ID   VGFR1_MOUSE             Reviewed;        1333 AA.
AC   P35969; O55094; Q61517;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   24-JAN-2024, entry version 212.
DE   RecName: Full=Vascular endothelial growth factor receptor 1;
DE            Short=VEGFR-1;
DE            EC=2.7.10.1;
DE   AltName: Full=Embryonic receptor kinase 2;
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=Emrk2, Flt, Vegfr1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Neonatal brain, and Placenta;
RX   PubMed=8393164;
RA   Finnerty H., Kelleher K., Morris G.E., Bean K., Merberg D.M., Kriz R.,
RA   Morris J.C., Sookdeo H., Turner K.J., Wood C.R.;
RT   "Molecular cloning of murine FLT and FLT4.";
RL   Oncogene 8:2293-2298(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=8134130;
RA   Choi K., Wall C., Hanratty R., Keller G.;
RT   "Isolation of a gene encoding a novel receptor tyrosine kinase from
RT   differentiated embryonic stem cells.";
RL   Oncogene 9:1261-1266(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Lung;
RX   PubMed=9524283; DOI=10.1016/s0378-1119(98)00006-7;
RA   Kondo K., Hiratsuka S., Subbalakshmi E., Matsushime H., Shibuya M.;
RT   "Genomic organization of the flt-1 gene encoding for vascular endothelial
RT   growth factor (VEGF) receptor-1 suggests an intimate evolutionary
RT   relationship between the 7-Ig and the 5-Ig tyrosine kinase receptors.";
RL   Gene 208:297-305(1998).
RN   [4]
RP   PROTEIN SEQUENCE OF 110-119 AND 185-191, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [5]
RP   DISRUPTION PHENOTYPE, AND FUNCTION IN BLOOD VESSEL DEVELOPMENT DURING
RP   EMBRYOGENESIS.
RX   PubMed=7596436; DOI=10.1038/376066a0;
RA   Fong G.H., Rossant J., Gertsenstein M., Breitman M.L.;
RT   "Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of
RT   vascular endothelium.";
RL   Nature 376:66-70(1995).
RN   [6]
RP   DISRUPTION PHENOTYPE, AND FUNCTION IN MACROPHAGE MIGRATION.
RX   PubMed=9689083; DOI=10.1073/pnas.95.16.9349;
RA   Hiratsuka S., Minowa O., Kuno J., Noda T., Shibuya M.;
RT   "Flt-1 lacking the tyrosine kinase domain is sufficient for normal
RT   development and angiogenesis in mice.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:9349-9354(1998).
RN   [7]
RP   FUNCTION IN ANGIOGENESIS.
RX   PubMed=11221852;
RA   Hiratsuka S., Maru Y., Okada A., Seiki M., Noda T., Shibuya M.;
RT   "Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor
RT   receptor-1) in pathological angiogenesis.";
RL   Cancer Res. 61:1207-1213(2001).
RN   [8]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=14982871; DOI=10.1182/blood-2003-07-2315;
RA   Kearney J.B., Kappas N.C., Ellerstrom C., DiPaola F.W., Bautch V.L.;
RT   "The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular
RT   sprout formation and branching morphogenesis.";
RL   Blood 103:4527-4535(2004).
RN   [9]
RP   FUNCTION IN ANGIOGENESIS.
RX   PubMed=18583712; DOI=10.1161/circresaha.108.174128;
RA   Nishi J., Minamino T., Miyauchi H., Nojima A., Tateno K., Okada S.,
RA   Orimo M., Moriya J., Fong G.H., Sunagawa K., Shibuya M., Komuro I.;
RT   "Vascular endothelial growth factor receptor-1 regulates postnatal
RT   angiogenesis through inhibition of the excessive activation of Akt.";
RL   Circ. Res. 103:261-268(2008).
RN   [10]
RP   FUNCTION.
RX   PubMed=20924106; DOI=10.1158/0008-5472.can-10-0202;
RA   Muramatsu M., Yamamoto S., Osawa T., Shibuya M.;
RT   "Vascular endothelial growth factor receptor-1 signaling promotes
RT   mobilization of macrophage lineage cells from bone marrow and stimulates
RT   solid tumor growth.";
RL   Cancer Res. 70:8211-8221(2010).
RN   [11]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=30936473; DOI=10.1038/s41556-019-0301-x;
RA   Nguyen M.T., Vemaraju S., Nayak G., Odaka Y., Buhr E.D., Alonzo N.,
RA   Tran U., Batie M., Upton B.A., Darvas M., Kozmik Z., Rao S., Hegde R.S.,
RA   Iuvone P.M., Van Gelder R.N., Lang R.A.;
RT   "An opsin 5-dopamine pathway mediates light-dependent vascular development
RT   in the eye.";
RL   Nat. Cell Biol. 21:420-429(2019).
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 (PubMed:30936473). 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, ECO:0000250|UniProtKB:P17948,
CC       ECO:0000269|PubMed:11221852, ECO:0000269|PubMed:14982871,
CC       ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:20924106,
CC       ECO:0000269|PubMed:30936473, ECO:0000269|PubMed:7596436,
CC       ECO:0000269|PubMed:9689083}.
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-1328 is important for
CC       endocytosis and for interaction with CBL, NCK1 and CRK. Is probably
CC       dephosphorylated by PTPRB (By similarity). {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality at about 9 dpc, due to
CC       defects in the formation and organization of the vascular network
CC       (PubMed:7596436, PubMed:9689083). Mice display abnormal blood island
CC       structures in the yolk sac, leading to defects in the organization of
CC       the vascular endothelium, excess growth and disorganization of
CC       embryonic and extraembryonic vasculature, including the endocardium and
CC       the microvasculature (PubMed:7596436). Reduced vascular sprout
CC       formation and migration (PubMed:14982871). Loss of retinal hyaloid
CC       vessel regression from postnatal day 3 (P3) to P8 (PubMed:30936473).
CC       Mice expressing a mutant protein that lacks the kinase domain survive
CC       and have no apparent phenotype (PubMed:9689083).
CC       {ECO:0000269|PubMed:14982871, ECO:0000269|PubMed:30936473,
CC       ECO:0000269|PubMed:7596436, ECO:0000269|PubMed:9689083}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00159}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; L07297; AAA40078.1; -; mRNA.
DR   EMBL; X78568; CAA55311.1; -; mRNA.
DR   EMBL; D88689; BAA24498.1; -; mRNA.
DR   CCDS; CCDS19879.1; -.
DR   PIR; I78875; I78875.
DR   PIR; S49010; S49010.
DR   RefSeq; NP_034358.2; NM_010228.3.
DR   AlphaFoldDB; P35969; -.
DR   SMR; P35969; -.
DR   BioGRID; 199706; 17.
DR   CORUM; P35969; -.
DR   DIP; DIP-39359N; -.
DR   IntAct; P35969; 8.
DR   MINT; P35969; -.
DR   STRING; 10090.ENSMUSP00000031653; -.
DR   BindingDB; P35969; -.
DR   ChEMBL; CHEMBL3516; -.
DR   GlyCosmos; P35969; 12 sites, No reported glycans.
DR   GlyGen; P35969; 13 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P35969; -.
DR   PhosphoSitePlus; P35969; -.
DR   MaxQB; P35969; -.
DR   PaxDb; 10090-ENSMUSP00000031653; -.
DR   PeptideAtlas; P35969; -.
DR   ProteomicsDB; 297594; -.
DR   Pumba; P35969; -.
DR   ABCD; P35969; 2 sequenced antibodies.
DR   DNASU; 14254; -.
DR   GeneID; 14254; -.
DR   KEGG; mmu:14254; -.
DR   UCSC; uc009aoh.1; mouse.
DR   AGR; MGI:95558; -.
DR   CTD; 2321; -.
DR   MGI; MGI:95558; Flt1.
DR   eggNOG; KOG0200; Eukaryota.
DR   InParanoid; P35969; -.
DR   OrthoDB; 1614410at2759; -.
DR   PhylomeDB; P35969; -.
DR   TreeFam; TF325768; -.
DR   BRENDA; 2.7.10.1; 3474.
DR   Reactome; R-MMU-194306; Neurophilin interactions with VEGF and VEGFR.
DR   Reactome; R-MMU-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR   BioGRID-ORCS; 14254; 3 hits in 80 CRISPR screens.
DR   ChiTaRS; Flt1; mouse.
DR   PRO; PR:P35969; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; P35969; Protein.
DR   GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR   GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0043235; C:receptor complex; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; ISO:MGI.
DR   GO; GO:0019838; F:growth factor binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR   GO; GO:0036332; F:placental growth factor receptor activity; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISO:MGI.
DR   GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IDA:MGI.
DR   GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR   GO; GO:0048514; P:blood vessel morphogenesis; IMP:UniProtKB.
DR   GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:MGI.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:MGI.
DR   GO; GO:0048598; P:embryonic morphogenesis; IMP:UniProtKB.
DR   GO; GO:1990384; P:hyaloid vascular plexus regression; IMP:UniProtKB.
DR   GO; GO:0030522; P:intracellular receptor signaling pathway; ISO:MGI.
DR   GO; GO:0002548; P:monocyte chemotaxis; ISO:MGI.
DR   GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:MGI.
DR   GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; ISO:MGI.
DR   GO; GO:1904046; P:negative regulation of vascular endothelial growth factor production; ISO:MGI.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR   GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR   GO; GO:1901534; P:positive regulation of hematopoietic progenitor cell differentiation; IMP:MGI.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR   GO; GO:0048597; P:post-embryonic camera-type eye morphogenesis; IGI:MGI.
DR   GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR   GO; GO:0006940; P:regulation of smooth muscle contraction; ISO:MGI.
DR   GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR   GO; GO:0002040; P:sprouting angiogenesis; IMP:MGI.
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; IMP:MGI.
DR   GO; GO:0036323; P:vascular endothelial growth factor receptor-1 signaling pathway; ISO:MGI.
DR   CDD; cd00096; Ig; 2.
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; 1.
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; 6.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 7.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50835; IG_LIKE; 5.
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   1: Evidence at protein level;
KW   Angiogenesis; ATP-binding; Cell membrane; Chemotaxis;
KW   Developmental protein; Differentiation; Direct protein sequencing;
KW   Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase;
KW   Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW   Repeat; Signal; Transferase; Transmembrane; Transmembrane helix;
KW   Tyrosine-protein kinase; Ubl conjugation.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..1333
FT                   /note="Vascular endothelial growth factor receptor 1"
FT                   /id="PRO_0000016769"
FT   TOPO_DOM        23..759
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        760..781
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        782..1333
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          32..124
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          152..215
FT                   /note="Ig-like C2-type 2"
FT   DOMAIN          231..328
FT                   /note="Ig-like C2-type 3"
FT   DOMAIN          334..429
FT                   /note="Ig-like C2-type 4"
FT   DOMAIN          430..550
FT                   /note="Ig-like C2-type 5"
FT   DOMAIN          557..656
FT                   /note="Ig-like C2-type 6"
FT   DOMAIN          662..748
FT                   /note="Ig-like C2-type 7"
FT   DOMAIN          828..1158
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          947..983
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        956..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         834..842
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         862
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   SITE            768..769
FT                   /note="Cleavage; by PSEN1"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         915
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         1322
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P17948"
FT   MOD_RES         1328
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P17948"
FT   CARBOHYD        101
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        252
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        324
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        418
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        475
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        517
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        598
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        626
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        667
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        714
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        53..108
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        159..208
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        253..312
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        455..536
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        578..637
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        683..732
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   CONFLICT        158
FT                   /note="Missing (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        211
FT                   /note="Missing (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        245
FT                   /note="H -> L (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        603
FT                   /note="H -> N (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        609..615
FT                   /note="KMATTQD -> NGHHSS (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        696
FT                   /note="F -> L (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        734
FT                   /note="A -> S (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        765
FT                   /note="C -> Y (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        820
FT                   /note="K -> N (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1009
FT                   /note="G -> R (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1181
FT                   /note="S -> G (in Ref. 3; BAA24498)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1181
FT                   /note="S -> N (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1193..1194
FT                   /note="LF -> RG (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1278..1279
FT                   /note="KS -> PR (in Ref. 2; CAA55311)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1333 AA;  149876 MW;  C06533B7ECBC404C CRC64;
     MVSCWDTAVL PYALLGCLLL TGYGSGSKLK VPELSLKGTQ HVMQAGQTLF LKCRGEAAHS
     WSLPTTVSQE DKRLSITPPS ACGRDNRQFC STLTLDTAQA NHTGLYTCRY LPTSTSKKKK
     AESSIYIFVS DAGSPFIEMH TDIPKLVHMT EGRQLIIPCR VTSPNVTVTL KKFPFDTLTP
     DGQRITWDSR RGFIIANATY KEIGLLNCEA TVNGHLYQTN YLTHRQTNTI LDVQIRPPSP
     VRLLHGQTLV LNCTATTELN TRVQMSWNYP GKATKRASIR QRIDRSHSHN NVFHSVLKIN
     NVESRDKGLY TCRVKSGSSF QSFNTSVHVY EKGFISVKHR KQPVQETTAG RRSYRLSMKV
     KAFPSPEIVW LKDGSPATLK SARYLVHGYS LIIKDVTTED AGDYTILLGI KQSRLFKNLT
     ATLIVNVKPQ IYEKSVSSLP SPPLYPLGSR QVLTCTVYGI PRPTITWLWH PCHHNHSKER
     YDFCTENEES FILDPSSNLG NRIESISQRM TVIEGTNKTV STLVVADSQT PGIYSCRAFN
     KIGTVERNIK FYVTDVPNGF HVSLEKMPAE GEDLKLSCVV NKFLYRDITW ILLRTVNNRT
     MHHSISKQKM ATTQDYSITL NLVIKNVSLE DSGTYACRAR NIYTGEDILR KTEVLVRDSE
     APHLLQNLSD YEVSISGSTT LDCQARGVPA PQITWFKNNH KIQQEPGIIL GPGNSTLFIE
     RVTEEDEGVY RCRATNQKGA VESAAYLTVQ GTSDKSNLEL ITLTCTCVAA TLFWLLLTLF
     IRKLKRSSSE VKTDYLSIIM DPDEVPLDEQ CERLPYDASK WEFARERLKL GKSLGRGAFG
     KVVQASAFGI KKSPTCRTVA VKMLKEGATA SEYKALMTEL KILTHIGHHL NVVNLLGACT
     KQGGPLMVIV EYCKYGNLSN YLKSKRDLFC LNKDAALHME LKKESLEPGL EQGQKPRLDS
     VSSSSVTSSS FPEDRSVSDV EGDEDYSEIS KQPLTMEDLI SYSFQVARGM EFLSSRKCIH
     RDLAARNILL SENNVVKICD FGLARDIYKN PDYVRRGDTR LPLKWMAPES IFDKVYSTKS
     DVWSYGVLLW EIFSLGGSPY PGVQMDEDFC SRLKEGMRMR TPEYATPEIY QIMLDCWHKD
     PKERPRFAEL VEKLGDLLQA NVQQDGKDYI PLNAILTRNS SFTYSTPTFS EDLFKDGFAD
     PHFHSGSSDD VRYVNAFKFM SLERIKTFEE LSPNSTSMFE DYQLDTSTLL GSPLLKRFTW
     TETKPKASMK IDLRIASKSK EAGLSDLPRP SFCFSSCGHI RPVQDDESEL GKESCCSPPP
     DYNSVVLYSS PPA
//