P54754 (EPHB3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Ephb3
Synonyms:	Etk2, Mdk5, Sek4

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	993 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 lobs 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 projection › dendrite 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 developping intestinal epithelium at the bottom of the intervillus pockets where undifferentiated cells are allocated (at protein level). Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10
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 process	Angiogenesis Neurogenesis
Cellular component	Cell membrane Cell projection Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from mutant phenotype Ref.5. 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. Source: MGI corpus callosum development Inferred from mutant phenotype Ref.4. Source: UniProtKB dendritic spine morphogenesis Inferred from mutant phenotype Ref.8. Source: UniProtKB digestive tract morphogenesis Inferred from mutant phenotype Ref.7. 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. Source: UniProtKB regulation of cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB retinal ganglion cell axon guidance Inferred from direct assay. 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 component	dendrite Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW axon guidance receptor activity Inferred from direct assay. Source: MGI transmembrane-ephrin receptor activity Traceable author statement. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 993	964	Ephrin type-B receptor 3		PRO_0000016832
Regions
	Topological domain	30 – 554	525	Extracellular Potential
	Transmembrane	555 – 575	21	Helical; Potential
	Topological domain	576 – 993	418	Cytoplasmic Potential
	Domain	31 – 209	179	Eph LBD
	Domain	332 – 438	107	Fibronectin type-III 1
	Domain	448 – 539	92	Fibronectin type-III 2
	Domain	628 – 891	264	Protein kinase
	Domain	920 – 984	65	SAM
	Nucleotide binding	634 – 642	9	ATP By similarity
	Motif	991 – 993	3	PDZ-binding Potential
	Compositional bias	191 – 328	138	Cys-rich
Sites
	Active site	753	1	Proton acceptor By similarity
	Binding site	660	1	ATP By similarity
Amino acid modifications
	Modified residue	595	1	Phosphotyrosine By similarity
	Modified residue	603	1	Phosphotyrosine By similarity
	Modified residue	609	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	787	1	Phosphotyrosine By similarity
	Modified residue	966	1	Phosphothreonine By similarity
	Glycosylation	343	1	N-linked (GlcNAc...) Potential
	Glycosylation	440	1	N-linked (GlcNAc...) Potential
	Disulfide bond	73 ↔ 191		By similarity
Experimental info
	Sequence conflict	200 – 201	2	FY → GD in CAA88910. Ref.1
	Sequence conflict	331	1	V → E in CAA88910. Ref.1
	Sequence conflict	567	1	V → M in CAA88910. Ref.1
	Sequence conflict	719	1	R → Q in CAA53599. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P54754 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 07C6EF2AC98AE1B4	FASTA	993	109,662
	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

References

	« Hide 'large scale' referencesShow '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: 7478528] [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: 15489334] [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: 7947319] [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: 8947026] [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: 9990854] [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: 10704386] [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: 12408869] [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: 14691139] [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: 15223334] [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: 19598115] [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.
IPI	IPI00130442.
PIR	I48653. I48761.
RefSeq	NP_034273.1. NM_010143.1.
UniGene	Mm.6972.
3D structure databases
HSSP	HSSP built from PDB template 1JPA based on UniProtKB P54763.
ProteinModelPortal	P54754.
SMR	P54754. Positions 30-543, 621-987.
ModBase	Search...
Protein-protein interaction databases
STRING	P54754.
PTM databases
PhosphoSite	P54754.
Proteomic databases
PRIDE	P54754.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000006112; ENSMUSP00000006112; ENSMUSG00000005958.
GeneID	13845.
KEGG	mmu:13845.
Organism-specific databases
CTD	2049.
MGI	MGI:104770. Ephb3.
Phylogenomic databases
eggNOG	roNOG12692.
HOGENOM	HBG755340.
HOVERGEN	HBG062180.
InParanoid	P54754.
OrthoDB	EOG4W9J35.
Enzyme and pathway databases
BRENDA	2.7.10.1. 3474.
Gene expression databases
ArrayExpress	P54754.
Bgee	P54754.
CleanEx	MM_EPHB3.
Genevestigator	P54754.
GermOnline	ENSMUSG00000005958. Mus musculus.
Family and domain databases
InterPro	IPR001090. Ephrin_rcpt_lig-bd. IPR003961. Fibronectin_type3. IPR008979. Galactose-bd-like. IPR013783. Ig-like_fold. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001660. SAM. IPR013761. SAM/pointed. IPR021129. SAM_type1. IPR001245. Ser-Thr/Tyr_kinase. 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]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 2 hits. G3DSA:1.10.150.50. SAM_type. 1 hit.
KO	K05112.
Pfam	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]
PIRSF	PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00615. EPH_lbd. 1 hit. SM00060. FN3. 2 hits. SM00454. SAM. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits. SSF49785. Gal_bind_like. 1 hit. SSF56112. Kinase_like. 1 hit. SSF47769. SAM_homology. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

EPHB3_MOUSE

Accession

Primary (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:	December 14, 2011
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program