Reviewed, UniProtKB/Swiss-Prot P49767 (VEGFC_HUMAN)

Names and origin

Protein names

Recommended name:
    Vascular endothelial growth factor C
      Short name=VEGF-C
Alternative name(s):
    Vascular endothelial growth factor-related protein
      Short name=VRP
    Flt4 ligand
      Short name=Flt4-L

Gene names

Name:

VEGFC

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	419 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, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis 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	Spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon and small intestine and fetal liver, lung and kidney, but not in peripheral blood lymphocyte.
Post-translational modification	Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed form could activate VEGFR-2. VEGF-C first form an antiparallel homodimer linked by disulfide bonds. Before secretion, a cleavage occurs between Arg-227 and Ser-228 producing an heterotetramer. The next extracellular step of the processing removes the N-terminal propeptide. Finally the mature VEGF-C 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.1 Traceable author statement. Source: ProtInc substrate-bound cell migration Ref.1 Traceable author statement. Source: ProtInc
Cellular component	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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31
	Propeptide	32 – 111	80	Or 102		PRO_0000023400
	Chain	112 – 227	116	Vascular endothelial growth factor C		PRO_0000023401
	Propeptide	228 – 419	192			PRO_0000023402
Regions
	Repeat	280 – 295	16	1
	Repeat	304 – 319	16	2
	Repeat	328 – 343	16	3
	Repeat	347 – 362	16	4
	Region	280 – 362	83	4 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C
Amino acid modifications
	Glycosylation	175	1	N-linked (GlcNAc...) Potential
	Glycosylation	205	1	N-linked (GlcNAc...) Potential
	Glycosylation	240	1	N-linked (GlcNAc...) Potential
	Disulfide bond	131 ↔ 173		By similarity
	Disulfide bond	156		Interchain By similarity
	Disulfide bond	162 ↔ 209		By similarity
	Disulfide bond	165		Interchain By similarity
	Disulfide bond	166 ↔ 211		By similarity
Experimental info
	Mutagenesis	227	1	R → S: No proteolytic processing and lower effect on VEGFR-2 and VEGFR-3

Sequences

	Sequence		Length	Mass (Da)
	P49767-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 9F598719DB3E014F	FASTA	419	46,883
	10 20 30 40 50 60 MHLLGFFSVA CSLLAAALLP GPREAPAAAA AFESGLDLSD AEPDAGEATA YASKDLEEQL 70 80 90 100 110 120 RSVSSVDELM TVLYPEYWKM YKCQLRKGGW QHNREQANLN SRTEETIKFA AAHYNTEILK 130 140 150 160 170 180 SIDNEWRKTQ CMPREVCIDV GKEFGVATNT FFKPPCVSVY RCGGCCNSEG LQCMNTSTSY 190 200 210 220 230 240 LSKTLFEITV PLSQGPKPVT ISFANHTSCR CMSKLDVYRQ VHSIIRRSLP ATLPQCQAAN 250 260 270 280 290 300 KTCPTNYMWN NHICRCLAQE DFMFSSDAGD DSTDGFHDIC GPNKELDEET CQCVCRAGLR 310 320 330 340 350 360 PASCGPHKEL DRNSCQCVCK NKLFPSQCGA NREFDENTCQ CVCKRTCPRN QPLNPGKCAC 370 380 390 400 410 ECTESPQKCL LKGKKFHHQT CSCYRRPCTN RQKACEPGFS YSEEVCRCVP SYWKRPQMS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases." Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K. EMBO J. 15:290-298(1996) [PubMed: 8617204] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 103-120.
[2]	Erratum Joukov V., Pajusola K., Kaipainen A., Chilov D., Lahtinen I., Kukk E., Saksela O., Kalkkinen N., Alitalo K. EMBO J. 15:1751-1751(1996) [PubMed: 8612600] [Abstract]
[3]	"Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4." Lee J., Gray A., Yuan J., Luoh S.-M., Avraham H., Wood W.I. Proc. Natl. Acad. Sci. U.S.A. 93:1988-1992(1996) [PubMed: 8700872] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Tissue: Glial tumor.
[4]	"Characterization of murine Flt4 ligand/VEGF-C." Fitz L.J., Morris J.C., Towler P., Long A., Burgess P., Greco R., Wang J., Gassaway R., Nickbarg E., Kovacic S., Ciarletta A., Giannotti J., Finnerty H., Zollner R., Beier D.R., Leak L.V., Turner K.J., Wood C.R. Oncogene 15:613-618(1997) [PubMed: 9247316] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"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: Skin and Urinary bladder.
[6]	"Proteolytic processing regulates receptor specificity and activity of VEGF-C." Joukov V., Sorsa T., Kumar V., Jeltsch M., Claesson-Welsh L., Cao Y., Saksela O., Kalkkinen N., Alitalo K. EMBO J. 16:3898-3911(1997) [PubMed: 9233800] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-41; 112-121 AND 228-233, MUTAGENESIS OF ARG-227.
[7]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-46.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X94216 mRNA. Translation: CAA63907.1. U43142 Unassigned DNA. Translation: AAA85214.1. U58111 mRNA. Translation: AAB02909.1. BC035212 mRNA. Translation: AAH35212.1. BC063685 mRNA. Translation: AAH63685.1.
PIR	S69207.
RefSeq	NP_005420.1.
UniGene	Hs.435215
3D structure databases
HSSP	HSSP built from PDB template 1FZV based on UniProtKB P49763.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:5738N. DIP:5747N.
PTM databases
PhosphoSite	P49767.
Genome annotation databases
Ensembl	ENSG00000150630. Homo sapiens. [Contig view]
GeneID	7424.
KEGG	hsa:7424.
Organism-specific databases
H-InvDB	HIX0024599.
HGNC	HGNC:12682. VEGFC.
MIM	601528. gene.
PharmGKB	PA37304.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P49767.
HOVERGEN	P49767.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P49767.
CleanEx	HS_VEGFC.
GermOnline	ENSG00000150630. Homo sapiens.
Family and domain databases
InterPro	IPR004153. CXCXC_repeat. IPR002400. GF_cysknot. IPR000072. PD_growth_factor. [Graphical view]
Pfam	PF03128. CXCXC. 5 hits. PF00341. PDGF. 1 hit. [Graphical view]
PRINTS	PR00438. GFCYSKNOT.
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	29082.
SOURCE	Search...

Entry information

Entry name

VEGFC_HUMAN

Accession

Primary (citable) accession number: P49767

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)