VGFR1_CHICK
ID VGFR1_CHICK Reviewed; 1327 AA.
AC Q8QHL3; Q8QHL2;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Vascular endothelial growth factor receptor 1;
DE Short=VEGFR-1;
DE EC=2.7.10.1;
DE Flags: Precursor;
GN Name=FLT1; Synonyms=VEGFR1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11855824; DOI=10.1006/bbrc.2002.6478;
RA Yamaguchi S., Iwata K., Shibuya M.;
RT "Soluble Flt-1 (soluble VEGFR-1), a potent natural antiangiogenic molecule
RT in mammals, is phylogenetically conserved in avians.";
RL Biochem. Biophys. Res. Commun. 291:554-559(2002).
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 regulation
CC of angiogenesis, cell survival, cell migration, macrophage function,
CC and chemotaxis. Acts as a positive regulator of postnatal retinal
CC hyaloid vessel regression (By similarity). Has very high affinity for
CC VEGFA and relatively low protein kinase activity; may function as a
CC negative regulator of VEGFA signaling by limiting the amount of free
CC VEGFA and preventing its binding to KDR. Ligand binding leads to the
CC activation of several signaling cascades. Activation of PLCG1 leads to
CC the production of the cellular signaling molecules diacylglycerol and
CC inositol 1,4,5-trisphosphate and the activation of protein kinase C.
CC Mediates phosphorylation of PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase, leading to 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 PLCG1. Promotes phosphorylation of AKT1 and CBL (By
CC similarity). {ECO:0000250|UniProtKB:P17948,
CC 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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein. Endosome {ECO:0000250}. Note=Autophosphorylation
CC promotes internalization and degradation. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Flt1;
CC IsoId=Q8QHL3-1; Sequence=Displayed;
CC Name=2; Synonyms=sFlt1;
CC IsoId=Q8QHL3-2; Sequence=VSP_020427, VSP_027160;
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC {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; AB065372; BAB84690.1; -; mRNA.
DR EMBL; AB065373; BAB84691.1; -; mRNA.
DR RefSeq; NP_989583.1; NM_204252.1. [Q8QHL3-1]
DR AlphaFoldDB; Q8QHL3; -.
DR SMR; Q8QHL3; -.
DR STRING; 9031.ENSGALP00000027556; -.
DR PaxDb; Q8QHL3; -.
DR GeneID; 374100; -.
DR KEGG; gga:374100; -.
DR CTD; 2321; -.
DR VEuPathDB; HostDB:geneid_374100; -.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q8QHL3; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; Q8QHL3; -.
DR PRO; PR:Q8QHL3; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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; IEA:InterPro.
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; IPR013151; Immunoglobulin.
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; PF00047; ig; 1.
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 Alternative splicing; 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; Secreted; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1327
FT /note="Vascular endothelial growth factor receptor 1"
FT /id="PRO_0000249462"
FT TOPO_DOM 25..749
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 750..770
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 771..1327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..121
FT /note="Ig-like C2-type 1"
FT DOMAIN 120..222
FT /note="Ig-like C2-type 2"
FT DOMAIN 227..323
FT /note="Ig-like C2-type 3"
FT DOMAIN 331..417
FT /note="Ig-like C2-type 4"
FT DOMAIN 424..545
FT /note="Ig-like C2-type 5"
FT DOMAIN 552..644
FT /note="Ig-like C2-type 6"
FT DOMAIN 651..737
FT /note="Ig-like C2-type 7"
FT DOMAIN 819..1151
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 950..971
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 950..966
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1015
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 825..833
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 853
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1046
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1162
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1202
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1231
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1316
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1322
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 398
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 512
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 543
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 593
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 615
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 663
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 154..203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 248..307
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 450..531
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 573..626
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 672..721
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 647..677
FT /note="AQEAPALLRQLMDQTVNTSNSAMLECQVHGI -> GEHCNKKAVYSRILKYK
FT NTRNDCTTQSNVKH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11855824"
FT /id="VSP_020427"
FT VAR_SEQ 678..1327
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11855824"
FT /id="VSP_027160"
SQ SEQUENCE 1327 AA; 149426 MW; 96352C59348DC22D CRC64;
MPRQLLSGTV LLGAAFLLAG STSGSKLKVP VLSVNGRQHV VQAGQTLNLT CRGEMLHSWS
LPEALSKDSK RLNVTKYACG RNGTQFCSTL TLSRTQANDT GRYSCRYPTS PVKKKRESIV
YVFINDTSNP FVEMHSDIPK IIHMTVGKEM IIPCRVTAPN IAVTLKKIPR ETLIPDGKTI
IWDNMRGFRI PEATYRFIGL LSCETTIGGH KYSTKYLTHR ETNTIFDIKL STPRLVKLLK
GDSLAINCTV KAAWNTRVQM TWTYPGEAMK RGSVTQRIDQ KNREANVFYS ILVIDKVRDI
DKGQYACHVK SGPSNKLVNT TVIVYDKRFI NLKRRRKTML EAVAGRKSYR LPMKVKAFPS
PEVTWLKDGL PAAEKCARYM VKNYSLIIKD VAEEDAGNYT IILSLRQWNL SKNLTVTLKV
NVKPQIYENA VSSFPDPNLY LLSSKQVLTC TVYGIPPPKI TWMWYPCRQN HSKTRRGFCS
RTDGSFNLKT GSNIGNRIQS IIERTAIIEG KNKTASTLVV AEAKSSGIYS CVASNKVGKA
ERNVSFLVTD VPSGFHISLE KVPIEGENLV LSCSANKFMY KDISWILPRT VTNQTKARKA
LNKEYSITLT LTIRNVSLAH SGTYTCRARN IFTGKEVLQK KDVSIRAQEA PALLRQLMDQ
TVNTSNSAML ECQVHGIPEP QITWFKNHEE IQQESGIILG PGSRMLFIER VKEEDEGLYQ
CIATNLKGSV ESTAYVTVQG TVERSNLELI TLTCTCVAAT LFWLLLTLFI RKLKRPYFSE
TKTNHYLSII MDPDEVPLDE QCECLPYDAS KWEIARERLK LGKSLGHGAF GKVVQASAFG
IKKSPTCRIV AVKMLKEGAT ASEYKALMTE LKILIHIGHH LNIVNLLGAC TKNGGPLMVI
VEYCKYGNLS NYLKSKRNFF SPTKDPSLQG ELMKDKKGIE PVEGKKQRLA SVTSSESFAS
SGFQEDKSLS DAEEDEEDAA ELYKLPLTME DLISYSFQVA RGMEFLSSRK CIHRDLAARN
ILLSENNVVK ICDFGLARDI YKNPDYVRKG DARLPLKWMA PESIFDKIYN TKSDVWSYGV
LLWEIFSLGA SPYPGVQIDE DFCSKLKEGT RMRAPEQATE EIYQIMLDCW RSNPNERPWF
SELVKRLGDL LQASVQQEGK DYIPLDTIFT AESGFPPASD PLCNEKFPVP SPNCRSTERA
RYINTFKIKP PQRIKTFEEL PIKEKLVFND YQADSGMVLA SEELKRFTWT GSKQKWTLFG
MKGVSRSKES GLSGITKPRS FCSFSCDQLS ESKRRYTYGN TVLEKMKACH SPPPDYSSVV
HYSQPSI
