PLGF_HUMAN
ID PLGF_HUMAN Reviewed; 221 AA.
AC P49763; Q07101; Q9BV78; Q9Y6S8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Placenta growth factor;
DE Short=PlGF;
DE Flags: Precursor;
GN Name=PGF; Synonyms=PGFL, PLGF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLGF-1).
RC TISSUE=Placenta;
RX PubMed=1924389; DOI=10.1073/pnas.88.20.9267;
RA Maglione D., Guerriero V., Viglietto G., Delli-Bovi P., Persico M.G.;
RT "Isolation of a human placenta cDNA coding for a protein related to the
RT vascular permeability factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9267-9271(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLGF-2).
RC TISSUE=Placenta;
RX PubMed=8148155; DOI=10.3109/08977199308991586;
RA Hauser S.D., Weich H.A.;
RT "A heparin-binding form of placenta growth factor (PlGF-2) is expressed in
RT human umbilical vein endothelial cells and in placenta.";
RL Growth Factors 9:259-268(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLGF-3).
RC TISSUE=Placenta;
RX PubMed=9207183; DOI=10.1006/bbrc.1997.6813;
RA Cao Y., Ji W.-R., Qi P., Rosin A., Cao Y.;
RT "Placenta growth factor: identification and characterization of a novel
RT isoform generated by RNA alternative splicing.";
RL Biochem. Biophys. Res. Commun. 235:493-498(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLGF-4).
RC TISSUE=Placenta;
RX PubMed=14568677; DOI=10.1016/s0165-0378(03)00082-2;
RA Yang W., Ahn H., Hinrichs M., Torry R.J., Torry D.S.;
RT "Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed
RT in human trophoblast and endothelial cells.";
RL J. Reprod. Immunol. 60:53-60(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PLGF-2).
RC TISSUE=Muscle, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 19-24, AND CHARACTERIZATION.
RX PubMed=7929268; DOI=10.1016/s0021-9258(18)47298-5;
RA Park J.E., Chen H.H., Winer J., Houck K.A., Ferrara N.;
RT "Placenta growth factor. Potentiation of vascular endothelial growth factor
RT bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but
RT not to Flk-1/KDR.";
RL J. Biol. Chem. 269:25646-25654(1994).
RN [8]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PLGF-2).
RX PubMed=7681160;
RA Maglione D., Guerriero V., Viglietto G., Ferraro M.G., Aprelikova O.,
RA Alitalo K., del Vecchio S., Lei K.-J., Chou J.Y., Persico M.G.;
RT "Two alternative mRNAs coding for the angiogenic factor, placenta growth
RT factor (PlGF), are transcribed from a single gene of chromosome 14.";
RL Oncogene 8:925-931(1993).
RN [9]
RP FUNCTION AS A TUMOR ACTIVATOR.
RX PubMed=21215706; DOI=10.1016/j.ccr.2010.11.009;
RA Rolny C., Mazzone M., Tugues S., Laoui D., Johansson I., Coulon C.,
RA Squadrito M.L., Segura I., Li X., Knevels E., Costa S., Vinckier S.,
RA Dresselaer T., Akerud P., De Mol M., Salomaki H., Phillipson M., Wyns S.,
RA Larsson E., Buysschaert I., Botling J., Himmelreich U.,
RA Van Ginderachter J.A., De Palma M., Dewerchin M., Claesson-Welsh L.,
RA Carmeliet P.;
RT "HRG inhibits tumor growth and metastasis by inducing macrophage
RT polarization and vessel normalization through downregulation of PlGF.";
RL Cancer Cell 19:31-44(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) (ISOFORM PLGF-1).
RX PubMed=11069911; DOI=10.1074/jbc.m008055200;
RA Iyer S., Leonidas D.D., Swaminathan G.J., Maglione D., Battisti M.,
RA Tucci M., Persico M.G., Acharya K.R.;
RT "The crystal structure of human placenta growth factor-1 (PlGF-1), an
RT angiogenic protein, at 2.0 A resolution.";
RL J. Biol. Chem. 276:12153-12161(2001).
CC -!- FUNCTION: Growth factor active in angiogenesis and endothelial cell
CC growth, stimulating their proliferation and migration. It binds to the
CC receptor FLT1/VEGFR-1. Isoform PlGF-2 binds NRP1/neuropilin-1 and
CC NRP2/neuropilin-2 in a heparin-dependent manner. Also promotes cell
CC tumor growth. {ECO:0000269|PubMed:21215706}.
CC -!- SUBUNIT: Antiparallel homodimer; disulfide-linked. Also found as
CC heterodimer with VEGFA/VEGF. Isoform PlGF-3 is found both as homodimer
CC and as monomer.
CC -!- INTERACTION:
CC P49763; P17948: FLT1; NbExp=2; IntAct=EBI-1037633, EBI-1026718;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=The three isoforms are secreted
CC but PlGF-2 appears to remain cell attached unless released by heparin.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=PlGF-3 {ECO:0000303|PubMed:9207183}; Synonyms=PlGF-203;
CC IsoId=P49763-1; Sequence=Displayed;
CC Name=PlGF-1 {ECO:0000303|PubMed:9207183}; Synonyms=PlGF-131;
CC IsoId=P49763-2; Sequence=VSP_004644;
CC Name=PlGF-2 {ECO:0000303|PubMed:8148155}; Synonyms=PlGF-152;
CC IsoId=P49763-3; Sequence=VSP_004644, VSP_004645;
CC Name=PlGF-4 {ECO:0000303|PubMed:14568677}; Synonyms=PlGF-224;
CC IsoId=P49763-4; Sequence=VSP_004645;
CC -!- TISSUE SPECIFICITY: While the three isoforms are present in most
CC placental tissues, PlGF-2 is specific to early (8 week) placenta and
CC only PlGF-1 is found in the colon and mammary carcinomas.
CC -!- DOMAIN: Isoform PlGF-2 contains a basic insert which acts as a cell
CC retention signal.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB25832.2; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; X54936; CAA38698.1; -; mRNA.
DR EMBL; S72960; AAB30462.2; -; mRNA.
DR EMBL; AC006530; AAD30179.1; -; Genomic_DNA.
DR EMBL; BC001422; AAH01422.1; -; mRNA.
DR EMBL; BC007789; AAH07789.1; -; mRNA.
DR EMBL; BC007255; AAH07255.1; -; mRNA.
DR EMBL; S57152; AAB25832.2; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS55932.1; -. [P49763-2]
DR CCDS; CCDS9835.1; -. [P49763-3]
DR PIR; A41236; A41236.
DR RefSeq; NP_001193941.1; NM_001207012.1. [P49763-2]
DR RefSeq; NP_002623.2; NM_002632.5. [P49763-3]
DR PDB; 1FZV; X-ray; 2.00 A; A/B=19-131, A/B=204-221.
DR PDB; 1RV6; X-ray; 2.45 A; V/W=37-136.
DR PDBsum; 1FZV; -.
DR PDBsum; 1RV6; -.
DR AlphaFoldDB; P49763; -.
DR SMR; P49763; -.
DR BioGRID; 111249; 7.
DR DIP; DIP-5752N; -.
DR IntAct; P49763; 2.
DR STRING; 9606.ENSP00000451040; -.
DR BindingDB; P49763; -.
DR ChEMBL; CHEMBL1697671; -.
DR DrugBank; DB08885; Aflibercept.
DR DrugCentral; P49763; -.
DR GlyGen; P49763; 2 sites.
DR iPTMnet; P49763; -.
DR PhosphoSitePlus; P49763; -.
DR BioMuta; PGF; -.
DR DMDM; 17380553; -.
DR MassIVE; P49763; -.
DR PaxDb; P49763; -.
DR PeptideAtlas; P49763; -.
DR PRIDE; P49763; -.
DR ProteomicsDB; 56100; -. [P49763-1]
DR ProteomicsDB; 56101; -. [P49763-2]
DR ProteomicsDB; 56102; -. [P49763-3]
DR ABCD; P49763; 12 sequenced antibodies.
DR Antibodypedia; 12927; 949 antibodies from 43 providers.
DR DNASU; 5228; -.
DR Ensembl; ENST00000405431.2; ENSP00000385365.2; ENSG00000119630.14. [P49763-1]
DR Ensembl; ENST00000553716.5; ENSP00000451413.1; ENSG00000119630.14. [P49763-2]
DR Ensembl; ENST00000555567.6; ENSP00000451040.1; ENSG00000119630.14. [P49763-3]
DR GeneID; 5228; -.
DR KEGG; hsa:5228; -.
DR MANE-Select; ENST00000555567.6; ENSP00000451040.1; NM_002632.6; NP_002623.2. [P49763-3]
DR UCSC; uc001xrb.4; human. [P49763-1]
DR CTD; 5228; -.
DR DisGeNET; 5228; -.
DR GeneCards; PGF; -.
DR HGNC; HGNC:8893; PGF.
DR HPA; ENSG00000119630; Tissue enhanced (placenta, thyroid gland).
DR MIM; 601121; gene.
DR neXtProt; NX_P49763; -.
DR OpenTargets; ENSG00000119630; -.
DR PharmGKB; PA33231; -.
DR VEuPathDB; HostDB:ENSG00000119630; -.
DR eggNOG; ENOG502S2DE; Eukaryota.
DR GeneTree; ENSGT00940000160164; -.
DR HOGENOM; CLU_042996_3_0_1; -.
DR InParanoid; P49763; -.
DR OMA; KQCECRP; -.
DR PhylomeDB; P49763; -.
DR TreeFam; TF319554; -.
DR PathwayCommons; P49763; -.
DR Reactome; R-HSA-194313; VEGF ligand-receptor interactions.
DR Reactome; R-HSA-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR SignaLink; P49763; -.
DR SIGNOR; P49763; -.
DR BioGRID-ORCS; 5228; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; PGF; human.
DR EvolutionaryTrace; P49763; -.
DR GeneWiki; Placental_growth_factor; -.
DR GenomeRNAi; 5228; -.
DR Pharos; P49763; Tclin.
DR PRO; PR:P49763; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P49763; protein.
DR Bgee; ENSG00000119630; Expressed in renal medulla and 204 other tissues.
DR ExpressionAtlas; P49763; baseline and differential.
DR Genevisible; P49763; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0042056; F:chemoattractant activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IMP:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0050930; P:induction of positive chemotaxis; IBA:GO_Central.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:0060754; P:positive regulation of mast cell chemotaxis; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0002040; P:sprouting angiogenesis; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IBA:GO_Central.
DR CDD; cd00135; PDGF; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR023581; PD_growth_factor_CS.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR Pfam; PF00341; PDGF; 1.
DR SMART; SM00141; PDGF; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00249; PDGF_1; 1.
DR PROSITE; PS50278; PDGF_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Growth factor; Heparin-binding; Mitogen; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:7929268"
FT CHAIN 19..221
FT /note="Placenta growth factor"
FT /id="PRO_0000023420"
FT REGION 175..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..213
FT /note="Heparin-binding"
FT /evidence="ECO:0000305"
FT COMPBIAS 205..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..94
FT DISULFID 77
FT /note="Interchain"
FT DISULFID 83..128
FT DISULFID 86
FT /note="Interchain"
FT DISULFID 87..130
FT VAR_SEQ 132..203
FT /note="Missing (in isoform PlGF-1 and isoform PlGF-2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1924389, ECO:0000303|PubMed:8148155"
FT /id="VSP_004644"
FT VAR_SEQ 213
FT /note="R -> RRRPKGRGKRRREKQRPTDCHL (in isoform PlGF-2 and
FT isoform PlGF-4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8148155, ECO:0000305|PubMed:14568677"
FT /id="VSP_004645"
FT CONFLICT 91
FT /note="N -> D (in Ref. 2; AAB30462)"
FT /evidence="ECO:0000305"
FT HELIX 43..50
FT /evidence="ECO:0007829|PDB:1FZV"
FT STRAND 51..60
FT /evidence="ECO:0007829|PDB:1FZV"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:1FZV"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:1FZV"
FT STRAND 73..84
FT /evidence="ECO:0007829|PDB:1FZV"
FT STRAND 92..108
FT /evidence="ECO:0007829|PDB:1FZV"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1RV6"
FT STRAND 116..132
FT /evidence="ECO:0007829|PDB:1FZV"
SQ SEQUENCE 221 AA; 24789 MW; D364C6A73C1C6987 CRC64;
MPVMRLFPCF LQLLAGLALP AVPPQQWALS AGNGSSEVEV VPFQEVWGRS YCRALERLVD
VVSEYPSEVE HMFSPSCVSL LRCTGCCGDE NLHCVPVETA NVTMQLLKIR SGDRPSYVEL
TFSQHVRCEC RHSPGRQSPD MPGDFRADAP SFLPPRRSLP MLFRMEWGCA LTGSQSAVWP
SSPVPEEIPR MHPGRNGKKQ QRKPLREKMK PERCGDAVPR R
