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P04085 (PDGFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
Synonyms:PDGF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length211 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentSecreted
   Coding sequence diversityAlternative splicing
   DomainSignal
   Molecular functionDevelopmental protein
Growth factor
Mitogen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

actin cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

blood coagulation

Traceable author statement. Source: Reactome

cell activation

Traceable author statement PubMed 10508235. Source: BHF-UCL

cell projection assembly

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell signaling

Traceable author statement PubMed 2842868. Source: ProtInc

embryo development

Traceable author statement PubMed 10508235. Source: BHF-UCL

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

hair follicle development

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

inner ear development

Inferred from electronic annotation. Source: Ensembl

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

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

organ morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

platelet degranulation

Traceable author statement. Source: Reactome

platelet-derived growth factor receptor signaling pathway

Inferred from direct assay PubMed 2439522PubMed 2536956PubMed 2836953. Source: BHF-UCL

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 MAPK cascade

Inferred from mutant phenotype PubMed 11788434. Source: UniProtKB

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell migration

Inferred from direct assay PubMed 11788434. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay PubMed 17470632PubMed 2836953PubMed 7073684. Source: BHF-UCL

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 signaling

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

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: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to inorganic substance

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from direct assay PubMed 2538439. Source: BHF-UCL

skin development

Inferred from sequence or structural similarity. Source: UniProtKB

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

wound healing

Traceable author statement PubMed 10508235. Source: BHF-UCL

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

cell surface

Inferred from direct assay PubMed 2538439PubMed 2836953PubMed 291037. Source: BHF-UCL

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular region

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_functioncollagen binding

Inferred from direct assay PubMed 8900172. Source: MGI

growth factor activity

Inferred from direct assay PubMed 12070119. Source: UniProtKB

platelet-derived growth factor binding

Inferred from physical interaction PubMed 7073684. Source: BHF-UCL

platelet-derived growth factor receptor binding

Inferred from direct assay PubMed 2836953. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 7679113. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 7073684. Source: BHF-UCL

protein homodimerization activity

Inferred from direct assay PubMed 2836953Ref.3. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PDGFRAP162345EBI-2881386,EBI-2861522

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Propeptide21 – 8666Removed in mature form
PRO_0000023356
Chain87 – 211125Platelet-derived growth factor subunit A
PRO_0000023357

Regions

Region158 – 1625Receptor binding site Potential

Amino acid modifications

Glycosylation1341N-linked (GlcNAc...) Potential
Disulfide bond96 ↔ 140 Ref.11 Ref.14
Disulfide bond123Interchain Ref.11 Ref.14
Disulfide bond129 ↔ 177 Ref.11 Ref.14
Disulfide bond132Interchain Ref.11 Ref.14
Disulfide bond133 ↔ 179 Ref.11 Ref.14

Natural variations

Alternative sequence194 – 1963GRP → DVR in isoform Short.
VSP_004602
Alternative sequence197 – 21115Missing in isoform Short.
VSP_004603

Experimental info

Sequence conflict64 – 663RAH → TRD in AAA60045. Ref.2

Secondary structure

............. 211
Helix Strand Turn

Details...

Sequences

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

Last modified November 1, 1986. Version 1.
Checksum: 48633DDE558EFA43

FASTA21124,043
        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 

« Hide

Isoform Short [UniParc].

Checksum: 5EDBDB62D565904B
Show »

FASTA19622,253

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X03795 mRNA. Translation: CAA27421.1.
X06374 mRNA. Translation: CAA29677.1.
M20494 expand/collapse EMBL AC list , M20488, M20489, M20490, M20491, M20492, M20493 Genomic DNA. Translation: AAA60045.1.
M19988 expand/collapse EMBL AC list , M21571, M19984, M19985, M19986, M19987 Genomic DNA. Translation: AAA60046.1.
M19989 expand/collapse EMBL AC list , 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.
CCDSCCDS34578.1. [P04085-1]
CCDS47524.1. [P04085-2]
PIRPFHUG1. A28964.
B28964.
RefSeqNP_002598.4. NM_002607.5. [P04085-1]
NP_148983.1. NM_033023.4. [P04085-2]
XP_006715796.1. XM_006715733.1. [P04085-1]
UniGeneHs.535898.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MJKX-ray2.40A/B/E/F/X/Y21-181[»]
ProteinModelPortalP04085.
SMRP04085. Positions 23-182.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111180. 11 interactions.
DIPDIP-5735N.
IntActP04085. 3 interactions.
STRING9606.ENSP00000346508.

PTM databases

PhosphoSiteP04085.

Proteomic databases

PaxDbP04085.
PRIDEP04085.

Protocols and materials databases

DNASU5154.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354513; ENSP00000346508; ENSG00000197461. [P04085-1]
ENST00000402802; ENSP00000383889; ENSG00000197461. [P04085-2]
GeneID5154.
KEGGhsa:5154.
UCSCuc003sir.3. human. [P04085-1]
uc003sis.3. human. [P04085-2]

Organism-specific databases

CTD5154.
GeneCardsGC07M000536.
H-InvDBHIX0167622.
HGNCHGNC:8799. PDGFA.
HPACAB005579.
MIM173430. gene.
neXtProtNX_P04085.
PharmGKBPA33144.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75094.
HOGENOMHOG000286027.
HOVERGENHBG053546.
InParanoidP04085.
KOK04359.
OMASNSDYRE.
OrthoDBEOG78H3VV.
PhylomeDBP04085.
TreeFamTF319554.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP04085.

Gene expression databases

ArrayExpressP04085.
BgeeP04085.
CleanExHS_PDGFA.
GenevestigatorP04085.

Family and domain databases

Gene3D2.10.90.10. 1 hit.
InterProIPR029034. Cystine-knot_cytokine.
IPR023581. 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]
SUPFAMSSF57501. SSF57501. 1 hit.
PROSITEPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP04085.
GeneWikiPDGFA.
GenomeRNAi5154.
NextBio19930.
PROP04085.
SOURCESearch...

Entry information

Entry namePDGFA_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM