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   24-JAN-2024, entry version 134.
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.
DR   AlphaFoldDB; Q8QHL3; -.
DR   SMR; Q8QHL3; -.
DR   STRING; 9031.ENSGALP00000027556; -.
DR   GlyCosmos; Q8QHL3; 17 sites, No reported glycans.
DR   PaxDb; 9031-ENSGALP00000027556; -.
DR   GeneID; 374100; -.
DR   KEGG; gga:374100; -.
DR   CTD; 2321; -.
DR   VEuPathDB; HostDB:geneid_374100; -.
DR   eggNOG; KOG0200; Eukaryota.
DR   InParanoid; Q8QHL3; -.
DR   PhylomeDB; Q8QHL3; -.
DR   PRO; PR:Q8QHL3; -.
DR   Proteomes; UP000000539; Unassembled WGS sequence.
DR   GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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   CDD; cd00096; Ig; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 7.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   PANTHER; PTHR24416:SF390; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 1; 1.
DR   Pfam; PF07679; I-set; 2.
DR   Pfam; PF00047; ig; 2.
DR   Pfam; PF13927; Ig_3; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF21339; VEGFR-1-like_Ig-like; 1.
DR   Pfam; PF17988; VEGFR-2_TMD; 1.
DR   PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR   PRINTS; PR01832; VEGFRECEPTOR.
DR   PRINTS; PR01833; VEGFRECEPTR1.
DR   SMART; SM00409; IG; 7.
DR   SMART; SM00408; IGc2; 5.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 7.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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
//