O43915 (VEGFD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 (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 process	Angiogenesis Differentiation
Cellular component	Secreted
Domain	Repeat Signal
Molecular function	Developmental protein Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Inferred from electronic annotation. Source: Compara 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 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_component	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_function	chemoattractant activity Inferred from direct assay PubMed 19275959. Source: UniProtKB platelet-derived growth factor receptor binding Traceable author statement Ref.2. 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...) Ref.8

Glycosylation

185

1

N-linked (GlcNAc...) Ref.8

Glycosylation

287

1

N-linked (GlcNAc...) Potential

Disulfide bond

111 ↔ 153

Ref.8

Disulfide bond

136

Interchain Ref.8

Disulfide bond

142 ↔ 189

Ref.8

Disulfide bond

145

Interchain Ref.8

Disulfide bond

146 ↔ 191

Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

354

Helix Strand Turn

Details...

Helix

93 – 108

16

Beta strand

110 – 119

10

Helix

120 – 123

4

Helix

127 – 129

3

Beta strand

133 – 143

11

Beta strand

152 – 166

15

Beta strand

169 – 171

3

Beta strand

178 – 192

15

Sequences

	Sequence		Length	Mass (Da)
	O43915 [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] [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. , 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. , 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 , 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.

IPI

IPI00004653.

RefSeq

NP_004460.1. NM_004469.4.

UniGene

Hs.11392.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XV7	X-ray	2.90	A	92-195	[»]

ProteinModelPortal

O43915.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000297904.

PTM databases

PhosphoSite

O43915.

Proteomic databases

PaxDb

O43915.

PRIDE

O43915.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000297904; ENSP00000297904; ENSG00000165197.

GeneID

2277.

KEGG

hsa:2277.

UCSC

uc004cwt.2. human.

Organism-specific databases

CTD

2277.

GeneCards

GC0XM015363.

HGNC

HGNC:3708. FIGF.

HPA

HPA027342.

MIM

300091. gene.

neXtProt

NX_O43915.

PharmGKB

PA28146.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG77707.

HOGENOM

HOG000231512.

HOVERGEN

HBG073119.

InParanoid

O43915.

KO

K05449.

OMA

PDTCSCE.

OrthoDB

EOG4VDQ0F.

PhylomeDB

O43915.

Enzyme and pathway databases

Pathway_Interaction_DB

lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

Bgee

O43915.

CleanEx

HS_FIGF.

Genevestigator

O43915.

GermOnline

ENSG00000165197. Homo sapiens.

Family and domain databases

InterPro

IPR000072. PD_growth_factor.
IPR023581. PD_growth_factor_CS.
[Graphical view]

Pfam

PF00341. PDGF. 1 hit.
[Graphical view]

SMART

SM00141. PDGF. 1 hit.
[Graphical view]

PROSITE

PS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O43915.

GenomeRNAi

2277.

NextBio

9261.

SOURCE

Search...

Entry information

Entry name

VEGFD_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.