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Reviewed, UniProtKB/Swiss-Prot P17948 (VGFR1_HUMAN)

Last modified June 16, 2009. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Vascular endothelial growth factor receptor 1
      Short name=VEGFR-1
    EC=2.7.10.1
Alternative name(s):
    Vascular permeability factor receptor
    Tyrosine-protein kinase receptor FLT
    Flt-1
    Tyrosine-protein kinase FRT
    Fms-like tyrosine kinase 1
Gene names
Name: FLT1
Synonyms: FLT, FRT
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1338 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Receptor for VEGF, VEGFB and PGF. Has a tyrosine-protein kinase activity. The VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability. Isoform SFlt1 may have an inhibitory role in angiogenesis.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Interacts in vitro with various phosphotyrosine-binding proteins, including PLC-gammas, PTPN11, GRB2, CRK and NCK1.

Subcellular location

Isoform Flt1: Cell membrane; Single-pass type I membrane protein.

Isoform sFlt1: Secreted.

Tissue specificity

Mostly in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. It is not expressed in tumor cell lines. Isoform sFlt1 is strongly expressed in placenta.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Contains 7 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

female pregnancy

Traceable author statement. Source: ProtInc

positive regulation of cell proliferation

Traceable author statement. Source: ProtInc

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from direct assay. Source: UniProtKB

protein amino acid phosphorylation

Inferred from electronic annotation. Source: InterPro

transmembrane receptor protein tyrosine kinase signaling pathway Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentextracellular space Ref.3

Traceable author statement. Source: ProtInc

integral to plasma membrane Ref.3

Traceable author statement. Source: ProtInc

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

growth factor binding

Inferred from physical interaction. Source: UniProtKB

vascular endothelial growth factor receptor activity

Inferred from direct assay. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Flt1 (identifier: P17948-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform sFlt1 (identifier: P17948-2)

The sequence of this isoform differs from the canonical sequence as follows:
     657-687: DQEAPYLLRNLSDHTVAISSSTTLDCHANGV → GEHCNKKAVFSRISKFKSTRNDCTTQSNVKH
     688-1338: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626
Chain27 – 13381312Vascular endothelial growth factor receptor 1
PRO_0000016768

Regions

Topological domain27 – 758732Extracellular Potential
Transmembrane759 – 78022 Potential
Topological domain781 – 1338558Cytoplasmic Potential
Domain32 – 12392Ig-like C2-type 1
Domain151 – 21464Ig-like C2-type 2
Domain230 – 32798Ig-like C2-type 3
Domain335 – 42187Ig-like C2-type 4
Domain428 – 553126Ig-like C2-type 5
Domain556 – 65499Ig-like C2-type 6
Domain661 – 74787Ig-like C2-type 7
Domain827 – 1158332Protein kinase
Nucleotide binding833 – 8419ATP By similarity

Sites

Active site10221Proton acceptor By similarity
Binding site8611ATP By similarity

Amino acid modifications

Modified residue10481Phosphotyrosine Ref.7
Modified residue10531Phosphotyrosine; by autocatalysis By similarity
Modified residue11691Phosphotyrosine; by autocatalysis By similarity
Modified residue12131Phosphotyrosine; by autocatalysis Ref.6
Modified residue12421Phosphotyrosine; by autocatalysis Ref.6
Modified residue13271Phosphotyrosine; by autocatalysis Ref.6
Modified residue13331Phosphotyrosine; by autocatalysis Ref.6
Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation1641N-linked (GlcNAc...) Potential
Glycosylation1961N-linked (GlcNAc...) Potential
Glycosylation2511N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Glycosylation4021N-linked (GlcNAc...) Potential
Glycosylation4171N-linked (GlcNAc...) Potential
Glycosylation4741N-linked (GlcNAc...) Potential
Glycosylation5471N-linked (GlcNAc...) Potential
Glycosylation5971N-linked (GlcNAc...) Potential
Glycosylation6201N-linked (GlcNAc...) Potential
Glycosylation6251N-linked (GlcNAc...) Potential
Glycosylation6661N-linked (GlcNAc...) Potential
Disulfide bond53 ↔ 107 Potential
Disulfide bond158 ↔ 207
Disulfide bond252 ↔ 311 Potential
Disulfide bond454 ↔ 535 Potential
Disulfide bond577 ↔ 636 Potential
Disulfide bond682 ↔ 731 Potential

Natural variations

Alternative sequence657 – 68731DQEAP…HANGV → GEHCNKKAVFSRISKFKSTR NDCTTQSNVKH in isoform sFlt1.
VSP_002955
Alternative sequence688 – 1338651Missing in isoform sFlt1.
VSP_002956
Natural variant601K → T Ref.9
VAR_042045
Natural variant1281I → L: dbSNP rs35073261.
VAR_049719
Natural variant1441E → K Ref.9
VAR_042046
Natural variant2811R → Q Ref.9
VAR_042047
Natural variant4221L → I in a lung adenocarcinoma sample; somatic mutation. Ref.9
VAR_042048
Natural variant7811R → Q in a glioma low grade oligodendroglioma sample; somatic mutation. Ref.9
VAR_042049
Natural variant9381M → V Ref.9
VAR_042050
Natural variant9821E → A: dbSNP rs35832528. Ref.9
VAR_042051
Natural variant10611L → V in a bladder transitional cell carcinoma sample; somatic mutation. Ref.9
VAR_042052

Experimental info

Mutagenesis9141Y → F: No loss of phosphorylation. Ref.6
Mutagenesis12131Y → F: Loss of phosphorylation. Ref.6
Mutagenesis12421Y → F: Loss of phosphorylation. Ref.6
Mutagenesis13271Y → F: Loss of phosphorylation. Ref.6
Mutagenesis13331Y → F: Loss of phosphorylation. Ref.6
Sequence conflict4901F → S in AAC16449. Ref.2
Sequence conflict7791F → L in CAA35946. Ref.1

Secondary structure

..................... 1338
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Flt1 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: FF3381EEFAF0787C

FASTA1,338150,769
        10         20         30         40         50         60 
MVSYWDTGVL LCALLSCLLL TGSSSGSKLK DPELSLKGTQ HIMQAGQTLH LQCRGEAAHK 

        70         80         90        100        110        120 
WSLPEMVSKE SERLSITKSA CGRNGKQFCS TLTLNTAQAN HTGFYSCKYL AVPTSKKKET 

       130        140        150        160        170        180 
ESAIYIFISD TGRPFVEMYS EIPEIIHMTE GRELVIPCRV TSPNITVTLK KFPLDTLIPD 

       190        200        210        220        230        240 
GKRIIWDSRK GFIISNATYK EIGLLTCEAT VNGHLYKTNY LTHRQTNTII DVQISTPRPV 

       250        260        270        280        290        300 
KLLRGHTLVL NCTATTPLNT RVQMTWSYPD EKNKRASVRR RIDQSNSHAN IFYSVLTIDK 

       310        320        330        340        350        360 
MQNKDKGLYT CRVRSGPSFK SVNTSVHIYD KAFITVKHRK QQVLETVAGK RSYRLSMKVK 

       370        380        390        400        410        420 
AFPSPEVVWL KDGLPATEKS ARYLTRGYSL IIKDVTEEDA GNYTILLSIK QSNVFKNLTA 

       430        440        450        460        470        480 
TLIVNVKPQI YEKAVSSFPD PALYPLGSRQ ILTCTAYGIP QPTIKWFWHP CNHNHSEARC 

       490        500        510        520        530        540 
DFCSNNEESF ILDADSNMGN RIESITQRMA IIEGKNKMAS TLVVADSRIS GIYICIASNK 

       550        560        570        580        590        600 
VGTVGRNISF YITDVPNGFH VNLEKMPTEG EDLKLSCTVN KFLYRDVTWI LLRTVNNRTM 

       610        620        630        640        650        660 
HYSISKQKMA ITKEHSITLN LTIMNVSLQD SGTYACRARN VYTGEEILQK KEITIRDQEA 

       670        680        690        700        710        720 
PYLLRNLSDH TVAISSSTTL DCHANGVPEP QITWFKNNHK IQQEPGIILG PGSSTLFIER 

       730        740        750        760        770        780 
VTEEDEGVYH CKATNQKGSV ESSAYLTVQG TSDKSNLELI TLTCTCVAAT LFWLLLTLFI 

       790        800        810        820        830        840 
RKMKRSSSEI KTDYLSIIMD PDEVPLDEQC ERLPYDASKW EFARERLKLG KSLGRGAFGK 

       850        860        870        880        890        900 
VVQASAFGIK KSPTCRTVAV KMLKEGATAS EYKALMTELK ILTHIGHHLN VVNLLGACTK 

       910        920        930        940        950        960 
QGGPLMVIVE YCKYGNLSNY LKSKRDLFFL NKDAALHMEP KKEKMEPGLE QGKKPRLDSV 

       970        980        990       1000       1010       1020 
TSSESFASSG FQEDKSLSDV EEEEDSDGFY KEPITMEDLI SYSFQVARGM EFLSSRKCIH 

      1030       1040       1050       1060       1070       1080 
RDLAARNILL SENNVVKICD FGLARDIYKN PDYVRKGDTR LPLKWMAPES IFDKIYSTKS 

      1090       1100       1110       1120       1130       1140 
DVWSYGVLLW EIFSLGGSPY PGVQMDEDFC SRLREGMRMR APEYSTPEIY QIMLDCWHRD 

      1150       1160       1170       1180       1190       1200 
PKERPRFAEL VEKLGDLLQA NVQQDGKDYI PINAILTGNS GFTYSTPAFS EDFFKESISA 

      1210       1220       1230       1240       1250       1260 
PKFNSGSSDD VRYVNAFKFM SLERIKTFEE LLPNATSMFD DYQGDSSTLL ASPMLKRFTW 

      1270       1280       1290       1300       1310       1320 
TDSKPKASLK IDLRVTSKSK ESGLSDVSRP SFCHSSCGHV SEGKRRFTYD HAELERKIAC 

      1330 
CSPPPDYNSV VLYSTPPI 

« Hide

Isoform sFlt1.

Checksum: 3F73F4942469DA36
Show »

FASTA68777,474

References

« Hide 'large scale' references
[1]"Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family."
Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M.
Oncogene 5:519-524(1990) [PubMed: 2158038] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FLT1).
Tissue: Placenta.
[2]"Coding region for human VEGF receptor FLT1 (VEGFR-1)."
Yu Y., Whitney R.G., Sato J.D.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM FLT1).
Tissue: Umbilical vein.
[3]"Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor."
Kendall R.L., Thomas K.A.
Proc. Natl. Acad. Sci. U.S.A. 90:10705-10709(1993) [PubMed: 8248162] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SFLT1), PROTEIN SEQUENCE OF N-TERMINUS.
Tissue: Umbilical vein.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SFLT1).
Tissue: Ovary.
[5]"A possible new member of tyrosine kinase family, human frt sequence, is highly conserved in vertebrates and located on human chromosome 13."
Matsushime H., Yoshida M.C., Sasaki M., Shibuya M.
Jpn. J. Cancer Res. 78:655-661(1987) [PubMed: 3040650] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1018-1058 (ISOFORM FLT1).
[6]"Identification of vascular endothelial growth factor receptor-1 tyrosine phosphorylation sites and binding of SH2 domain-containing molecules."
Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.
J. Biol. Chem. 273:23410-23418(1998) [PubMed: 9722576] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT TYR-1213; TYR-1242; TYR-1327 AND TYR-1333, MUTAGENESIS OF TYR-914; TYR-1213; TYR-1242; TYR-1327 AND TYR-1333.
[7]"Global survey of phosphotyrosine signaling identifies oncogenic kinases 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. expand/collapse author list , 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) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1048 AND TYR-1053, MASS SPECTROMETRY.
[8]"Solution structure of the VEGF-binding domain of Flt-1: comparison of its free and bound states."
Starovasnik M.A., Christinger H.W., Wiesmann C., Champe M.A., de Vos A.M., Skelton N.J.
J. Mol. Biol. 293:531-544(1999) [PubMed: 10543948] [Abstract]
Cited for: STRUCTURE BY NMR OF 129-229.
[9]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-60; LYS-144; GLN-281; ILE-422; GLN-781; VAL-938; ALA-982 AND VAL-1061.
+Additional computationally mapped references.

Cross-references

Sequence databases

X51602 mRNA. Translation: CAA35946.1.
AF063657 mRNA. Translation: AAC16449.2.
U01134 mRNA. Translation: AAC50060.1.
BC039007 mRNA. Translation: AAH39007.1.
D00133 Genomic DNA. Translation: BAA00080.1.
IPIIPI00018335.
IPI00216043.
PIRA49636.
S09982.
RefSeqNP_002010.2.
UniGeneHs.654360

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1FLTX-ray1.70X/Y132-226[»]
1QSVNMR-A129-229[»]
1QSZNMR-A129-229[»]
1QTYX-ray2.70T/U/X/Y129-229[»]
1RV6X-ray2.45X/Y130-229[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:643N.

PTM databases

PhosphoSiteP17948.

Proteomic databases

PRIDEP17948.

Genome annotation databases

EnsemblENSG00000102755. Homo sapiens. [Contig view]
GeneID2321.
KEGGhsa:2321.

Organism-specific databases

GeneCardsGC13M027773.
H-InvDBHIX0026543.
HIX0037569.
HGNCHGNC:3763. FLT1.
MIM165070. gene.
PharmGKBPA28180.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP17948.
HOVERGENP17948.
OMAP17948. DYNSVVL.

Enzyme and pathway databases

BRENDA2.7.10.1. 247.
Pathway_Interaction_DBglypican_1pathway. Glypican 1 network.
s1p_s1p3_pathway. S1P3 pathway.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
vegfr1_pathway. VEGFR1 specific signals.
ReactomeREACT_12529. Signaling by VEGF.

Gene expression databases

ArrayExpressP17948.
BgeeP17948.
CleanExHS_FLT1.
GermOnlineENSG00000102755. Homo sapiens.

Family and domain databases

InterProIPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR001824. Recept_tyr_kinase-III_CS.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR009135. VEGFR1_N.
IPR009134. VEGFR_N.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 6 hits.
PfamPF07679. I-set. 2 hits.
PF00047. ig. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR01832. VEGFRECEPTOR.
PR01833. VEGFRECEPTR1.
ProDomPD000001. Prot_kinase. 2 hits.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00409. IG. 5 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 6 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01268. Sunitinib.
NextBio9421.
SOURCESearch...

Entry information

Entry nameVGFR1_HUMAN
AccessionPrimary (citable) accession number: P17948
Secondary accession number(s): O60722, P16057, Q12954
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 3, 2007
Last modified: June 16, 2009
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents