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P49763

- PLGF_HUMAN

UniProt

P49763 - PLGF_HUMAN

Protein

Placenta growth factor

Gene

PGF

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 2 (16 Nov 2001)
      Previous versions | rss
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    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
    3. protein binding Source: IntAct

    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

    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

    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

    ArrayExpressiP49763.
    BgeeiP49763.
    CleanExiHS_PGF.
    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 – 508
    Beta strandi51 – 6010
    Helixi62 – 643
    Beta strandi65 – 673
    Beta strandi73 – 8412
    Beta strandi92 – 10817
    Beta strandi111 – 1133
    Beta strandi116 – 13116

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MPVMRLFPCF LQLLAGLALP AVPPQQWALS AGNGSSEVEV VPFQEVWGRS    50
    YCRALERLVD VVSEYPSEVE HMFSPSCVSL LRCTGCCGDE NLHCVPVETA 100
    NVTMQLLKIR SGDRPSYVEL TFSQHVRCEC RHSPGRQSPD MPGDFRADAP 150
    SFLPPRRSLP MLFRMEWGCA LTGSQSAVWP SSPVPEEIPR MHPGRNGKKQ 200
    QRKPLREKMK PERCGDAVPR R 221
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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.

    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.
    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

    ArrayExpressi P49763.
    Bgeei P49763.
    CleanExi HS_PGF.
    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

    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 1, 2014
    This is version 144 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