CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004631
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Vascular endothelial growth factor receptor 1 
Protein Synonyms/Alias
 VEGFR-1; Fms-like tyrosine kinase 1; FLT-1; Tyrosine-protein kinase FRT; Tyrosine-protein kinase receptor FLT; FLT; Vascular permeability factor receptor 
Gene Name
 FLT1 
Gene Synonyms/Alias
 FLT; FRT; VEGFR1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
831RERLKLGKSLGRGAFmethylation[1]
Reference
 [1] The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3.
 Kunizaki M, Hamamoto R, Silva FP, Yamaguchi K, Nagayasu T, Shibuya M, Nakamura Y, Furukawa Y.
 Cancer Res. 2007 Nov 15;67(22):10759-65. [PMID: 18006819] 
Functional Description
 Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. 
Sequence Annotation
 DOMAIN 32 123 Ig-like C2-type 1.
 DOMAIN 151 214 Ig-like C2-type 2.
 DOMAIN 230 327 Ig-like C2-type 3.
 DOMAIN 335 421 Ig-like C2-type 4.
 DOMAIN 428 553 Ig-like C2-type 5.
 DOMAIN 556 654 Ig-like C2-type 6.
 DOMAIN 661 747 Ig-like C2-type 7.
 DOMAIN 827 1158 Protein kinase.
 NP_BIND 833 841 ATP (By similarity).
 ACT_SITE 1022 1022 Proton acceptor (By similarity).
 BINDING 861 861 ATP (By similarity).
 MOD_RES 914 914 Phosphotyrosine; by autocatalysis
 MOD_RES 1053 1053 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1169 1169 Phosphotyrosine; by autocatalysis.
 MOD_RES 1213 1213 Phosphotyrosine; by autocatalysis.
 MOD_RES 1242 1242 Phosphotyrosine; by autocatalysis.
 MOD_RES 1309 1309 Phosphotyrosine; by autocatalysis.
 MOD_RES 1327 1327 Phosphotyrosine; by autocatalysis.
 MOD_RES 1333 1333 Phosphotyrosine; by autocatalysis.
 CARBOHYD 100 100 N-linked (GlcNAc...) (Potential).
 CARBOHYD 164 164 N-linked (GlcNAc...) (Potential).
 CARBOHYD 196 196 N-linked (GlcNAc...) (Potential).
 CARBOHYD 251 251 N-linked (GlcNAc...) (Potential).
 CARBOHYD 323 323 N-linked (GlcNAc...) (Potential).
 CARBOHYD 402 402 N-linked (GlcNAc...) (Potential).
 CARBOHYD 417 417 N-linked (GlcNAc...) (Potential).
 CARBOHYD 474 474 N-linked (GlcNAc...) (Potential).
 CARBOHYD 547 547 N-linked (GlcNAc...) (Potential).
 CARBOHYD 597 597 N-linked (GlcNAc...) (Potential).
 CARBOHYD 620 620 N-linked (GlcNAc...) (Potential).
 CARBOHYD 625 625 N-linked (GlcNAc...) (Potential).
 CARBOHYD 666 666 N-linked (GlcNAc...) (Potential).
 DISULFID 53 107 By similarity.
 DISULFID 158 207
 DISULFID 252 311 By similarity.
 DISULFID 454 535 By similarity.
 DISULFID 577 636 By similarity.
 DISULFID 682 731 By similarity.  
Keyword
 3D-structure; Alternative splicing; Angiogenesis; ATP-binding; Cell membrane; Chemotaxis; Complete proteome; Cytoplasm; Developmental protein; Differentiation; Direct protein sequencing; Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1338 AA 
Protein Sequence
MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK 60
WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET 120
ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD 180
GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV 240
KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 300
MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK 360
AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA 420
TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC 480
DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK 540
VGTVGRNISF YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM 600
HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK KEITIRDQEA 660
PYLLRNLSDH TVAISSSTTL DCHANGVPEP QITWFKNNHK IQQEPGIILG PGSSTLFIER 720
VTEEDEGVYH CKATNQKGSV ESSAYLTVQG TSDKSNLELI TLTCTCVAAT LFWLLLTLFI 780
RKMKRSSSEI KTDYLSIIMD PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK 840
VVQASAFGIK KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK 900
QGGPLMVIVE YCKYGNLSNY LKSKRDLFFL NKDAALHMEP KKEKMEPGLE QGKKPRLDSV 960
TSSESFASSG FQEDKSLSDV EEEEDSDGFY KEPITMEDLI SYSFQVARGM EFLSSRKCIH 1020
RDLAARNILL SENNVVKICD FGLARDIYKN PDYVRKGDTR LPLKWMAPES IFDKIYSTKS 1080
DVWSYGVLLW EIFSLGGSPY PGVQMDEDFC SRLREGMRMR APEYSTPEIY QIMLDCWHRD 1140
PKERPRFAEL VEKLGDLLQA NVQQDGKDYI PINAILTGNS GFTYSTPAFS EDFFKESISA 1200
PKFNSGSSDD VRYVNAFKFM SLERIKTFEE LLPNATSMFD DYQGDSSTLL ASPMLKRFTW 1260
TDSKPKASLK IDLRVTSKSK ESGLSDVSRP SFCHSSCGHV SEGKRRFTYD HAELERKIAC 1320
CSPPPDYNSV VLYSTPPI 1338 
Gene Ontology
 GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
 GO:0005615; C:extracellular space; TAS:ProtInc.
 GO:0005794; C:Golgi apparatus; IDA:HPA.
 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0036332; F:placental growth factor-activated receptor activity; IDA:UniProtKB.
 GO:0036326; F:VEGF-A-activated receptor activity; IDA:UniProtKB.
 GO:0036327; F:VEGF-B-activated receptor activity; IDA:UniProtKB.
 GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0048598; P:embryonic morphogenesis; ISS:UniProtKB.
 GO:0002548; P:monocyte chemotaxis; IDA:UniProtKB.
 GO:0001569; P:patterning of blood vessels; IEA:Compara.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
 GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
 GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
 GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IMP:UniProtKB.
 GO:0010863; P:positive regulation of phospholipase C activity; IMP:UniProtKB.
 GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IDA:BHF-UCL.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0002040; P:sprouting angiogenesis; IEA:Compara. 
Interpro
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003599; Ig_sub.
 IPR003598; Ig_sub2.
 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.
 IPR009135; Tyr_kinase_VEGFR1_rcpt_N.
 IPR009134; Tyr_kinase_VEGFR_rcpt_N. 
Pfam
 PF07679; I-set
 PF07714; Pkinase_Tyr 
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.
 PR01833; VEGFRECEPTR1.