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P54761 (EPHB4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. 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 4

EC=2.7.10.1
Alternative name(s):
Developmental kinase 2
Short name=mDK-2
Hepatoma transmembrane kinase
Tyrosine kinase MYK-1
Gene names
Name:Ephb4
Synonyms:Htk, Mdk2, Myk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length987 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. 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. Ref.5

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 By similarity.

Tissue specificity

Expressed in various organ systems, including lung, liver, kidney, intestine, muscle and heart. Ref.1

Developmental stage

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. Ref.5

Post-translational modification

Phosphorylated; autophosphorylation is stimulated by EFNB2 By similarity.

Disruption phenotype

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. Ref.5

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
   Cellular componentCell membrane
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

cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

cell migration involved in sprouting angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from genetic interaction Ref.5. Source: UniProtKB

heart morphogenesis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentintegral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ephrin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12971893. Source: MGI

transmembrane receptor protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1515 Potential
Chain16 – 987972Ephrin type-B receptor 4
PRO_0000016835

Regions

Topological domain16 – 539524Extracellular Potential
Transmembrane540 – 56021Helical; Potential
Topological domain561 – 987427Cytoplasmic Potential
Domain17 – 202186Eph LBD
Domain323 – 432110Fibronectin type-III 1
Domain436 – 52994Fibronectin type-III 2
Domain615 – 899285Protein kinase
Domain907 – 97165SAM
Nucleotide binding621 – 6299ATP By similarity
Motif985 – 9873PDZ-binding Potential
Compositional bias184 – 320137Cys-rich

Sites

Active site7401Proton acceptor By similarity
Binding site6471ATP By similarity

Amino acid modifications

Modified residue9111Phosphoserine By similarity
Glycosylation2031N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Ref.6 Ref.7
Glycosylation4261N-linked (GlcNAc...) Potential
Disulfide bond61 ↔ 184 By similarity
Disulfide bond97 ↔ 107 By similarity

Experimental info

Sequence conflict1201A → R in CAA88909. Ref.1
Sequence conflict1201A → R in AAA18591. Ref.2
Sequence conflict351 – 3533GRE → RPR in AAA18591. Ref.2
Sequence conflict3891P → R in AAA18591. Ref.2
Sequence conflict6591R → A in AAA18591. Ref.2
Sequence conflict7831P → S in CAA88909. Ref.1
Sequence conflict8051S → R in AAA18591. Ref.2
Sequence conflict9131G → V in AAA18591. Ref.2
Sequence conflict9381V → M in AAA18591. Ref.2
Sequence conflict970 – 9712SQ → WE in AAA18591. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P54761 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: E4FC5B2210723974

FASTA987108,848
        10         20         30         40         50         60 
MELRALLCWA SLATALEETL LNTKLETADL KWVTYPQAEG QWEELSGLDE EQHSVRTYEV 

        70         80         90        100        110        120 
CDMKRPGGQA HWLRTGWVPR RGAVHVYATI RFTMMECLSL PRASRSCKET FTVFYYESEA 

       130        140        150        160        170        180 
DTATAHTPAW MENPYIKVDT VAAEHLTRKR PGAEATGKVN IKTLRLGPLS KAGFYLAFQD 

       190        200        210        220        230        240 
QGACMALLSL HLFYKKCSWL ITNLTYFPET VPRELVVPVA GSCVANAVPT ANPSPSLYCR 

       250        260        270        280        290        300 
EDGQWAEQQV TGCSCAPGYE AAESNKVCRA CGQGTFKPQI GDESCLPCPA NSHSNNIGSP 

       310        320        330        340        350        360 
VCLCRIGYYR ARSDPRSSPC TTPPSAPRSV VHHLNGSTLR LEWSAPLESG GREDLTYAVR 

       370        380        390        400        410        420 
CRECRPGGSC LPCGGDMTFD PGPRDLVEPW VAIRGLRPDV TYTFEVAALN GVSTLATGPP 

       430        440        450        460        470        480 
PFEPVNVTTD REVPPAVSDI RVTRSSPSSL ILSWAIPRAP SGAVLDYEVK YHEKGAEGPS 

       490        500        510        520        530        540 
SVRFLKTSEN RAELRGLKRG ASYLVQVRAR SEAGYGPFGQ EHHSQTQLDE SESWREQLAL 

       550        560        570        580        590        600 
IAGTAVVGVV LVLVVVIIAV LCLRKQSNGR EVEYSDKHGQ YLIGHGTKVY IDPFTYEDPN 

       610        620        630        640        650        660 
EAVREFAKEI DVSYVKIEEV IGAGEFGEVC RGRLKAPGKK ESCVAIKTLK GGYTERQRRE 

       670        680        690        700        710        720 
FLSEASIMGQ FEHPNIIRLE GVVTNSVPVM ILTEFMENGA LDSFLRLNDG QFTVIQLVGM 

       730        740        750        760        770        780 
LRGIASGMRY LAEMSYVHRD LAARNILVNS NLVCKVSDFG LSRFLEENSS DPTYTSSLGG 

       790        800        810        820        830        840 
KIPIRWTAPE AIAFRKFTSA SDAWSYGIVM WEVMSFGERP YWDMSNQDVI NAIEQDYRLP 

       850        860        870        880        890        900 
PPPDCPTSLH QLMLDCWQKD RNARPRFPQV VSALDKMIRN PASLKIVARE NGGASHPLLD 

       910        920        930        940        950        960 
QRQPHYSAFG SVGEWLRAIK MGRYEESFAA AGFGSFEVVS QISAEDLLRI GVTLAGHQKK 

       970        980 
ILASVQHMKS QAKPGAPGGT GGPAQQF 

« 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], TISSUE SPECIFICITY.
Strain: BALB/c.
Tissue: Kidney.
[2]"Expression of two novel eph-related receptor protein tyrosine kinases in mammary gland development and carcinogenesis."
Andres A.-C., Reid H.H., Zurcher G., Blaschke R.J., Albrecht D., Ziemiecki A.
Oncogene 9:1461-1467(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Lung.
[3]"Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5."
Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P., Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C., Miller W., Koop B.F.
Nucleic Acids Res. 29:1352-1365(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development."
Gerety S.S., Wang H.U., Chen Z.F., Anderson D.J.
Mol. Cell 4:403-414(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION IN ANGIOGENESIS, DEVELOPMENTAL STAGE.
[6]"The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation."
Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.
Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-335.
Tissue: Myoblast.
[7]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-335.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS19767.1.
PIRI48652.
I48953.
RefSeqNP_034274.4. NM_010144.6.
UniGeneMm.34533.

3D structure databases

ProteinModelPortalP54761.
SMRP54761. Positions 15-533, 564-973.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000106684.

PTM databases

PhosphoSiteP54761.

Proteomic databases

PaxDbP54761.
PRIDEP54761.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000061244; ENSMUSP00000051622; ENSMUSG00000029710.
ENSMUST00000144296; ENSMUSP00000115731; ENSMUSG00000029710.
ENSMUST00000166239; ENSMUSP00000130275; ENSMUSG00000029710.
GeneID13846.
KEGGmmu:13846.
UCSCuc009aci.2. mouse.

Organism-specific databases

CTD2050.
MGIMGI:104757. Ephb4.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115081.
HOGENOMHOG000233856.
HOVERGENHBG062180.
KOK05113.
OrthoDBEOG7VTDM6.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressP54761.
BgeeP54761.
CleanExMM_EPHB4.
GenevestigatorP54761.

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.
IPR009030. Growth_fac_rcpt_N_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
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.
PF07647. SAM_2. 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.
SSF57184. SSF57184. 2 hits.
PROSITEPS01186. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEPHB4. mouse.
NextBio284692.
PROP54761.
SOURCESearch...

Entry information

Entry nameEPHB4_MOUSE
AccessionPrimary (citable) accession number: P54761
Secondary accession number(s): Q60627, Q99MR2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 142 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