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Q9GZP0 (PDGFD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 D

Short name=PDGF-D
Alternative name(s):
Iris-expressed growth factor
Spinal cord-derived growth factor B
Short name=SCDGF-B

Cleaved into the following 2 chains:

  1. Platelet-derived growth factor D, latent form
    Short name=PDGFD latent form
  2. Platelet-derived growth factor D, receptor-binding form
    Short name=PDGFD receptor-binding form
Gene names
Name:PDGFD
Synonyms:IEGF, SCDGFB
ORF Names:MSTP036, UNQ1899/PRO4345
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length370 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. Plays an important role in wound healing. Induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Can initiate events that lead to a mesangial proliferative glomerulonephritis, including influx of monocytes and macrophages and production of extracellular matrix By similarity. Ref.2 Ref.14

Subunit structure

Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Ref.2 Ref.3

Subcellular location

Secreted. Note: Released by platelets upon wounding. Ref.3

Tissue specificity

Expressed at high levels in the heart, pancreas, adrenal gland and ovary and at low levels in placenta, liver, kidney, prostate, testis, small intestine, spleen and colon. In the kidney, expressed by the visceral epithelial cells of the glomeruli. A widespread expression is also seen in the medial smooth muscle cells of arteries and arterioles, as well as in smooth muscle cells of vasa rectae in the medullary area. Expressed in the adventitial connective tissue surrounding the suprarenal artery. In chronic obstructive nephropathy, a persistent expression is seen in glomerular visceral epithelial cells and vascular smooth muscle cells, as well as de novo expression by periglomerular interstitial cells and by some neointimal cells of atherosclerotic vessels. Expression in normal prostate is seen preferentially in the mesenchyme of the gland while expression is increased and more profuse in prostate carcinoma. Expressed in many ovarian, lung, renal and brain cancer-derived cell lines. Ref.2 Ref.3 Ref.10 Ref.11 Ref.12 Ref.13 Ref.16

Developmental stage

Not detectable in the earliest stages of glomerulogenesis, and not detected in the metanephric blastema or surrounding cortical interstitial cells. In later stages of glomerulogenesis, localized to epithelial cells transitioning from the early developing nephrons of the comma- and S-shaped stages to the visceral epithelial cells of differentiated glomeruli. In the developing pelvis, expressed at the basement membrane of immature collecting ducts and by presumptive fibroblastic cells in the interstitium. Ref.10

Post-translational modification

Activated by proteolytic cleavage. Proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor-binding epitopes of the core domain. Cleavage after Arg-247 or Arg-249 by urokinase plasminogen activator gives rise to the active form.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Contains 1 CUB domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9GZP0-1)

Also known as: Long; SCDGF-B-L;

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 2 (identifier: Q9GZP0-2)

Also known as: Short; SCDGF-B-S;

The sequence of this isoform differs from the canonical sequence as follows:
     42-47: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 370352Platelet-derived growth factor D, latent form
PRO_0000250188
Chain250 – 370121Platelet-derived growth factor D, receptor-binding form Potential
PRO_0000250189

Regions

Domain52 – 170119CUB

Sites

Site247 – 2482Cleavage Potential
Site249 – 2502Cleavage Potential

Amino acid modifications

Glycosylation2761N-linked (GlcNAc...) Potential
Disulfide bond109 ↔ 131 By similarity
Disulfide bond296Interchain By similarity
Disulfide bond302 ↔ 360 By similarity
Disulfide bond306 ↔ 362 By similarity

Natural variations

Alternative sequence42 – 476Missing in isoform 2.
VSP_020615
Natural variant1901I → V.
Corresponds to variant rs35045740 [ dbSNP | Ensembl ].
VAR_051563
Natural variant2021D → Y in a colorectal cancer sample; somatic mutation. Ref.18
VAR_036418

Experimental info

Mutagenesis2471R → A: Abolishes cleavage into active form; when associated with A-249. Ref.16
Mutagenesis2491R → A: Abolishes cleavage into active form; when associated with A-247. Ref.16

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) (SCDGF-B-L) [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: D387F485E7BB7674

FASTA37042,848
        10         20         30         40         50         60 
MHRLIFVYTL ICANFCSCRD TSATPQSASI KALRNANLRR DESNHLTDLY RRDETIQVKG 

        70         80         90        100        110        120 
NGYVQSPRFP NSYPRNLLLT WRLHSQENTR IQLVFDNQFG LEEAENDICR YDFVEVEDIS 

       130        140        150        160        170        180 
ETSTIIRGRW CGHKEVPPRI KSRTNQIKIT FKSDDYFVAK PGFKIYYSLL EDFQPAAASE 

       190        200        210        220        230        240 
TNWESVTSSI SGVSYNSPSV TDPTLIADAL DKKIAEFDTV EDLLKYFNPE SWQEDLENMY 

       250        260        270        280        290        300 
LDTPRYRGRS YHDRKSKVDL DRLNDDAKRY SCTPRNYSVN IREELKLANV VFFPRCLLVQ 

       310        320        330        340        350        360 
RCGGNCGCGT VNWRSCTCNS GKTVKKYHEV LQFEPGHIKR RGRAKTMALV DIQLDHHERC 

       370 
DCICSSRPPR 

« Hide

Isoform 2 (Short) (SCDGF-B-S) [UniParc].

Checksum: 245C53E8DDEA9EAC
Show »

FASTA36442,167

References

« Hide 'large scale' references
[1]"Molecular cloning of SCDGF-B, a novel growth factor homologous to SCDGF/PDGF-C/fallotein."
Hamada T., Ui-Tei K., Imaki J., Miyata Y.
Biochem. Biophys. Res. Commun. 280:733-737(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]"PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor."
Bergsten E., Uutela M., Li X., Pietras K., Oestman A., Heldin C.-H., Alitalo K., Eriksson U.
Nat. Cell Biol. 3:512-516(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
[3]"PDGF D, a novel protease-activated growth factor."
LaRochelle W.J., Jeffers M., McDonald W.F., Chillakuru R.A., Giese N.A., Lokker N.A., Sullivan C., Boldog F.L., Yang M., Vernet C., Burgess C.E., Fernandez E., Deegler L.L., Rittman B., Shimkets J., Shimkets R.A., Rothberg J.M., Lichenstein H.S.
Nat. Cell Biol. 3:517-521(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Expressed sequence tag analysis of adult human iris for the NEIBank project: steroid-response factors and similarities with retinal pigment epithelium."
Wistow G., Bernstein S.L., Ray S., Wyatt M.K., Behal A., Touchman J.W., Bouffard G., Smith D., Peterson K.
Mol. Vis. 8:185-195(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Iris.
[5]Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y., Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y., Liu L.S., Ding J.F. expand/collapse author list , Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C., Zhao M.S., Hui R.T.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Aorta.
[6]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Trachea.
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[10]"Platelet-derived growth factor-D expression in developing and mature human kidneys."
Changsirikulchai S., Hudkins K.L., Goodpaster T.A., Volpone J., Topouzis S., Gilbertson D.G., Alpers C.E.
Kidney Int. 62:2043-2054(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 64-369, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[11]"Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFC genes."
Uutela M., Lauren J., Bergsten E., Li X., Horelli-Kuitunen N., Eriksson U., Alitalo K.
Circulation 103:2242-2247(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[12]"Platelet-derived growth factor D: tumorigenicity in mice and dysregulated expression in human cancer."
LaRochelle W.J., Jeffers M., Corvalan J.R.F., Jia X.-C., Feng X., Vanegas S., Vickroy J.D., Yang X.-D., Chen F., Gazit G., Mayotte J., Macaluso J., Rittman B., Wu F., Dhanabal M., Herrmann J., Lichenstein H.S.
Cancer Res. 62:2468-2473(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[13]"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.
[14]"PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis."
Uutela M., Wirzenius M., Paavonen K., Rajantie I., He Y., Karpanen T., Lohela M., Wiig H., Salven P., Pajusola K., Eriksson U., Alitalo K.
Blood 104:3198-3204(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Structural and functional specificities of PDGF-C and PDGF-D, the novel members of the platelet-derived growth factors family."
Reigstad L.J., Varhaug J.E., Lillehaug J.R.
FEBS J. 272:5723-5741(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"Platelet-derived growth factor D is activated by urokinase plasminogen activator in prostate carcinoma cells."
Ustach C.V., Kim H.-R.C.
Mol. Cell. Biol. 25:6279-6288(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, PTM, MUTAGENESIS OF ARG-247 AND ARG-249.
[17]"Emerging roles of PDGF-D signaling pathway in tumor development and progression."
Wang Z., Ahmad A., Li Y., Kong D., Azmi A.S., Banerjee S., Sarkar F.H.
Biochim. Biophys. Acta 1806:122-130(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[18]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] TYR-202.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB033832 mRNA. Translation: BAB18903.1.
AF336376 mRNA. Translation: AAK56136.1.
AF335584 mRNA. Translation: AAK38840.1.
AY027517 mRNA. Translation: AAK20081.1.
AY027518 mRNA. Translation: AAK20082.1.
AF113216 mRNA. Translation: AAG39287.1.
AY359116 mRNA. Translation: AAQ89474.1.
AK292801 mRNA. Translation: BAF85490.1.
CH471065 Genomic DNA. Translation: EAW67045.1.
BC030645 mRNA. Translation: AAH30645.1.
PIRJC7591.
RefSeqNP_079484.1. NM_025208.4.
NP_149126.1. NM_033135.3.
UniGeneHs.352298.

3D structure databases

ProteinModelPortalQ9GZP0.
SMRQ9GZP0. Positions 9-175, 257-364.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123223. 1 interaction.
STRING9606.ENSP00000376865.

PTM databases

PhosphoSiteQ9GZP0.

Polymorphism databases

DMDM74717921.

Proteomic databases

PaxDbQ9GZP0.
PRIDEQ9GZP0.

Protocols and materials databases

DNASU80310.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302251; ENSP00000302193; ENSG00000170962. [Q9GZP0-2]
ENST00000393158; ENSP00000376865; ENSG00000170962. [Q9GZP0-1]
GeneID80310.
KEGGhsa:80310.
UCSCuc001php.3. human. [Q9GZP0-2]
uc001phq.3. human. [Q9GZP0-1]

Organism-specific databases

CTD80310.
GeneCardsGC11M103777.
HGNCHGNC:30620. PDGFD.
MIM609673. gene.
neXtProtNX_Q9GZP0.
PharmGKBPA134892327.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG148355.
HOGENOMHOG000261610.
HOVERGENHBG057324.
InParanoidQ9GZP0.
KOK05450.
OMAHYRGRSY.
OrthoDBEOG7VB2FN.
PhylomeDBQ9GZP0.
TreeFamTF332130.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9GZP0.

Gene expression databases

ArrayExpressQ9GZP0.
BgeeQ9GZP0.
CleanExHS_PDGFD.
GenevestigatorQ9GZP0.

Family and domain databases

Gene3D2.60.120.290. 1 hit.
InterProIPR000859. CUB_dom.
IPR000072. PDGF/VEGF_dom.
IPR027123. PDGFC/D.
[Graphical view]
PANTHERPTHR10127:SF13. PTHR10127:SF13. 1 hit.
PfamPF00431. CUB. 1 hit.
PF00341. PDGF. 1 hit.
[Graphical view]
SMARTSM00042. CUB. 1 hit.
SM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMSSF49854. SSF49854. 1 hit.
PROSITEPS01180. CUB. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDGFD. human.
GeneWikiPDGFD.
GenomeRNAi80310.
NextBio70792.
PMAP-CutDBQ9GZP0.
PROQ9GZP0.
SOURCESearch...

Entry information

Entry namePDGFD_HUMAN
AccessionPrimary (citable) accession number: Q9GZP0
Secondary accession number(s): A8K9T6, Q9BWV5
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 100 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM