P49763 (PLGF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Placenta growth factor
Short name=PlGF

Gene names

Name:	PGF
Synonyms:	PGFL, PLGF

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	221 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. 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 process	Angiogenesis Differentiation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Ligand	Heparin-binding
Molecular function	Developmental protein Growth factor Mitogen
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	branching involved in ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara 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: Compara female pregnancy Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara positive regulation of angiogenesis 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 Ref.8. Source: UniProtKB positive regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara regulation of morphogenesis of a branching structure Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara sprouting angiogenesis Inferred from electronic annotation. Source: Compara vascular endothelial growth factor receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	growth 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.7

Chain

19 – 221

203

Placenta growth factor

PRO_0000023420

Regions

Region

193 – 213

21

Heparin-binding Probable

Amino acid modifications

Glycosylation

33

1

N-linked (GlcNAc...) Potential

Glycosylation

101

1

N-linked (GlcNAc...) Potential

Disulfide bond

52 ↔ 94

Disulfide bond

77

Interchain

Disulfide bond

83 ↔ 128

Disulfide bond

86

Interchain

Disulfide bond

87 ↔ 130

Natural variations

Alternative sequence

132 – 203

72

Missing in isoform PlGF-1 and isoform PlGF-2.

VSP_004644

Alternative sequence

213

1

R → RRRPKGRGKRRREKQRPTDC HL in isoform PlGF-2.

VSP_004645

Experimental info

Sequence conflict

91

1

N → D in AAB30462. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

221

Helix Strand Turn

Details...

Helix

43 – 50

8

Beta strand

51 – 60

10

Helix

62 – 64

3

Beta strand

65 – 67

3

Beta strand

73 – 84

12

Beta strand

92 – 108

17

Beta strand

111 – 113

3

Beta strand

116 – 131

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform PlGF-3 [UniParc]. Last modified November 16, 2001. Version 2. Checksum: D364C6A73C1C6987	FASTA	221	24,789
	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
	Isoform PlGF-1 (PlGF-131) [UniParc]. Checksum: 0E69DC4F84518352	FASTA	149	16,725
	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 TFSQHVRCEC RPLREKMKPE RCGDAVPRR
	Isoform PlGF-2 (PlGF-152) [UniParc]. Checksum: 02CDE4CC54A09637	FASTA	170	19,338
	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 TFSQHVRCEC RPLREKMKPE RRRPKGRGKR RREKQRPTDC HLCGDAVPRR

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00028074.
IPI00219514.
IPI00219515.

PIR

A41236.

RefSeq

NP_001193941.1. NM_001207012.1.
NP_002623.2. NM_002632.5.

UniGene

Hs.252820.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FZV	X-ray	2.00	A/B	19-221	[»]
1RV6	X-ray	2.45	V/W	37-131	[»]

ProteinModelPortal

P49763.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5746N.
DIP-5752N.

IntAct

P49763. 1 interaction.

STRING

9606.ENSP00000238607.

Polymorphism databases

DMDM

17380553.

Proteomic databases

PaxDb

P49763.

PRIDE

P49763.

Protocols and materials databases

DNASU

5228.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000405431; ENSP00000385365; ENSG00000119630.
ENST00000553716; ENSP00000451413; ENSG00000119630.
ENST00000555567; ENSP00000451040; ENSG00000119630.

GeneID

5228.

KEGG

hsa:5228.

UCSC

uc001xrb.3. human.
uc010ase.2. human.

Organism-specific databases

CTD

5228.

GeneCards

GC14M075408.

HGNC

HGNC:8893. PGF.

HPA

HPA041624.

MIM

601121. gene.

neXtProt

NX_P49763.

PharmGKB

PA33231.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG84541.

HOGENOM

HOG000230896.

InParanoid

P49763.

KO

K16859.

OMA

CECRPLR.

PhylomeDB

P49763.

Enzyme and pathway databases

Pathway_Interaction_DB

vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P49763.

Bgee

P49763.

CleanEx

HS_PGF.

Genevestigator

P49763.

GermOnline

ENSG00000119630. 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

BindingDB

P49763.

ChEMBL

CHEMBL1697671.

EvolutionaryTrace

P49763.

GenomeRNAi

5228.

NextBio

20210.

SOURCE

Search...

Entry information

Entry name

PLGF_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 130 of the entry and version 2 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.