VGFR1_RAT
ID VGFR1_RAT Reviewed; 1336 AA.
AC P53767;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Vascular endothelial growth factor receptor 1;
DE Short=VEGFR-1;
DE EC=2.7.10.1;
DE AltName: Full=Fms-like tyrosine kinase 1;
DE Short=FLT-1;
DE AltName: Full=Tyrosine-protein kinase receptor FLT;
DE Flags: Precursor;
GN Name=Flt1; Synonyms=Flt-1, Vegfr1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344; TISSUE=Lung, and Testis;
RX PubMed=8058332;
RA Yamane A., Seetharam L., Yamaguchi S., Gotoh N., Takahashi T., Neufeld G.,
RA Shibuya M.;
RT "A new communication system between hepatocytes and sinusoidal endothelial
RT cells in liver through vascular endothelial growth factor and Flt tyrosine
RT kinase receptor family (Flt-1 and KDR/Flk-1).";
RL Oncogene 9:2683-2690(1994).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for VEGFA, VEGFB and PGF, and plays an essential role in the
CC development of embryonic vasculature, the regulation of angiogenesis,
CC cell survival, cell migration, macrophage function, chemotaxis, and
CC cancer cell invasion. Acts as a positive regulator of postnatal retinal
CC hyaloid vessel regression (By similarity). May play an essential role
CC as a negative regulator of embryonic angiogenesis by inhibiting
CC excessive proliferation of endothelial cells. Can promote endothelial
CC cell proliferation, survival and angiogenesis in adulthood. Its
CC function in promoting cell proliferation seems to be cell-type
CC specific. Promotes PGF-mediated proliferation of endothelial cells, and
CC proliferation of some types of cancer cells, but does not promote
CC proliferation of normal fibroblasts. Has very high affinity for VEGFA
CC and relatively low protein kinase activity; may function as a negative
CC regulator of VEGFA signaling by limiting the amount of free VEGFA and
CC preventing its binding to KDR. Modulates KDR signaling by forming
CC heterodimers with KDR. Ligand binding leads to the activation of
CC several signaling cascades. Activation of PLCG leads to the production
CC of the cellular signaling molecules diacylglycerol and inositol 1,4,5-
CC trisphosphate and the activation of protein kinase C. Mediates
CC phosphorylation of PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase, leading to the activation of
CC phosphatidylinositol kinase and the downstream signaling pathway.
CC Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase
CC signaling pathway, as well as of the AKT1 signaling pathway.
CC Phosphorylates SRC, YES1 and PLCG, and may also phosphorylate CBL.
CC Promotes phosphorylation of AKT1 and PTK2/FAK1 (By similarity).
CC {ECO:0000250|UniProtKB:P17948, ECO:0000250|UniProtKB:P35969}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization
CC and activation by autophosphorylation on tyrosine residues (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of
CC bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA,
CC VEGFB and PGF. Can also form a heterodimer with KDR. Interacts
CC (tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG,
CC PSEN1 and PTPN11. Probably interacts with PTPRB. Interacts with RACK1.
CC Identified in a complex with CBL and CD2AP (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Endosome {ECO:0000250}. Note=Autophosphorylation promotes
CC ubiquitination and endocytosis. {ECO:0000250}.
CC -!- DOMAIN: The second and third Ig-like C2-type (immunoglobulin-like)
CC domains are sufficient for VEGFA binding. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- PTM: Ubiquitinated after VEGFA-mediated autophosphorylation, leading to
CC proteolytic degradation. {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric
CC receptor phosphorylates tyrosine residues on the other subunit.
CC Phosphorylation at Tyr-1169 is important for interaction with PLCG.
CC Phosphorylation at Tyr-1213 is important for interaction with PIK3R1,
CC PTPN11, GRB2, and PLCG. Phosphorylation at Tyr-1331 is important for
CC endocytosis and for interaction with CBL, NCK1 and CRK. Is probably
CC dephosphorylated by PTPRB (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; D28498; BAA05857.1; -; mRNA.
DR PIR; I60598; I60598.
DR AlphaFoldDB; P53767; -.
DR SMR; P53767; -.
DR BioGRID; 248474; 1.
DR IntAct; P53767; 1.
DR MINT; P53767; -.
DR STRING; 10116.ENSRNOP00000001248; -.
DR GlyGen; P53767; 12 sites.
DR iPTMnet; P53767; -.
DR PhosphoSitePlus; P53767; -.
DR jPOST; P53767; -.
DR PaxDb; P53767; -.
DR PRIDE; P53767; -.
DR UCSC; RGD:2621; rat.
DR RGD; 2621; Flt1.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; P53767; -.
DR PhylomeDB; P53767; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-194306; Neurophilin interactions with VEGF and VEGFR.
DR Reactome; R-RNO-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR PRO; PR:P53767; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0019838; F:growth factor binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0036332; F:placental growth factor receptor activity; ISO:RGD.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:RGD.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IMP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:RGD.
DR GO; GO:0048598; P:embryonic morphogenesis; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB.
DR GO; GO:0030522; P:intracellular receptor signaling pathway; IMP:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0002548; P:monocyte chemotaxis; ISO:RGD.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IDA:RGD.
DR GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; ISO:RGD.
DR GO; GO:1904046; P:negative regulation of vascular endothelial growth factor production; IDA:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:RGD.
DR GO; GO:1901534; P:positive regulation of hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:RGD.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; ISO:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:RGD.
DR GO; GO:0048597; P:post-embryonic camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; IDA:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0002040; P:sprouting angiogenesis; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0036323; P:vascular endothelial growth factor receptor-1 signaling pathway; ISO:RGD.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR InterPro; IPR041348; VEGFR-2_TMD.
DR InterPro; IPR009135; VEGFR1_rcpt.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF17988; VEGFR-2_TMD; 1.
DR PRINTS; PR01833; VEGFRECEPTR1.
DR SMART; SM00409; IG; 7.
DR SMART; SM00408; IGc2; 5.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 7.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 6.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 2: Evidence at transcript level;
KW Angiogenesis; ATP-binding; Cell membrane; Chemotaxis;
KW Developmental protein; Differentiation; Disulfide bond; Endosome;
KW Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1336
FT /note="Vascular endothelial growth factor receptor 1"
FT /id="PRO_0000016770"
FT TOPO_DOM 23..758
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 759..780
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..1336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..121
FT /note="Ig-like C2-type 1"
FT DOMAIN 151..214
FT /note="Ig-like C2-type 2"
FT DOMAIN 230..327
FT /note="Ig-like C2-type 3"
FT DOMAIN 335..421
FT /note="Ig-like C2-type 4"
FT DOMAIN 429..549
FT /note="Ig-like C2-type 5"
FT DOMAIN 556..655
FT /note="Ig-like C2-type 6"
FT DOMAIN 661..747
FT /note="Ig-like C2-type 7"
FT DOMAIN 827..1158
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 941..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1304..1326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 941..957
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 958..975
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1022
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 833..841
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 861
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 767..768
FT /note="Cleavage; by PSEN1"
FT /evidence="ECO:0000250"
FT MOD_RES 914
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17948"
FT MOD_RES 1053
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1169
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17948"
FT MOD_RES 1213
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17948"
FT MOD_RES 1242
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17948"
FT MOD_RES 1325
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17948"
FT MOD_RES 1331
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17948"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 474
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 516
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 597
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 625
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 666
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 713
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 53..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 158..207
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 252..311
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 454..535
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 577..636
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 682..731
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1336 AA; 150250 MW; 0CCCD68C1F3D20CE CRC64;
MVSCWDTAVL PCALLGCLLL TGYCSGSKLK GPELSLKGTQ HVMQAGQTLF LKCRGEAAHS
WSLPTTVSQE DKKLSVTRSA CGRNNRQFCS TLTLNMAQAN HTGLYSCRYL PKSTSKEKKM
ESAIYIFVSD AGSPFIEMHS DIPKLVHMTE GRELIIPCRV TSPNITVTLK KFPFDALTPD
GQRIAWDSRR GFIIANATYK EIGLLTCEAT VNGHLYQTSY LTHRQTNTIL DVQISPPSPV
RFLRGQTLVL NCTVTTDLNT RVQMSWNYPG KATKRASIRQ RIDQSNPHSN VFHSVLKINN
VESRDKGLYT CRVKSGSSFR TFNTSVHVYE KGFISVKHRK QQVQETIAGK RSHRLSMKVK
AFPSPEVVWL KDGVPATEKS ARYSVHGYSL IIKDVTAEDA GDYTILLGIK QSKLFRNLTA
TLIVNVKPQI YEKSVSSLPS PPLYPLGSRQ VLTCTVYGIP QPTIKWLWHP CHYNHSKERN
DFCFGSEESF ILDSSSNIGN RIEGITQRMM VIEGTNKTVS TLVVADSRTP GSYSCKAFNK
IGTVERDIRF YVTDVPNGFH VSLEKIPTEG EDLKLSCVVS KFLYRDITWI LLRTVNNRTM
HHSISKQKMA TTQDYSITLN LVIKNVSLED SGTYACRARN IYTGEEILRK TEVLVRDLEA
PLLLQNLSDH EVSISGSTTL DCQARGVPAP QITWFKNNHK IQQEPGIILG PGNSTLFIER
VTEEDEGVYR CRATNQKGVV ESSAYLTVQG TSDKSNLELI TLTCTCVAAT LFWLLLTLFI
RKLKRSSSEV KTDYLSIIMD PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK
VVQASAFGIK KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK
QGGPLMVIVE YCKYGNLSNY LKSKRDFFCL NKDAALHMEP KKEKLEPDLE QDQKPRLDSV
SSSESFTSSG FQEDKSVSDV EGGEDYSEIS KQPLTMEDLI SYSFQVARGM EFLSSRKCIH
RDLAARNILL SENNVVKICD FGLARDIYKN PDYVRRGDTR LPLKWMAPES IFDKVYSTKS
DVWSYGVLLW EIFSLGGSPY PGVQMDEDFC SRLKEGMRMR TPEYATPEIY QIMLDCWHKD
PKERPRFAEL VEKLGDLLQA NVQQDGKDYI PLNAILTRNS GFTYSVPTFS EDFFKDGFTD
PKFHSGSSDD VRYVNAFKFM SLERIKTFEE LSPNATSMFE DYHLDTSSLL TSPLLKRFTW
TETKPKASMK IDLRITSKSK EAGLSDLPGP SFCFSSCGHI RPVRQEDEDD PELGKESCCS
PPPDYNSVVL YSSPPA
