P97953 (VEGFC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vascular endothelial growth factor C
Short name=VEGF-C

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

Gene names

Name:

Vegfc

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	415 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 (KDR/FLK1) and VEGFR-3 (FLT4) receptors.
Subunit structure	Homodimer; non-covalent and antiparallel.
Subcellular location	Secreted.
Tissue specificity	Expression detected in mesenchymal cells of postimplantation embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions, and in the developing mesenterium. Expressed in adult heart, brain, spleen, lung, liver, skeletal muscle and kidney.
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-223 and Ser-224 producing a 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 By similarity.
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	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW induction of positive chemotaxis Inferred from electronic annotation. Source: Compara morphogenesis of embryonic epithelium Inferred from mutant phenotype PubMed 14634646. Source: MGI negative regulation of blood pressure Inferred from electronic annotation. Source: Compara organ morphogenesis Inferred from mutant phenotype PubMed 14634646. Source: MGI positive regulation of blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from mutant phenotype PubMed 16462734. Source: MGI positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of lymphangiogenesis Inferred from direct assay PubMed 20133819. Source: MGI positive regulation of mast cell chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of protein autophosphorylation Inferred from electronic annotation. Source: Compara positive regulation of protein secretion Inferred from electronic annotation. Source: Compara regulation of vascular endothelial growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara vascular endothelial growth factor receptor signaling pathway Inferred from direct assay Ref.1. Source: MGI
Cellular_component	extracellular space Inferred from direct assay Ref.2. Source: MGI membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	chemoattractant activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	By similarity
	Propeptide	32 – 107	76	Potential		PRO_0000023403
	Chain	108 – 223	116	Vascular endothelial growth factor C		PRO_0000023404
	Propeptide	224 – 415	192	Potential		PRO_0000023405
Regions
	Repeat	276 – 291	16	1
	Repeat	300 – 315	16	2
	Repeat	324 – 339	16	3
	Repeat	343 – 358	16	4
	Region	276 – 358	83	4 X 16 AA repeats of C-X(10)-C-X-C-X(1,3)-C
Amino acid modifications
	Glycosylation	171	1	N-linked (GlcNAc...) Potential
	Glycosylation	201	1	N-linked (GlcNAc...) Potential
	Glycosylation	236	1	N-linked (GlcNAc...) Potential
	Disulfide bond	127 ↔ 169		By similarity
	Disulfide bond	152		Interchain By similarity
	Disulfide bond	158 ↔ 205		By similarity
	Disulfide bond	161		Interchain By similarity
	Disulfide bond	162 ↔ 207		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P97953 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: D9D3DD3CECC659D6	FASTA	415	46,471
	10 20 30 40 50 60 MHLLCFLSLA CSLLAAALIP SPREAPATVA AFESGLGFSE AEPDGGEVKA FEGKDLEEQL 70 80 90 100 110 120 RSVSSVDELM SVLYPDYWKM YKCQLRKGGW QQPTLNTRTG DSVKFAAAHY NTEILKSIDN 130 140 150 160 170 180 EWRKTQCMPR EVCIDVGKEF GAATNTFFKP PCVSVYRCGG CCNSEGLQCM NTSTGYLSKT 190 200 210 220 230 240 LFEITVPLSQ GPKPVTISFA NHTSCRCMSK LDVYRQVHSI IRRSLPATLP QCQAANKTCP 250 260 270 280 290 300 TNYVWNNYMC RCLAQQDFIF YSNVEDDSTN GFHDVCGPNK ELDEDTCQCV CKGGLRPSSC 310 320 330 340 350 360 GPHKELDRDS CQCVCKNKLF PNSCGANREF DENTCQCVCK RTCPRNQPLN PGKCACECTE 370 380 390 400 410 NTQKCFLKGK KFHHQTCSCY RRPCANRLKH CDPGLSFSEE VCRCVPSYWK RPHLN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development." Kukk E., Lymboussaki A., Taira S., Kaipainen A., Jeltsch M., Joukov V., Alitalo K. Development 122:3829-3837(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 108-126. Strain: BALB/c.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Head.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N-3. Tissue: Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U73620 mRNA. Translation: AAC52984.1. U58112 mRNA. Translation: AAB46707.1. AK047844 mRNA. Translation: BAC33172.1. BC096377 mRNA. Translation: AAH96377.1.
IPI	IPI00131065.
RefSeq	NP_033532.1. NM_009506.2.
UniGene	Mm.1402.
3D structure databases
ProteinModelPortal	P97953.
SMR	P97953. Positions 113-211.
ModBase	Search...
PTM databases
PhosphoSite	P97953.
Proteomic databases
PRIDE	P97953.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033919; ENSMUSP00000033919; ENSMUSG00000031520.
GeneID	22341.
KEGG	mmu:22341.
UCSC	uc009lsc.1. mouse.
Organism-specific databases
CTD	7424.
MGI	MGI:109124. Vegfc.
Phylogenomic databases
eggNOG	NOG79308.
GeneTree	ENSGT00530000062930.
HOGENOM	HOG000231512.
HOVERGEN	HBG073119.
InParanoid	P97953.
KO	K05449.
OMA	KCFLKGK.
OrthoDB	EOG4D7Z62.
Gene expression databases
Bgee	P97953.
CleanEx	MM_VEGFC.
Genevestigator	P97953.
GermOnline	ENSMUSG00000031520. Mus musculus.
Family and domain databases
InterPro	IPR004153. CXCXC_repeat. IPR000072. PD_growth_factor. IPR023581. PD_growth_factor_CS. [Graphical view]
Pfam	PF03128. CXCXC. 3 hits. 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
NextBio	302605.
SOURCE	Search...

Entry information

Entry name

VEGFC_MOUSE

Accession

Primary (citable) accession number: P97953
Secondary accession number(s): Q543R6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 1, 1997
Last modified:	April 3, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program