Reviewed, UniProtKB/Swiss-Prot P04085 (PDGFA_HUMAN)

Names and origin

Protein names

Recommended name:
    Platelet-derived growth factor subunit A
      Short name=PDGF subunit A
Alternative name(s):
    Platelet-derived growth factor A chain
    Platelet-derived growth factor alpha polypeptide
    PDGF-1

Gene names

Name:	PDGFA
Synonyms:	PDGF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 protein level.

General annotation (Comments)

Function	Platelet-derived growth factor is a potent mitogen for cells of mesenchymal origin. Binding of this growth factor to its affinity receptor elicits a variety of cellular responses. It is released by platelets upon wounding and plays an important role in stimulating adjacent cells to grow and thereby heals the wound.
Subunit structure	Antiparallel disulfide-linked dimer of non-identical (A and B) chains. Homodimers of A and B chains are implicated in transformation processes. Interacts with CSPG4. Ref.10 Ref.11
Subcellular location	Secreted.
Domain	The long form contains a basic insert which acts as a cell retention signal.
Miscellaneous	A-A and B-B, as well as A-B, dimers can bind to the PDGF receptor.
Sequence similarities	Belongs to the PDGF/VEGF growth factor family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	cell activation Traceable author statement. Source: UniProtKB cell proliferation Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Traceable author statement. Source: ProtInc embryonic development Traceable author statement. Source: UniProtKB negative chemotaxis Inferred from direct assay. Source: UniProtKB negative regulation of phosphatidylinositol biosynthetic process Inferred from direct assay. Source: UniProtKB negative regulation of platelet activation Inferred from direct assay. Source: UniProtKB platelet-derived growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of DNA replication Inferred from direct assay. Source: UniProtKB positive regulation of cell migration Inferred from direct assay. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from direct assay. Source: UniProtKB regulation of actin cytoskeleton organization Traceable author statement. Source: UniProtKB regulation of smooth muscle cell migration Inferred from direct assay. Source: UniProtKB wound healing Traceable author statement. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB extracellular space Ref.3 Inferred from direct assay. Source: UniProtKB membrane Inferred from electronic annotation. Source: InterPro platelet dense granule lumen Inferred from Experiment. Source: Reactome
Molecular function	cell surface binding Inferred from direct assay. Source: UniProtKB collagen binding Inferred from direct assay. Source: MGI growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW platelet-derived growth factor binding Inferred from physical interaction. Source: UniProtKB platelet-derived growth factor receptor binding Inferred from direct assay. Source: UniProtKB protein heterodimerization activity Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Ref.3 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P04085-1)

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: P04085-2)

The sequence of this isoform differs from the canonical sequence as follows:
     194-196: GRP → 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_0000023356
	Chain	87 – 211	125	Platelet-derived growth factor subunit A		PRO_0000023357
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 Ref.10
	Disulfide bond	129 ↔ 177		By similarity
	Disulfide bond	132		Interchain Ref.10
	Disulfide bond	133 ↔ 179		By similarity
Natural variations
	Alternative sequence	194 – 196	3	GRP → DVR in isoform Short.		VSP_004602
	Alternative sequence	197 – 211	15	Missing in isoform Short.		VSP_004603
Experimental info
	Sequence conflict	64 – 66	3	RAH → TRD in AAA60045. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 1, 1986. Version 1. Checksum: 48633DDE558EFA43	FASTA	211	24,043
	10 20 30 40 50 60 MRTLACLLLL GCGYLAHVLA EEAEIPREVI ERLARSQIHS IRDLQRLLEI DSVGSEDSLD 70 80 90 100 110 120 TSLRAHGVHA TKHVPEKRPL PIRRKRSIEE AVPAVCKTRT VIYEIPRSQV DPTSANFLIW 130 140 150 160 170 180 PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV KVAKVEYVRK KPKLKEVQVR LEEHLECACA 190 200 210 TTSLNPDYRE EDTGRPRESG KKRKRKRLKP T
	Isoform Short. Checksum: 5EDBDB62D565904B	FASTA	196	22,253
	10 20 30 40 50 60 MRTLACLLLL GCGYLAHVLA EEAEIPREVI ERLARSQIHS IRDLQRLLEI DSVGSEDSLD 70 80 90 100 110 120 TSLRAHGVHA TKHVPEKRPL PIRRKRSIEE AVPAVCKTRT VIYEIPRSQV DPTSANFLIW 130 140 150 160 170 180 PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV KVAKVEYVRK KPKLKEVQVR LEEHLECACA 190 TTSLNPDYRE EDTDVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing." Bonthron D.T., Morton C.C., Orkin S.H., Collins T. Proc. Natl. Acad. Sci. U.S.A. 85:1492-1496(1988) [PubMed: 3422746] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: alternative exon usage predicts two different precursor proteins." Rorsman F., Bywater M., Knott T.J., Scott J., Betsholtz C. Mol. Cell. Biol. 8:571-577(1988) [PubMed: 2832727] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines." Betsholtz C., Johnsson A., Heldin C.H., Westermark B., Lind P., Urdea M.S., Eddy R., Shows T.B., Philpott K., Mellor A.L., Knott T.J., Scott J. Nature 320:695-699(1986) [PubMed: 3754619] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The long 3'-untranslated regions of the PDGF-A and -B mRNAs are only distantly related." Hoppe J., Schumacher L., Eichner W., Weich H.A. FEBS Lett. 223:243-246(1987) [PubMed: 3666150] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
[6]	"Nucleotide sequence of the 5' region of the human platelet-derived growth factor A-chain gene." Takimoto Y., Li W.Y., Wang Z.Y., Tong B.D., Deuel T.F. Hiroshima J. Med. Sci. 42:47-52(1993) [PubMed: 8486521] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53.
[7]	"Platelet-derived growth factor A chain: confirmation of localization of PDGFA to chromosome 7p22 and description of an unusual minisatellite." Bonthron D., Collins T., Grzeschik K.H., van Roy N., Speleman F. Genomics 13:257-263(1992) [PubMed: 1612586] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 152-211.
[8]	"cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains." Tong B.D., Auer D.E., Jaye M., Kaplow J.M., Ricca G., McConathy E., Drohan W., Deuel T.F. Nature 328:619-621(1987) [PubMed: 3614363] [Abstract] Cited for: ALTERNATIVE SPLICING.
[9]	"Alternative RNA splicing affects function of encoded platelet-derived growth factor A chain." Collins T., Bonthron D.T., Orkin S.H. Nature 328:621-624(1987) [PubMed: 3614364] [Abstract] Cited for: ALTERNATIVE SPLICING.
[10]	"Assignment of interchain disulfide bonds in platelet-derived growth factor (PDGF) and evidence for agonist activity of monomeric PDGF." Andersson M., Oestman A., Baeckstroem G., Hellman U., George-Nascimento C., Westermark B., Heldin C.-H. J. Biol. Chem. 267:11260-11266(1992) [PubMed: 1317862] [Abstract] Cited for: INTERCHAIN DISULFIDE BONDS.
[11]	"High-affinity binding of basic fibroblast growth factor and platelet-derived growth factor-AA to the core protein of the NG2 proteoglycan." Goretzki L., Burg M.A., Grako K.A., Stallcup W.B. J. Biol. Chem. 274:16831-16837(1999) [PubMed: 10358027] [Abstract] Cited for: INTERACTION WITH CSPG4.
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine mini-reviews: PDGF

Cross-references

Sequence databases
EMBLGenBankDDBJ	X03795 mRNA. Translation: CAA27421.1. X06374 mRNA. Translation: CAA29677.1. M20494 , M20488, M20489, M20490, M20491, M20492, M20493 Genomic DNA. Translation: AAA60045.1. M19988 , M21571, M19984, M19985, M19986, M19987 Genomic DNA. Translation: AAA60046.1. M19989 , M21571, M19984, M19985, M19986, M19987 Genomic DNA. Translation: AAA60047.1. A09204 Unassigned RNA. Translation: CAA00830.1. AB451309 mRNA. Translation: BAG70123.1. AB451439 mRNA. Translation: BAG70253.1. S62078 Genomic DNA. Translation: AAB26566.1.
IPI	IPI00021833. IPI00220454.
PIR	PFHUG1. A28964. B28964.
RefSeq	NP_002598.4. NP_148983.1.
UniGene	Hs.535898
3D structure databases
HSSP	HSSP built from PDB template 1PDG based on UniProtKB P01127.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:5735N.
Proteomic databases
PRIDE	P04085.
Genome annotation databases
Ensembl	ENSG00000197461. Homo sapiens. [Contig view]
GeneID	5154.
KEGG	hsa:5154.
Organism-specific databases
GeneCards	GC07M000503.
H-InvDB	HIX0042124.
HGNC	HGNC:8799. PDGFA.
HPA	CAB005579.
MIM	173430. gene.
PharmGKB	PA33144.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P04085.
HOVERGEN	P04085.
OMA	P04085. DYREEET.
Enzyme and pathway databases
Pathway_Interaction_DB	ceramidepathway. Ceramide signaling pathway. pdgfrapathway. PDGFR-alpha signaling pathway.
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P04085.
Bgee	P04085.
CleanEx	HS_PDGFA.
GermOnline	ENSG00000197461. Homo sapiens.
Family and domain databases
InterPro	IPR000072. PD_growth_factor. IPR006782. PDGF_N. [Graphical view]
Pfam	PF00341. PDGF. 1 hit. PF04692. PDGF_N. 1 hit. [Graphical view]
ProDom	PD001629. PD_growth_factor. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00141. PDGF. 1 hit. [Graphical view]
PROSITE	PS00249. PDGF_1. 1 hit. PS50278. PDGF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	19930.
SOURCE	Search...

Entry information

Entry name

PDGFA_HUMAN

Accession

Primary (citable) accession number: P04085
Secondary accession number(s): B5BU73

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)