CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005762
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ephrin type-A receptor 2 
Protein Synonyms/Alias
 Epithelial cell kinase; Tyrosine-protein kinase receptor ECK 
Gene Name
 EPHA2 
Gene Synonyms/Alias
 ECK 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
136DYGTNFQKRLFTKIDubiquitination[1, 2]
141FQKRLFTKIDTIAPDubiquitination[1, 2, 3]
162DFEARHVKLNVEERSubiquitination[1, 2]
578PEDVYFSKSEQLKPLubiquitination[1, 2, 4, 5]
583FSKSEQLKPLKTYVDubiquitination[1, 2]
586SEQLKPLKTYVDPHTubiquitination[1, 2]
603DPNQAVLKFTTEIHPubiquitination[3, 5]
617PSCVTRQKVIGAGEFubiquitination[1, 2, 5]
639LKTSSGKKEVPVAIKubiquitination[1]
686EGVISKYKPMMIITEubiquitination[1]
728RGIAAGMKYLANMNYubiquitination[5]
754VNSNLVCKVSDFGLSubiquitination[2, 6]
778TYTTSGGKIPIRWTAubiquitination[1, 2, 3]
882IRAPDSLKTLADFDPubiquitination[1, 2]
935AGYTAIEKVVQMTNDubiquitination[2]
945QMTNDDIKRIGVRLPubiquitination[1]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] 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]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 
Functional Description
 Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand- independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. 
Sequence Annotation
 DOMAIN 28 206 Eph LBD.
 DOMAIN 328 429 Fibronectin type-III 1.
 DOMAIN 435 526 Fibronectin type-III 2.
 DOMAIN 613 875 Protein kinase.
 DOMAIN 904 968 SAM.
 NP_BIND 619 627 ATP (By similarity).
 REGION 1 206 Mediates interaction with CLDN4.
 REGION 606 906 Mediates interaction with ARHGEF16 and
 REGION 886 976 Negatively regulates interaction with
 MOTIF 974 976 PDZ-binding (Potential).
 ACT_SITE 739 739 Proton acceptor (By similarity).
 BINDING 646 646 ATP (By similarity).
 MOD_RES 153 153 Phosphoserine.
 MOD_RES 373 373 Phosphoserine.
 MOD_RES 570 570 Phosphoserine.
 MOD_RES 575 575 Phosphotyrosine.
 MOD_RES 579 579 Phosphoserine.
 MOD_RES 587 587 Phosphothreonine.
 MOD_RES 588 588 Phosphotyrosine; by autocatalysis (By
 MOD_RES 593 593 Phosphothreonine.
 MOD_RES 594 594 Phosphotyrosine; by autocatalysis.
 MOD_RES 628 628 Phosphotyrosine.
 MOD_RES 647 647 Phosphothreonine.
 MOD_RES 735 735 Phosphotyrosine; by autocatalysis (By
 MOD_RES 771 771 Phosphothreonine.
 MOD_RES 772 772 Phosphotyrosine; by autocatalysis.
 MOD_RES 790 790 Phosphoserine.
 MOD_RES 791 791 Phosphotyrosine.
 MOD_RES 869 869 Phosphoserine.
 MOD_RES 880 880 Phosphoserine.
 MOD_RES 892 892 Phosphoserine.
 MOD_RES 897 897 Phosphoserine; by PKB.
 MOD_RES 898 898 Phosphothreonine.
 MOD_RES 899 899 Phosphoserine.
 MOD_RES 901 901 Phosphoserine.
 MOD_RES 910 910 Phosphoserine.
 MOD_RES 921 921 Phosphotyrosine; by autocatalysis
 MOD_RES 930 930 Phosphotyrosine.
 MOD_RES 960 960 Phosphotyrosine.
 CARBOHYD 407 407 N-linked (GlcNAc...) (Potential).
 CARBOHYD 435 435 N-linked (GlcNAc...).
 DISULFID 70 188
 DISULFID 105 115  
Keyword
 3D-structure; Angiogenesis; Apoptosis; ATP-binding; Cataract; Cell adhesion; Cell junction; Cell membrane; Cell projection; Complete proteome; Differentiation; Disease mutation; Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 976 AA 
Protein Sequence
MELQAARACF ALLWGCALAA AAAAQGKEVV LLDFAAAGGE LGWLTHPYGK GWDLMQNIMN 60
DMPIYMYSVC NVMSGDQDNW LRTNWVYRGE AERIFIELKF TVRDCNSFPG GASSCKETFN 120
LYYAESDLDY GTNFQKRLFT KIDTIAPDEI TVSSDFEARH VKLNVEERSV GPLTRKGFYL 180
AFQDIGACVA LLSVRVYYKK CPELLQGLAH FPETIAGSDA PSLATVAGTC VDHAVVPPGG 240
EEPRMHCAVD GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEASESPC LECPEHTLPS 300
PEGATSCECE EGFFRAPQDP ASMPCTRPPS APHYLTAVGM GAKVELRWTP PQDSGGREDI 360
VYSVTCEQCW PESGECGPCE ASVRYSEPPH GLTRTSVTVS DLEPHMNYTF TVEARNGVSG 420
LVTSRSFRTA SVSINQTEPP KVRLEGRSTT SLSVSWSIPP PQQSRVWKYE VTYRKKGDSN 480
SYNVRRTEGF SVTLDDLAPD TTYLVQVQAL TQEGQGAGSK VHEFQTLSPE GSGNLAVIGG 540
VAVGVVLLLV LAGVGFFIHR RRKNQRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA 600
VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG MLKTSSGKKE VPVAIKTLKA GYTEKQRVDF 660
LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEYMENGAL DKFLREKDGE FSVLQLVGML 720
RGIAAGMKYL ANMNYVHRDL AARNILVNSN LVCKVSDFGL SRVLEDDPEA TYTTSGGKIP 780
IRWTAPEAIS YRKFTSASDV WSFGIVMWEV MTYGERPYWE LSNHEVMKAI NDGFRLPTPM 840
DCPSAIYQLM MQCWQQERAR RPKFADIVSI LDKLIRAPDS LKTLADFDPR VSIRLPSTSG 900
SEGVPFRTVS EWLESIKMQQ YTEHFMAAGY TAIEKVVQMT NDDIKRIGVR LPGHQKRIAY 960
SLLGLKDQVN TVGIPI 976 
Gene Ontology
 GO:0005925; C:focal adhesion; IDA:UniProtKB.
 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
 GO:0031256; C:leading edge membrane; IDA:UniProtKB.
 GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005003; F:ephrin receptor activity; IEA:InterPro.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0032863; P:activation of Rac GTPase activity; IMP:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0048320; P:axial mesoderm formation; IEA:Compara.
 GO:0046849; P:bone remodeling; ISS:UniProtKB.
 GO:0060444; P:branching involved in mammary gland duct morphogenesis; ISS:UniProtKB.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
 GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
 GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB.
 GO:0070309; P:lens fiber cell morphogenesis; ISS:UniProtKB.
 GO:0033598; P:mammary gland epithelial cell proliferation; ISS:UniProtKB.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; IDA:UniProtKB.
 GO:0021915; P:neural tube development; IEA:Compara.
 GO:0030182; P:neuron differentiation; IEA:Compara.
 GO:0060035; P:notochord cell development; IEA:Compara.
 GO:0014028; P:notochord formation; IEA:Compara.
 GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
 GO:0030316; P:osteoclast differentiation; ISS:UniProtKB.
 GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IMP:UniProtKB.
 GO:0036342; P:post-anal tail morphogenesis; IEA:Compara.
 GO:0043491; P:protein kinase B signaling cascade; IDA:UniProtKB.
 GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
 GO:0043535; P:regulation of blood vessel endothelial cell migration; ISS:UniProtKB.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
 GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
 GO:0010591; P:regulation of lamellipodium assembly; IMP:UniProtKB.
 GO:0070848; P:response to growth factor stimulus; IMP:UniProtKB.
 GO:0001501; P:skeletal system development; IEA:Compara.
 GO:0001570; P:vasculogenesis; IEA:Compara. 
Interpro
 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_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001660; SAM.
 IPR013761; SAM/pointed.
 IPR021129; SAM_type1.
 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
 PF00536; SAM_1 
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.