PDGFD_MOUSE
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 03-AUG-2022, entry version 141.
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}.
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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 GlyGen; Q925I7; 1 site.
DR PhosphoSitePlus; Q925I7; -.
DR MaxQB; Q925I7; -.
DR PaxDb; Q925I7; -.
DR PeptideAtlas; Q925I7; -.
DR PRIDE; Q925I7; -.
DR ProteomicsDB; 294046; -. [Q925I7-1]
DR ProteomicsDB; 294047; -. [Q925I7-2]
DR ProteomicsDB; 294048; -. [Q925I7-3]
DR Antibodypedia; 31835; 285 antibodies from 27 providers.
DR DNASU; 71785; -.
DR Ensembl; ENSMUST00000058692; ENSMUSP00000056240; ENSMUSG00000032006. [Q925I7-2]
DR Ensembl; ENSMUST00000168039; ENSMUSP00000128388; ENSMUSG00000032006. [Q925I7-1]
DR Ensembl; ENSMUST00000214892; ENSMUSP00000149162; ENSMUSG00000032006. [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 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; FVYTLVC; -.
DR OrthoDB; 962163at2759; -.
DR PhylomeDB; Q925I7; -.
DR TreeFam; TF332130; -.
DR Reactome; R-MMU-186797; Signaling by PDGF.
DR BioGRID-ORCS; 71785; 2 hits in 72 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 201 other tissues.
DR Genevisible; Q925I7; MM.
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:0070851; F:growth factor receptor binding; IBA:GO_Central.
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:0043406; P:positive regulation of MAP kinase activity; IBA:GO_Central.
DR GO; GO:2000439; P:positive regulation of monocyte extravasation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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; -; 1.
DR Gene3D; 2.60.120.290; -; 1.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR InterPro; IPR027123; PDGFD.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR11633:SF4; PTHR11633:SF4; 1.
DR Pfam; PF00431; CUB; 1.
DR Pfam; PF00341; PDGF; 1.
DR SMART; SM00042; CUB; 1.
DR SMART; SM00141; PDGF; 1.
DR SUPFAM; SSF49854; SSF49854; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS01180; CUB; 1.
DR PROSITE; PS50278; PDGF_2; 1.
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
