Summary: PDGF/VEGF domain
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Platelet-derived growth factor Edit Wikipedia article
|Platelet-derived growth factor (PDGF)|
Platelet-derived growth factor BB monomer, Human
|SCOPe||1pdg / SUPFAM|
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood vessel tissue, mitogenesis, i.e. proliferation, of mesenchymal cells such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells and mesenchymal stem cells as well as chemotaxis, the directed migration, of mesenchymal cells. Platelet-derived growth factor is a dimeric glycoprotein that can be composed of two A subunits (PDGF-AA), two B subunits (PDGF-BB), or one of each (PDGF-AB).
PDGF is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of five ligands, PDGF-AA through -DD (including -AB), and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked homodimers, but only PDGFA and B can form functional heterodimers.
Though PDGF is synthesized, stored (in the alpha granules of platelets), and released by platelets upon activation, it is also produced by other cells including smooth muscle cells, activated macrophages, and endothelial cells
Types and classification
There are five different isoforms of PDGF that activate cellular response through two different receptors. Known ligands include: PDGF-AA (PDGFA), -BB (PDGFB), -CC (PDGFC), and -DD (PDGFD), and -AB (a PDGFA and PDGFB heterodimer). The ligands interact with the two tyrosine kinase receptor monomers, PDGFRÎ± (PDGFRA) and -RÎ² (PDGFRB). The PDGF family also includes a few other members of the family, including the VEGF sub-family.
The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of PDGFRs have been identified: alpha-type and beta-type PDGFRs. The alpha type binds to PDGF-AA, PDGF-BB and PDGF-AB, whereas the beta type PDGFR binds with high affinity to PDGF-BB and PDGF-AB. PDGF binds to the PDGFR ligand binding pocket located within the second and third immunoglobulin domains. Upon activation by PDGF, these receptors dimerise, and are "switched on" by auto-phosphorylation of several sites on their cytosolic domains, which serve to mediate binding of cofactors and subsequently activate signal transduction, for example, through the PI3K pathway or through reactive oxygen species (ROS)-mediated activation of the STAT3 pathway. Downstream effects of this include regulation of gene expression and the cell cycle. The role of PI3K has been investigated by several laboratories. Accumulating data suggests that, while this molecule is, in general, part of growth signaling complex, it plays a more profound role in controlling cell migration. The different ligand isoforms have variable affinities for the receptor isoforms, and the receptor isoforms may variably form hetero- or homo- dimers. This leads to specificity of downstream signaling. It has been shown that the sis oncogene is derived from the PDGF B-chain gene. PDGF-BB is the highest-affinity ligand for the PDGFR-beta; PDGFR-beta is a key marker of hepatic stellate cell activation in the process of fibrogenesis.
PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal. Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.
PDGF plays a role in embryonic development, cell proliferation, cell migration, and angiogenesis. Over-expression of PDGF has been linked to several diseases such as atherosclerosis, fibrotic disorders and malignancies. Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.
PDGF is a required element in cellular division for fibroblasts, a type of connective tissue cell that is especially prevalent in wound healing. In essence, the PDGFs allow a cell to skip the G1 checkpoints in order to divide. It has been shown that in monocytes-macrophages and fibroblasts, exogenously administered PDGF stimulates chemotaxis, proliferation, and gene expression and significantly augmented the influx of inflammatory cells and fibroblasts, accelerating extracellular matrix and collagen formation and thus reducing the time for the healing process to occur.
In terms of osteogenic differentiation of mesenchymal stem cells, comparing PDGF to epidermal growth factor (EGF), which is also implicated in stimulating cell growth, proliferation, and differentiation, MSCs were shown to have stronger osteogenic differentiation into bone-forming cells when stimulated by epidermal growth factor (EGF) versus PDGF. However, comparing the signaling pathways between them reveals that the PI3K pathway is exclusively activated by PDGF, with EGF having no effect. Chemically inhibiting the PI3K pathway in PDGF-stimulated cells negates the differential effect between the two growth factors, and actually gives PDGF an edge in osteogenic differentiation. Wortmannin is a PI3K-specific inhibitor, and treatment of cells with Wortmannin in combination with PDGF resulted in enhanced osteoblast differentiation compared to just PDGF alone, as well as compared to EGF. These results indicate that the addition of Wortmannin can significantly increase the response of cells into an osteogenic lineage in the presence of PDGF, and thus might reduce the need for higher concentrations of PDGF or other growth factors, making PDGF a more viable growth factor for osteogenic differentiation than other, more expensive growth factors currently used in the field such as BMP2.
PDGF is also known to maintain proliferation of oligodendrocyte progenitor cells. It has also been shown that fibroblast growth factor (FGF) activates a signaling pathway that positively regulates the PDGF receptors in oligodendrocyte progenitor cells.
PDGF was one of the first growth factors characterized, and has led to an understanding of the mechanism of many growth factor signaling pathways.The first engineered dominant negative protein was designed to inhibit PDGF 
Recombinant PDGF is used to help heal chronic ulcers and in orthopedic surgery and periodontics to stimulate bone regeneration and repair. PDGF may be beneficial when used by itself or especially in combination with other growth factors to stimulate soft and hard tissue healing (Lynch et al. 1987, 1989, 1991, 1995).
Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for receptor antagonists to treat disease. Such antagonists include (but are not limited to) specific antibodies that target the molecule of interest, which act only in a neutralizing manner.
Age related downregulation of the PDGF receptor on islet beta cells has been demonstrated to prevent islet beta cell proliferation in both animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin secretion.
A non-viral PDGF "bio patch" can regenerate missing or damaged bone by delivering DNA in a nano-sized particle directly into cells via genes. Repairing bone fractures, fixing craniofacial defects and improving dental implants are among potential uses. The patch employs a collagen platform seeded with particles containing the genes needed for producing bone. In experiments, it new bone fully covered skull wounds in test animals and stimulated growth in human bone marrow stromal cells.
The addition of PDGF at specific timeâ€points has been shown to stabilise vasculature in collagenâ€glycosaminoglycan scaffolds.
Human genes encoding proteins that belong to the platelet-derived growth factor family include:
- Platelet-activating factor
- Platelet-derived growth factor receptor
- atheroma platelet involvement in smooth muscle proliferation
- Withaferin A potent inhibitor of angiogenesis
- Hannink M, Donoghue DJ (1989). "Structure and function of platelet-derived growth factor (PDGF) and related proteins". Biochim. Biophys. Acta. 989 (1): 1â€“10. doi:10.1016/0304-419x(89)90031-0. PMID 2546599.
- Heldin CH (1992). "Structural and functional studies on platelet-derived growth factor". EMBO J. 11 (12): 4251â€“4259. doi:10.1002/j.1460-2075.1992.tb05523.x. PMC 556997. PMID 1425569.
- Minarcik, John. "Global Path Course: Video". Retrieved 2011-06-27.
- "The Basic Biology of Platelet Growth Factors". Retrieved 2014-05-08.
- Kumar, Vinay (2010). Robbins and Coltran Pathologic Basis of Disease. China: Elsevier. pp. 88â€“89. ISBN 978-1-4160-3121-5.
- Fredriksson, Linda; Li, Hong; Eriksson, Ulf (August 2004). "The PDGF family: four gene products form five dimeric isoforms". Cytokine & Growth Factor Reviews. 15 (4): 197â€“204. doi:10.1016/j.cytogfr.2004.03.007. PMID 15207811.
- Tischer, Edmund; Gospodarowicz, Denis; Mitchell, Richard; Silva, Maria; Schilling, James; Lau, Kenneth; Crisp, Tracey; Fiddes, John C.; Abraham, Judith A. (December 1989). "Vascular endothelial growth factor: A new member of the platelet-derived growth factor gene family". Biochemical and Biophysical Research Communications. 165 (3): 1198â€“1206. doi:10.1016/0006-291X(89)92729-0. PMID 2610687.
- Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M, Pierce J, Aaronson S (1989). "Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes". Science. 243 (4892): 800â€“4. doi:10.1126/science.2536956. PMID 2536956.
- Heidaran MA, Pierce JH, Yu JC, Lombardi D, Artrip JE, Fleming TP, Thomason A, Aaronson SA (25 October 1991). "Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB". J. Biol. Chem. 266 (30): 20232â€“7. PMID 1657917.
- Heidaran MA, Pierce JH, Jensen RA, Matsui T, Aaronson SA (5 November 1990). "Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity". J. Biol. Chem. 265 (31): 18741â€“4. PMID 2172231.
- Blazevic T, Schwaiberger AV, Schreiner CE, Schachner D, Schaible AM, Grojer CS, Atanasov AG, Werz O, Dirsch VM, Heiss EH (December 2013). "12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of Transcription 3". J. Biol. Chem. 288 (49): 35592â€“603. doi:10.1074/jbc.M113.489013. PMC 3853304. PMID 24165129.
- Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA (1995). "Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth". J. Biol. Chem. 270 (13): 7033â€“6. doi:10.1074/jbc.270.13.7033. PMID 7706238.
- Ataliotis, P; Symes, K; Chou, MM; Ho, L; Mercola, M (September 1995). "PDGF signalling is required for gastrulation of Xenopus laevis". Development. 121 (9): 3099â€“110. PMID 7555734.
- Symes, K; Mercola, M (3 September 1996). "Embryonic mesoderm cells spread in response to platelet-derived growth factor and signaling by phosphatidylinositol 3-kinase". Proceedings of the National Academy of Sciences of the United States of America. 93 (18): 9641â€“4. doi:10.1073/pnas.93.18.9641. PMC 38481. PMID 8790383.
- Hoch RV, Soriano P (2003). "Roles of PDGF in animal development". Development. 130 (20): 4769â€“4784. doi:10.1242/dev.00721. PMID 12952899.
- Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U (1996). "Vascular endothelial growth factor B, a novel growth factor for endothelial cells". Proc. Natl. Acad. Sci. U.S.A. 93 (6): 2567â€“2581. doi:10.1073/pnas.93.6.2576. PMC 39839. PMID 8637916.
- Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K (1996). "A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases". EMBO J. 15 (2): 290â€“298. doi:10.1002/j.1460-2075.1996.tb00359.x. PMC 449944. PMID 8617204.
- Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG (1993). "Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14". Oncogene. 8 (4): 925â€“931. PMID 7681160.
- "PDGF Pathways". Archived from the original on 2006-11-13. Retrieved 2007-11-17.
- Alvarez RH, Kantarjian HM, Cortes JE (September 2006). "Biology of platelet-derived growth factor and its involvement in disease". Mayo Clin. Proc. 81 (9): 1241â€“57. doi:10.4065/81.9.1241. PMID 16970222.
- Song G, Ouyang G, Bao S (2005). "The activation of Akt/PKB signaling pathway and cell survival". J. Cell. Mol. Med. 9 (1): 59â€“71. doi:10.1111/j.1582-4934.2005.tb00337.x. PMC 6741304. PMID 15784165.
- Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A (April 1991). "Role of platelet-derived growth factor in wound healing". J. Cell. Biochem. 45 (4): 319â€“26. doi:10.1002/jcb.240450403. PMID 2045423.
- Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M (June 2005). "Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation". Science. 308 (5727): 1472â€“7. doi:10.1126/science.1107627. PMID 15933201.
- Hayashi, A. The New Standard of Care for Nonunions?. AAOS Now. 2009.
- Barres BA, Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992). "Cell Death and Control of Cell Survival in the Oligodendrocyte Lineage". Cell. 70 (1): 31â€“46. doi:10.1016/0092-8674(92)90531-G. PMID 1623522.
- Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH)
- McKinnon RD, Matsui T, Dubois-Dalcq M, Aaronson SA (November 1990). "FGF modulates the PDGF-driven pathway of oligodendrocyte development". Neuron. 5 (5): 603â€“14. doi:10.1016/0896-6273(90)90215-2. PMID 2171589.
- Paul D, Lipton A, Klinger I (1971). "Serum factor requirements of normal and simian virus 40-transformed 3T3 mouse fibroplasts". Proc Natl Acad Sci U S A. 68 (3): 645â€“52. doi:10.1073/pnas.68.3.645. PMC 389008. PMID 5276775.
- Mercola, M; Deininger, P L; Shamah, S M; Porter, J; Wang, C Y; Stiles, C D (1 December 1990). "Dominant-negative mutants of a platelet-derived growth factor gene". Genes & Development. 4 (12b): 2333â€“2341. doi:10.1101/gad.4.12b.2333. PMID 2279701.
- Friedlaender GE, Lin S, Solchaga LA, Snel LB, Lynch SE (2013). "The role of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in orthopaedic bone repair and regeneration". Current Pharmaceutical Design. 19 (19): 3384â€“90. doi:10.2174/1381612811319190005. PMID 23432673.
Demonstration of the safety and efficacy of rhPDGF-BB in the healing of chronic foot ulcers in diabetic patients and regeneration of alveolar (jaw) bone lost due to chronic infection from periodontal disease has resulted in two FDA-approved products based on this molecule
- Shulman T, Sauer FG, Jackman RM, Chang CN, Landolfi NF (July 1997). "An antibody reactive with domain 4 of the platelet-derived growth factor beta receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization". J. Biol. Chem. 272 (28): 17400â€“4. doi:10.1074/jbc.272.28.17400. PMID 9211881.
- McClintock JT, Chan IJ, Thaker SR, Katial A, Taub FE, Aotaki-Keen AE, Hjelmeland LM (1992). "Detection of c-sis proto-oncogene transcripts by direct enzyme-labeled cDNA probes and in situ hybridization". In Vitro Cell Dev Biol. 28A (2): 102â€“8. doi:10.1007/BF02631013. PMID 1537750.
- "Researchers make older beta cells act young again". Eurekalert.org. 2011-10-12. Retrieved 2013-12-28.
- "New Stanford molecular target for diabetes treatment discovered - Office of Communications & Public Affairs - Stanford University School of Medicine". Med.stanford.edu. 2011-10-12. Archived from the original on 2013-10-21. Retrieved 2013-12-28.
- Elangovan, S.; d'Mello, S. R.; Hong, L.; Ross, R. D.; Allamargot, C.; Dawson, D. V.; Stanford, C. M.; Johnson, G. K.; Sumner, D. R.; Salem, A. K. (2013-11-12). "Bio patch can regrow bone for dental implants and craniofacial defects". Biomaterials. KurzweilAI. 35 (2): 10.1016/j.biomaterials.2013.10.021. doi:10.1016/j.biomaterials.2013.10.021. PMC 3855224. PMID 24161167. Retrieved 2013-12-28.
- Elangovan S, D'Mello SR, Hong L, Ross RD, Allamargot C, Dawson DV, Stanford CM, Johnson GK, Sumner DR, Salem AK (2014). "The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor". Biomaterials. 35 (2): 737â€“747. doi:10.1016/j.biomaterials.2013.10.021. PMC 3855224. PMID 24161167.
- Amaral, Ronaldo Jose Farias Correa; Cavanagh, Brenton; O'Brien, Fergal Joseph; Kearney, Cathal John (16 December 2018). "Plateletâ€derived growth factor stabilises vascularisation in collagenâ€glycosaminoglycan scaffolds". Journal of Tissue Engineering and Regenerative Medicine. 13 (2): 261â€“273. doi:10.1002/term.2789. PMID 30554484.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
PDGF/VEGF domain Provide feedback
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This tab holds annotation information from the InterPro database.
InterPro entry IPR000072
Platelet-derived growth factor (PDGF) [PUBMED:2546599, PUBMED:1425569,PUBMED:7640655] is a potent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked homodimers, but only PDGFA and B can form functional heterodimers. PDGFRs also function as homo- and heterodimers. All known PDGFs have characteristic 'PDGF domains', which include eight conserved cysteines that are involved in inter- and intramolecular bonds. Alternate splicing of the A chain transcript can give rise to two different forms that differ only in their C-terminal extremity. The transforming protein of Woolly monkey sarcoma virus (WMSV) (Simian sarcoma virus), encoded by the v-sis oncogene, is derived from the B chain of PDGF.
PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal [PUBMED:12952899].
Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) [PUBMED:8637916, PUBMED:8617204] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis [PUBMED:7681160]. VEGF is a potent mitogen in embryonic and somatic angiogenesis with a unique specificity for vascular endothelial cells. VEGF forms homodimers and exists in 4 different isoforms. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended.
PDGF is structurally related to a number of other growth factors which also form disulphide-linked homo- or heterodimers. A cysteine knot motif is a common feature of this domain [PUBMED:8323751,PUBMED:9207067,PUBMED:11345501].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
|Molecular function||growth factor activity (GO:0008083)|
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The cytokine families in this clan have the cystine-knot fold. In this 6 cysteines form three disulphide bridges that are interlinked.
The clan contains the following 14 members:Coagulin Cys_knot Cys_Knot_tox D_CNTX DAN Hormone_6 IL17 m_DGTX_Dc1a_b_c NGF Noggin PDGF Sclerostin Spaetzle TGF_beta
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|Author:||Finn RD , Bateman A|
|Number in seed:||30|
|Number in full:||1607|
|Average length of the domain:||81.70 aa|
|Average identity of full alignment:||34 %|
|Average coverage of the sequence by the domain:||29.25 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||17|
|Download:||download the raw HMM for this family|
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 5 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PDGF domain has been found. There are 128 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...