P04085 (PDGFA_HUMAN) 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
Synonyms:	PDGF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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 By similarity.
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. Ref.11 Ref.12 Ref.14
Subcellular location	Secreted. Note: Released by platelets upon wounding.
Domain	The long form contains a basic insert which acts as a cell retention signal.
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB cell projection assembly Inferred from sequence or structural similarity. Source: UniProtKB embryo development Traceable author statement PubMed 10508235. Source: BHF-UCL hair follicle development Inferred from sequence or structural similarity. Source: UniProtKB inner ear development Inferred from electronic annotation. Source: Compara lung alveolus development Inferred from sequence or structural similarity. Source: UniProtKB negative chemotaxis Inferred from direct assay PubMed 9409235. Source: BHF-UCL negative regulation of phosphatidylinositol biosynthetic process Inferred from direct assay PubMed 2538439. Source: BHF-UCL negative regulation of platelet activation Inferred from direct assay PubMed 2538439. Source: BHF-UCL organ morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of DNA replication Inferred from direct assay PubMed 10806482PubMed 2439522PubMed 2836953. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 11788434. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay PubMed 11788434. Source: UniProtKB positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of fibroblast proliferation Inferred from direct assay PubMed 10806482PubMed 2439522. Source: BHF-UCL positive regulation of mesenchymal cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway Inferred from direct assay PubMed 19019919. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay PubMed 11788434. Source: UniProtKB positive regulation of protein autophosphorylation Inferred from direct assay PubMed 12070119. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 19019919. Source: UniProtKB regulation of actin cytoskeleton organization Traceable author statement PubMed 10508235. Source: BHF-UCL regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling Inferred from sequence or structural similarity. Source: UniProtKB regulation of peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of smooth muscle cell migration Inferred from direct assay PubMed 9409235. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to inorganic substance Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from electronic annotation. Source: Compara skin development Inferred from sequence or structural similarity. Source: UniProtKB transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome cell surface Inferred from direct assay PubMed 2836953PubMed 291037. Source: BHF-UCL endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular space Inferred from direct assay Ref.3. Source: BHF-UCL microvillus Inferred from sequence or structural similarity. Source: UniProtKB platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	collagen binding Inferred from direct assay PubMed 8900172. Source: MGI eukaryotic cell surface binding Inferred from direct assay PubMed 12070119. Source: UniProtKB platelet-derived growth factor receptor binding Inferred from direct assay PubMed 2836953. Source: BHF-UCL protein homodimerization activity Inferred from direct assay PubMed 2836953Ref.3. Source: BHF-UCL
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

Ref.11 Ref.14

Disulfide bond

123

Interchain Ref.11 Ref.14

Disulfide bond

129 ↔ 177

Ref.11 Ref.14

Disulfide bond

132

Interchain Ref.11 Ref.14

Disulfide bond

133 ↔ 179

Ref.11 Ref.14

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

211

Helix Strand Turn

Details...

Helix

27 – 34

8

Helix

41 – 47

7

Beta strand

96 – 104

9

Helix

107 – 109

3

Beta strand

118 – 130

13

Beta strand

134 – 180

47

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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 152-211.
[9]	"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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[10]	"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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERCHAIN DISULFIDE BONDS.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSPG4.
[13]	"Role of platelet-derived growth factors in physiology and medicine." Andrae J., Gallini R., Betsholtz C. Genes Dev. 22:1276-1312(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN DEVELOPMENT AND DISEASE.
[14]	"Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex." Shim A.H., Liu H., Focia P.J., Chen X., Lin P.C., He X. Proc. Natl. Acad. Sci. U.S.A. 107:11307-11312(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 21-181, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine mini-reviews: PDGF

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AB451309 mRNA. Translation: BAG70123.1.
AB451439 mRNA. Translation: BAG70253.1.
AC147651 Genomic DNA. No translation available.
S62078 Genomic DNA. Translation: AAB26566.1.

IPI

IPI00021833.
IPI00220454.

PIR

PFHUG1. A28964.
B28964.

RefSeq

NP_002598.4. NM_002607.5.
NP_148983.1. NM_033023.4.

UniGene

Hs.535898.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MJK	X-ray	2.40	A/B/E/F/X/Y	21-181	[»]

ProteinModelPortal

P04085.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5735N.

STRING

9606.ENSP00000346508.

PTM databases

PhosphoSite

P04085.

Polymorphism databases

DMDM

129719.

Proteomic databases

PaxDb

P04085.

PRIDE

P04085.

Protocols and materials databases

DNASU

5154.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000354513; ENSP00000346508; ENSG00000197461.
ENST00000402802; ENSP00000383889; ENSG00000197461.
ENST00000405692; ENSP00000384673; ENSG00000197461.

GeneID

5154.

KEGG

hsa:5154.

UCSC

uc003sir.3. human.
uc003sis.3. human.

Organism-specific databases

CTD

5154.

GeneCards

GC07M000536.

H-InvDB

HIX0167622.

HGNC

HGNC:8799. PDGFA.

HPA

CAB005579.

MIM

173430. gene.

neXtProt

NX_P04085.

PharmGKB

PA33144.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG75094.

HOGENOM

HOG000286027.

HOVERGEN

HBG053546.

InParanoid

P04085.

KO

K04359.

Enzyme and pathway databases

Pathway_Interaction_DB

ceramidepathway. Ceramide signaling pathway.
pdgfrapathway. PDGFR-alpha signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P04085.

Bgee

P04085.

CleanEx

HS_PDGFA.

Genevestigator

P04085.

GermOnline

ENSG00000197461. Homo sapiens.

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

EvolutionaryTrace

P04085.

GenomeRNAi

5154.

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:	May 1, 2013
This is version 143 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.