P20033 (PDGFA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Developmental protein Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from direct assay PubMed 12176888. Source: MGI angiogenesis Inferred from direct assay PubMed 12101409. Source: MGI 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 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 cell division Inferred from electronic annotation. Source: UniProtKB-KW 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 cascade 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 cascade 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_component	cell 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_function	collagen binding Inferred from sequence or structural similarity. Source: UniProtKB eukaryotic cell surface binding 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20
	Propeptide	21 – 86	66	Removed in mature form		PRO_0000023358
	Chain	87 – 211	125	Platelet-derived growth factor subunit A		PRO_0000023359
Regions
	Region	158 – 162	5	Receptor binding site Potential
Amino acid modifications
	Glycosylation	134	1	N-linked (GlcNAc...) Potential
	Disulfide bond	96 ↔ 140		By similarity
	Disulfide bond	123		Interchain By similarity
	Disulfide bond	129 ↔ 177		By similarity
	Disulfide bond	132		Interchain By similarity
	Disulfide bond	133 ↔ 179		By similarity
Natural variations
	Alternative sequence	194 – 196	3	GRR → DVR in isoform Short.		VSP_004604
	Alternative sequence	197 – 211	15	Missing in isoform Short.		VSP_004605
Experimental info
	Sequence conflict	92	1	V → I in AAA39903. Ref.2
	Sequence conflict	174	1	H → D in AAB28740. Ref.1
	Sequence conflict	174	1	H → D in AAB28741. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 1, 1996. Version 2. Checksum: AC4345A10ECF4B39	FASTA	211	24,102
	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
	Isoform Short [UniParc]. Checksum: 3F219DA70E4007D4	FASTA	196	22,267
	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 TSNLNPDHRE EETDVR

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 , S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28740.2. S66874 , S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28741.2. M29464 mRNA. Translation: AAA39903.1.
IPI	IPI00115478. IPI00381438.
PIR	A37359.
RefSeq	NP_032834.1. NM_008808.3.
UniGene	Mm.2675.
3D structure databases
ProteinModelPortal	P20033.
SMR	P20033. Positions 23-182.
ModBase	Search...
PTM databases
PhosphoSite	P20033.
Proteomic databases
PaxDb	P20033.
PRIDE	P20033.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	18590.
KEGG	mmu:18590.
Organism-specific databases
CTD	5154.
MGI	MGI:97527. Pdgfa.
Phylogenomic databases
eggNOG	NOG75094.
HOGENOM	HOG000286027.
HOVERGEN	HBG053546.
InParanoid	P20033.
KO	K04359.
OrthoDB	EOG49W2GM.
Gene expression databases
CleanEx	MM_PDGFA.
Genevestigator	P20033.
GermOnline	ENSMUSG00000025856. Mus musculus.
Family and domain databases
InterPro	IPR000072. PD_growth_factor. IPR023581. PD_growth_factor_CS. IPR006782. PDGF_N. [Graphical view]
Pfam	PF00341. PDGF. 1 hit. PF04692. PDGF_N. 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
NextBio	294472.
SOURCE	Search...

Entry information

Entry name

PDGFA_MOUSE

Accession

Primary (citable) accession number: P20033

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program