CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011040
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; Tyrosine-protein kinase receptor MPK-5; Tyrosine-protein kinase receptor SEK-2 
Gene Name
 Epha2 
Gene Synonyms/Alias
 Eck; Myk2; Sek2 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
579SEDVRFSKSEQLKPLubiquitination[1]
584FSKSEQLKPLKTYVDubiquitination[1]
604DPNQAVLKFTTEIHPubiquitination[1]
618PSCVARQKVIGAGEFubiquitination[1]
883IRAPDSLKTLADFDPubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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 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 27 205 Eph LBD.
 DOMAIN 329 430 Fibronectin type-III 1.
 DOMAIN 436 527 Fibronectin type-III 2.
 DOMAIN 614 876 Protein kinase.
 DOMAIN 905 969 SAM.
 NP_BIND 620 628 ATP (By similarity).
 REGION 1 205 Mediates interaction with CLDN4 (By
 REGION 607 907 Mediates interaction with ARHGEF16 (By
 REGION 887 977 Negatively regulates interaction with
 MOTIF 975 977 PDZ-binding (Potential).
 ACT_SITE 740 740 Proton acceptor (By similarity).
 BINDING 647 647 ATP (By similarity).
 MOD_RES 152 152 Phosphoserine (By similarity).
 MOD_RES 374 374 Phosphoserine (By similarity).
 MOD_RES 571 571 Phosphoserine (By similarity).
 MOD_RES 580 580 Phosphoserine (By similarity).
 MOD_RES 588 588 Phosphothreonine (By similarity).
 MOD_RES 589 589 Phosphotyrosine; by autocatalysis (By
 MOD_RES 594 594 Phosphothreonine (By similarity).
 MOD_RES 595 595 Phosphotyrosine; by autocatalysis.
 MOD_RES 629 629 Phosphotyrosine (By similarity).
 MOD_RES 648 648 Phosphothreonine (By similarity).
 MOD_RES 736 736 Phosphotyrosine; by autocatalysis.
 MOD_RES 772 772 Phosphothreonine (By similarity).
 MOD_RES 773 773 Phosphotyrosine; by autocatalysis.
 MOD_RES 791 791 Phosphoserine (By similarity).
 MOD_RES 792 792 Phosphotyrosine (By similarity).
 MOD_RES 870 870 Phosphoserine (By similarity).
 MOD_RES 881 881 Phosphoserine (By similarity).
 MOD_RES 893 893 Phosphoserine (By similarity).
 MOD_RES 898 898 Phosphoserine (By similarity).
 MOD_RES 899 899 Phosphothreonine (By similarity).
 MOD_RES 900 900 Phosphoserine (By similarity).
 MOD_RES 902 902 Phosphoserine (By similarity).
 MOD_RES 911 911 Phosphoserine (By similarity).
 MOD_RES 922 922 Phosphotyrosine; by autocatalysis
 MOD_RES 931 931 Phosphotyrosine (By similarity).
 MOD_RES 961 961 Phosphotyrosine (By similarity).
 CARBOHYD 408 408 N-linked (GlcNAc...).
 CARBOHYD 436 436 N-linked (GlcNAc...).
 DISULFID 69 187 By similarity.
 DISULFID 104 114 By similarity.  
Keyword
 Angiogenesis; Apoptosis; ATP-binding; Cell adhesion; Cell junction; Cell membrane; Cell projection; Complete proteome; Differentiation; Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 977 AA 
Protein Sequence
MELRAVGFCL ALLWGCALAA AAAQGKEVVL LDFAAMKGEL GWLTHPYGKG WDLMQNIMDD 60
MPIYMYSVCN VVSGDQDNWL RTNWVYREEA ERIFIELKFT VRDCNSFPGG ASSCKETFNL 120
YYAESDVDYG TNFQKRQFTK IDTIAPDEIT VSSDFEARNV KLNVEERMVG PLTRKGFYLA 180
FQDIGACVAL LSVRVYYKKC PEMLQSLARF PETIAVAVSD TQPLATVAGT CVDHAVVPYG 240
GEGPLMHCTV DGEWLVPIGQ CLCQEGYEKV EDACRACSPG FFKSEASESP CLECPEHTLP 300
STEGATSCQC EEGYFRAPED PLSMSCTRPP SAPNYLTAIG MGAKVELRWT APKDTGGRQD 360
IVYSVTCEQC WPESGECGPC EASVRYSEPP HALTRTSVTV SDLEPHMNYT FAVEARNGVS 420
GLVTSRSFRT ASVSINQTEP PKVRLEDRST TSLSVTWSIP VSQQSRVWKY EVTYRKKGDA 480
NSYNVRRTEG FSVTLDDLAP DTTYLVQVQA LTQEGQGAGS KVHEFQTLST EGSANMAVIG 540
GVAVGVVLLL VLAGVGLFIH RRRRNLRARQ SSEDVRFSKS EQLKPLKTYV DPHTYEDPNQ 600
AVLKFTTEIH PSCVARQKVI GAGEFGEVYK GTLKASSGKK EIPVAIKTLK AGYTEKQRVD 660
FLSEASIMGQ FSHHNIIRLE GVVSKYKPMM IITEYMENGA LDKFLREKDG EFSVLQLVGM 720
LRGIASGMKY LANMNYVHRD LAARNILVNS NLVCKVSDFG LSRVLEDDPE ATYTTSGGKI 780
PIRWTAPEAI SYRKFTSASD VWSYGIVMWE VMTYGERPYW ELSNHEVMKA INDGFRLPTP 840
MDCPSAIYQL MMQCWQQERS RRPKFADIVS ILDKLIRAPD SLKTLADFDP RVSIRLPSTS 900
GSEGVPFRTV SEWLESIKMQ QYTEHFMVAG YTAIEKVVQM SNEDIKRIGV RLPGHQKRIA 960
YSLLGLKDQV NTVGIPI 977 
Gene Ontology
 GO:0005925; C:focal adhesion; ISS:UniProtKB.
 GO:0005887; C:integral to plasma membrane; ISS:UniProtKB.
 GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
 GO:0031256; C:leading edge membrane; ISS: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; ISS:UniProtKB.
 GO:0032863; P:activation of Rac GTPase activity; ISS:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0048320; P:axial mesoderm formation; IMP:MGI.
 GO:0046849; P:bone remodeling; IMP:UniProtKB.
 GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:UniProtKB.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
 GO:0048013; P:ephrin receptor signaling pathway; IMP:UniProtKB.
 GO:0030216; P:keratinocyte differentiation; IEA:Compara.
 GO:0070309; P:lens fiber cell morphogenesis; IDA:UniProtKB.
 GO:0033598; P:mammary gland epithelial cell proliferation; IMP:UniProtKB.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; ISS:UniProtKB.
 GO:0021915; P:neural tube development; IMP:MGI.
 GO:0030182; P:neuron differentiation; IDA:MGI.
 GO:0060035; P:notochord cell development; IMP:MGI.
 GO:0014028; P:notochord formation; IMP:MGI.
 GO:0001649; P:osteoblast differentiation; IMP:UniProtKB.
 GO:0030316; P:osteoclast differentiation; IDA:UniProtKB.
 GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; ISS:UniProtKB.
 GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
 GO:0043491; P:protein kinase B signaling cascade; ISS:UniProtKB.
 GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
 GO:0043535; P:regulation of blood vessel endothelial cell migration; IDA:UniProtKB.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
 GO:0070372; P:regulation of ERK1 and ERK2 cascade; IEA:Compara.
 GO:0010591; P:regulation of lamellipodium assembly; ISS:UniProtKB.
 GO:0070848; P:response to growth factor stimulus; ISS:UniProtKB.
 GO:0001501; P:skeletal system development; IMP:MGI.
 GO:0001570; P:vasculogenesis; IMP:MGI. 
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
 PS01186; EGF_2
 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.