CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006558
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Vascular endothelial growth factor receptor 2 
Protein Synonyms/Alias
 VEGFR-2; Fetal liver kinase 1; FLK-1; Kinase NYK; Protein-tyrosine kinase receptor flk-1; CD309 
Gene Name
 Kdr 
Gene Synonyms/Alias
 Flk-1; Flk1 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
796RANEGELKTGYLSIVubiquitination[1]
824RLPYDASKWEFPRDRubiquitination[1]
856ADAFGIDKTATCKTVubiquitination[1]
861IDKTATCKTVAVKMLubiquitination[1]
947GARFRQGKDYVGELSubiquitination[1]
958GELSVDLKRRLDSITubiquitination[1]
1037RNILLSEKNVVKICDubiquitination[1]
1053GLARDIYKDPDYVRKubiquitination[1]
1287FGGMMPSKSRESVASubiquitination[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
 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as a negative regulator of VEGFA- and VEGFC- mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and by preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. 
Sequence Annotation
 DOMAIN 46 111 Ig-like C2-type 1.
 DOMAIN 143 209 Ig-like C2-type 2.
 DOMAIN 226 325 Ig-like C2-type 3.
 DOMAIN 330 416 Ig-like C2-type 4.
 DOMAIN 423 542 Ig-like C2-type 5.
 DOMAIN 549 656 Ig-like C2-type 6.
 DOMAIN 665 751 Ig-like C2-type 7.
 DOMAIN 832 1160 Protein kinase.
 NP_BIND 838 846 ATP (By similarity).
 ACT_SITE 1026 1026 Proton acceptor (By similarity).
 BINDING 866 866 ATP (By similarity).
 MOD_RES 799 799 Phosphotyrosine (By similarity).
 MOD_RES 949 949 Phosphotyrosine; by autocatalysis (By
 MOD_RES 980 980 Phosphoserine (By similarity).
 MOD_RES 982 982 Phosphoserine (By similarity).
 MOD_RES 994 994 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1052 1052 Phosphotyrosine; by autocatalysis.
 MOD_RES 1057 1057 Phosphotyrosine; by autocatalysis.
 MOD_RES 1173 1173 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1212 1212 Phosphotyrosine; by autocatalysis.
 MOD_RES 1303 1303 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1307 1307 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1317 1317 Phosphotyrosine; by autocatalysis (By
 CARBOHYD 46 46 N-linked (GlcNAc...) (Potential).
 CARBOHYD 98 98 N-linked (GlcNAc...) (Potential).
 CARBOHYD 145 145 N-linked (GlcNAc...) (Potential).
 CARBOHYD 160 160 N-linked (GlcNAc...) (Potential).
 CARBOHYD 247 247 N-linked (GlcNAc...) (Potential).
 CARBOHYD 320 320 N-linked (GlcNAc...) (Potential).
 CARBOHYD 376 376 N-linked (GlcNAc...) (Potential).
 CARBOHYD 397 397 N-linked (GlcNAc...) (Potential).
 CARBOHYD 509 509 N-linked (GlcNAc...) (Potential).
 CARBOHYD 521 521 N-linked (GlcNAc...) (Potential).
 CARBOHYD 578 578 N-linked (GlcNAc...) (Potential).
 CARBOHYD 611 611 N-linked (GlcNAc...) (Potential).
 CARBOHYD 617 617 N-linked (GlcNAc...) (Potential).
 CARBOHYD 629 629 N-linked (GlcNAc...) (Potential).
 CARBOHYD 673 673 N-linked (GlcNAc...) (Potential).
 CARBOHYD 702 702 N-linked (GlcNAc...) (Potential).
 CARBOHYD 719 719 N-linked (GlcNAc...) (Potential).
 DISULFID 53 105 By similarity.
 DISULFID 152 202 By similarity.
 DISULFID 248 309 By similarity.
 DISULFID 447 528 By similarity.
 DISULFID 569 640 By similarity.
 DISULFID 686 735 By similarity.  
Keyword
 Alternative splicing; Angiogenesis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Developmental protein; Differentiation; Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1367 AA 
Protein Sequence
MESKALLAVA LWFCVETRAA SVGLPGDFLH PPKLSTQKDI LTILANTTLQ ITCRGQRDLD 60
WLWPNAQRDS EERVLVTECG GGDSIFCKTL TIPRVVGNDT GAYKCSYRDV DIASTVYVYV 120
RDYRSPFIAS VSDQHGIVYI TENKNKTVVI PCRGSISNLN VSLCARYPEK RFVPDGNRIS 180
WDSEIGFTLP SYMISYAGMV FCEAKINDET YQSIMYIVVV VGYRIYDVIL SPPHEIELSA 240
GEKLVLNCTA RTELNVGLDF TWHSPPSKSH HKKIVNRDVK PFPGTVAKMF LSTLTIESVT 300
KSDQGEYTCV ASSGRMIKRN RTFVRVHTKP FIAFGSGMKS LVEATVGSQV RIPVKYLSYP 360
APDIKWYRNG RPIESNYTMI VGDELTIMEV TERDAGNYTV ILTNPISMEK QSHMVSLVVN 420
VPPQIGEKAL ISPMDSYQYG TMQTLTCTVY ANPPLHHIQW YWQLEEACSY RPGQTSPYAC 480
KEWRHVEDFQ GGNKIEVTKN QYALIEGKNK TVSTLVIQAA NVSALYKCEA INKAGRGERV 540
ISFHVIRGPE ITVQPAAQPT EQESVSLLCT ADRNTFENLT WYKLGSQATS VHMGESLTPV 600
CKNLDALWKL NGTMFSNSTN DILIVAFQNA SLQDQGDYVC SAQDKKTKKR HCLVKQLIIL 660
ERMAPMITGN LENQTTTIGE TIEVTCPASG NPTPHITWFK DNETLVEDSG IVLRDGNRNL 720
TIRRVRKEDG GLYTCQACNV LGCARAETLF IIEGAQEKTN LEVIILVGTA VIAMFFWLLL 780
VILVRTVKRA NEGELKTGYL SIVMDPDELP LDERCERLPY DASKWEFPRD RLKLGKPLGR 840
GAFGQVIEAD AFGIDKTATC KTVAVKMLKE GATHSEHRAL MSELKILIHI GHHLNVVNLL 900
GACTKPGGPL MVIVEFSKFG NLSTYLRGKR NEFVPYKSKG ARFRQGKDYV GELSVDLKRR 960
LDSITSSQSS ASSGFVEEKS LSDVEEEEAS EELYKDFLTL EHLICYSFQV AKGMEFLASR 1020
KCIHRDLAAR NILLSEKNVV KICDFGLARD IYKDPDYVRK GDARLPLKWM APETIFDRVY 1080
TIQSDVWSFG VLLWEIFSLG ASPYPGVKID EEFCRRLKEG TRMRAPDYTT PEMYQTMLDC 1140
WHEDPNQRPS FSELVEHLGN LLQANAQQDG KDYIVLPMSE TLSMEEDSGL SLPTSPVSCM 1200
EEEEVCDPKF HYDNTAGISH YLQNSKRKSR PVSVKTFEDI PLEEPEVKVI PDDSQTDSGM 1260
VLASEELKTL EDRNKLSPSF GGMMPSKSRE SVASEGSNQT SGYQSGYHSD DTDTTVYSSD 1320
EAGLLKMVDA AVHADSGTTL QLTSCLNGSG PVPAPPPTPG NHERGAA 1367 
Gene Ontology
 GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:UniProtKB-SubCell.
 GO:0005769; C:early endosome; IDA:BHF-UCL.
 GO:0009897; C:external side of plasma membrane; IDA:MGI.
 GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
 GO:0005887; C:integral to plasma membrane; ISS:UniProtKB.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005021; F:vascular endothelial growth factor-activated receptor activity; ISS:UniProtKB.
 GO:0060837; P:blood vessel endothelial cell differentiation; TAS:DFLAT.
 GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
 GO:0055074; P:calcium ion homeostasis; IDA:MGI.
 GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
 GO:0045165; P:cell fate commitment; IMP:MGI.
 GO:0048469; P:cell maturation; IMP:MGI.
 GO:0002042; P:cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
 GO:0035162; P:embryonic hemopoiesis; IMP:UniProtKB.
 GO:0003157; P:endocardium development; IMP:UniProtKB.
 GO:0048286; P:lung alveolus development; IMP:MGI.
 GO:0001945; P:lymph vessel development; IGI:MGI.
 GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
 GO:0001541; P:ovarian follicle development; IMP:MGI.
 GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:BHF-UCL.
 GO:0045766; P:positive regulation of angiogenesis; IDA:DFLAT.
 GO:0030513; P:positive regulation of BMP signaling pathway; IDA:DFLAT.
 GO:0010595; P:positive regulation of endothelial cell migration; TAS:DFLAT.
 GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
 GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:UniProtKB.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; ISS:UniProtKB.
 GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
 GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; TAS:DFLAT.
 GO:0043129; P:surfactant homeostasis; IMP:MGI.
 GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
 GO:0001570; P:vasculogenesis; IMP:UniProtKB. 
Interpro
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003599; Ig_sub.
 IPR003598; Ig_sub2.
 IPR013106; Ig_V-set.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR001824; Tyr_kinase_rcpt_3_CS.
 IPR009136; Tyr_kinase_VEGFR2_rcpt.
 IPR009134; Tyr_kinase_VEGFR_rcpt_N. 
Pfam
 PF07679; I-set
 PF07714; Pkinase_Tyr
 PF07686; V-set 
SMART
 SM00409; IG
 SM00408; IGc2
 SM00219; TyrKc 
PROSITE
 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00240; RECEPTOR_TYR_KIN_III 
PRINTS
 PR01832; VEGFRECEPTOR.
 PR01834; VEGFRECEPTR2.