Reviewed, UniProtKB/Swiss-Prot O43915 (VEGFD_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 (Flk1) and VEGFR-3 (Flt4) receptors.
Subunit structure	Homodimer; non-covalent and antiparallel.
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 process	Angiogenesis Differentiation
Cellular component	Secreted
Domain	Repeat Signal
Molecular function	Developmental protein Growth factor Mitogen
PTM	Cleavage on pair of basic residues Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Ref.2 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.2 Traceable author statement. Source: ProtInc membrane Inferred from electronic annotation. Source: InterPro platelet alpha granule lumen Inferred from Experiment. Source: Reactome
Molecular function	growth factor activity Inferred from electronic annotation. Source: InterPro platelet-derived growth factor receptor binding Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 88	67	Or 99 (in a minor form)		PRO_0000023408
	Chain	89 – 205	117	Vascular endothelial growth factor D		PRO_0000023409
	Propeptide	206 – 354	149			PRO_0000023410
Regions
	Repeat	222 – 237	16	1; approximate
	Repeat	258 – 273	16	2
	Repeat	277 – 293	17	3
	Repeat	301 – 318	18	4
	Region	222 – 318	97	4 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C
Amino acid modifications
	Glycosylation	155	1	N-linked (GlcNAc...) Potential
	Glycosylation	185	1	N-linked (GlcNAc...) Potential
	Glycosylation	287	1	N-linked (GlcNAc...) Potential
	Disulfide bond	111 ↔ 153		By similarity
	Disulfide bond	136		Interchain By similarity
	Disulfide bond	142 ↔ 189		By similarity
	Disulfide bond	145		Interchain By similarity
	Disulfide bond	146 ↔ 191		By similarity

Sequences

	Sequence		Length	Mass (Da)
	O43915-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 2048D769D735173E	FASTA	354	40,444
	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

References

	« Hide 'large scale' referencesShow '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: 9205122] [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: 9479493] [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: 9435229] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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]. Tissue: Lung.
[5]	"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: 10542248] [Abstract] Cited for: PROTEIN SEQUENCE OF 89-94; 100-105 AND 206-213, PROTEOLYTIC PROCESSING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D89630 mRNA. Translation: BAA24264.1. Y12863 mRNA. Translation: CAA73370.1. Y12864 , Y12865, Y12866, Y12867, Y12868, Y12869, Y12870 Genomic DNA. Translation: CAA73371.1. AJ000185 mRNA. Translation: CAA03942.1. BC027948 mRNA. Translation: AAH27948.1.
RefSeq	NP_004460.1.
UniGene	Hs.11392
3D structure databases
HSSP	HSSP built from PDB template 1PDG based on UniProtKB P01127.
ModBase	Search...
PTM databases
PhosphoSite	O43915.
Genome annotation databases
Ensembl	ENSG00000165197. Homo sapiens. [Contig view]
GeneID	2277.
KEGG	hsa:2277.
Organism-specific databases
H-InvDB	HIX0016668.
HGNC	HGNC:3708. FIGF.
MIM	300091. gene.
PharmGKB	PA28146.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	O43915.
HOVERGEN	O43915.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	O43915.
CleanEx	HS_FIGF.
GermOnline	ENSG00000165197. Homo sapiens.
Family and domain databases
InterPro	IPR000072. PD_growth_factor. [Graphical view]
Pfam	PF00341. PDGF. 1 hit. [Graphical view]
ProDom	PD001629. PD_growth_factor. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00141. PDGF. 1 hit. [Graphical view]
PROSITE	PS00249. PDGF_1. 1 hit. PS50278. PDGF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	9261.
SOURCE	Search...

Entry information

Entry name

VEGFD_HUMAN

Accession

Primary (citable) accession number: O43915

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	June 1, 1998
Last modified:	November 25, 2008
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)