CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008892
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ephrin type-A receptor 4 
Protein Synonyms/Alias
 EPH-like kinase 8; EK8; hEK8; Tyrosine-protein kinase TYRO1; Tyrosine-protein kinase receptor SEK 
Gene Name
 EPHA4 
Gene Synonyms/Alias
 HEK8; SEK; TYRO1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
735RGIGSGMKYLSDMSYubiquitination[1]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 
Functional Description
 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. Beside 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. 
Sequence Annotation
 DOMAIN 30 209 Eph LBD.
 DOMAIN 328 433 Fibronectin type-III 1.
 DOMAIN 441 532 Fibronectin type-III 2.
 DOMAIN 621 882 Protein kinase.
 DOMAIN 911 975 SAM.
 NP_BIND 627 635 ATP (By similarity).
 MOTIF 984 986 PDZ-binding (Potential).
 ACT_SITE 746 746 Proton acceptor (By similarity).
 BINDING 653 653 ATP (By similarity).
 MOD_RES 596 596 Phosphotyrosine; by autocatalysis (By
 MOD_RES 602 602 Phosphotyrosine; by autocatalysis (By
 MOD_RES 779 779 Phosphotyrosine; by autocatalysis
 MOD_RES 928 928 Phosphotyrosine; by autocatalysis
 CARBOHYD 235 235 N-linked (GlcNAc...) (Potential).
 CARBOHYD 340 340 N-linked (GlcNAc...) (Potential).
 CARBOHYD 408 408 N-linked (GlcNAc...) (Potential).
 CARBOHYD 545 545 N-linked (GlcNAc...) (Potential).  
Keyword
 3D-structure; ATP-binding; Cell adhesion; Cell junction; Cell membrane; Cell projection; Complete proteome; Developmental protein; Endosome; Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein; Polymorphism; Postsynaptic cell membrane; Receptor; Reference proteome; Repeat; Signal; Synapse; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 986 AA 
Protein Sequence
MAGIFYFALF SCLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM 60
DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIT REGAQRVYIE IKFTLRDCNS LPGVMGTCKE 120
TFNLYYYESD NDKERFIREN QFVKIDTIAA DESFTQVDIG DRIMKLNTEI RDVGPLSKKG 180
FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK 240
DVPKMYCGAD GEWLVPIGNC LCNAGHEERS GECQACKIGY YKALSTDATC AKCPPHSYSV 300
WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS PQNTGGRQDI 360
SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTKVSI TDLLAHTNYT FEIWAVNGVS 420
KYNPNPDQSV SVTVTTNQAA PSSIALVQAK EVTRYSVALA WLEPDRPNGV ILEYEVKYYE 480
KDQNERSYRI VRTAARNTDI KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII 540
GDGANSTVLL VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 600
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT 660
DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV 720
IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT 780
TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG 840
YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGTESSRPNT 900
ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHVNQED LARIGITAIT 960
HQNKILSSVQ AMRTQMQQMH GRMVPV 986 
Gene Ontology
 GO:0030424; C:axon; ISS:UniProtKB.
 GO:0043679; C:axon terminus; IEA:Compara.
 GO:0044295; C:axonal growth cone; IEA:Compara.
 GO:0030054; C:cell junction; IEA:UniProtKB-KW.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0030425; C:dendrite; ISS:UniProtKB.
 GO:0031901; C:early endosome membrane; ISS:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IEA:Compara.
 GO:0030175; C:filopodium; IEA:Compara.
 GO:0005794; C:Golgi apparatus; IEA:Compara.
 GO:0005887; C:integral to plasma membrane; ISS:UniProtKB.
 GO:0005741; C:mitochondrial outer membrane; IEA:Compara.
 GO:0031594; C:neuromuscular junction; IEA:Compara.
 GO:0043204; C:perikaryon; IEA:Compara.
 GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
 GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0097161; F:DH domain binding; IDA:UniProtKB.
 GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
 GO:0005005; F:transmembrane-ephrin receptor activity; ISS:UniProtKB.
 GO:0007628; P:adult walking behavior; IEA:Compara.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0021957; P:corticospinal tract morphogenesis; ISS:UniProtKB.
 GO:0097156; P:fasciculation of motor neuron axon; ISS:UniProtKB.
 GO:0097155; P:fasciculation of sensory neuron axon; ISS:UniProtKB.
 GO:0008347; P:glial cell migration; IEA:Compara.
 GO:0008045; P:motor neuron axon guidance; ISS:UniProtKB.
 GO:0048681; P:negative regulation of axon regeneration; ISS:UniProtKB.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0050775; P:positive regulation of dendrite morphogenesis; IEA:Compara.
 GO:0043507; P:positive regulation of JUN kinase activity; IEA:Compara.
 GO:2001108; P:positive regulation of Rho guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0048710; P:regulation of astrocyte differentiation; ISS:UniProtKB.
 GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:UniProtKB.
 GO:0032314; P:regulation of Rac GTPase activity; ISS:UniProtKB.
 GO:0032317; P:regulation of Rap GTPase activity; ISS:UniProtKB. 
Interpro
 IPR001090; Ephrin_rcpt_lig-bd_dom.
 IPR003961; Fibronectin_type3.
 IPR008979; Galactose-bd-like.
 IPR013783; Ig-like_fold.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_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. 
Pfam
 PF01404; Ephrin_lbd
 PF00041; fn3
 PF07714; Pkinase_Tyr
 PF07647; SAM_2 
SMART
 SM00615; EPH_lbd
 SM00060; FN3
 SM00454; SAM
 SM00219; TyrKc 
PROSITE
 PS51550; EPH_LBD
 PS50853; FN3
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00790; RECEPTOR_TYR_KIN_V_1
 PS00791; RECEPTOR_TYR_KIN_V_2
 PS50105; SAM_DOMAIN 
PRINTS
 PR00109; TYRKINASE.