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P20033 (PDGFA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Platelet-derived growth factor subunit A

Short name=PDGF subunit A
Alternative name(s):
PDGF-1
Platelet-derived growth factor A chain
Platelet-derived growth factor alpha polypeptide
Gene names
Name:Pdgfa
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length211 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal lung alveolar septum formation during embryogenesis, normal development of the gastrointestinal tract, normal development of Leydig cells and spermatogenesis. Required for normal oligodendrocyte development and normal myelination in the spinal cord and cerebellum. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFB. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.12

Subunit structure

Homodimer; antiparallel disulfide-linked dimer. Heterodimer with PDGFB; antiparallel disulfide-linked dimer. The PDGFA homodimer interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts with CSPG4 By similarity.

Subcellular location

Secreted. Note: Released by platelets upon wounding.

Tissue specificity

Expression primarily localized in papillary regions with presumable expression in tubular cells comprising the loop of Henle. In the renal cortex, a widespread expression seen in the vascular smooth muscle cells and is barely detectable in interstitial cells. Ref.9

Domain

The long form contains a basic insert which acts as a cell retention signal.

Disruption phenotype

Lethal, due to defects in cell proliferation and migration, leading to defects in the development of the embryonic lung, gastrointestinal tract, oligodendrocytes and Leydig cells. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.11

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainSignal
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from direct assay PubMed 12176888. Source: MGI

angiogenesis

Inferred from direct assay PubMed 12101409. Source: MGI

blood coagulation

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell projection assembly

Inferred from direct assay PubMed 12176888. Source: MGI

digestive tract development

Inferred from mutant phenotype Ref.6. Source: UniProtKB

hair follicle development

Inferred from mutant phenotype PubMed 10331973. Source: MGI

lung alveolus development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

negative chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of phosphatidylinositol biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of platelet activation

Inferred from sequence or structural similarity. Source: UniProtKB

organ morphogenesis

Inferred from mutant phenotype PubMed 14522834. Source: MGI

platelet-derived growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of DNA replication

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MAP kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 10331973. Source: MGI

positive regulation of fibroblast proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 10331973. Source: MGI

positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling

Inferred from mutant phenotype PubMed 18559345. Source: MGI

regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 11940581. Source: MGI

regulation of smooth muscle cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

response to wounding

Inferred from sequence or structural similarity. Source: UniProtKB

skin development

Inferred from mutant phenotype PubMed 10331973. Source: MGI

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 19734317. Source: BHF-UCL

membrane

Inferred from electronic annotation. Source: InterPro

microvillus

Inferred from direct assay PubMed 12101409. Source: MGI

   Molecular_functioncollagen binding

Inferred from sequence or structural similarity. Source: UniProtKB

growth factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

platelet-derived growth factor receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P20033-1)

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 Short (identifier: P20033-2)

The sequence of this isoform differs from the canonical sequence as follows:
     194-196: GRR → DVR
     197-211: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Propeptide21 – 8666Removed in mature form
PRO_0000023358
Chain87 – 211125Platelet-derived growth factor subunit A
PRO_0000023359

Regions

Region158 – 1625Receptor binding site Potential

Amino acid modifications

Glycosylation1341N-linked (GlcNAc...) Potential
Disulfide bond96 ↔ 140 By similarity
Disulfide bond123Interchain By similarity
Disulfide bond129 ↔ 177 By similarity
Disulfide bond132Interchain By similarity
Disulfide bond133 ↔ 179 By similarity

Natural variations

Alternative sequence194 – 1963GRR → DVR in isoform Short.
VSP_004604
Alternative sequence197 – 21115Missing in isoform Short.
VSP_004605

Experimental info

Sequence conflict921V → I in AAA39903. Ref.2
Sequence conflict1741H → D in AAB28740. Ref.1
Sequence conflict1741H → D in AAB28741. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: AC4345A10ECF4B39

FASTA21124,102
        10         20         30         40         50         60 
MRTWACLLLL GCGYLAHALA EEAEIPRELI ERLARSQIHS IRDLQRLLEI DSVGAEDALE 

        70         80         90        100        110        120 
TSLRAHGSHA INHVPEKRPV PIRRKRSIEE AVPAVCKTRT VIYEIPRSQV DPTSANFLIW 

       130        140        150        160        170        180 
PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV KVAKVEYVRK KPKLKEVQVR LEEHLECACA 

       190        200        210 
TSNLNPDHRE EETGRRRESG KNRKRKRLKP T 

« Hide

Isoform Short [UniParc].

Checksum: 3F219DA70E4007D4
Show »

FASTA19622,267

References

[1]"Characterization of the mouse PDGF A-chain gene. Evolutionary conservation of gene structure, nucleotide sequence and alternative splicing."
Rorsman F., Betsholtz C.
Growth Factors 6:303-313(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS LONG AND SHORT).
Strain: BALB/c.
[2]"Selective expression of PDGF A and its receptor during early mouse embryogenesis."
Mercola M., Wang C., Kelly J., Brownlee C., Jackson-Grusby L., Stiles C., Bowen-Pope D.F.
Dev. Biol. 138:114-122(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
Strain: F9.
[3]"PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis."
Bostrom H., Willetts K., Pekny M., Leveen P., Lindahl P., Hedstrand H., Pekna M., Hellstrom M., Gebre-Medhin S., Schalling M., Nilsson M., Kurland S., Tornell J., Heath J.K., Betsholtz C.
Cell 85:863-873(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[4]"Alveogenesis failure in PDGF-A-deficient mice is coupled to lack of distal spreading of alveolar smooth muscle cell progenitors during lung development."
Lindahl P., Karlsson L., Hellstrom M., Gebre-Medhin S., Willetts K., Heath J.K., Betsholtz C.
Development 124:3943-3953(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[5]"Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice."
Fruttiger M., Karlsson L., Hall A.C., Abramsson A., Calver A.R., Bostrom H., Willetts K., Bertold C.H., Heath J.K., Betsholtz C., Richardson W.D.
Development 126:457-467(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[6]"Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis."
Karlsson L., Lindahl P., Heath J.K., Betsholtz C.
Development 127:3457-3466(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[7]"Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice."
Gnessi L., Basciani S., Mariani S., Arizzi M., Spera G., Wang C., Bondjers C., Karlsson L., Betsholtz C.
J. Cell Biol. 149:1019-1026(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[8]"PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis."
Bostrom H., Gritli-Linde A., Betsholtz C.
Dev. Dyn. 223:155-162(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[9]"Obstructive uropathy in mice and humans: potential role for PDGF-D in the progression of tubulointerstitial injury."
Taneda S., Hudkins K.L., Topouzis S., Gilbertson D.G., Ophascharoensuk V., Truong L., Johnson R.J., Alpers C.E.
J. Am. Soc. Nephrol. 14:2544-2555(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"PDGF signaling in cells and mice."
Tallquist M., Kazlauskas A.
Cytokine Growth Factor Rev. 15:205-213(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Insight into the physiological functions of PDGF through genetic studies in mice."
Betsholtz C.
Cytokine Growth Factor Rev. 15:215-228(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, DISRUPTION PHENOTYPE.
[12]"Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells."
Wu E., Palmer N., Tian Z., Moseman A.P., Galdzicki M., Wang X., Berger B., Zhang H., Kohane I.S.
PLoS ONE 3:E3794-E3794(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S66873 expand/collapse EMBL AC list , S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28740.2.
S66874 expand/collapse EMBL AC list , S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28741.2.
M29464 mRNA. Translation: AAA39903.1.
PIRA37359.
RefSeqNP_032834.1. NM_008808.3.
UniGeneMm.2675.

3D structure databases

ProteinModelPortalP20033.
SMRP20033. Positions 23-182.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP20033.

Proteomic databases

PaxDbP20033.
PRIDEP20033.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID18590.
KEGGmmu:18590.

Organism-specific databases

CTD5154.
MGIMGI:97527. Pdgfa.

Phylogenomic databases

eggNOGNOG75094.
HOGENOMHOG000286027.
HOVERGENHBG053546.
InParanoidP20033.
KOK04359.
PhylomeDBP20033.

Gene expression databases

CleanExMM_PDGFA.
GenevestigatorP20033.

Family and domain databases

InterProIPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
IPR006782. PDGF_N.
[Graphical view]
PfamPF00341. PDGF. 1 hit.
PF04692. PDGF_N. 1 hit.
[Graphical view]
SMARTSM00141. PDGF. 1 hit.
[Graphical view]
PROSITEPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294472.
PROP20033.
SOURCESearch...

Entry information

Entry namePDGFA_MOUSE
AccessionPrimary (citable) accession number: P20033
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot