InterProi | View 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 |
Pfami | View protein in Pfam PF14575, EphA2_TM, 1 hit PF01404, Ephrin_lbd, 1 hit PF07699, Ephrin_rec_like, 1 hit PF00041, fn3, 2 hits PF07714, PK_Tyr_Ser-Thr, 1 hit PF00536, SAM_1, 1 hit |
PIRSFi | PIRSF000666, TyrPK_ephrin_receptor, 1 hit |
PRINTSi | PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00615, EPH_lbd, 1 hit SM00060, FN3, 2 hits SM00454, SAM, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF47769, SSF47769, 1 hit SSF49265, SSF49265, 1 hit SSF49785, SSF49785, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | EPHB3_MOUSE | |
Accessioni | P54754Primary (citable) accession number: P54754 Secondary accession number(s): Q62214, Q91YS9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | July 27, 2011 | |
Last modified: | April 7, 2021 | |
This is version 191 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- 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 - SIMILARITY comments
Index of protein domains and families