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P49763

- PLGF_HUMAN

UniProt

P49763 - PLGF_HUMAN

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Protein

Placenta growth factor

Gene

PGF

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. growth factor activity Source: UniProtKB
  2. heparin binding Source: UniProtKB-KW

GO - Biological processi

  1. branching involved in ureteric bud morphogenesis Source: Ensembl
  2. cell-cell signaling Source: ProtInc
  3. cell differentiation Source: UniProtKB-KW
  4. cellular response to hormone stimulus Source: Ensembl
  5. female pregnancy Source: Ensembl
  6. organ regeneration Source: Ensembl
  7. positive regulation of angiogenesis Source: Ensembl
  8. positive regulation of cell division Source: UniProtKB-KW
  9. positive regulation of cell proliferation Source: UniProtKB
  10. positive regulation of endothelial cell proliferation Source: Ensembl
  11. regulation of morphogenesis of a branching structure Source: Ensembl
  12. response to drug Source: Ensembl
  13. response to hypoxia Source: Ensembl
  14. signal transduction Source: ProtInc
  15. sprouting angiogenesis Source: Ensembl
  16. vascular endothelial growth factor receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, Differentiation

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_12380. VEGF ligand-receptor interactions.
REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.

Names & Taxonomyi

Protein namesi
Recommended name:
Placenta growth factor
Short name:
PlGF
Gene namesi
Name:PGF
Synonyms:PGFL, PLGF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:8893. PGF.

Subcellular locationi

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

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: Ensembl
  3. membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33231.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 18181 PublicationAdd
BLAST
Chaini19 – 221203Placenta growth factorPRO_0000023420Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi52 ↔ 94
Disulfide bondi77 – 77Interchain
Disulfide bondi83 ↔ 128
Disulfide bondi86 – 86Interchain
Disulfide bondi87 ↔ 130
Glycosylationi101 – 1011N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP49763.
PRIDEiP49763.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiP49763.
CleanExiHS_PGF.
ExpressionAtlasiP49763. baseline and differential.
GenevestigatoriP49763.

Organism-specific databases

HPAiHPA041624.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
FLT1P179482EBI-1037633,EBI-1026718

Protein-protein interaction databases

BioGridi111249. 4 interactions.
DIPiDIP-5746N.
DIP-5752N.
IntActiP49763. 2 interactions.
STRINGi9606.ENSP00000238607.

Structurei

Secondary structure

1
221
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 508Combined sources
Beta strandi51 – 6010Combined sources
Helixi62 – 643Combined sources
Beta strandi65 – 673Combined sources
Beta strandi73 – 8412Combined sources
Beta strandi92 – 10817Combined sources
Beta strandi111 – 1133Combined sources
Beta strandi116 – 13116Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FZVX-ray2.00A/B19-221[»]
1RV6X-ray2.45V/W37-136[»]
ProteinModelPortaliP49763.
SMRiP49763. Positions 35-131.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49763.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni193 – 21321Heparin-bindingCuratedAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG84541.
GeneTreeiENSGT00730000110791.
HOGENOMiHOG000230896.
InParanoidiP49763.
KOiK16859.
OMAiRCECRPL.
OrthoDBiEOG74R1S0.
PhylomeDBiP49763.
TreeFamiTF319554.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform PlGF-3 (identifier: P49763-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MPVMRLFPCF LQLLAGLALP AVPPQQWALS AGNGSSEVEV VPFQEVWGRS
60 70 80 90 100
YCRALERLVD VVSEYPSEVE HMFSPSCVSL LRCTGCCGDE NLHCVPVETA
110 120 130 140 150
NVTMQLLKIR SGDRPSYVEL TFSQHVRCEC RHSPGRQSPD MPGDFRADAP
160 170 180 190 200
SFLPPRRSLP MLFRMEWGCA LTGSQSAVWP SSPVPEEIPR MHPGRNGKKQ
210 220
QRKPLREKMK PERCGDAVPR R
Length:221
Mass (Da):24,789
Last modified:November 16, 2001 - v2
Checksum:iD364C6A73C1C6987
GO
Isoform PlGF-1 (identifier: P49763-2) [UniParc]FASTAAdd to Basket

Also known as: PlGF-131

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

Show »
Length:149
Mass (Da):16,725
Checksum:i0E69DC4F84518352
GO
Isoform PlGF-2 (identifier: P49763-3) [UniParc]FASTAAdd to Basket

Also known as: PlGF-152

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

Show »
Length:170
Mass (Da):19,338
Checksum:i02CDE4CC54A09637
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti91 – 911N → D in AAB30462. (PubMed:8148155)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei132 – 20372Missing in isoform PlGF-1 and isoform PlGF-2. 3 PublicationsVSP_004644Add
BLAST
Alternative sequencei213 – 2131R → RRRPKGRGKRRREKQRPTDC HL in isoform PlGF-2. 2 PublicationsVSP_004645

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS55932.1. [P49763-2]
CCDS9835.1. [P49763-3]
PIRiA41236.
RefSeqiNP_001193941.1. NM_001207012.1. [P49763-2]
NP_002623.2. NM_002632.5. [P49763-3]
UniGeneiHs.252820.

Genome annotation databases

EnsembliENST00000405431; ENSP00000385365; ENSG00000119630. [P49763-1]
ENST00000553716; ENSP00000451413; ENSG00000119630. [P49763-2]
ENST00000555567; ENSP00000451040; ENSG00000119630. [P49763-3]
GeneIDi5228.
KEGGihsa:5228.
UCSCiuc001xrb.3. human. [P49763-2]
uc010ase.2. human. [P49763-1]

Polymorphism databases

DMDMi17380553.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS55932.1. [P49763-2 ]
CCDS9835.1. [P49763-3 ]
PIRi A41236.
RefSeqi NP_001193941.1. NM_001207012.1. [P49763-2 ]
NP_002623.2. NM_002632.5. [P49763-3 ]
UniGenei Hs.252820.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1FZV X-ray 2.00 A/B 19-221 [» ]
1RV6 X-ray 2.45 V/W 37-136 [» ]
ProteinModelPortali P49763.
SMRi P49763. Positions 35-131.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111249. 4 interactions.
DIPi DIP-5746N.
DIP-5752N.
IntActi P49763. 2 interactions.
STRINGi 9606.ENSP00000238607.

Chemistry

BindingDBi P49763.
ChEMBLi CHEMBL1697671.
DrugBanki DB08885. Aflibercept.

Polymorphism databases

DMDMi 17380553.

Proteomic databases

PaxDbi P49763.
PRIDEi P49763.

Protocols and materials databases

DNASUi 5228.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000405431 ; ENSP00000385365 ; ENSG00000119630 . [P49763-1 ]
ENST00000553716 ; ENSP00000451413 ; ENSG00000119630 . [P49763-2 ]
ENST00000555567 ; ENSP00000451040 ; ENSG00000119630 . [P49763-3 ]
GeneIDi 5228.
KEGGi hsa:5228.
UCSCi uc001xrb.3. human. [P49763-2 ]
uc010ase.2. human. [P49763-1 ]

Organism-specific databases

CTDi 5228.
GeneCardsi GC14M075408.
HGNCi HGNC:8893. PGF.
HPAi HPA041624.
MIMi 601121. gene.
neXtProti NX_P49763.
PharmGKBi PA33231.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG84541.
GeneTreei ENSGT00730000110791.
HOGENOMi HOG000230896.
InParanoidi P49763.
KOi K16859.
OMAi RCECRPL.
OrthoDBi EOG74R1S0.
PhylomeDBi P49763.
TreeFami TF319554.

Enzyme and pathway databases

Reactomei REACT_12380. VEGF ligand-receptor interactions.
REACT_12583. VEGF binds to VEGFR leading to receptor dimerization.

Miscellaneous databases

EvolutionaryTracei P49763.
GeneWikii Placental_growth_factor.
GenomeRNAii 5228.
NextBioi 20210.
PROi P49763.
SOURCEi Search...

Gene expression databases

Bgeei P49763.
CleanExi HS_PGF.
ExpressionAtlasi P49763. baseline and differential.
Genevestigatori P49763.

Family and domain databases

Gene3Di 2.10.90.10. 1 hit.
InterProi IPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
[Graphical view ]
Pfami PF00341. PDGF. 1 hit.
[Graphical view ]
SMARTi SM00141. PDGF. 1 hit.
[Graphical view ]
SUPFAMi SSF57501. SSF57501. 1 hit.
PROSITEi PS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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).

Entry informationi

Entry nameiPLGF_HUMAN
AccessioniPrimary (citable) accession number: P49763
Secondary accession number(s): Q07101, Q9BV78, Q9Y6S8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 16, 2001
Last modified: October 29, 2014
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3