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P54764

- EPHA4_HUMAN

UniProt

P54764 - EPHA4_HUMAN

Protein

Ephrin type-A receptor 4

Gene

EPHA4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Receptor tyrosine kinase which binds membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.1 Publication

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei653 – 6531ATPPROSITE-ProRule annotation
    Active sitei746 – 7461Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi627 – 6359ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. DH domain binding Source: UniProtKB
    3. GPI-linked ephrin receptor activity Source: UniProtKB
    4. PH domain binding Source: UniProtKB
    5. protein binding Source: UniProtKB
    6. protein kinase activity Source: UniProtKB
    7. transmembrane-ephrin receptor activity Source: UniProtKB

    GO - Biological processi

    1. adult walking behavior Source: Ensembl
    2. cell adhesion Source: UniProtKB-KW
    3. corticospinal tract morphogenesis Source: UniProtKB
    4. fasciculation of motor neuron axon Source: UniProtKB
    5. fasciculation of sensory neuron axon Source: UniProtKB
    6. glial cell migration Source: Ensembl
    7. motor neuron axon guidance Source: UniProtKB
    8. negative regulation of axon regeneration Source: UniProtKB
    9. peptidyl-tyrosine phosphorylation Source: UniProtKB
    10. positive regulation of dendrite morphogenesis Source: Ensembl
    11. positive regulation of JUN kinase activity Source: Ensembl
    12. positive regulation of Rho guanyl-nucleotide exchange factor activity Source: UniProtKB
    13. protein autophosphorylation Source: UniProtKB
    14. regulation of astrocyte differentiation Source: UniProtKB
    15. regulation of axonogenesis Source: UniProtKB
    16. regulation of dendritic spine morphogenesis Source: UniProtKB
    17. regulation of Rac GTPase activity Source: UniProtKB
    18. regulation of Rap GTPase activity Source: UniProtKB

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Cell adhesion, Neurogenesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    SignaLinkiP54764.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ephrin type-A receptor 4 (EC:2.7.10.1)
    Alternative name(s):
    EPH-like kinase 8
    Short name:
    EK8
    Short name:
    hEK8
    Tyrosine-protein kinase TYRO1
    Tyrosine-protein kinase receptor SEK
    Gene namesi
    Name:EPHA4
    Synonyms:HEK8, SEK, TYRO1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:3388. EPHA4.

    Subcellular locationi

    Cell membrane By similarity; Single-pass type I membrane protein By similarity. Cell projectionaxon By similarity. Cell projectiondendrite By similarity. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity. Early endosome By similarity
    Note: Clustered upon activation and targeted to early endosome.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. axonal growth cone Source: Ensembl
    3. axon terminus Source: Ensembl
    4. cell junction Source: UniProtKB-KW
    5. cell surface Source: Ensembl
    6. cytoplasm Source: UniProtKB
    7. dendrite Source: UniProtKB
    8. dendritic spine Source: Ensembl
    9. early endosome membrane Source: UniProtKB
    10. endoplasmic reticulum Source: Ensembl
    11. filopodium Source: Ensembl
    12. Golgi apparatus Source: Ensembl
    13. integral component of plasma membrane Source: UniProtKB
    14. mitochondrial outer membrane Source: Ensembl
    15. neuromuscular junction Source: Ensembl
    16. perikaryon Source: Ensembl
    17. postsynaptic density Source: UniProtKB-SubCell
    18. postsynaptic membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Endosome, Membrane, Postsynaptic cell membrane, Synapse

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi40 – 401Q → A: 10-fold reduced affinity for EFNB2; when associated with A-42. 1 Publication
    Mutagenesisi42 – 421E → A: 10-fold reduced affinity for EFNB2; when associated with A-40. 1 Publication

    Organism-specific databases

    PharmGKBiPA27820.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Chaini20 – 986967Ephrin type-A receptor 4PRO_0000016807Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi340 – 3401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi408 – 4081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi545 – 5451N-linked (GlcNAc...)Sequence Analysis
    Modified residuei596 – 5961Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei602 – 6021Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei779 – 7791Phosphotyrosine; by autocatalysisSequence Analysis
    Modified residuei928 – 9281Phosphotyrosine; by autocatalysisSequence Analysis

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiP54764.
    PaxDbiP54764.
    PeptideAtlasiP54764.
    PRIDEiP54764.

    PTM databases

    PhosphoSiteiP54764.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Gene expression databases

    ArrayExpressiP54764.
    BgeeiP54764.
    CleanExiHS_EPHA4.
    GenevestigatoriP54764.

    Organism-specific databases

    HPAiCAB004654.

    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. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation By similarity. Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases.By similarity3 Publications

    Protein-protein interaction databases

    BioGridi108357. 13 interactions.
    DIPiDIP-48294N.
    IntActiP54764. 2 interactions.
    STRINGi9606.ENSP00000281821.

    Structurei

    Secondary structure

    1
    986
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi30 – 356
    Helixi36 – 383
    Turni40 – 423
    Beta strandi46 – 6116
    Beta strandi65 – 739
    Beta strandi76 – 783
    Beta strandi82 – 854
    Beta strandi93 – 964
    Beta strandi97 – 1059
    Helixi108 – 1103
    Turni115 – 1173
    Beta strandi120 – 13011
    Beta strandi131 – 1333
    Helixi139 – 1413
    Beta strandi143 – 1497
    Beta strandi154 – 1574
    Turni159 – 1624
    Beta strandi164 – 17310
    Beta strandi178 – 18912
    Beta strandi191 – 20212
    Beta strandi207 – 2093
    Beta strandi212 – 2143
    Beta strandi226 – 2305
    Beta strandi237 – 24812
    Beta strandi257 – 2626
    Beta strandi266 – 2694
    Beta strandi272 – 2754
    Beta strandi304 – 3063
    Beta strandi333 – 3408
    Beta strandi343 – 3497
    Beta strandi361 – 3688
    Turni373 – 3753
    Beta strandi385 – 3884
    Beta strandi390 – 3934
    Beta strandi395 – 4017
    Beta strandi405 – 41612
    Beta strandi418 – 4236
    Helixi426 – 4283
    Beta strandi429 – 4357
    Beta strandi447 – 4526
    Beta strandi457 – 4615
    Beta strandi473 – 48311
    Beta strandi489 – 50012
    Beta strandi508 – 51710
    Beta strandi528 – 5314
    Turni538 – 5403

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2LW8NMR-A29-209[»]
    2WO1X-ray1.85A/B30-202[»]
    2WO2X-ray2.45A30-202[»]
    2WO3X-ray2.35A30-202[»]
    3CKHX-ray2.80A/B29-209[»]
    3GXUX-ray2.50A29-203[»]
    4BK4X-ray3.65A/B20-547[»]
    4BK5X-ray4.00A20-547[»]
    4BKAX-ray5.30A20-547[»]
    4BKFX-ray4.65A/B20-547[»]
    4M4PX-ray2.08A27-543[»]
    4M4RX-ray3.13A/C/E/G27-543[»]
    ProteinModelPortaliP54764.
    SMRiP54764. Positions 27-981.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP54764.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini20 – 547528ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini570 – 986417CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei548 – 56922HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini30 – 209180Eph LBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini328 – 439112Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini440 – 53798Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini621 – 882262Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini911 – 97565SAMPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi984 – 9863PDZ-bindingSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi191 – 325135Cys-richAdd
    BLAST

    Domaini

    The protein kinase domain mediates interaction with NGEF.By similarity

    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.
    InParanoidiP54764.
    KOiK05105.
    OMAiDWIPREG.
    PhylomeDBiP54764.
    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.
    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.
    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.
    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.
    PROSITEiPS51550. 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 (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P54764-1) [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

    MAGIFYFALF SCLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL    50
    EGGWEEVSIM DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIT REGAQRVYIE 100
    IKFTLRDCNS LPGVMGTCKE TFNLYYYESD NDKERFIREN QFVKIDTIAA 150
    DESFTQVDIG DRIMKLNTEI RDVGPLSKKG FYLAFQDVGA CIALVSVRVF 200
    YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK DVPKMYCGAD 250
    GEWLVPIGNC LCNAGHEERS GECQACKIGY YKALSTDATC AKCPPHSYSV 300
    WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS 350
    PQNTGGRQDI SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTKVSI 400
    TDLLAHTNYT FEIWAVNGVS KYNPNPDQSV SVTVTTNQAA PSSIALVQAK 450
    EVTRYSVALA WLEPDRPNGV ILEYEVKYYE KDQNERSYRI VRTAARNTDI 500
    KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII GDGANSTVLL 550
    VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 600
    TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV 650
    AIKTLKAGYT DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE 700
    YMENGSLDAF LRKNDGRFTV IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR 750
    NILVNSNLVC KVSDFGMSRV LEDDPEAAYT TRGGKIPIRW TAPEAIAYRK 800
    FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG YRLPPPMDCP 850
    IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGTESSRPNT 900
    ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHVNQED 950
    LARIGITAIT HQNKILSSVQ AMRTQMQQMH GRMVPV 986
    Length:986
    Mass (Da):109,860
    Last modified:October 1, 1996 - v1
    Checksum:i0C39C1152EDDD46F
    GO
    Isoform 2 (identifier: P54764-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-53: MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGG → MK

    Note: No experimental confirmation available.

    Show »
    Length:935
    Mass (Da):104,507
    Checksum:i588D6FDA5FCCDCE4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti71 – 711Q → P in BAF82995. (PubMed:14702039)Curated
    Sequence conflicti102 – 1021K → R in BAF82995. (PubMed:14702039)Curated
    Sequence conflicti137 – 1371I → V in BAG35298. (PubMed:14702039)Curated
    Sequence conflicti362 – 3621Y → H in BAF82995. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti269 – 2691R → Q.1 Publication
    Corresponds to variant rs35084379 [ dbSNP | Ensembl ].
    VAR_042135
    Natural varianti370 – 3701G → E in a bladder carcinoma NOS sample; somatic mutation. 1 Publication
    VAR_042136
    Natural varianti399 – 3991S → F in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_042137
    Natural varianti953 – 9531R → K.
    Corresponds to variant rs35341687 [ dbSNP | Ensembl ].
    VAR_049721

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5353MAGIF…PLEGG → MK in isoform 2. 1 PublicationVSP_056016Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L36645 mRNA. Translation: AAA74246.1.
    AK290306 mRNA. Translation: BAF82995.1.
    AK300772 mRNA. Translation: BAH13344.1.
    AK312380 mRNA. Translation: BAG35298.1.
    AC010899 Genomic DNA. No translation available.
    AC079834 Genomic DNA. No translation available.
    BC105000 mRNA. Translation: AAI05001.1.
    BC105002 mRNA. Translation: AAI05003.1.
    CCDSiCCDS2447.1.
    PIRiI78844.
    RefSeqiNP_004429.1. NM_004438.3.
    UniGeneiHs.371218.

    Genome annotation databases

    EnsembliENST00000281821; ENSP00000281821; ENSG00000116106.
    ENST00000392071; ENSP00000375923; ENSG00000116106.
    ENST00000409938; ENSP00000386829; ENSG00000116106.
    GeneIDi2043.
    KEGGihsa:2043.
    UCSCiuc002vmq.3. human.

    Polymorphism databases

    DMDMi1711371.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L36645 mRNA. Translation: AAA74246.1 .
    AK290306 mRNA. Translation: BAF82995.1 .
    AK300772 mRNA. Translation: BAH13344.1 .
    AK312380 mRNA. Translation: BAG35298.1 .
    AC010899 Genomic DNA. No translation available.
    AC079834 Genomic DNA. No translation available.
    BC105000 mRNA. Translation: AAI05001.1 .
    BC105002 mRNA. Translation: AAI05003.1 .
    CCDSi CCDS2447.1.
    PIRi I78844.
    RefSeqi NP_004429.1. NM_004438.3.
    UniGenei Hs.371218.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2LW8 NMR - A 29-209 [» ]
    2WO1 X-ray 1.85 A/B 30-202 [» ]
    2WO2 X-ray 2.45 A 30-202 [» ]
    2WO3 X-ray 2.35 A 30-202 [» ]
    3CKH X-ray 2.80 A/B 29-209 [» ]
    3GXU X-ray 2.50 A 29-203 [» ]
    4BK4 X-ray 3.65 A/B 20-547 [» ]
    4BK5 X-ray 4.00 A 20-547 [» ]
    4BKA X-ray 5.30 A 20-547 [» ]
    4BKF X-ray 4.65 A/B 20-547 [» ]
    4M4P X-ray 2.08 A 27-543 [» ]
    4M4R X-ray 3.13 A/C/E/G 27-543 [» ]
    ProteinModelPortali P54764.
    SMRi P54764. Positions 27-981.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108357. 13 interactions.
    DIPi DIP-48294N.
    IntActi P54764. 2 interactions.
    STRINGi 9606.ENSP00000281821.

    Chemistry

    BindingDBi P54764.
    ChEMBLi CHEMBL3988.
    GuidetoPHARMACOLOGYi 1824.

    PTM databases

    PhosphoSitei P54764.

    Polymorphism databases

    DMDMi 1711371.

    Proteomic databases

    MaxQBi P54764.
    PaxDbi P54764.
    PeptideAtlasi P54764.
    PRIDEi P54764.

    Protocols and materials databases

    DNASUi 2043.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000281821 ; ENSP00000281821 ; ENSG00000116106 .
    ENST00000392071 ; ENSP00000375923 ; ENSG00000116106 .
    ENST00000409938 ; ENSP00000386829 ; ENSG00000116106 .
    GeneIDi 2043.
    KEGGi hsa:2043.
    UCSCi uc002vmq.3. human.

    Organism-specific databases

    CTDi 2043.
    GeneCardsi GC02M222248.
    HGNCi HGNC:3388. EPHA4.
    HPAi CAB004654.
    MIMi 602188. gene.
    neXtProti NX_P54764.
    PharmGKBi PA27820.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233856.
    HOVERGENi HBG062180.
    InParanoidi P54764.
    KOi K05105.
    OMAi DWIPREG.
    PhylomeDBi P54764.
    TreeFami TF315608.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    SignaLinki P54764.

    Miscellaneous databases

    ChiTaRSi EPHA4. human.
    EvolutionaryTracei P54764.
    GeneWikii EPH_receptor_A4.
    GenomeRNAii 2043.
    NextBioi 35463929.
    PROi P54764.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P54764.
    Bgeei P54764.
    CleanExi HS_EPHA4.
    Genevestigatori P54764.

    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.
    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.
    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.
    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.
    PROSITEi 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. "cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases."
      Fox G.M., Holst P.L., Chute H.T., Lindberg R.A., Janssen A.M., Basu R., Welcher A.A.
      Oncogene 10:897-905(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Fetal brain.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Amygdala and Tongue.
    3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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).
      Tissue: Brain.
    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. "The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases."
      Richter M., Murai K.K., Bourgin C., Pak D.T., Pasquale E.B.
      J. Neurosci. 27:14205-14215(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIPA1L1.
    7. "Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism."
      Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.
      Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF CDK5, AUTOPHOSPHORYLATION.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "Crystal structure and NMR binding reveal that two small molecule antagonists target the high affinity ephrin-binding channel of the EphA4 receptor."
      Qin H., Shi J., Noberini R., Pasquale E.B., Song J.
      J. Biol. Chem. 283:29473-29484(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 29-209.
    10. "Structural plasticity of EPH receptor A4 facilitates cross-class ephrin signaling."
      Bowden T.A., Aricescu A.R., Nettleship J.E., Siebold C., Rahman-Huq N., Owens R.J., Stuart D.I., Jones E.Y.
      Structure 17:1386-1397(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 30-202 IN COMPLEX WITH EFNA2 OR EFNB2, LIGAND-BINDING.
    11. "Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity."
      Qin H., Noberini R., Huan X., Shi J., Pasquale E.B., Song J.
      J. Biol. Chem. 285:644-654(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 29-203 IN COMPLEX WITH EFNB2, MUTAGENESIS OF GLN-40 AND GLU-42.
    12. "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] GLN-269; GLU-370 AND PHE-399.

    Entry informationi

    Entry nameiEPHA4_HUMAN
    AccessioniPrimary (citable) accession number: P54764
    Secondary accession number(s): A8K2P1
    , B2R601, B7Z6Q8, Q2M380
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 156 of the entry and version 1 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 2
      Human chromosome 2: 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