ID PDGFD_MOUSE Reviewed; 370 AA. AC Q925I7; Q3URF6; Q8K2L3; Q9D1L8; DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 24-JAN-2024, entry version 149. DE RecName: Full=Platelet-derived growth factor D; DE Short=PDGF-D; DE AltName: Full=Spinal cord-derived growth factor B; DE Short=SCDGF-B; DE Contains: DE RecName: Full=Platelet-derived growth factor D, latent form; DE Short=PDGFD latent form; DE Contains: DE RecName: Full=Platelet-derived growth factor D, receptor-binding form; DE Short=PDGFD receptor-binding form; DE Flags: Precursor; GN Name=Pdgfd; Synonyms=Scdgfb; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=BALB/cJ; RX PubMed=11331882; DOI=10.1038/35074593; RA LaRochelle W.J., Jeffers M., McDonald W.F., Chillakuru R.A., Giese N.A., RA Lokker N.A., Sullivan C., Boldog F.L., Yang M., Vernet C., Burgess C.E., RA Fernandez E., Deegler L.L., Rittman B., Shimkets J., Shimkets R.A., RA Rothberg J.M., Lichenstein H.S.; RT "PDGF D, a novel protease-activated growth factor."; RL Nat. Cell Biol. 3:517-521(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND TISSUE SPECIFICITY. RX PubMed=12890490; DOI=10.1016/s0006-291x(03)01346-9; RA Zhuo Y., Hoyle G.W., Zhang J., Morris G., Lasky J.A.; RT "A novel murine PDGF-D splicing variant results in significant differences RT in peptide expression and function."; RL Biochem. Biophys. Res. Commun. 308:126-132(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J; TISSUE=Hippocampus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC STRAIN=FVB/N; TISSUE=Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=11331881; DOI=10.1038/35074588; RA Bergsten E., Uutela M., Li X., Pietras K., Oestman A., Heldin C.-H., RA Alitalo K., Eriksson U.; RT "PDGF-D is a specific, protease-activated ligand for the PDGF beta- RT receptor."; RL Nat. Cell Biol. 3:512-516(2001). RN [6] RP FUNCTION. RX PubMed=11980634; RA LaRochelle W.J., Jeffers M., Corvalan J.R.F., Jia X.-C., Feng X., RA Vanegas S., Vickroy J.D., Yang X.-D., Chen F., Gazit G., Mayotte J., RA Macaluso J., Rittman B., Wu F., Dhanabal M., Herrmann J., Lichenstein H.S.; RT "Platelet-derived growth factor D: tumorigenicity in mice and dysregulated RT expression in human cancer."; RL Cancer Res. 62:2468-2473(2002). RN [7] RP REVIEW. RX PubMed=15207812; DOI=10.1016/j.cytogfr.2004.03.003; RA Tallquist M., Kazlauskas A.; RT "PDGF signaling in cells and mice."; RL Cytokine Growth Factor Rev. 15:205-213(2004). RN [8] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=14747375; DOI=10.1097/01.asn.0000108522.79652.63; RA Hudkins K.L., Gilbertson D.G., Carling M., Taneda S., Hughes S.D., RA Holdren M.S., Palmer T.E., Topouzis S., Haran A.C., Feldhaus A.L., RA Alpers C.E.; RT "Exogenous PDGF-D is a potent mesangial cell mitogen and causes a severe RT mesangial proliferative glomerulopathy."; RL J. Am. Soc. Nephrol. 15:286-298(2004). RN [9] RP TISSUE SPECIFICITY. RX PubMed=14514732; DOI=10.1097/01.asn.0000089828.73014.c8; RA Taneda S., Hudkins K.L., Topouzis S., Gilbertson D.G., Ophascharoensuk V., RA Truong L., Johnson R.J., Alpers C.E.; RT "Obstructive uropathy in mice and humans: potential role for PDGF-D in the RT progression of tubulointerstitial injury."; RL J. Am. Soc. Nephrol. 14:2544-2555(2003). RN [10] RP FUNCTION. RX PubMed=15271796; DOI=10.1182/blood-2004-04-1485; RA Uutela M., Wirzenius M., Paavonen K., Rajantie I., He Y., Karpanen T., RA Lohela M., Wiig H., Salven P., Pajusola K., Eriksson U., Alitalo K.; RT "PDGF-D induces macrophage recruitment, increased interstitial pressure, RT and blood vessel maturation during angiogenesis."; RL Blood 104:3198-3204(2004). CC -!- FUNCTION: Growth factor that plays an essential role in the regulation CC of embryonic development, cell proliferation, cell migration, survival CC and chemotaxis. Potent mitogen for cells of mesenchymal origin. Plays CC an important role in wound healing (By similarity). Has oncogenic CC potential and can induce tumor formation. Induces macrophage CC recruitment, increased interstitial pressure, and blood vessel CC maturation during angiogenesis. Can initiate events that lead to a CC mesangial proliferative glomerulonephritis, including influx of CC monocytes and macrophages and production of extracellular matrix. CC {ECO:0000250, ECO:0000269|PubMed:11980634, ECO:0000269|PubMed:14747375, CC ECO:0000269|PubMed:15271796}. CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, CC and with heterodimers formed by PDGFRA and PDGFRB (By similarity). CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Note=Released by CC platelets upon wounding. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Long; CC IsoId=Q925I7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q925I7-2; Sequence=VSP_020616; CC Name=3; Synonyms=Short; CC IsoId=Q925I7-3; Sequence=VSP_020617, VSP_020618; CC -!- TISSUE SPECIFICITY: Expressed at high levels in developing heart, lung, CC kidney and some muscle derivatives. Moderately expressed in liver, CC brain and testis. In the kidney, localized to glomerular mesangial CC cells and vascular smooth muscle cells. Up-regulated in areas of renal CC fibrosis. In mice with unilateral ureteral obstruction, expressed in CC interstitial cells at day 4, with an increased to maximal expression at CC day 14. {ECO:0000269|PubMed:11331881, ECO:0000269|PubMed:12890490, CC ECO:0000269|PubMed:14514732, ECO:0000269|PubMed:14747375}. CC -!- PTM: Activated by proteolytic cleavage. Proteolytic removal of the N- CC terminal CUB domain releasing the core domain is necessary for CC unmasking the receptor-binding epitopes of the core domain. Cleavage CC after Arg-247 or Arg-249 by urokinase plasminogen activator gives rise CC to the active form (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF335583; AAK38839.1; -; mRNA. DR EMBL; AK003359; BAB22735.2; -; mRNA. DR EMBL; AK141551; BAE24732.1; -; mRNA. DR EMBL; BC030896; AAH30896.1; -; mRNA. DR CCDS; CCDS22801.1; -. [Q925I7-1] DR CCDS; CCDS90489.1; -. [Q925I7-3] DR CCDS; CCDS90490.1; -. [Q925I7-2] DR RefSeq; NP_082200.1; NM_027924.2. [Q925I7-1] DR RefSeq; XP_006509948.1; XM_006509885.3. DR RefSeq; XP_006509949.1; XM_006509886.3. DR AlphaFoldDB; Q925I7; -. DR SMR; Q925I7; -. DR ComplexPortal; CPX-2915; Platelet-derived growth factor DD complex. DR ComplexPortal; CPX-2916; PDGF receptor alpha-beta - PDGF-DD complex. DR ComplexPortal; CPX-2917; PDGF receptor beta - PDGF-DD complex. DR STRING; 10090.ENSMUSP00000128388; -. DR GlyCosmos; Q925I7; 1 site, No reported glycans. DR GlyGen; Q925I7; 1 site. DR PhosphoSitePlus; Q925I7; -. DR MaxQB; Q925I7; -. DR PaxDb; 10090-ENSMUSP00000128388; -. DR PeptideAtlas; Q925I7; -. DR ProteomicsDB; 294046; -. [Q925I7-1] DR ProteomicsDB; 294047; -. [Q925I7-2] DR ProteomicsDB; 294048; -. [Q925I7-3] DR Antibodypedia; 31835; 337 antibodies from 27 providers. DR DNASU; 71785; -. DR Ensembl; ENSMUST00000058692.9; ENSMUSP00000056240.7; ENSMUSG00000032006.16. [Q925I7-2] DR Ensembl; ENSMUST00000168039.8; ENSMUSP00000128388.2; ENSMUSG00000032006.16. [Q925I7-1] DR Ensembl; ENSMUST00000214892.2; ENSMUSP00000149162.2; ENSMUSG00000032006.16. [Q925I7-3] DR GeneID; 71785; -. DR KEGG; mmu:71785; -. DR UCSC; uc009oby.1; mouse. [Q925I7-1] DR UCSC; uc009obz.1; mouse. [Q925I7-2] DR UCSC; uc012gnq.1; mouse. [Q925I7-3] DR AGR; MGI:1919035; -. DR CTD; 80310; -. DR MGI; MGI:1919035; Pdgfd. DR VEuPathDB; HostDB:ENSMUSG00000032006; -. DR eggNOG; ENOG502QPQY; Eukaryota. DR GeneTree; ENSGT00940000159575; -. DR HOGENOM; CLU_037859_1_0_1; -. DR InParanoid; Q925I7; -. DR OMA; HHETCEC; -. DR OrthoDB; 3908391at2759; -. DR PhylomeDB; Q925I7; -. DR TreeFam; TF332130; -. DR Reactome; R-MMU-186797; Signaling by PDGF. DR BioGRID-ORCS; 71785; 2 hits in 77 CRISPR screens. DR ChiTaRS; Pdgfd; mouse. DR PRO; PR:Q925I7; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; Q925I7; Protein. DR Bgee; ENSMUSG00000032006; Expressed in interventricular septum and 204 other cell types or tissues. DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISO:MGI. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI. DR GO; GO:0072126; P:positive regulation of glomerular mesangial cell proliferation; ISO:MGI. DR GO; GO:2000439; P:positive regulation of monocyte extravasation; ISO:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IBA:GO_Central. DR GO; GO:0071673; P:positive regulation of smooth muscle cell chemotaxis; ISO:MGI. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI. DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IDA:MGI. DR CDD; cd00041; CUB; 1. DR CDD; cd00135; PDGF; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 1. DR InterPro; IPR000859; CUB_dom. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR000072; PDGF/VEGF_dom. DR InterPro; IPR035914; Sperma_CUB_dom_sf. DR PANTHER; PTHR11633; PLATELET-DERIVED GROWTH FACTOR; 1. DR PANTHER; PTHR11633:SF4; PLATELET-DERIVED GROWTH FACTOR D; 1. DR Pfam; PF00431; CUB; 1. DR Pfam; PF00341; PDGF; 1. DR SMART; SM00042; CUB; 1. DR SMART; SM00141; PDGF; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 1. DR PROSITE; PS01180; CUB; 1. DR PROSITE; PS50278; PDGF_2; 1. DR Genevisible; Q925I7; MM. PE 2: Evidence at transcript level; KW Alternative splicing; Cleavage on pair of basic residues; KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor; KW Mitogen; Proto-oncogene; Reference proteome; Secreted; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..370 FT /note="Platelet-derived growth factor D, latent form" FT /id="PRO_0000250190" FT CHAIN 250..370 FT /note="Platelet-derived growth factor D, receptor-binding FT form" FT /evidence="ECO:0000255" FT /id="PRO_0000250191" FT DOMAIN 52..170 FT /note="CUB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT SITE 247..248 FT /note="Cleavage" FT /evidence="ECO:0000255" FT SITE 249..250 FT /note="Cleavage" FT /evidence="ECO:0000255" FT CARBOHYD 276 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 109..131 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DISULFID 296 FT /note="Interchain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DISULFID 302..360 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DISULFID 306..362 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT VAR_SEQ 42..47 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_020616" FT VAR_SEQ 258..261 FT /note="VDLD -> GIEV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12890490, FT ECO:0000303|PubMed:15489334" FT /id="VSP_020617" FT VAR_SEQ 262..370 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12890490, FT ECO:0000303|PubMed:15489334" FT /id="VSP_020618" FT CONFLICT 173 FT /note="F -> S (in Ref. 4; AAH30896)" FT /evidence="ECO:0000305" SQ SEQUENCE 370 AA; 42809 MW; 9E80B4CF6813BFBE CRC64; MQRLVLVSIL LCANFSCYPD TFATPQRASI KALRNANLRR DESNHLTDLY QREENIQVTS NGHVQSPRFP NSYPRNLLLT WWLRSQEKTR IQLSFDHQFG LEEAENDICR YDFVEVEEVS ESSTVVRGRW CGHKEIPPRI TSRTNQIKIT FKSDDYFVAK PGFKIYYSFV EDFQPEAASE TNWESVTSSF SGVSYHSPSI TDPTLTADAL DKTVAEFDTV EDLLKHFNPV SWQDDLENLY LDTPHYRGRS YHDRKSKVDL DRLNDDVKRY SCTPRNHSVN LREELKLTNA VFFPRCLLVQ RCGGNCGCGT VNWKSCTCSS GKTVKKYHEV LKFEPGHFKR RGKAKNMALV DIQLDHHERC DCICSSRPPR //