EPHA4_MOUSE
ID EPHA4_MOUSE Reviewed; 986 AA.
AC Q03137; Q80VZ2;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Ephrin type-A receptor 4;
DE EC=2.7.10.1;
DE AltName: Full=Tyrosine-protein kinase receptor MPK-3;
DE AltName: Full=Tyrosine-protein kinase receptor SEK-1;
DE Flags: Precursor;
GN Name=Epha4; Synonyms=Sek, Sek1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
RX PubMed=1281307;
RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A.,
RA Wilkinson D.G., Charnay P.;
RT "An Eph-related receptor protein tyrosine kinase gene segmentally expressed
RT in the developing mouse hindbrain.";
RL Oncogene 7:2499-2506(1992).
RN [2]
RP ERRATUM OF PUBMED:1281307.
RX PubMed=8455939;
RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A.,
RA Wilkinson D.G., Charnay P.;
RL Oncogene 8:1103-1103(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION AT TYR-596 AND TYR-602, AND INTERACTION WITH FYN.
RX PubMed=8622893;
RA Ellis C., Kasmi F., Ganju P., Walls E., Panayotou G., Reith A.D.;
RT "A juxtamembrane autophosphorylation site in the Eph family receptor
RT tyrosine kinase, Sek, mediates high affinity interaction with p59fyn.";
RL Oncogene 12:1727-1736(1996).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN AXON GUIDANCE.
RX PubMed=9789074; DOI=10.1073/pnas.95.22.13248;
RA Dottori M., Hartley L., Galea M., Paxinos G., Polizzotto M., Kilpatrick T.,
RA Bartlett P.F., Murphy M., Koentgen F., Boyd A.W.;
RT "EphA4 (Sek1) receptor tyrosine kinase is required for the development of
RT the corticospinal tract.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13248-13253(1998).
RN [8]
RP INTERACTION WITH NGEF, AND MUTAGENESIS OF VAL-635.
RX PubMed=11336673; DOI=10.1016/s0092-8674(01)00314-2;
RA Shamah S.M., Lin M.Z., Goldberg J.L., Estrach S., Sahin M., Hu L.,
RA Bazalakova M., Neve R.L., Corfas G., Debant A., Greenberg M.E.;
RT "EphA receptors regulate growth cone dynamics through the novel guanine
RT nucleotide exchange factor ephexin.";
RL Cell 105:233-244(2001).
RN [9]
RP DEVELOPMENTAL STAGE.
RX PubMed=14516691; DOI=10.1016/s0925-4773(03)00122-9;
RA Greferath U., Canty A.J., Messenger J., Murphy M.;
RT "Developmental expression of EphA4-tyrosine kinase receptor in the mouse
RT brain and spinal cord.";
RL Mech. Dev. 119:S231-S238(2002).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN AXONAL REGENERATION.
RX PubMed=15537875; DOI=10.1523/jneurosci.2981-04.2004;
RA Goldshmit Y., Galea M.P., Wise G., Bartlett P.F., Turnley A.M.;
RT "Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient
RT mice.";
RL J. Neurosci. 24:10064-10073(2004).
RN [11]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=16802330; DOI=10.1002/cne.21029;
RA Goldshmit Y., Galea M.P., Bartlett P.F., Turnley A.M.;
RT "EphA4 regulates central nervous system vascular formation.";
RL J. Comp. Neurol. 497:864-875(2006).
RN [12]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN THYMUS DEVELOPMENT.
RX PubMed=16818734; DOI=10.4049/jimmunol.177.2.804;
RA Munoz J.J., Alfaro D., Garcia-Ceca J., Alonso-C L.M., Jimenez E.,
RA Zapata A.;
RT "Thymic alterations in EphA4-deficient mice.";
RL J. Immunol. 177:804-813(2006).
RN [13]
RP FUNCTION IN RAC1 REGULATION, FUNCTION IN AXON GUIDANCE, AND INTERACTION
RP WITH CHN1.
RX PubMed=17719550; DOI=10.1016/j.cell.2007.07.022;
RA Iwasato T., Katoh H., Nishimaru H., Ishikawa Y., Inoue H., Saito Y.M.,
RA Ando R., Iwama M., Takahashi R., Negishi M., Itohara S.;
RT "Rac-GAP alpha-chimerin regulates motor-circuit formation as a key mediator
RT of EphrinB3/EphA4 forward signaling.";
RL Cell 130:742-753(2007).
RN [14]
RP FUNCTION IN NEURON MORPHOLOGY, AND INTERACTION WITH SIPA1L1.
RX PubMed=18094260; DOI=10.1523/jneurosci.2746-07.2007;
RA Richter M., Murai K.K., Bourgin C., Pak D.T., Pasquale E.B.;
RT "The EphA4 receptor regulates neuronal morphology through SPAR-mediated
RT inactivation of Rap GTPases.";
RL J. Neurosci. 27:14205-14215(2007).
RN [15]
RP FUNCTION IN DENDRITIC SPINE MORPHOGENESIS, TOPOLOGY, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH NGEF.
RX PubMed=17143272; DOI=10.1038/nn1811;
RA Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O.,
RA Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.;
RT "Cdk5 regulates EphA4-mediated dendritic spine retraction through an
RT ephexin1-dependent mechanism.";
RL Nat. Neurosci. 10:67-76(2007).
RN [16]
RP FUNCTION IN AXON GUIDANCE, INTERACTION WITH CHN1, AND MUTAGENESIS OF
RP VAL-635.
RX PubMed=17785183; DOI=10.1016/j.neuron.2007.07.036;
RA Beg A.A., Sommer J.E., Martin J.H., Scheiffele P.;
RT "alpha2-Chimaerin is an essential EphA4 effector in the assembly of
RT neuronal locomotor circuits.";
RL Neuron 55:768-778(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-602, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [18]
RP FUNCTION IN MOTOR AND SENSORY AXONS SEGREGATION.
RX PubMed=18403711; DOI=10.1126/science.1153758;
RA Gallarda B.W., Bonanomi D., Mueller D., Brown A., Alaynick W.A.,
RA Andrews S.E., Lemke G., Pfaff S.L., Marquardt T.;
RT "Segregation of axial motor and sensory pathways via heterotypic trans-
RT axonal signaling.";
RL Science 320:233-236(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=27446912; DOI=10.3389/fcell.2016.00058;
RA Alonso-Martin S., Rochat A., Mademtzoglou D., Morais J., de Reynies A.,
RA Aurade F., Chang T.H., Zammit P.S., Relaix F.;
RT "Gene expression profiling of muscle stem cells identifies novel regulators
RT of postnatal myogenesis.";
RL Front. Cell Dev. Biol. 4:58-58(2016).
RN [21]
RP FUNCTION, IDENTIFICATION IN COMPLEX WITH ADAM10 AND CADH1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30639848; DOI=10.1016/j.isci.2018.12.017;
RA Defourny J., Peuckert C., Kullander K., Malgrange B.;
RT "EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through
RT Local Disruption of Adherens Junctions.";
RL IScience 11:246-257(2019).
CC -!- FUNCTION: Receptor tyrosine kinase which binds membrane-bound ephrin
CC family ligands residing on adjacent cells, leading to contact-dependent
CC bidirectional signaling into neighboring cells. The signaling pathway
CC downstream of the receptor is referred to as forward signaling while
CC the signaling pathway downstream of the ephrin ligand is referred to as
CC reverse signaling. Highly promiscuous, it has the unique property among
CC Eph receptors to bind and to be physiologically activated by both GPI-
CC anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1
CC and EFNB3. Upon activation by ephrin ligands, modulates cell morphology
CC and integrin-dependent cell adhesion through regulation of the Rac, Rap
CC and Rho GTPases activity. Plays an important role in the development of
CC the nervous system controlling different steps of axonal guidance
CC including the establishment of the corticospinal projections. May also
CC control the segregation of motor and sensory axons during neuromuscular
CC circuit development. In addition to its role in axonal guidance plays a
CC role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at
CC 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and
CC dendritic spine morphogenesis. In the nervous system, also plays a role
CC in repair after injury preventing axonal regeneration and in
CC angiogenesis playing a role in central nervous system vascular
CC formation. Additionally, its promiscuity makes it available to
CC participate in a variety of cell-cell signaling regulating for instance
CC the development of the thymic epithelium. During development of the
CC cochlear organ of Corti, regulates pillar cell separation by forming a
CC ternary complex with ADAM10 and CADH1 which facilitates the cleavage of
CC CADH1 by ADAM10 and disruption of adherens junctions (PubMed:30639848).
CC {ECO:0000269|PubMed:15537875, ECO:0000269|PubMed:16802330,
CC ECO:0000269|PubMed:16818734, ECO:0000269|PubMed:17143272,
CC ECO:0000269|PubMed:17719550, ECO:0000269|PubMed:17785183,
CC ECO:0000269|PubMed:18094260, ECO:0000269|PubMed:18403711,
CC ECO:0000269|PubMed:30639848, ECO:0000269|PubMed:9789074}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Heterotetramer upon binding of the ligand. The heterotetramer
CC is composed of an ephrin dimer and a receptor dimer. Oligomerization is
CC probably required to induce biological responses. Interacts
CC (phosphorylated at position Tyr-602) with FYN. Interacts (via PDZ
CC motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology
CC through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B
CC or RAP2C) GTPases. Interacts with CDK5, CDK5R1 and NGEF; upon
CC activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5.
CC Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4
CC activation to RAC1 regulation. Forms a ternary complex composed of
CC ADAM10, CADH1 and EPHA4; within the complex, CADH1 is cleaved by ADAM10
CC which disrupts adherens junctions (PubMed:30639848).
CC {ECO:0000269|PubMed:11336673, ECO:0000269|PubMed:17143272,
CC ECO:0000269|PubMed:17719550, ECO:0000269|PubMed:17785183,
CC ECO:0000269|PubMed:18094260, ECO:0000269|PubMed:30639848,
CC ECO:0000269|PubMed:8622893}.
CC -!- INTERACTION:
CC Q03137; Q91V57-1: Chn1; NbExp=2; IntAct=EBI-1539152, EBI-1539203;
CC Q03137; P52800: Efnb2; NbExp=2; IntAct=EBI-1539152, EBI-1032676;
CC Q03137; Q03145: Epha2; NbExp=3; IntAct=EBI-1539152, EBI-529701;
CC Q03137; Q03137: Epha4; NbExp=2; IntAct=EBI-1539152, EBI-1539152;
CC Q03137; P54763: Ephb2; NbExp=3; IntAct=EBI-1539152, EBI-537711;
CC Q03137; Q921Q7: Rin1; NbExp=2; IntAct=EBI-1539152, EBI-15724937;
CC Q03137; O95292: VAPB; Xeno; NbExp=2; IntAct=EBI-1539152, EBI-1188298;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17143272};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:17143272}. Cell
CC projection, axon {ECO:0000269|PubMed:17143272}. Cell projection,
CC dendrite {ECO:0000269|PubMed:17143272}. Postsynaptic density membrane
CC {ECO:0000250}. Early endosome {ECO:0000269|PubMed:17143272}. Cell
CC junction, adherens junction {ECO:0000269|PubMed:30639848}.
CC Note=Clustered upon activation and targeted to early endosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q03137-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q03137-2; Sequence=VSP_002998;
CC -!- TISSUE SPECIFICITY: Expressed in inner and outer pillar cells of the
CC organ of Corti (at protein level) (PubMed:30639848). Highest expression
CC in the adult brain and retina and also detectable in kidney, lung,
CC skeletal muscle and thymus. Not detected in heart and liver. Expressed
CC in myogenic progenitor cells (PubMed:27446912).
CC {ECO:0000269|PubMed:27446912, ECO:0000269|PubMed:30639848}.
CC -!- DEVELOPMENTAL STAGE: Found in both the 10-day embryonic brain and body
CC tissues. In the embryonic brain, expressed in the developing cortex of
CC the telencephalon and major cortical tracts. Also expressed in the
CC hippocampus, fornix and striatal cells and tracts. In the diencephalon,
CC strongly expressed in thalamus, hypothalamus and thalamo-cortical
CC projection. Also expressed in red nuclei of the mesencephalon and in
CC the cerebellum. In the spinal cord, persistent expression occurs in the
CC dorsal funiculus and ventral gray matter. In myogenic progenitor cells,
CC highly expressed at 11.5 dpc and ceases its expression at the late
CC fetal stage (17.5 dpc) (PubMed:27446912). {ECO:0000269|PubMed:14516691,
CC ECO:0000269|PubMed:27446912}.
CC -!- DOMAIN: The protein kinase domain mediates interaction with NGEF.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but display a loss of
CC coordination of limb movement associated with disruptions of cortico-
CC spinal tract. They also display altered development of the thymic
CC epithelium which leads to a defective T-cells development.
CC {ECO:0000269|PubMed:15537875, ECO:0000269|PubMed:16818734,
CC ECO:0000269|PubMed:9789074}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X65138; CAA46268.1; -; mRNA.
DR EMBL; X57241; CAA40517.1; -; mRNA.
DR EMBL; S57168; AAB25836.1; -; mRNA.
DR EMBL; AK147698; BAE28081.1; -; mRNA.
DR EMBL; CH466548; EDL00429.1; -; Genomic_DNA.
DR EMBL; BC052164; AAH52164.1; -; mRNA.
DR CCDS; CCDS35627.1; -. [Q03137-1]
DR PIR; S78059; S78059.
DR RefSeq; NP_031962.2; NM_007936.3. [Q03137-1]
DR PDB; 1B0X; X-ray; 2.00 A; A=890-981.
DR PDB; 2HEL; X-ray; 2.35 A; A=591-896.
DR PDB; 2XYU; X-ray; 2.12 A; A=612-896.
DR PDB; 2Y6M; X-ray; 1.70 A; A=606-896.
DR PDB; 2Y6O; X-ray; 1.54 A; A=606-896.
DR PDBsum; 1B0X; -.
DR PDBsum; 2HEL; -.
DR PDBsum; 2XYU; -.
DR PDBsum; 2Y6M; -.
DR PDBsum; 2Y6O; -.
DR AlphaFoldDB; Q03137; -.
DR SMR; Q03137; -.
DR BioGRID; 199471; 6.
DR DIP; DIP-1019N; -.
DR IntAct; Q03137; 12.
DR MINT; Q03137; -.
DR STRING; 10090.ENSMUSP00000027451; -.
DR BindingDB; Q03137; -.
DR ChEMBL; CHEMBL1293259; -.
DR GuidetoPHARMACOLOGY; 1824; -.
DR GlyConnect; 2295; 1 N-Linked glycan (1 site).
DR GlyGen; Q03137; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q03137; -.
DR PhosphoSitePlus; Q03137; -.
DR SwissPalm; Q03137; -.
DR MaxQB; Q03137; -.
DR PaxDb; Q03137; -.
DR PeptideAtlas; Q03137; -.
DR PRIDE; Q03137; -.
DR ProteomicsDB; 275755; -. [Q03137-1]
DR ProteomicsDB; 275756; -. [Q03137-2]
DR Antibodypedia; 34350; 703 antibodies from 38 providers.
DR DNASU; 13838; -.
DR Ensembl; ENSMUST00000027451; ENSMUSP00000027451; ENSMUSG00000026235. [Q03137-1]
DR Ensembl; ENSMUST00000188797; ENSMUSP00000140954; ENSMUSG00000026235. [Q03137-1]
DR Ensembl; ENSMUST00000188952; ENSMUSP00000139640; ENSMUSG00000026235. [Q03137-1]
DR GeneID; 13838; -.
DR KEGG; mmu:13838; -.
DR UCSC; uc007bpz.1; mouse. [Q03137-1]
DR CTD; 2043; -.
DR MGI; MGI:98277; Epha4.
DR VEuPathDB; HostDB:ENSMUSG00000026235; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000156948; -.
DR HOGENOM; CLU_000288_141_4_1; -.
DR InParanoid; Q03137; -.
DR OMA; DRMIREP; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; Q03137; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-2682334; EPH-Ephrin signaling.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR BioGRID-ORCS; 13838; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Epha4; mouse.
DR EvolutionaryTrace; Q03137; -.
DR PRO; PR:Q03137; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q03137; protein.
DR Bgee; ENSMUSG00000026235; Expressed in rostral migratory stream and 292 other tissues.
DR ExpressionAtlas; Q03137; baseline and differential.
DR Genevisible; Q03137; MM.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0044295; C:axonal growth cone; ISO:MGI.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030175; C:filopodium; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0097161; F:DH domain binding; ISS:UniProtKB.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:MGI.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0042731; F:PH domain binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IDA:UniProtKB.
DR GO; GO:0034332; P:adherens junction organization; IMP:ARUK-UCL.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0090102; P:cochlea development; IMP:UniProtKB.
DR GO; GO:0021957; P:corticospinal tract morphogenesis; IMP:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISO:MGI.
DR GO; GO:0097156; P:fasciculation of motor neuron axon; IMP:UniProtKB.
DR GO; GO:0097155; P:fasciculation of sensory neuron axon; IMP:UniProtKB.
DR GO; GO:0008347; P:glial cell migration; ISO:MGI.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IMP:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; ISO:MGI.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IGI:ARUK-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:ARUK-UCL.
DR GO; GO:1903051; P:negative regulation of proteolysis involved in protein catabolic process; ISO:MGI.
DR GO; GO:0072178; P:nephric duct morphogenesis; IGI:MGI.
DR GO; GO:0106030; P:neuron projection fasciculation; IDA:ARUK-UCL.
DR GO; GO:0097485; P:neuron projection guidance; IDA:ARUK-UCL.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISO:MGI.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:BHF-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IGI:ARUK-UCL.
DR GO; GO:2001108; P:positive regulation of Rho guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0048710; P:regulation of astrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:UniProtKB.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; IMP:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:1905244; P:regulation of modification of synaptic structure; IGI:ARUK-UCL.
DR GO; GO:0098883; P:synapse pruning; IDA:SynGO.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10482; EphR_LBD_A4; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd09545; SAM_EPH-A4; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034270; EphA4_rcpt_lig-bd.
DR InterPro; IPR030602; EphA4_SAM.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 1.
DR Pfam; PF07699; Ephrin_rec_like; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF07647; SAM_2; 1.
DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00615; EPH_lbd; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51550; EPH_LBD; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1.
DR PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell adhesion;
KW Cell junction; Cell membrane; Cell projection; Developmental protein;
KW Endosome; Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Repeat; Signal; Synapse; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..986
FT /note="Ephrin type-A receptor 4"
FT /id="PRO_0000016808"
FT TOPO_DOM 20..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..569
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 570..986
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..209
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 328..439
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 440..537
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 621..882
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 911..975
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 984..986
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 746
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 627..635
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 653
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 596
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8622893"
FT MOD_RES 602
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8622893,
FT ECO:0007744|PubMed:18034455"
FT MOD_RES 779
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 928
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 783..832
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_002998"
FT MUTAGEN 635
FT /note="V->M: Kinase dead; loss of autophosphorylation and
FT loss of CHN1 phosphorylation. No effect on interaction with
FT NGEF."
FT /evidence="ECO:0000269|PubMed:11336673,
FT ECO:0000269|PubMed:17785183"
FT CONFLICT 145
FT /note="I -> T (in Ref. 1; CAA46268/AAB25836)"
FT /evidence="ECO:0000305"
FT HELIX 618..620
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 621..629
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 631..640
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 648..655
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 661..674
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 685..689
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 691..694
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 696..700
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 707..712
FT /evidence="ECO:0007829|PDB:2Y6O"
FT TURN 713..716
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 720..739
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 749..751
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 752..754
FT /evidence="ECO:0007829|PDB:2Y6O"
FT STRAND 760..762
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 788..790
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 793..798
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 803..818
FT /evidence="ECO:0007829|PDB:2Y6O"
FT TURN 824..827
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 830..838
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 851..860
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 865..867
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 871..883
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 885..888
FT /evidence="ECO:0007829|PDB:2Y6O"
FT HELIX 916..922
FT /evidence="ECO:0007829|PDB:1B0X"
FT HELIX 926..928
FT /evidence="ECO:0007829|PDB:1B0X"
FT HELIX 929..934
FT /evidence="ECO:0007829|PDB:1B0X"
FT HELIX 940..943
FT /evidence="ECO:0007829|PDB:1B0X"
FT HELIX 948..954
FT /evidence="ECO:0007829|PDB:1B0X"
FT HELIX 959..977
FT /evidence="ECO:0007829|PDB:1B0X"
FT HELIX 978..980
FT /evidence="ECO:0007829|PDB:1B0X"
SQ SEQUENCE 986 AA; 109814 MW; 89BEB2C7CDB54A55 CRC64;
MAGIFYFILF SFLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM
DEKNTPIRTY QVCNVMEASQ NNWLRTDWIT REGAQRVYIE IKFTLRDCNS LPGVMGTCKE
TFNLYYYESD NDKERFIRES QFGKIDTIAA DESFTQVDIG DRIMKLNTEI RDVGPLSKKG
FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK
DVPKMYCGAD GEWLVPIGNC LCNAGHEEQN GECQACKIGY YKALSTDASC AKCPPHSYSV
WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS PQNTGGRQDI
SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTRVSI TDLLAHTNYT FEIWAVNGVS
KYNPSPDQSV SVTVTTNQAA PSSIALVQAK EVTRYSVALA WLEPDRPNGV ILEYEVKYYE
KDQNERSYRI VRTAARNTDI KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII
GDGANSTVLL VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT
DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV
IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT
TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG
YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGSESSRPNT
ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHMSQDD LARIGITAIT
HQNKILSSVQ AMRTQMQQMH GRMVPV
