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P54760

- EPHB4_HUMAN

UniProt

P54760 - EPHB4_HUMAN

Protein

Ephrin type-B receptor 4

Gene

EPHB4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 164 (01 Oct 2014)
      Sequence version 2 (18 Oct 2001)
      Previous versions | rss
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    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.2 Publications

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei647 – 6471ATPPROSITE-ProRule annotation
    Active sitei740 – 7401Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi621 – 6299ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. ephrin receptor activity Source: UniProtKB
    3. protein binding Source: UniProtKB
    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

    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. 2681.
    SignaLinkiP54760.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ephrin type-B receptor 4 (EC:2.7.10.1)
    Alternative name(s):
    Hepatoma transmembrane kinase
    Tyrosine-protein kinase TYRO11
    Gene namesi
    Name:EPHB4
    Synonyms:HTK, MYK1, TYRO11
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:3395. EPHB4.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. integral component of plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi95 – 951L → R: Reduces binding affinity for EFNB2. 1 Publication

    Organism-specific databases

    PharmGKBiPA27827.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1515Sequence AnalysisAdd
    BLAST
    Chaini16 – 987972Ephrin type-B receptor 4PRO_0000016834Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi61 ↔ 184
    Disulfide bondi97 ↔ 107
    Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi426 – 4261N-linked (GlcNAc...)Sequence Analysis
    Modified residuei911 – 9111Phosphoserine2 Publications
    Modified residuei976 – 9761Phosphothreonine3 Publications
    Modified residuei987 – 9871Phosphotyrosine1 Publication

    Post-translational modificationi

    Phosphorylated; autophosphorylation is stimulated by EFNB2.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiP54760.
    PaxDbiP54760.
    PRIDEiP54760.

    2D gel databases

    DOSAC-COBS-2DPAGEP54760.

    PTM databases

    PhosphoSiteiP54760.

    Expressioni

    Tissue specificityi

    Abundantly expressed in placenta but also detected in kidney, liver, lung, pancreas, skeletal muscle and heart. Expressed in primitive and myeloid, but not lymphoid, hematopoietic cells. Also observed in cell lines derived from liver, breast, colon, lung, melanocyte and cervix.1 Publication

    Developmental stagei

    Expressed in fetal heart, lung, liver and to a lower extent in brain. Not expressed in adult brain.1 Publication

    Gene expression databases

    ArrayExpressiP54760.
    BgeeiP54760.
    CleanExiHS_EPHB4.
    GenevestigatoriP54760.

    Organism-specific databases

    HPAiCAB013537.

    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

    BioGridi108364. 4 interactions.
    IntActiP54760. 3 interactions.
    STRINGi9606.ENSP00000350896.

    Structurei

    Secondary structure

    1
    987
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi17 – 226
    Helixi23 – 253
    Beta strandi33 – 364
    Beta strandi43 – 486
    Beta strandi54 – 618
    Beta strandi63 – 653
    Beta strandi70 – 745
    Beta strandi84 – 9512
    Helixi97 – 993
    Beta strandi109 – 12113
    Beta strandi130 – 1323
    Beta strandi135 – 1428
    Beta strandi160 – 1667
    Beta strandi171 – 18212
    Beta strandi184 – 19613
    Beta strandi441 – 4466
    Beta strandi449 – 4535
    Beta strandi460 – 4623
    Beta strandi466 – 4738
    Turni479 – 4813
    Beta strandi482 – 49615
    Beta strandi503 – 5108
    Helixi612 – 6143
    Beta strandi615 – 6239
    Beta strandi625 – 63410
    Beta strandi637 – 6393
    Beta strandi642 – 6498
    Helixi655 – 66814
    Beta strandi679 – 6835
    Beta strandi685 – 69410
    Helixi701 – 7077
    Turni708 – 7103
    Helixi714 – 73320
    Helixi743 – 7453
    Beta strandi746 – 7483
    Beta strandi754 – 7563
    Helixi765 – 7673
    Helixi784 – 7863
    Helixi789 – 7946
    Helixi799 – 81416
    Turni815 – 8173
    Turni820 – 8234
    Helixi826 – 8349
    Helixi847 – 85610
    Helixi861 – 8633
    Helixi867 – 87913
    Helixi881 – 8855
    Helixi912 – 9187
    Helixi922 – 9243
    Helixi925 – 9306
    Helixi936 – 9394
    Helixi944 – 9507
    Helixi955 – 96511

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2BBAX-ray1.65A17-196[»]
    2E7HNMR-A434-529[»]
    2HLEX-ray2.05A17-196[»]
    2QKQX-ray2.10A/B896-977[»]
    2VWUX-ray2.00A598-887[»]
    2VWVX-ray1.90A598-899[»]
    2VWWX-ray1.90A598-899[»]
    2VWXX-ray1.65A598-899[»]
    2VWYX-ray1.65A598-899[»]
    2VWZX-ray1.65A598-899[»]
    2VX0X-ray2.10A598-899[»]
    2VX1X-ray1.65A598-899[»]
    2X9FX-ray1.75A598-899[»]
    2XVDX-ray1.70A598-899[»]
    2YN8X-ray2.11A/B598-892[»]
    3ZEWX-ray2.50A/B598-892[»]
    4AW5X-ray2.33A605-890[»]
    4BB4X-ray1.65A598-899[»]
    ProteinModelPortaliP54760.
    SMRiP54760. Positions 15-529, 608-973.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP54760.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini16 – 539524ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini561 – 987427CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei540 – 56021HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini17 – 202186Eph LBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini323 – 432110Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini436 – 52994Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini615 – 899285Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini907 – 97165SAMPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi985 – 9873PDZ-bindingSequence Analysis

    Compositional bias

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

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
    Contains 1 Eph LBD (Eph ligand-binding) domain.PROSITE-ProRule annotation
    Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233856.
    HOVERGENiHBG062180.
    InParanoidiP54760.
    KOiK05113.
    OMAiTVFYFES.
    PhylomeDBiP54760.
    TreeFamiTF315608.

    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.
    IPR021129. SAM_type1.
    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.
    PF00536. SAM_1. 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]

    Sequences (4)i

    Sequence statusi: Complete.

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

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P54760-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MELRVLLCWA SLAAALEETL LNTKLETADL KWVTFPQVDG QWEELSGLDE    50
    EQHSVRTYEV CDVQRAPGQA HWLRTGWVPR RGAVHVYATL RFTMLECLSL 100
    PRAGRSCKET FTVFYYESDA DTATALTPAW MENPYIKVDT VAAEHLTRKR 150
    PGAEATGKVN VKTLRLGPLS KAGFYLAFQD QGACMALLSL HLFYKKCAQL 200
    TVNLTRFPET VPRELVVPVA GSCVVDAVPA PGPSPSLYCR EDGQWAEQPV 250
    TGCSCAPGFE AAEGNTKCRA CAQGTFKPLS GEGSCQPCPA NSHSNTIGSA 300
    VCQCRVGYFR ARTDPRGAPC TTPPSAPRSV VSRLNGSSLH LEWSAPLESG 350
    GREDLTYALR CRECRPGGSC APCGGDLTFD PGPRDLVEPW VVVRGLRPDF 400
    TYTFEVTALN GVSSLATGPV PFEPVNVTTD REVPPAVSDI RVTRSSPSSL 450
    SLAWAVPRAP SGAVLDYEVK YHEKGAEGPS SVRFLKTSEN RAELRGLKRG 500
    ASYLVQVRAR SEAGYGPFGQ EHHSQTQLDE SEGWREQLAL IAGTAVVGVV 550
    LVLVVIVVAV LCLRKQSNGR EAEYSDKHGQ YLIGHGTKVY IDPFTYEDPN 600
    EAVREFAKEI DVSYVKIEEV IGAGEFGEVC RGRLKAPGKK ESCVAIKTLK 650
    GGYTERQRRE FLSEASIMGQ FEHPNIIRLE GVVTNSMPVM 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 AGFGSFELVS QISAEDLLRI 950
    GVTLAGHQKK ILASVQHMKS QAKPGTPGGT GGPAPQY 987
    Length:987
    Mass (Da):108,270
    Last modified:October 18, 2001 - v2
    Checksum:i11A004622F194706
    GO
    Isoform 2 (identifier: P54760-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         507-516: VRARSEAGYG → RARAGGSSWP
         517-987: Missing.

    Show »
    Length:516
    Mass (Da):55,975
    Checksum:i076696B61467596C
    GO
    Isoform 3 (identifier: P54760-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         270-306: ACAQGTFKPLSGEGSCQPCPANSHSNTIGSAVCQCRV → GRRGSQQRAVPEDVRKPGRAAGAEAGSQLPGAGTGAL
         307-987: Missing.

    Show »
    Length:306
    Mass (Da):33,342
    Checksum:iAAAB50A132494B86
    GO
    Isoform 4 (identifier: P54760-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         406-414: VTALNGVSS → YLLQCLTSG
         415-987: Missing.

    Show »
    Length:414
    Mass (Da):45,195
    Checksum:iA9596D1E38B18785
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti62 – 621D → E in AAA20598. (PubMed:8188704)Curated
    Sequence conflicti308 – 3081Y → D in AAA20598. (PubMed:8188704)Curated
    Sequence conflicti464 – 4641V → W in AAA20598. (PubMed:8188704)Curated
    Sequence conflicti926 – 9272ES → AR in AAA20598. (PubMed:8188704)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti67 – 671P → L.1 Publication
    Corresponds to variant rs34653459 [ dbSNP | Ensembl ].
    VAR_042181
    Natural varianti113 – 1131V → I.1 Publication
    Corresponds to variant rs55866373 [ dbSNP | Ensembl ].
    VAR_042182
    Natural varianti162 – 1621K → R.1 Publication
    Corresponds to variant rs17854760 [ dbSNP | Ensembl ].
    VAR_071163
    Natural varianti346 – 3461P → L in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_042183
    Natural varianti371 – 3711A → V.1 Publication
    Corresponds to variant rs55720981 [ dbSNP | Ensembl ].
    VAR_042184
    Natural varianti576 – 5761D → E.1 Publication
    Corresponds to variant rs36050247 [ dbSNP | Ensembl ].
    VAR_042185
    Natural varianti678 – 6781R → H.1 Publication
    Corresponds to variant rs55692440 [ dbSNP | Ensembl ].
    VAR_042186
    Natural varianti882 – 8821A → T.1 Publication
    Corresponds to variant rs34918225 [ dbSNP | Ensembl ].
    VAR_042187
    Natural varianti889 – 8891R → W in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_042188
    Natural varianti890 – 8901E → D.1 Publication
    Corresponds to variant rs35638378 [ dbSNP | Ensembl ].
    VAR_042189

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei270 – 30637ACAQG…CQCRV → GRRGSQQRAVPEDVRKPGRA AGAEAGSQLPGAGTGAL in isoform 3. 1 PublicationVSP_056020Add
    BLAST
    Alternative sequencei307 – 987681Missing in isoform 3. 1 PublicationVSP_056021Add
    BLAST
    Alternative sequencei406 – 4149VTALNGVSS → YLLQCLTSG in isoform 4. 1 PublicationVSP_056022
    Alternative sequencei415 – 987573Missing in isoform 4. 1 PublicationVSP_056023Add
    BLAST
    Alternative sequencei507 – 51610VRARSEAGYG → RARAGGSSWP in isoform 2. 1 PublicationVSP_056024
    Alternative sequencei517 – 987471Missing in isoform 2. 1 PublicationVSP_056025Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U07695 mRNA. Translation: AAA20598.1.
    AF312032 Genomic DNA. Translation: AAK21010.1.
    EU826608 mRNA. Translation: ACF47644.1.
    EU826609 mRNA. Translation: ACF47645.1.
    EU826610 mRNA. Translation: ACF47646.1.
    BC004264 mRNA. Translation: AAH04264.1.
    BC052804 mRNA. Translation: AAH52804.1.
    CCDSiCCDS5706.1.
    PIRiA54092.
    RefSeqiNP_004435.3. NM_004444.4.
    UniGeneiHs.437008.

    Genome annotation databases

    EnsembliENST00000358173; ENSP00000350896; ENSG00000196411.
    GeneIDi2050.
    KEGGihsa:2050.
    UCSCiuc003uwm.1. human.

    Polymorphism databases

    DMDMi19860819.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U07695 mRNA. Translation: AAA20598.1 .
    AF312032 Genomic DNA. Translation: AAK21010.1 .
    EU826608 mRNA. Translation: ACF47644.1 .
    EU826609 mRNA. Translation: ACF47645.1 .
    EU826610 mRNA. Translation: ACF47646.1 .
    BC004264 mRNA. Translation: AAH04264.1 .
    BC052804 mRNA. Translation: AAH52804.1 .
    CCDSi CCDS5706.1.
    PIRi A54092.
    RefSeqi NP_004435.3. NM_004444.4.
    UniGenei Hs.437008.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2BBA X-ray 1.65 A 17-196 [» ]
    2E7H NMR - A 434-529 [» ]
    2HLE X-ray 2.05 A 17-196 [» ]
    2QKQ X-ray 2.10 A/B 896-977 [» ]
    2VWU X-ray 2.00 A 598-887 [» ]
    2VWV X-ray 1.90 A 598-899 [» ]
    2VWW X-ray 1.90 A 598-899 [» ]
    2VWX X-ray 1.65 A 598-899 [» ]
    2VWY X-ray 1.65 A 598-899 [» ]
    2VWZ X-ray 1.65 A 598-899 [» ]
    2VX0 X-ray 2.10 A 598-899 [» ]
    2VX1 X-ray 1.65 A 598-899 [» ]
    2X9F X-ray 1.75 A 598-899 [» ]
    2XVD X-ray 1.70 A 598-899 [» ]
    2YN8 X-ray 2.11 A/B 598-892 [» ]
    3ZEW X-ray 2.50 A/B 598-892 [» ]
    4AW5 X-ray 2.33 A 605-890 [» ]
    4BB4 X-ray 1.65 A 598-899 [» ]
    ProteinModelPortali P54760.
    SMRi P54760. Positions 15-529, 608-973.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108364. 4 interactions.
    IntActi P54760. 3 interactions.
    STRINGi 9606.ENSP00000350896.

    Chemistry

    BindingDBi P54760.
    ChEMBLi CHEMBL5147.
    GuidetoPHARMACOLOGYi 1833.

    PTM databases

    PhosphoSitei P54760.

    Polymorphism databases

    DMDMi 19860819.

    2D gel databases

    DOSAC-COBS-2DPAGE P54760.

    Proteomic databases

    MaxQBi P54760.
    PaxDbi P54760.
    PRIDEi P54760.

    Protocols and materials databases

    DNASUi 2050.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000358173 ; ENSP00000350896 ; ENSG00000196411 .
    GeneIDi 2050.
    KEGGi hsa:2050.
    UCSCi uc003uwm.1. human.

    Organism-specific databases

    CTDi 2050.
    GeneCardsi GC07M100402.
    H-InvDB HIX0025312.
    HGNCi HGNC:3395. EPHB4.
    HPAi CAB013537.
    MIMi 600011. gene.
    neXtProti NX_P54760.
    PharmGKBi PA27827.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233856.
    HOVERGENi HBG062180.
    InParanoidi P54760.
    KOi K05113.
    OMAi TVFYFES.
    PhylomeDBi P54760.
    TreeFami TF315608.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    SignaLinki P54760.

    Miscellaneous databases

    ChiTaRSi EPHB4. human.
    EvolutionaryTracei P54760.
    GeneWikii EPH_receptor_B4.
    GenomeRNAii 2050.
    NextBioi 8335.
    PROi P54760.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P54760.
    Bgeei P54760.
    CleanExi HS_EPHB4.
    Genevestigatori P54760.

    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.
    IPR021129. SAM_type1.
    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.
    PF00536. SAM_1. 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

    1. "Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily."
      Bennett B.D., Wang Z., Kuang W.J., Wang A., Groopman J.E., Goeddel D.V., Scadden D.T.
      J. Biol. Chem. 269:14211-14218(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    2. "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].
    3. "Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
      Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
      Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), ALTERNATIVE SPLICING.
    4. "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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-162.
      Tissue: Ovary and Pancreas.
    5. "Unified nomenclature for Eph family receptors and their ligands, the ephrins."
      Eph nomenclature committee
      Cell 90:403-404(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NOMENCLATURE.
    6. "Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells."
      Fueller T., Korff T., Kilian A., Dandekar G., Augustin H.G.
      J. Cell Sci. 116:2461-2470(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ANGIOGENESIS, FUNCTION IN CELL ADHESION, FUNCTION IN CELL MIGRATION.
    7. "EphB4 controls blood vascular morphogenesis during postnatal angiogenesis."
      Erber R., Eichelsbacher U., Powajbo V., Korn T., Djonov V., Lin J., Hammes H.P., Grobholz R., Ullrich A., Vajkoczy P.
      EMBO J. 25:628-641(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN POSTNATAL AND TUMOR ANGIOGENESIS.
    8. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-911 AND THR-976, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-976, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    10. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-911; THR-976 AND TYR-987, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Structural and biophysical characterization of the EphB4*ephrinB2 protein-protein interaction and receptor specificity."
      Chrencik J.E., Brooun A., Kraus M.L., Recht M.I., Kolatkar A.R., Han G.W., Seifert J.M., Widmer H., Auer M., Kuhn P.
      J. Biol. Chem. 281:28185-28192(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 17-196 IN COMPLEX WITH EFNB2, MUTAGENESIS OF LEU-95, DISULFIDE BOND.
    14. "Structure and thermodynamic characterization of the EphB4/Ephrin-B2 antagonist peptide complex reveals the determinants for receptor specificity."
      Chrencik J.E., Brooun A., Recht M.I., Kraus M.L., Koolpe M., Kolatkar A.R., Bruce R.H., Martiny-Baron G., Widmer H., Pasquale E.B., Kuhn P.
      Structure 14:321-330(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 17-196 IN COMPLEX WITH ANTAGONISTIC PEPTIDE, DISULFIDE BOND.
    15. "Solution structure of the second FN3 domain from human ephrin type-B receptor 4."
      RIKEN structural genomics initiative (RSGI)
      Submitted (JUL-2007) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 434-529.
    16. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-67; ILE-113; LEU-346; VAL-371; GLU-576; HIS-678; THR-882; TRP-889 AND ASP-890.

    Entry informationi

    Entry nameiEPHB4_HUMAN
    AccessioniPrimary (citable) accession number: P54760
    Secondary accession number(s): B5A970
    , B5A971, B5A972, Q7Z635, Q9BTA5, Q9BXP0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 18, 2001
    Last modified: October 1, 2014
    This is version 164 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3