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P54761

- EPHB4_MOUSE

UniProt

P54761 - EPHB4_MOUSE

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Protein
Ephrin type-B receptor 4
Gene
Ephb4, Htk, Mdk2, Myk1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei647 – 6471ATP By similarity
Active sitei740 – 7401Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi621 – 6299ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. ephrin receptor activity Source: UniProtKB
  3. protein binding Source: MGI
  4. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: UniProtKB
  2. cell adhesion Source: UniProtKB
  3. cell migration involved in sprouting angiogenesis Source: UniProtKB
  4. ephrin receptor signaling pathway Source: UniProtKB
  5. heart morphogenesis Source: UniProtKB
  6. peptidyl-tyrosine phosphorylation Source: GOC
  7. protein autophosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Angiogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:104757. Ephb4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini16 – 539524Extracellular Reviewed prediction
Add
BLAST
Transmembranei540 – 56021Helical; Reviewed prediction
Add
BLAST
Topological domaini561 – 987427Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1515 Reviewed prediction
Add
BLAST
Chaini16 – 987972Ephrin type-B receptor 4
PRO_0000016835Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi61 ↔ 184 By similarity
Disulfide bondi97 ↔ 107 By similarity
Glycosylationi203 – 2031N-linked (GlcNAc...) Reviewed prediction
Glycosylationi335 – 3351N-linked (GlcNAc...)2 Publications
Glycosylationi426 – 4261N-linked (GlcNAc...) Reviewed prediction
Modified residuei911 – 9111Phosphoserine By similarity

Post-translational modificationi

Phosphorylated; autophosphorylation is stimulated by EFNB2 By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP54761.
PRIDEiP54761.

PTM databases

PhosphoSiteiP54761.

Expressioni

Tissue specificityi

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

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.1 Publication

Gene expression databases

ArrayExpressiP54761.
BgeeiP54761.
CleanExiMM_EPHB4.
GenevestigatoriP54761.

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.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000106684.

Structurei

3D structure databases

ProteinModelPortaliP54761.
SMRiP54761. Positions 15-533, 564-973.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 202186Eph LBD
Add
BLAST
Domaini323 – 432110Fibronectin type-III 1
Add
BLAST
Domaini436 – 52994Fibronectin type-III 2
Add
BLAST
Domaini615 – 899285Protein kinase
Add
BLAST
Domaini907 – 97165SAM
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi985 – 9873PDZ-binding Reviewed prediction

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi184 – 320137Cys-rich
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00740000115081.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
KOiK05113.
OrthoDBiEOG7VTDM6.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. 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]
PfamiPF14575. 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]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS01186. 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]

Sequencei

Sequence statusi: Complete.

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

P54761-1 [UniParc]FASTAAdd to Basket

« Hide

MELRALLCWA SLATALEETL LNTKLETADL KWVTYPQAEG QWEELSGLDE    50
EQHSVRTYEV CDMKRPGGQA HWLRTGWVPR RGAVHVYATI RFTMMECLSL 100
PRASRSCKET FTVFYYESEA DTATAHTPAW MENPYIKVDT VAAEHLTRKR 150
PGAEATGKVN IKTLRLGPLS KAGFYLAFQD QGACMALLSL HLFYKKCSWL 200
ITNLTYFPET VPRELVVPVA GSCVANAVPT ANPSPSLYCR EDGQWAEQQV 250
TGCSCAPGYE AAESNKVCRA CGQGTFKPQI GDESCLPCPA NSHSNNIGSP 300
VCLCRIGYYR ARSDPRSSPC TTPPSAPRSV VHHLNGSTLR LEWSAPLESG 350
GREDLTYAVR CRECRPGGSC LPCGGDMTFD PGPRDLVEPW VAIRGLRPDV 400
TYTFEVAALN GVSTLATGPP PFEPVNVTTD REVPPAVSDI RVTRSSPSSL 450
ILSWAIPRAP SGAVLDYEVK YHEKGAEGPS SVRFLKTSEN RAELRGLKRG 500
ASYLVQVRAR SEAGYGPFGQ EHHSQTQLDE SESWREQLAL IAGTAVVGVV 550
LVLVVVIIAV LCLRKQSNGR EVEYSDKHGQ YLIGHGTKVY IDPFTYEDPN 600
EAVREFAKEI DVSYVKIEEV IGAGEFGEVC RGRLKAPGKK ESCVAIKTLK 650
GGYTERQRRE FLSEASIMGQ FEHPNIIRLE GVVTNSVPVM ILTEFMENGA 700
LDSFLRLNDG QFTVIQLVGM LRGIASGMRY LAEMSYVHRD LAARNILVNS 750
NLVCKVSDFG LSRFLEENSS DPTYTSSLGG KIPIRWTAPE AIAFRKFTSA 800
SDAWSYGIVM WEVMSFGERP YWDMSNQDVI NAIEQDYRLP PPPDCPTSLH 850
QLMLDCWQKD RNARPRFPQV VSALDKMIRN PASLKIVARE NGGASHPLLD 900
QRQPHYSAFG SVGEWLRAIK MGRYEESFAA AGFGSFEVVS QISAEDLLRI 950
GVTLAGHQKK ILASVQHMKS QAKPGAPGGT GGPAQQF 987
Length:987
Mass (Da):108,848
Last modified:July 27, 2011 - v2
Checksum:iE4FC5B2210723974
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti120 – 1201A → R in CAA88909. 1 Publication
Sequence conflicti120 – 1201A → R in AAA18591. 1 Publication
Sequence conflicti351 – 3533GRE → RPR in AAA18591. 1 Publication
Sequence conflicti389 – 3891P → R in AAA18591. 1 Publication
Sequence conflicti659 – 6591R → A in AAA18591. 1 Publication
Sequence conflicti783 – 7831P → S in CAA88909. 1 Publication
Sequence conflicti805 – 8051S → R in AAA18591. 1 Publication
Sequence conflicti913 – 9131G → V in AAA18591. 1 Publication
Sequence conflicti938 – 9381V → M in AAA18591. 1 Publication
Sequence conflicti970 – 9712SQ → WE in AAA18591. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS19767.1.
PIRi I48652.
I48953.
RefSeqi NP_034274.4. NM_010144.6.
UniGenei Mm.34533.

3D structure databases

ProteinModelPortali P54761.
SMRi P54761. Positions 15-533, 564-973.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000106684.

PTM databases

PhosphoSitei P54761.

Proteomic databases

PaxDbi P54761.
PRIDEi P54761.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000061244 ; ENSMUSP00000051622 ; ENSMUSG00000029710 .
ENSMUST00000144296 ; ENSMUSP00000115731 ; ENSMUSG00000029710 .
ENSMUST00000166239 ; ENSMUSP00000130275 ; ENSMUSG00000029710 .
GeneIDi 13846.
KEGGi mmu:13846.
UCSCi uc009aci.2. mouse.

Organism-specific databases

CTDi 2050.
MGIi MGI:104757. Ephb4.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00740000115081.
HOGENOMi HOG000233856.
HOVERGENi HBG062180.
KOi K05113.
OrthoDBi EOG7VTDM6.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 3474.

Miscellaneous databases

ChiTaRSi EPHB4. mouse.
NextBioi 284692.
PROi P54761.
SOURCEi Search...

Gene expression databases

ArrayExpressi P54761.
Bgeei P54761.
CleanExi MM_EPHB4.
Genevestigatori P54761.

Family and domain databases

Gene3Di 1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProi IPR027936. 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 ]
Pfami PF14575. 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 ]
PIRSFi PIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSi PR00109. TYRKINASE.
SMARTi SM00615. EPH_lbd. 1 hit.
SM00060. FN3. 2 hits.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiEPHB4_MOUSE
AccessioniPrimary (citable) accession number: P54761
Secondary accession number(s): Q60627, Q99MR2
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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