VGFR1_HUMAN - dbPTM
VGFR1_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID VGFR1_HUMAN
UniProt AC P17948
Protein Name Vascular endothelial growth factor receptor 1
Gene Name FLT1
Organism Homo sapiens (Human).
Sequence Length 1338
Subcellular Localization Isoform 1: Cell membrane
Single-pass type I membrane protein. Endosome. Autophosphorylation promotes ubiquitination and endocytosis.
Isoform 2: Secreted .
Isoform 3: Secreted.
Isoform 4: Secreted.
Isoform 5: Cytoplasm .
Isoform 6: Cytoplasm .
Protein 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..
Protein Sequence MVSYWDTGVLLCALLSCLLLTGSSSGSKLKDPELSLKGTQHIMQAGQTLHLQCRGEAAHKWSLPEMVSKESERLSITKSACGRNGKQFCSTLTLNTAQANHTGFYSCKYLAVPTSKKKETESAIYIFISDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVQISTPRPVKLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKNKRASVRRRIDQSNSHANIFYSVLTIDKMQNKDKGLYTCRVRSGPSFKSVNTSVHIYDKAFITVKHRKQQVLETVAGKRSYRLSMKVKAFPSPEVVWLKDGLPATEKSARYLTRGYSLIIKDVTEEDAGNYTILLSIKQSNVFKNLTATLIVNVKPQIYEKAVSSFPDPALYPLGSRQILTCTAYGIPQPTIKWFWHPCNHNHSEARCDFCSNNEESFILDADSNMGNRIESITQRMAIIEGKNKMASTLVVADSRISGIYICIASNKVGTVGRNISFYITDVPNGFHVNLEKMPTEGEDLKLSCTVNKFLYRDVTWILLRTVNNRTMHYSISKQKMAITKEHSITLNLTIMNVSLQDSGTYACRARNVYTGEEILQKKEITIRDQEAPYLLRNLSDHTVAISSSTTLDCHANGVPEPQITWFKNNHKIQQEPGIILGPGSSTLFIERVTEEDEGVYHCKATNQKGSVESSAYLTVQGTSDKSNLELITLTCTCVAATLFWLLLTLFIRKMKRSSSEIKTDYLSIIMDPDEVPLDEQCERLPYDASKWEFARERLKLGKSLGRGAFGKVVQASAFGIKKSPTCRTVAVKMLKEGATASEYKALMTELKILTHIGHHLNVVNLLGACTKQGGPLMVIVEYCKYGNLSNYLKSKRDLFFLNKDAALHMEPKKEKMEPGLEQGKKPRLDSVTSSESFASSGFQEDKSLSDVEEEEDSDGFYKEPITMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKGDTRLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGGSPYPGVQMDEDFCSRLREGMRMRAPEYSTPEIYQIMLDCWHRDPKERPRFAELVEKLGDLLQANVQQDGKDYIPINAILTGNSGFTYSTPAFSEDFFKESISAPKFNSGSSDDVRYVNAFKFMSLERIKTFEELLPNATSMFDDYQGDSSTLLASPMLKRFTWTDSKPKASLKIDLRVTSKSKESGLSDVSRPSFCHSSCGHVSEGKRRFTYDHAELERKIACCSPPPDYNSVVLYSTPPI
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
9 (in isoform 8)Phosphorylation-3.9125159151
71PhosphorylationPEMVSKESERLSITK
HHHHCCHHHHHCCCH		31.5820860994
75PhosphorylationSKESERLSITKSACG
CCHHHHHCCCHHHCC		34.1424719451
87UbiquitinationACGRNGKQFCSTLTL
HCCCCCCEEEEEEEE		46.08-
100N-linked_GlycosylationTLNTAQANHTGFYSC
EECCCCCCCCCEEEE		22.60UniProtKB CARBOHYD
120PhosphorylationPTSKKKETESAIYIF
ECCCCCCCCCEEEEE		44.0825072903
122PhosphorylationSKKKETESAIYIFIS
CCCCCCCCEEEEEEC		27.6425072903
125PhosphorylationKETESAIYIFISDTG
CCCCCEEEEEECCCC		6.9025072903
129PhosphorylationSAIYIFISDTGRPFV
CEEEEEECCCCCCHH		20.5425072903
131PhosphorylationIYIFISDTGRPFVEM
EEEEECCCCCCHHHH		28.4425072903
164N-linked_GlycosylationPCRVTSPNITVTLKK
EEEECCCCEEEEEEE		42.18UniProtKB CARBOHYD
176MethylationLKKFPLDTLIPDGKR
EEECCCCEECCCCCE		33.98-
196N-linked_GlycosylationRKGFIISNATYKEIG
CCCEEEECCCEEEEE		26.37UniProtKB CARBOHYD
218PhosphorylationVNGHLYKTNYLTHRQ
ECCEEEEEEEEECCC		18.6222817900
222PhosphorylationLYKTNYLTHRQTNTI
EEEEEEEECCCCCEE		12.4922817900
251N-linked_GlycosylationRGHTLVLNCTATTPL
CCCEEEEECEEECCC		17.39UniProtKB CARBOHYD
255PhosphorylationLVLNCTATTPLNTRV
EEEECEEECCCCCEE		15.70-
265PhosphorylationLNTRVQMTWSYPDEK
CCCEEEEEEECCCCC		8.31-
267PhosphorylationTRVQMTWSYPDEKNK
CEEEEEEECCCCCCC		20.02-
285PhosphorylationVRRRIDQSNSHANIF
HHHHHHCCCCCHHEE		36.2329396449
287PhosphorylationRRIDQSNSHANIFYS
HHHHCCCCCHHEEEE		29.2629396449
293PhosphorylationNSHANIFYSVLTIDK
CCCHHEEEEEEEEHH		8.2829396449
294PhosphorylationSHANIFYSVLTIDKM
CCHHEEEEEEEEHHC		10.4129396449
297PhosphorylationNIFYSVLTIDKMQNK
HEEEEEEEEHHCCCC		25.6029396449
306MethylationDKMQNKDKGLYTCRV
HHCCCCCCCEEEEEE		53.04-
306TrimethylationDKMQNKDKGLYTCRV
HHCCCCCCCEEEEEE		53.04-
323N-linked_GlycosylationGPSFKSVNTSVHIYD
CCCCCEEEEEEEEEE		33.45UniProtKB CARBOHYD
383PhosphorylationATEKSARYLTRGYSL
CCHHHHHHHHHCCEE		16.4922817900
388PhosphorylationARYLTRGYSLIIKDV
HHHHHHCCEEEEEEC		9.3022817900
402N-linked_GlycosylationVTEEDAGNYTILLSI
CCHHHCCCEEEEEEE		32.28UniProtKB CARBOHYD
404PhosphorylationEEDAGNYTILLSIKQ
HHHCCCEEEEEEEEC		14.78-
408PhosphorylationGNYTILLSIKQSNVF
CCEEEEEEEECCCCC		25.0524719451
410UbiquitinationYTILLSIKQSNVFKN
EEEEEEEECCCCCCC		44.27-
417N-linked_GlycosylationKQSNVFKNLTATLIV
ECCCCCCCEEEEEEE		31.03UniProtKB CARBOHYD
474N-linked_GlycosylationFWHPCNHNHSEARCD
EEECCCCCCCCCCCC		26.79UniProtKB CARBOHYD
547N-linked_GlycosylationKVGTVGRNISFYITD
CCCCCCCEEEEEEEE		28.47UniProtKB CARBOHYD
588PhosphorylationKFLYRDVTWILLRTV
CHHHCCCHHEEEEEC		15.86-
597N-linked_GlycosylationILLRTVNNRTMHYSI
EEEEECCCCEEEEEE		36.14UniProtKB CARBOHYD
599PhosphorylationLRTVNNRTMHYSISK
EEECCCCEEEEEEEC		15.49-
603PhosphorylationNNRTMHYSISKQKMA
CCCEEEEEEECCCCE		13.0020726782
605PhosphorylationRTMHYSISKQKMAIT
CEEEEEEECCCCEEE		24.0820726782
618PhosphorylationITKEHSITLNLTIMN
EECCEEEEEEEEEEE		16.77-
620N-linked_GlycosylationKEHSITLNLTIMNVS
CCEEEEEEEEEEEEE		26.87UniProtKB CARBOHYD
625N-linked_GlycosylationTLNLTIMNVSLQDSG
EEEEEEEEEEECCCC		19.17UniProtKB CARBOHYD
631PhosphorylationMNVSLQDSGTYACRA
EEEEECCCCCEEECE		21.77-
633PhosphorylationVSLQDSGTYACRARN
EEECCCCCEEECEEC		16.34-
666N-linked_GlycosylationEAPYLLRNLSDHTVA
CHHHHHHCCCCCEEE		43.81UniProtKB CARBOHYD
681 (in isoform 2)Phosphorylation-21.77-
683 (in isoform 2)Phosphorylation-23.15-
739PhosphorylationKATNQKGSVESSAYL
EECCCCCCEEEEEEE		29.73-
742PhosphorylationNQKGSVESSAYLTVQ
CCCCCEEEEEEEEEE		20.36-
743PhosphorylationQKGSVESSAYLTVQG
CCCCEEEEEEEEEEC		13.87-
745PhosphorylationGSVESSAYLTVQGTS
CCEEEEEEEEEECCC		12.59-
747PhosphorylationVESSAYLTVQGTSDK
EEEEEEEEEECCCCC		9.71-
751PhosphorylationAYLTVQGTSDKSNLE
EEEEEECCCCCCCCE		19.36-
794PhosphorylationSSEIKTDYLSIIMDP
CCCCCCCEEEEECCC		13.9516946136
815PhosphorylationEQCERLPYDASKWEF
HHHHCCCCCHHHHHH		28.82-
831MethylationRERLKLGKSLGRGAF
HHHHHHCCCCCCCHH		53.6018006819
831"N6,N6-dimethyllysine"RERLKLGKSLGRGAF
HHHHHHCCCCCCCHH		53.60-
911PhosphorylationPLMVIVEYCKYGNLS
CEEEEEEEECCCCHH		5.37-
914PhosphorylationVIVEYCKYGNLSNYL
EEEEEECCCCHHHHH		14.009722576
920PhosphorylationKYGNLSNYLKSKRDL
CCCCHHHHHHCCCCE		16.4821403953
932MethylationRDLFFLNKDAALHME
CCEEEECCCHHHCCC		51.39-
1001PhosphorylationITMEDLISYSFQVAR
CCHHHHHHHHHHHHH		23.2524043423
1002PhosphorylationTMEDLISYSFQVARG
CHHHHHHHHHHHHHH		13.4024043423
1003PhosphorylationMEDLISYSFQVARGM
HHHHHHHHHHHHHHC		11.4724043423
1048PhosphorylationFGLARDIYKNPDYVR
CCCCCHHHHCCCCCC		14.7029341593
1053PhosphorylationDIYKNPDYVRKGDTR
HHHHCCCCCCCCCCC		11.9229341593
1064UbiquitinationGDTRLPLKWMAPESI
CCCCCCCCCCCCHHH		32.74-
1153"N6,N6-dimethyllysine"RFAELVEKLGDLLQA
HHHHHHHHHHHHHHH		50.74-
1153MethylationRFAELVEKLGDLLQA
HHHHHHHHHHHHHHH		50.7423644510
1169PhosphorylationVQQDGKDYIPINAIL
HCCCCCCCEEEEEEE		16.4511513746
1197PhosphorylationSEDFFKESISAPKFN
CHHHHHHHCCCCCCC		23.57-
1199PhosphorylationDFFKESISAPKFNSG
HHHHHHCCCCCCCCC		48.04-
1202UbiquitinationKESISAPKFNSGSSD
HHHCCCCCCCCCCCC		57.82-
1205PhosphorylationISAPKFNSGSSDDVR
CCCCCCCCCCCCCCE		43.0921406692
1207PhosphorylationAPKFNSGSSDDVRYV
CCCCCCCCCCCCEEE		30.3421406692
1208PhosphorylationPKFNSGSSDDVRYVN
CCCCCCCCCCCEEEE		41.1627251275
1213PhosphorylationGSSDDVRYVNAFKFM
CCCCCCEEEEEEEEE		9.6323403867
1242PhosphorylationATSMFDDYQGDSSTL
CCHHCCCCCCCHHHC		19.0811513746
1309PhosphorylationEGKRRFTYDHAELER
CCCCCCCCCHHHHHH		11.7412796773
1322PhosphorylationERKIACCSPPPDYNS
HHHEEECCCCCCCCC		40.0828450419
1327PhosphorylationCCSPPPDYNSVVLYS
ECCCCCCCCCEEEEE		18.3428450419
1329PhosphorylationSPPPDYNSVVLYSTP
CCCCCCCCEEEEECC		13.8428450419
1333PhosphorylationDYNSVVLYSTPPI--
CCCCEEEEECCCC--		10.0116286478
1334PhosphorylationYNSVVLYSTPPI---
CCCEEEEECCCC---		30.2128450419
1335PhosphorylationNSVVLYSTPPI----
CCEEEEECCCC----		21.3728450419
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
1169YPhosphorylationKinaseFLT1P17948
GPS
1213YPhosphorylationKinaseFLT1P17948
GPS
1242YPhosphorylationKinaseFLT1P17948
GPS
1327YPhosphorylationKinaseFLT1P17948
GPS
1333YPhosphorylationKinaseFLT1P17948
GPS
-KUbiquitinationE3 ubiquitin ligaseCBLP22681
PMID:15001553
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference

Oops, there are no descriptions of PTM sites of VGFR1_HUMAN !!
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of VGFR1_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
SHC1_HUMANSHC1physical
10749680
VGFR2_HUMANKDRphysical
12796773
PLGF_HUMANPGFphysical
9452434
VEGFB_HUMANVEGFBphysical
9751730
SHC2_HUMANSHC2physical
10749680
PLCG1_HUMANPLCG1physical
9398617
VEGFB_HUMANVEGFBphysical
10409677
CBL_HUMANCBLphysical
25387128
VGFR2_HUMANKDRphysical
25387128
PTN11_HUMANPTPN11physical
25241761
P85A_HUMANPIK3R1physical
20805333
SHC2_HUMANSHC2physical
9790910
Drug and Disease Associations
Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D03218 Axitinib (JAN/USAN); Inlyta (TN)
D05380 Pazopanib hydrochloride (JAN/USAN); Votrient (TN)
D06285 Vatalanib (USAN/INN)
D06402 Sunitinib malate (JAN/USAN); Sutent (TN)
D06678 Motesanib; AMG 706
D08503 Toceranib (USAN)
D08544 Toceranib phosphate (USAN)
D08552 Sunitinib (INN)
D08881 Cediranib (USAN/INN)
D08883 Cediranib maleate (JAN/USAN)
D08907 Dovitinib lactate (USAN)
D08947 Motesanib phosphate (JAN); Motesanib diphosphate (USAN)
D09635 Linifanib (USAN/INN)
D09683 Tivozanib (USAN/INN)
D09919 Lenvatinib (USAN/INN)
D09920 Lenvatinib mesilate (JAN); Lenvatinib mesylate (USAN)
D09926 Icrucumab (USAN/INN)
D10062 Cabozantinib (USAN)
D10095 Cabozantinib s-malate (USAN); Cometriq (TN)
D10137 Regorafenib hydrate (JAN); Stivarga (TN)
D10138 Regorafenib (USAN/INN)
D10190 Tivozanib hydrochloride (USAN); Tivozanib hydrochloride monohydrate
D10396 Nintedanib esylate (USAN)
D10423 Ilorasertib (USAN)
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of VGFR1_HUMAN

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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1048 AND TYR-1053, ANDMASS SPECTROMETRY.
"Role of PlGF in the intra- and intermolecular cross talk between theVEGF receptors Flt1 and Flk1.";
Autiero M., Waltenberger J., Communi D., Kranz A., Moons L.,Lambrechts D., Kroll J., Plaisance S., De Mol M., Bono F., Kliche S.,Fellbrich G., Ballmer-Hofer K., Maglione D., Mayr-Beyrle U.,Dewerchin M., Dombrowski S., Stanimirovic D., Van Hummelen P.,Dehio C., Hicklin D.J., Persico G., Herbert J.M., Communi D.,Shibuya M., Collen D., Conway E.M., Carmeliet P.;
Nat. Med. 9:936-943(2003).
Cited for: INTERACTION WITH PGF AND KDR, FUNCTION IN PHOSPHORYLATION OF KDR;VEGFA AND PGF SIGNALING, CATALYTIC ACTIVITY, MASS SPECTROMETRY, ANDPHOSPHORYLATION AT TYR-1213; TYR-1327 AND TYR-1309.
"Direct identification of a major autophosphorylation site on vascularendothelial growth factor receptor Flt-1 that mediatesphosphatidylinositol 3'-kinase binding.";
Yu Y., Hulmes J.D., Herley M.T., Whitney R.G., Crabb J.W., Sato J.D.;
Biochem. J. 358:465-472(2001).
Cited for: INTERACTION WITH PIK3R1 AND VEGFA, AUTOPHOSPHORYLATION,PHOSPHORYLATION AT TYR-1213, SUBCELLULAR LOCATION, MASS SPECTROMETRY,AND GLYCOSYLATION.
"Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2.";
Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I.;
Biochem. Biophys. Res. Commun. 246:95-99(1998).
Cited for: INTERACTION WITH PIK3R1; PTPN11 AND NCK1, AND PHOSPHORYLATION ATTYR-1213.
"The phosphorylated 1169-tyrosine containing region of flt-1 kinase(VEGFR-1) is a major binding site for PLCgamma.";
Sawano A., Takahashi T., Yamaguchi S., Shibuya M.;
Biochem. Biophys. Res. Commun. 238:487-491(1997).
Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1 AND ACTIVATION OF MAP KINASES,INTERACTION WITH PLCG1, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-861 ANDTYR-1169, AND PHOSPHORYLATION AT TYR-1169 AND TYR-1213.
"Identification of vascular endothelial growth factor receptor-1tyrosine phosphorylation sites and binding of SH2 domain-containingmolecules.";
Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.;
J. Biol. Chem. 273:23410-23418(1998).
Cited for: PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, PHOSPHORYLATION ATTYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333, MUTAGENESIS OFTYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333, AND INTERACTIONWITH PLCG1; GRB2; CRK; NCK1 AND PTPN11.

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