Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P49763 (PLGF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 138. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Placenta growth factor

Short name=PlGF
Gene names
Name:PGF
Synonyms:PGFL, PLGF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length221 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 and endothelial cell growth, stimulating their proliferation and migration. It binds to the receptor FLT1/VEGFR-1. Isoform PlGF-2 binds NRP1/neuropilin-1 and NRP2/neuropilin-2 in a heparin-dependent manner. Also promotes cell tumor growth. Ref.8

Subunit structure

Antiparallel homodimer; disulfide-linked. Also found as heterodimer with VEGFA/VEGF. Isoform PlGF-3 is found both as homodimer and as monomer.

Subcellular location

Secreted. Note: The three isoforms are secreted but PlGF-2 appears to remain cell attached unless released by heparin.

Tissue specificity

While the three isoforms are present in most placental tissues, PlGF-2 is specific to early (8 week) placenta and only PlGF-1 is found in the colon and mammary carcinomas.

Domain

Isoform PlGF-2 contains a basic insert which acts as a cell retention signal.

Post-translational modification

N-glycosylated.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainSignal
   LigandHeparin-binding
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbranching involved in ureteric bud morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

cell-cell signaling

Traceable author statement PubMed 9467961. Source: ProtInc

cellular response to hormone stimulus

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of morphogenesis of a branching structure

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

sprouting angiogenesis

Inferred from electronic annotation. Source: Ensembl

vascular endothelial growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from electronic annotation. Source: InterPro

   Molecular_functiongrowth factor activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform PlGF-3 (identifier: P49763-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform PlGF-1 (identifier: P49763-2)

Also known as: PlGF-131;

The sequence of this isoform differs from the canonical sequence as follows:
     132-203: Missing.
Isoform PlGF-2 (identifier: P49763-3)

Also known as: PlGF-152;

The sequence of this isoform differs from the canonical sequence as follows:
     132-203: Missing.
     213-213: R → RRRPKGRGKRRREKQRPTDCHL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.7
Chain19 – 221203Placenta growth factor
PRO_0000023420

Regions

Region193 – 21321Heparin-binding Probable

Amino acid modifications

Glycosylation331N-linked (GlcNAc...) Potential
Glycosylation1011N-linked (GlcNAc...) Potential
Disulfide bond52 ↔ 94
Disulfide bond77Interchain
Disulfide bond83 ↔ 128
Disulfide bond86Interchain
Disulfide bond87 ↔ 130

Natural variations

Alternative sequence132 – 20372Missing in isoform PlGF-1 and isoform PlGF-2.
VSP_004644
Alternative sequence2131R → RRRPKGRGKRRREKQRPTDC HL in isoform PlGF-2.
VSP_004645

Experimental info

Sequence conflict911N → D in AAB30462. Ref.2

Secondary structure

............... 221
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PlGF-3 [UniParc].

Last modified November 16, 2001. Version 2.
Checksum: D364C6A73C1C6987

FASTA22124,789
        10         20         30         40         50         60 
MPVMRLFPCF LQLLAGLALP AVPPQQWALS AGNGSSEVEV VPFQEVWGRS YCRALERLVD 

        70         80         90        100        110        120 
VVSEYPSEVE HMFSPSCVSL LRCTGCCGDE NLHCVPVETA NVTMQLLKIR SGDRPSYVEL 

       130        140        150        160        170        180 
TFSQHVRCEC RHSPGRQSPD MPGDFRADAP SFLPPRRSLP MLFRMEWGCA LTGSQSAVWP 

       190        200        210        220 
SSPVPEEIPR MHPGRNGKKQ QRKPLREKMK PERCGDAVPR R 

« Hide

Isoform PlGF-1 (PlGF-131) [UniParc].

Checksum: 0E69DC4F84518352
Show »

FASTA14916,725
Isoform PlGF-2 (PlGF-152) [UniParc].

Checksum: 02CDE4CC54A09637
Show »

FASTA17019,338

References

« Hide 'large scale' references
[1]"Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor."
Maglione D., Guerriero V., Viglietto G., Delli-Bovi P., Persico M.G.
Proc. Natl. Acad. Sci. U.S.A. 88:9267-9271(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLGF-1).
Tissue: Placenta.
[2]"A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta."
Hauser S.D., Weich H.A.
Growth Factors 9:259-268(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLGF-2).
Tissue: Placenta.
[3]"Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14."
Maglione D., Guerriero V., Viglietto G., Ferraro M.G., Aprelikova O., Alitalo K., del Vecchio S., Lei K.-J., Chou J.Y., Persico M.G.
Oncogene 8:925-931(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PLGF-2).
[4]"Placenta growth factor: identification and characterization of a novel isoform generated by RNA alternative splicing."
Cao Y., Ji W.-R., Qi P., Rosin A., Cao Y.
Biochem. Biophys. Res. Commun. 235:493-498(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM PLGF-3).
Tissue: Placenta.
[5]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM PLGF-1).
[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] (ISOFORM PLGF-2).
Tissue: Muscle and Placenta.
[7]"Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR."
Park J.E., Chen H.H., Winer J., Houck K.A., Ferrara N.
J. Biol. Chem. 269:25646-25654(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, PROTEIN SEQUENCE OF 19-24.
[8]"HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF."
Rolny C., Mazzone M., Tugues S., Laoui D., Johansson I., Coulon C., Squadrito M.L., Segura I., Li X., Knevels E., Costa S., Vinckier S., Dresselaer T., Akerud P., De Mol M., Salomaki H., Phillipson M., Wyns S. expand/collapse author list , Larsson E., Buysschaert I., Botling J., Himmelreich U., Van Ginderachter J.A., De Palma M., Dewerchin M., Claesson-Welsh L., Carmeliet P.
Cancer Cell 19:31-44(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A TUMOR ACTIVATOR.
[9]"The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution."
Iyer S., Leonidas D.D., Swaminathan G.J., Maglione D., Battisti M., Tucci M., Persico M.G., Acharya K.R.
J. Biol. Chem. 276:12153-12161(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) (ISOFORM PLGF-1).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54936 mRNA. Translation: CAA38698.1.
S72960 mRNA. Translation: AAB30462.2.
S57152 Genomic DNA. Translation: AAB25832.2. Sequence problems.
AC006530 Genomic DNA. Translation: AAD30179.1.
BC001422 mRNA. Translation: AAH01422.1.
BC007789 mRNA. Translation: AAH07789.1.
BC007255 mRNA. Translation: AAH07255.1.
PIRA41236.
RefSeqNP_001193941.1. NM_001207012.1.
NP_002623.2. NM_002632.5.
UniGeneHs.252820.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FZVX-ray2.00A/B19-221[»]
1RV6X-ray2.45V/W37-131[»]
ProteinModelPortalP49763.
SMRP49763. Positions 35-131.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111249. 4 interactions.
DIPDIP-5746N.
DIP-5752N.
IntActP49763. 1 interaction.
STRING9606.ENSP00000238607.

Chemistry

BindingDBP49763.
ChEMBLCHEMBL1697671.

Polymorphism databases

DMDM17380553.

Proteomic databases

PaxDbP49763.
PRIDEP49763.

Protocols and materials databases

DNASU5228.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000405431; ENSP00000385365; ENSG00000119630. [P49763-1]
ENST00000553716; ENSP00000451413; ENSG00000119630. [P49763-2]
ENST00000555567; ENSP00000451040; ENSG00000119630. [P49763-3]
GeneID5228.
KEGGhsa:5228.
UCSCuc001xrb.3. human. [P49763-2]
uc010ase.2. human. [P49763-1]

Organism-specific databases

CTD5228.
GeneCardsGC14M075408.
HGNCHGNC:8893. PGF.
HPAHPA041624.
MIM601121. gene.
neXtProtNX_P49763.
PharmGKBPA33231.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84541.
HOGENOMHOG000230896.
InParanoidP49763.
KOK16859.
OMARCECRPL.
OrthoDBEOG74R1S0.
PhylomeDBP49763.
TreeFamTF319554.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP49763.
BgeeP49763.
CleanExHS_PGF.
GenevestigatorP49763.

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

EvolutionaryTraceP49763.
GeneWikiPlacental_growth_factor.
GenomeRNAi5228.
NextBio20210.
PROP49763.
SOURCESearch...

Entry information

Entry namePLGF_HUMAN
AccessionPrimary (citable) accession number: P49763
Secondary accession number(s): Q07101, Q9BV78, Q9Y6S8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 16, 2001
Last modified: March 19, 2014
This is version 138 of the entry and version 2 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 14

Human chromosome 14: entries, gene names and cross-references to MIM