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Protein

Ephrin type-B receptor 4

Gene

Ephb4

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. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei647ATPPROSITE-ProRule annotation1
Active sitei740Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi621 – 629ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processAngiogenesis
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 4 (EC:2.7.10.1)
Alternative name(s):
Developmental kinase 2
Short name:
mDK-2
Hepatoma transmembrane kinase
Tyrosine kinase MYK-1
Gene namesi
Name:Ephb4
Synonyms:Htk, Mdk2, Myk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:104757 Ephb4

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 domaini16 – 539ExtracellularSequence analysisAdd BLAST524
Transmembranei540 – 560HelicalSequence analysisAdd BLAST21
Topological domaini561 – 987CytoplasmicSequence analysisAdd BLAST427

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Embryo display cardiovascular defects and lethality with very high penetrance. Growth retardation is observed at E9.5 with arrested heart development and lack of blood flow. By E10.5 degeneration and necrosis are apparent throughout the embryo. Conditional lymphovenous valves knockouts show a complete loss of lymphatic valves (PubMed:27400125).2 Publications

Chemistry databases

GuidetoPHARMACOLOGYi1833

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 15Sequence analysisAdd BLAST15
ChainiPRO_000001683516 – 987Ephrin type-B receptor 4Add BLAST972

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi61 ↔ 184By similarity
Disulfide bondi97 ↔ 107By similarity
Glycosylationi203N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi335N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi426N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei769PhosphoserineBy similarity1
Modified residuei770PhosphoserineBy similarity1
Modified residuei911PhosphoserineBy similarity1
Modified residuei943PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated; autophosphorylation is stimulated by EFNB2.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP54761
PaxDbiP54761
PRIDEiP54761

PTM databases

iPTMnetiP54761
PhosphoSitePlusiP54761
SwissPalmiP54761

Expressioni

Tissue specificityi

Expressed in various organ systems, including lung, liver, kidney, intestine, muscle and heart (PubMed:7478528). Expressed in myogenic progenitor cells (PubMed:27446912).2 Publications

Developmental stagei

Specifically expressed in the developing cardiovascular system with higher expression in veins. First detected in the developing anterior cardinal vein at E8.75. Abundant expression at E16.5 in various organ systems, including thymus, heart, lung and kidney, where it is associated with cells of endothelial origin. In myogenic progenitor cells, highly expressed during early development (E11.5) and progressively repressed as developments proceeds (PubMed:27446912).2 Publications

Gene expression databases

BgeeiENSMUSG00000029710 Expressed in 205 organ(s), highest expression level in ear vesicle
CleanExiMM_EPHB4
ExpressionAtlasiP54761 baseline and differential
GenevisibleiP54761 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

BioGridi199478, 2 interactors
STRINGi10090.ENSMUSP00000106684

Structurei

3D structure databases

ProteinModelPortaliP54761
SMRiP54761
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 202Eph LBDPROSITE-ProRule annotationAdd BLAST186
Domaini323 – 432Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST110
Domaini436 – 529Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST94
Domaini615 – 899Protein kinasePROSITE-ProRule annotationAdd BLAST285
Domaini907 – 971SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi985 – 987PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi184 – 320Cys-richAdd BLAST137

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
InParanoidiP54761
KOiK05113

Family and domain databases

CDDicd10474 EphR_LBD_B4, 1 hit
cd00063 FN3, 2 hits
cd09554 SAM_EPH-B4, 1 hit
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR037636 EPH-B4_SAM
IPR027936 Eph_TM
IPR034290 EphB4_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_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
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
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 2 potential isoforms that are computationally mapped.Show allAlign All

P54761-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MELRALLCWA SLATALEETL LNTKLETADL KWVTYPQAEG QWEELSGLDE
60 70 80 90 100
EQHSVRTYEV CDMKRPGGQA HWLRTGWVPR RGAVHVYATI RFTMMECLSL
110 120 130 140 150
PRASRSCKET FTVFYYESEA DTATAHTPAW MENPYIKVDT VAAEHLTRKR
160 170 180 190 200
PGAEATGKVN IKTLRLGPLS KAGFYLAFQD QGACMALLSL HLFYKKCSWL
210 220 230 240 250
ITNLTYFPET VPRELVVPVA GSCVANAVPT ANPSPSLYCR EDGQWAEQQV
260 270 280 290 300
TGCSCAPGYE AAESNKVCRA CGQGTFKPQI GDESCLPCPA NSHSNNIGSP
310 320 330 340 350
VCLCRIGYYR ARSDPRSSPC TTPPSAPRSV VHHLNGSTLR LEWSAPLESG
360 370 380 390 400
GREDLTYAVR CRECRPGGSC LPCGGDMTFD PGPRDLVEPW VAIRGLRPDV
410 420 430 440 450
TYTFEVAALN GVSTLATGPP PFEPVNVTTD REVPPAVSDI RVTRSSPSSL
460 470 480 490 500
ILSWAIPRAP SGAVLDYEVK YHEKGAEGPS SVRFLKTSEN RAELRGLKRG
510 520 530 540 550
ASYLVQVRAR SEAGYGPFGQ EHHSQTQLDE SESWREQLAL IAGTAVVGVV
560 570 580 590 600
LVLVVVIIAV LCLRKQSNGR EVEYSDKHGQ YLIGHGTKVY IDPFTYEDPN
610 620 630 640 650
EAVREFAKEI DVSYVKIEEV IGAGEFGEVC RGRLKAPGKK ESCVAIKTLK
660 670 680 690 700
GGYTERQRRE FLSEASIMGQ FEHPNIIRLE GVVTNSVPVM ILTEFMENGA
710 720 730 740 750
LDSFLRLNDG QFTVIQLVGM LRGIASGMRY LAEMSYVHRD LAARNILVNS
760 770 780 790 800
NLVCKVSDFG LSRFLEENSS DPTYTSSLGG KIPIRWTAPE AIAFRKFTSA
810 820 830 840 850
SDAWSYGIVM WEVMSFGERP YWDMSNQDVI NAIEQDYRLP PPPDCPTSLH
860 870 880 890 900
QLMLDCWQKD RNARPRFPQV VSALDKMIRN PASLKIVARE NGGASHPLLD
910 920 930 940 950
QRQPHYSAFG SVGEWLRAIK MGRYEESFAA AGFGSFEVVS QISAEDLLRI
960 970 980
GVTLAGHQKK ILASVQHMKS QAKPGAPGGT GGPAQQF
Length:987
Mass (Da):108,848
Last modified:July 27, 2011 - v2
Checksum:iE4FC5B2210723974
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8C8K1Q8C8K1_MOUSE
Ephrin type-B receptor 4
Ephb4
996Annotation score:
E9PWK7E9PWK7_MOUSE
Ephrin type-B receptor 4
Ephb4
935Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti120A → R in CAA88909 (PubMed:7478528).Curated1
Sequence conflicti120A → R in AAA18591 (PubMed:8152808).Curated1
Sequence conflicti351 – 353GRE → RPR in AAA18591 (PubMed:8152808).Curated3
Sequence conflicti389P → R in AAA18591 (PubMed:8152808).Curated1
Sequence conflicti659R → A in AAA18591 (PubMed:8152808).Curated1
Sequence conflicti783P → S in CAA88909 (PubMed:7478528).Curated1
Sequence conflicti805S → R in AAA18591 (PubMed:8152808).Curated1
Sequence conflicti913G → V in AAA18591 (PubMed:8152808).Curated1
Sequence conflicti938V → M in AAA18591 (PubMed:8152808).Curated1
Sequence conflicti970 – 971SQ → WE in AAA18591 (PubMed:8152808).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49085 mRNA Translation: CAA88909.1
U06834 mRNA Translation: AAA18591.1
AF312033 Genomic DNA Translation: AAK28823.1
CH466529 Genomic DNA Translation: EDL19273.1
CH466529 Genomic DNA Translation: EDL19275.1
CCDSiCCDS19767.1
PIRiI48652
I48953
RefSeqiNP_034274.4, NM_010144.6
UniGeneiMm.34533

Genome annotation databases

EnsembliENSMUST00000061244; ENSMUSP00000051622; ENSMUSG00000029710
ENSMUST00000144296; ENSMUSP00000115731; ENSMUSG00000029710
ENSMUST00000166239; ENSMUSP00000130275; ENSMUSG00000029710
GeneIDi13846
KEGGimmu:13846
UCSCiuc009aci.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49085 mRNA Translation: CAA88909.1
U06834 mRNA Translation: AAA18591.1
AF312033 Genomic DNA Translation: AAK28823.1
CH466529 Genomic DNA Translation: EDL19273.1
CH466529 Genomic DNA Translation: EDL19275.1
CCDSiCCDS19767.1
PIRiI48652
I48953
RefSeqiNP_034274.4, NM_010144.6
UniGeneiMm.34533

3D structure databases

ProteinModelPortaliP54761
SMRiP54761
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199478, 2 interactors
STRINGi10090.ENSMUSP00000106684

Chemistry databases

GuidetoPHARMACOLOGYi1833

PTM databases

iPTMnetiP54761
PhosphoSitePlusiP54761
SwissPalmiP54761

Proteomic databases

MaxQBiP54761
PaxDbiP54761
PRIDEiP54761

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000061244; ENSMUSP00000051622; ENSMUSG00000029710
ENSMUST00000144296; ENSMUSP00000115731; ENSMUSG00000029710
ENSMUST00000166239; ENSMUSP00000130275; ENSMUSG00000029710
GeneIDi13846
KEGGimmu:13846
UCSCiuc009aci.2 mouse

Organism-specific databases

CTDi2050
MGIiMGI:104757 Ephb4

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP54761
KOiK05113

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

ChiTaRSiEphb4 mouse
PROiPR:P54761
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029710 Expressed in 205 organ(s), highest expression level in ear vesicle
CleanExiMM_EPHB4
ExpressionAtlasiP54761 baseline and differential
GenevisibleiP54761 MM

Family and domain databases

CDDicd10474 EphR_LBD_B4, 1 hit
cd00063 FN3, 2 hits
cd09554 SAM_EPH-B4, 1 hit
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR037636 EPH-B4_SAM
IPR027936 Eph_TM
IPR034290 EphB4_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_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
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
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 nameiEPHB4_MOUSE
AccessioniPrimary (citable) accession number: P54761
Secondary accession number(s): Q60627, Q99MR2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 176 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
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