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O43915 (VEGFD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vascular endothelial growth factor D

Short name=VEGF-D
Alternative name(s):
c-Fos-induced growth factor
Short name=FIGF
Gene names
Name:FIGF
Synonyms:VEGFD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in the formation of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates VEGFR-2 (KDR/FLK1) and VEGFR-3 (FLT4) receptors. Ref.8

Subunit structure

Homodimer; non-covalent and antiparallel. Ref.8

Subcellular location

Secreted.

Tissue specificity

Highly expressed in lung, heart, small intestine and fetal lung, and at lower levels in skeletal muscle, colon, and pancreas.

Post-translational modification

Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3 and VEGFR-2. VEGF-D first form an antiparallel homodimer linked by disulfide bonds before secretion. The fully processed VEGF-D is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentSecreted
   DomainRepeat
Signal
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood coagulation

Traceable author statement. Source: Reactome

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from electronic annotation. Source: Ensembl

induction of positive chemotaxis

Inferred from direct assay PubMed 19275959. Source: UniProtKB

platelet activation

Traceable author statement. Source: Reactome

platelet degranulation

Traceable author statement. Source: Reactome

positive chemotaxis

Inferred from direct assay PubMed 19275959. Source: GOC

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell proliferation

Traceable author statement Ref.2. Source: ProtInc

positive regulation of mast cell chemotaxis

Inferred from direct assay PubMed 19275959. Source: UniProtKB

vascular endothelial growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Traceable author statement Ref.2. Source: ProtInc

membrane

Inferred from electronic annotation. Source: InterPro

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functionchemoattractant activity

Inferred from direct assay PubMed 19275959. Source: UniProtKB

platelet-derived growth factor receptor binding

Traceable author statement Ref.2. Source: ProtInc

vascular endothelial growth factor receptor binding

Inferred from physical interaction Ref.3. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Propeptide22 – 8867Or 99 (in a minor form)
PRO_0000023408
Chain89 – 205117Vascular endothelial growth factor D
PRO_0000023409
Propeptide206 – 354149
PRO_0000023410

Regions

Repeat222 – 237161; approximate
Repeat258 – 273162
Repeat277 – 293173
Repeat301 – 318184
Region222 – 318974 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C

Amino acid modifications

Glycosylation1551N-linked (GlcNAc...) Ref.8
Glycosylation1851N-linked (GlcNAc...) Ref.8
Glycosylation2871N-linked (GlcNAc...) Potential
Disulfide bond111 ↔ 153 Ref.8
Disulfide bond136Interchain Ref.8
Disulfide bond142 ↔ 189 Ref.8
Disulfide bond145Interchain Ref.8
Disulfide bond146 ↔ 191 Ref.8

Secondary structure

................ 354
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43915 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 2048D769D735173E

FASTA35440,444
        10         20         30         40         50         60 
MYREWVVVNV FMMLYVQLVQ GSSNEHGPVK RSSQSTLERS EQQIRAASSL EELLRITHSE 

        70         80         90        100        110        120 
DWKLWRCRLR LKSFTSMDSR SASHRSTRFA ATFYDIETLK VIDEEWQRTQ CSPRETCVEV 

       130        140        150        160        170        180 
ASELGKSTNT FFKPPCVNVF RCGGCCNEES LICMNTSTSY ISKQLFEISV PLTSVPELVP 

       190        200        210        220        230        240 
VKVANHTGCK CLPTAPRHPY SIIRRSIQIP EEDRCSHSKK LCPIDMLWDS NKCKCVLQEE 

       250        260        270        280        290        300 
NPLAGTEDHS HLQEPALCGP HMMFDEDRCE CVCKTPCPKD LIQHPKNCSC FECKESLETC 

       310        320        330        340        350 
CQKHKLFHPD TCSCEDRCPF HTRPCASGKT ACAKHCRFPK EKRAAQGPHS RKNP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a novel vascular endothelial growth factor, VEGF-D."
Yamada Y., Nezu J., Shimane M., Hirata Y.
Genomics 42:483-488(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung.
[2]"Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes."
Rocchigiani M., Lestingi M., Luddi A., Orlandini M., Franco B., Rossi E., Ballabio A., Zuffardi O., Oliviero S.
Genomics 47:207-216(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Lung.
[3]"Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)."
Achen M.G., Jeltsch M., Kukk E., Maekinen T., Vitali A., Wilks A.F., Alitalo K., Stacker S.A.
Proc. Natl. Acad. Sci. U.S.A. 95:548-553(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[7]"Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers."
Stacker S.A., Stenvers K.L., Caesar C., Vitali A., Domagala T., Nice E.C., Roufail S., Simpson R.J., Moritz R., Karpanen T., Alitalo K., Achen M.G.
J. Biol. Chem. 274:32127-32136(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 89-94; 100-105 AND 206-213, PROTEOLYTIC PROCESSING.
[8]"Structural determinants of vascular endothelial growth factor-D - receptor binding and specificity."
Leppanen V.M., Jeltsch M., Anisimov A., Tvorogov D., Aho K., Kalkkinen N., Toivanen P., Yla-Herttuala S., Ballmer-Hofer K., Alitalo K.
Blood 117:1507-1515(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 92-195 OF MUTANT ALA-117, FUNCTION, SUBUNIT, GLYCOSYLATION AT ASN-155 AND ASN-185, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D89630 mRNA. Translation: BAA24264.1.
Y12863 mRNA. Translation: CAA73370.1.
Y12864 expand/collapse EMBL AC list , Y12865, Y12866, Y12867, Y12868, Y12869, Y12870 Genomic DNA. Translation: CAA73371.1.
AJ000185 mRNA. Translation: CAA03942.1.
AK313173 mRNA. Translation: BAG35990.1.
CH471074 Genomic DNA. Translation: EAW98885.1.
BC027948 mRNA. Translation: AAH27948.1.
RefSeqNP_004460.1. NM_004469.4.
UniGeneHs.11392.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XV7X-ray2.90A92-195[»]
ProteinModelPortalO43915.
SMRO43915. Positions 92-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108567. 3 interactions.
STRING9606.ENSP00000297904.

PTM databases

PhosphoSiteO43915.

Proteomic databases

PaxDbO43915.
PRIDEO43915.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297904; ENSP00000297904; ENSG00000165197.
GeneID2277.
KEGGhsa:2277.
UCSCuc004cwt.2. human.

Organism-specific databases

CTD2277.
GeneCardsGC0XM015363.
HGNCHGNC:3708. FIGF.
HPAHPA027342.
MIM300091. gene.
neXtProtNX_O43915.
PharmGKBPA28146.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77707.
HOGENOMHOG000231512.
HOVERGENHBG073119.
InParanoidO43915.
KOK05449.
OMADTCSCED.
OrthoDBEOG7J17ZS.
PhylomeDBO43915.
TreeFamTF319554.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

BgeeO43915.
CleanExHS_FIGF.
GenevestigatorO43915.

Family and domain databases

InterProIPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamPF00341. PDGF. 1 hit.
[Graphical view]
SMARTSM00141. PDGF. 1 hit.
[Graphical view]
PROSITEPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO43915.
GeneWikiC-fos_induced_growth_factor.
GenomeRNAi2277.
NextBio9261.
PROO43915.
SOURCESearch...

Entry information

Entry nameVEGFD_HUMAN
AccessionPrimary (citable) accession number: O43915
Secondary accession number(s): B2R7Z3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome X

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