PDGFC_HUMAN
ID PDGFC_HUMAN Reviewed; 345 AA.
AC Q9NRA1; B4DU34; B9EGR8; Q4W5M9; Q9UL22;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Platelet-derived growth factor C;
DE Short=PDGF-C;
DE AltName: Full=Fallotein;
DE AltName: Full=Spinal cord-derived growth factor;
DE Short=SCDGF;
DE AltName: Full=VEGF-E;
DE Contains:
DE RecName: Full=Platelet-derived growth factor C, latent form;
DE Short=PDGFC latent form;
DE Contains:
DE RecName: Full=Platelet-derived growth factor C, receptor-binding form;
DE Short=PDGFC receptor-binding form;
DE Flags: Precursor;
GN Name=PDGFC; Synonyms=SCDGF; ORFNames=UNQ174/PRO200;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Uterus;
RX PubMed=11004490; DOI=10.1016/s0167-4781(00)00066-x;
RA Tsai Y.J., Lee R.K., Lin S.P., Chen Y.H.;
RT "Identification of a novel platelet-derived growth factor-like gene,
RT fallotein, in the human reproductive tract.";
RL Biochim. Biophys. Acta 1492:196-202(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=10858496; DOI=10.1016/s0014-5793(00)01640-9;
RA Hamada T., Ui-Tei K., Miyata Y.;
RT "A novel gene derived from developing spinal cords, SCDGF, is a unique
RT member of the PDGF/VEGF family.";
RL FEBS Lett. 475:97-102(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Lung;
RX PubMed=10806482; DOI=10.1038/35010579;
RA Li X., Ponten A., Aase K., Karlsson L., Abramsson A., Uutela M.,
RA Backstrom G., Hellstrom M., Bostrom H., Li H., Soriano P., Betsholtz C.,
RA Heldin C.H., Alitalo K., Ostman A., Eriksson U.;
RT "PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.";
RL Nat. Cell Biol. 2:302-309(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11297552; DOI=10.1074/jbc.m101056200;
RA Gilbertson D.G., Duff M.E., West J.W., Kelly J.D., Sheppard P.O.,
RA Hofstrand P.D., Gao Z., Shoemaker K., Bukowski T.R., Moore M.,
RA Feldhaus A.L., Humes J.M., Palmer T.E., Hart C.E.;
RT "Platelet-derived growth factor C (PDGF-C), a novel growth factor that
RT binds to PDGF alpha and beta receptor.";
RL J. Biol. Chem. 276:27406-27414(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Fetal brain;
RA Zhao J., Liu Z., Liu T., Nilsson S., Nister M.;
RT "An N-terminally truncated isoform of human PDGF-C regulates the secretion
RT of full-length PDGF-C and is deregulated in renal cell carcinoma.";
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Prostate;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [11]
RP TISSUE SPECIFICITY.
RX PubMed=11342471; DOI=10.1161/01.cir.103.18.2242;
RA Uutela M., Lauren J., Bergsten E., Li X., Horelli-Kuitunen N., Eriksson U.,
RA Alitalo K.;
RT "Chromosomal location, exon structure, and vascular expression patterns of
RT the human PDGFC and PDGFC genes.";
RL Circulation 103:2242-2247(2001).
RN [12]
RP INDUCTION.
RX PubMed=11313995; DOI=10.1038/sj.onc.1204133;
RA Zwerner J.P., May W.A.;
RT "PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family
RT tumors.";
RL Oncogene 20:626-633(2001).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=12176024; DOI=10.1016/s0006-291x(02)00917-8;
RA Andrae J., Molander C., Smits A., Funa K., Nister M.;
RT "Platelet-derived growth factor-B and -C and active alpha-receptors in
RT medulloblastoma cells.";
RL Biochem. Biophys. Res. Commun. 296:604-611(2002).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING (ISOFORMS 2 AND 3),
RP GLYCOSYLATION, AND MUTAGENESIS OF CYS-124.
RX PubMed=11854040; DOI=10.1016/s1357-2725(01)00124-8;
RA Dijkmans J., Xu J., Masure S., Dhanaraj S., Gosiewska A., Geesin J.,
RA Sprengel J., Harris S., Verhasselt P., Gordon R., Yon J.;
RT "Characterization of platelet-derived growth factor-C (PDGF-C): expression
RT in normal and tumor cells, biological activity and chromosomal
RT localization.";
RL Int. J. Biochem. Cell Biol. 34:414-426(2002).
RN [15]
RP FUNCTION.
RX PubMed=12032822; DOI=10.1038/sj.onc.1205486;
RA Zwerner J.P., May W.A.;
RT "Dominant negative PDGF-C inhibits growth of Ewing family tumor cell
RT lines.";
RL Oncogene 21:3847-3854(2002).
RN [16]
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=12707385; DOI=10.1097/01.asn.0000062964.75006.a8;
RA Eitner F., Ostendorf T., Kretzler M., Cohen C.D., Eriksson U., Grone H.J.,
RA Floege J.;
RT "PDGF-C expression in the developing and normal adult human kidney and in
RT glomerular diseases.";
RL J. Am. Soc. Nephrol. 14:1145-1153(2003).
RN [17]
RP CHARACTERIZATION OF SECRETED ACTIVE FORM, SUBUNIT, DISULFIDE BONDS, AND
RP 3D-STRUCTURE MODELING.
RX PubMed=12598536; DOI=10.1074/jbc.m301728200;
RA Reigstad L.J., Sande H.M., Fluge O., Bruland O., Muga A., Varhaug J.E.,
RA Martinez A., Lillehaug J.R.;
RT "Platelet-derived growth factor (PDGF)-C, a PDGF family member with a
RT vascular endothelial growth factor-like structure.";
RL J. Biol. Chem. 278:17114-17120(2003).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15061151; DOI=10.1161/01.atv.0000120785.82268.8b;
RA Fang L., Yan Y., Komuves L.G., Yonkovich S., Sullivan C.M., Stringer B.,
RA Galbraith S., Lokker N.A., Hwang S.S., Nurden P., Phillips D.R.,
RA Giese N.A.;
RT "PDGF C is a selective alpha platelet-derived growth factor receptor
RT agonist that is highly expressed in platelet alpha granules and vascular
RT smooth muscle.";
RL Arterioscler. Thromb. Vasc. Biol. 24:787-792(2004).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PLAT.
RX PubMed=15372073; DOI=10.1038/sj.emboj.7600397;
RA Fredriksson L., Li H., Fieber C., Li X., Eriksson U.;
RT "Tissue plasminogen activator is a potent activator of PDGF-CC.";
RL EMBO J. 23:3793-3802(2004).
RN [20]
RP INDUCTION BY EGR1.
RX PubMed=15247255; DOI=10.1074/jbc.m406063200;
RA Midgley V.C., Khachigian L.M.;
RT "Fibroblast growth factor-2 induction of platelet-derived growth factor-C
RT chain transcription in vascular smooth muscle cells is ERK-dependent but
RT not JNK-dependent and mediated by Egr-1.";
RL J. Biol. Chem. 279:40289-40295(2004).
RN [21]
RP REVIEW.
RX PubMed=16279938; DOI=10.1111/j.1742-4658.2005.04989.x;
RA Reigstad L.J., Varhaug J.E., Lillehaug J.R.;
RT "Structural and functional specificities of PDGF-C and PDGF-D, the novel
RT members of the platelet-derived growth factors family.";
RL FEBS J. 272:5723-5741(2005).
RN [22]
RP FUNCTION, INTERACTION WITH PLAT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ARG-231; LYS-232 AND ARG-234.
RX PubMed=15911618; DOI=10.1074/jbc.m503388200;
RA Fredriksson L., Ehnman M., Fieber C., Eriksson U.;
RT "Structural requirements for activation of latent platelet-derived growth
RT factor CC by tissue plasminogen activator.";
RL J. Biol. Chem. 280:26856-26862(2005).
RN [23]
RP FUNCTION.
RX PubMed=15389578; DOI=10.1002/jcp.20154;
RA Jinnin M., Ihn H., Mimura Y., Asano Y., Yamane K., Tamaki K.;
RT "Regulation of fibrogenic/fibrolytic genes by platelet-derived growth
RT factor C, a novel growth factor, in human dermal fibroblasts.";
RL J. Cell. Physiol. 202:510-517(2005).
RN [24]
RP FUNCTION.
RX PubMed=15728360; DOI=10.1073/pnas.0409722102;
RA Campbell J.S., Hughes S.D., Gilbertson D.G., Palmer T.E., Holdren M.S.,
RA Haran A.C., Odell M.M., Bauer R.L., Ren H.P., Haugen H.S., Yeh M.M.,
RA Fausto N.;
RT "Platelet-derived growth factor C induces liver fibrosis, steatosis, and
RT hepatocellular carcinoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:3389-3394(2005).
RN [25]
RP FUNCTION, AND INDUCTION.
RX PubMed=16439802; DOI=10.1165/rcmb.2005-0309oc;
RA Bosse Y., Thompson C., Stankova J., Rola-Pleszczynski M.;
RT "Fibroblast growth factor 2 and transforming growth factor beta1 synergism
RT in human bronchial smooth muscle cell proliferation.";
RL Am. J. Respir. Cell Mol. Biol. 34:746-753(2006).
RN [26]
RP SUBCELLULAR LOCATION, AND SUMOYLATION.
RX PubMed=16443219; DOI=10.1016/j.yexcr.2005.11.035;
RA Reigstad L.J., Martinez A., Varhaug J.E., Lillehaug J.R.;
RT "Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid
RT tissue and cell lines.";
RL Exp. Cell Res. 312:782-795(2006).
RN [27]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18055825; DOI=10.1167/iovs.07-0327;
RA Li R., Maminishkis A., Wang F.E., Miller S.S.;
RT "PDGF-C and -D induced proliferation/migration of human RPE is abolished by
RT inflammatory cytokines.";
RL Invest. Ophthalmol. Vis. Sci. 48:5722-5732(2007).
RN [28]
RP TISSUE SPECIFICITY.
RX PubMed=17482170; DOI=10.1016/j.fertnstert.2007.02.031;
RA Hwu Y.M., Li S.H., Lee R.K., Tsai Y.H., Yeh T.S., Lin S.Y.;
RT "Increased expression of platelet-derived growth factor C messenger
RT ribonucleic acid in uterine leiomyomata.";
RL Fertil. Steril. 89:468-471(2008).
RN [29]
RP CLEAVAGE BY PLG.
RX PubMed=18172073; DOI=10.1167/iovs.07-0776;
RA Lei H., Velez G., Hovland P., Hirose T., Kazlauskas A.;
RT "Plasmin is the major protease responsible for processing PDGF-C in the
RT vitreous of patients with proliferative vitreoretinopathy.";
RL Invest. Ophthalmol. Vis. Sci. 49:42-48(2008).
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 and chemoattractant for cells of
CC mesenchymal origin. Required for normal skeleton formation during
CC embryonic development, especially for normal development of the
CC craniofacial skeleton and for normal development of the palate.
CC Required for normal skin morphogenesis during embryonic development.
CC Plays an important role in wound healing, where it appears to be
CC involved in three stages: inflammation, proliferation and remodeling.
CC Plays an important role in angiogenesis and blood vessel development.
CC Involved in fibrotic processes, in which transformation of interstitial
CC fibroblasts into myofibroblasts plus collagen deposition occurs. The
CC CUB domain has mitogenic activity in coronary artery smooth muscle
CC cells, suggesting a role beyond the maintenance of the latency of the
CC PDGF domain. In the nucleus, PDGFC seems to have additional function.
CC {ECO:0000269|PubMed:10806482, ECO:0000269|PubMed:10858496,
CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11854040,
CC ECO:0000269|PubMed:12032822, ECO:0000269|PubMed:15061151,
CC ECO:0000269|PubMed:15372073, ECO:0000269|PubMed:15389578,
CC ECO:0000269|PubMed:15728360, ECO:0000269|PubMed:15911618,
CC ECO:0000269|PubMed:16439802, ECO:0000269|PubMed:18055825}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with PDGFRA homodimers,
CC and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB
CC domain) with PLAT (via kringle domain). {ECO:0000269|PubMed:12598536,
CC ECO:0000269|PubMed:15372073, ECO:0000269|PubMed:15911618}.
CC -!- INTERACTION:
CC Q9NRA1; P16234: PDGFRA; NbExp=2; IntAct=EBI-8833587, EBI-2861522;
CC Q9NRA1-1; P16234-1: PDGFRA; NbExp=2; IntAct=EBI-15499301, EBI-15499330;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16443219}.
CC Secreted {ECO:0000269|PubMed:10806482, ECO:0000269|PubMed:10858496,
CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:15061151,
CC ECO:0000269|PubMed:15372073, ECO:0000269|PubMed:15911618}. Nucleus
CC {ECO:0000269|PubMed:16443219}. Cytoplasmic granule
CC {ECO:0000269|PubMed:15061151}. Cell membrane
CC {ECO:0000269|PubMed:16443219}. Note=Sumoylated form is predominant in
CC the nucleus (PubMed:15247255). Stored in alpha granules in platelets
CC (PubMed:15061151). {ECO:0000269|PubMed:16443219}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9NRA1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NRA1-2; Sequence=VSP_034703;
CC Name=3;
CC IsoId=Q9NRA1-3; Sequence=VSP_034701, VSP_034702;
CC Name=4;
CC IsoId=Q9NRA1-4; Sequence=VSP_047606;
CC -!- TISSUE SPECIFICITY: Expressed in the fallopian tube, vascular smooth
CC muscle cells in kidney, breast and colon and in visceral smooth muscle
CC of the gastrointestinal tract. Highly expressed in retinal pigment
CC epithelia. Expressed in medulloblastoma. In the kidney, constitutively
CC expressed in parietal epithelial cells of Bowman's capsule, tubular
CC epithelial cells and in arterial endothelial cells (at protein level).
CC Highly expressed in the platelets, prostate, testis and uterus. Higher
CC expression is observed in uterine leiomyomata. Weaker expression in the
CC spleen, thymus, heart, pancreas, liver, ovary cells and small
CC intestine, and negligible expression in the colon and peripheral blood
CC leukocytes. {ECO:0000269|PubMed:10806482, ECO:0000269|PubMed:11004490,
CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11342471,
CC ECO:0000269|PubMed:11854040, ECO:0000269|PubMed:12176024,
CC ECO:0000269|PubMed:15061151, ECO:0000269|PubMed:17482170,
CC ECO:0000269|PubMed:18055825}.
CC -!- DEVELOPMENTAL STAGE: In the fetal kidney, detected in the developing
CC mesangium, ureteric bud epithelium and the undifferentiated mesenchyme
CC (at protein level). {ECO:0000269|PubMed:12707385}.
CC -!- INDUCTION: Up-regulated by EWS-FLI1 chimeric transcription factor in
CC tumor derived cells. Up-regulated in podocytes and interstitial cells
CC after injury/activation of these cells. FGF2 activates PDGFC
CC transcription via EGR1. Up-regulated by TGFB1 in concert with FGF2.
CC {ECO:0000269|PubMed:11313995, ECO:0000269|PubMed:12707385,
CC ECO:0000269|PubMed:15247255, ECO:0000269|PubMed:16439802}.
CC -!- PTM: Proteolytic removal of the N-terminal CUB domain releasing the
CC core domain is necessary for unmasking the receptor-binding epitopes of
CC the core domain. Cleavage after basic residues in the hinge region
CC (region connecting the CUB and growth factor domains) gives rise to the
CC receptor-binding form. Cleaved by PLAT and PLG.
CC -!- PTM: Sumoylated with SUMO1. {ECO:0000269|PubMed:16443219}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11854040}.
CC -!- MISCELLANEOUS: A lower molecular weight form (around 43 kDa) is present
CC in patients with papillary thyroid carcinoma.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; AF091434; AAF00049.1; -; mRNA.
DR EMBL; AB033831; BAB03266.1; -; mRNA.
DR EMBL; AF244813; AAF80597.1; -; mRNA.
DR EMBL; AF260738; AAK51637.1; -; mRNA.
DR EMBL; AM922296; CAP58278.1; -; mRNA.
DR EMBL; AY358493; AAQ88857.1; -; mRNA.
DR EMBL; AK300480; BAG62196.1; -; mRNA.
DR EMBL; AC092608; AAY40906.1; -; Genomic_DNA.
DR EMBL; AC093325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX04874.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04875.1; -; Genomic_DNA.
DR EMBL; BC136662; AAI36663.1; -; mRNA.
DR CCDS; CCDS3795.1; -. [Q9NRA1-1]
DR RefSeq; NP_057289.1; NM_016205.2. [Q9NRA1-1]
DR RefSeq; XP_016863945.1; XM_017008456.1. [Q9NRA1-2]
DR AlphaFoldDB; Q9NRA1; -.
DR SMR; Q9NRA1; -.
DR BioGRID; 121032; 12.
DR ComplexPortal; CPX-2879; Platelet-derived growth factor CC complex.
DR ComplexPortal; CPX-2887; PDGF receptor alpha - PDGF-CC complex.
DR ComplexPortal; CPX-2888; PDGF receptor alpha-beta - PDGF-CC complex.
DR ComplexPortal; CPX-2891; PDGF receptor beta - PDGF-CC complex.
DR DIP; DIP-59339N; -.
DR IntAct; Q9NRA1; 5.
DR STRING; 9606.ENSP00000422464; -.
DR GlyGen; Q9NRA1; 2 sites.
DR iPTMnet; Q9NRA1; -.
DR PhosphoSitePlus; Q9NRA1; -.
DR BioMuta; PDGFC; -.
DR DMDM; 205830662; -.
DR EPD; Q9NRA1; -.
DR MassIVE; Q9NRA1; -.
DR PaxDb; Q9NRA1; -.
DR PeptideAtlas; Q9NRA1; -.
DR PRIDE; Q9NRA1; -.
DR ProteomicsDB; 5147; -.
DR ProteomicsDB; 82318; -. [Q9NRA1-1]
DR ProteomicsDB; 82319; -. [Q9NRA1-2]
DR ProteomicsDB; 82320; -. [Q9NRA1-3]
DR Antibodypedia; 28096; 309 antibodies from 29 providers.
DR DNASU; 56034; -.
DR Ensembl; ENST00000422544.2; ENSP00000410048.2; ENSG00000145431.11. [Q9NRA1-2]
DR Ensembl; ENST00000502773.6; ENSP00000422464.1; ENSG00000145431.11. [Q9NRA1-1]
DR GeneID; 56034; -.
DR KEGG; hsa:56034; -.
DR MANE-Select; ENST00000502773.6; ENSP00000422464.1; NM_016205.3; NP_057289.1.
DR UCSC; uc003iph.3; human. [Q9NRA1-1]
DR CTD; 56034; -.
DR DisGeNET; 56034; -.
DR GeneCards; PDGFC; -.
DR HGNC; HGNC:8801; PDGFC.
DR HPA; ENSG00000145431; Tissue enhanced (parathyroid).
DR MIM; 608452; gene.
DR neXtProt; NX_Q9NRA1; -.
DR OpenTargets; ENSG00000145431; -.
DR PharmGKB; PA33146; -.
DR VEuPathDB; HostDB:ENSG00000145431; -.
DR eggNOG; ENOG502QUUR; Eukaryota.
DR GeneTree; ENSGT00940000158645; -.
DR HOGENOM; CLU_037859_0_0_1; -.
DR InParanoid; Q9NRA1; -.
DR OMA; LDENVWI; -.
DR OrthoDB; 962163at2759; -.
DR PhylomeDB; Q9NRA1; -.
DR TreeFam; TF332130; -.
DR PathwayCommons; Q9NRA1; -.
DR Reactome; R-HSA-186797; Signaling by PDGF. [Q9NRA1-1]
DR SignaLink; Q9NRA1; -.
DR SIGNOR; Q9NRA1; -.
DR BioGRID-ORCS; 56034; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; PDGFC; human.
DR GeneWiki; PDGFC; -.
DR GenomeRNAi; 56034; -.
DR Pharos; Q9NRA1; Tbio.
DR PRO; PR:Q9NRA1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NRA1; protein.
DR Bgee; ENSG00000145431; Expressed in parotid gland and 197 other tissues.
DR ExpressionAtlas; Q9NRA1; baseline and differential.
DR Genevisible; Q9NRA1; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; TAS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; IEA:Ensembl.
DR GO; GO:0048568; P:embryonic organ development; IEA:InterPro.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:BHF-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
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; IDA:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IBA:GO_Central.
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:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
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; IPR029817; PDGF-C.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR PANTHER; PTHR11633:SF5; PTHR11633:SF5; 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 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues;
KW Cytoplasm; Developmental protein; Disulfide bond; Glycoprotein;
KW Growth factor; Membrane; Mitogen; Nucleus; Reference proteome; Secreted;
KW Signal; Ubl conjugation.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..345
FT /note="Platelet-derived growth factor C, latent form"
FT /id="PRO_0000343871"
FT CHAIN ?..345
FT /note="Platelet-derived growth factor C, receptor-binding
FT form"
FT /id="PRO_0000343872"
FT DOMAIN 46..163
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT SITE 225..226
FT /note="Cleavage"
FT SITE 231..232
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT SITE 234..235
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 104..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DISULFID 250..294
FT /evidence="ECO:0000305|PubMed:12598536"
FT DISULFID 274
FT /note="Interchain (with C-286)"
FT /evidence="ECO:0000305|PubMed:12598536"
FT DISULFID 280..335
FT /evidence="ECO:0000305|PubMed:12598536"
FT DISULFID 286
FT /note="Interchain (with C-274)"
FT /evidence="ECO:0000305|PubMed:12598536"
FT DISULFID 287..337
FT /evidence="ECO:0000305|PubMed:12598536"
FT VAR_SEQ 1..163
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.5"
FT /id="VSP_047606"
FT VAR_SEQ 155..167
FT /note="GFCIHYNIVMPQF -> SNRGGKIIQLHTS (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_034701"
FT VAR_SEQ 168..345
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_034702"
FT VAR_SEQ 244..306
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034703"
FT MUTAGEN 124
FT /note="C->S: Loss of mitogenic activity of CUB domain in
FT coronary artery smooth muscle cells."
FT /evidence="ECO:0000269|PubMed:11854040"
FT MUTAGEN 231
FT /note="R->A: Essential for cleavage by PLAT."
FT /evidence="ECO:0000269|PubMed:15911618"
FT MUTAGEN 232
FT /note="K->A: Not essential for cleavage by PLAT."
FT /evidence="ECO:0000269|PubMed:15911618"
FT MUTAGEN 234
FT /note="R->A: Not essential for cleavage by PLAT."
FT /evidence="ECO:0000269|PubMed:15911618"
FT CONFLICT 9
FT /note="L -> V (in Ref. 3; AAF80597)"
FT /evidence="ECO:0000305"
FT CONFLICT 18
FT /note="Q -> R (in Ref. 3; AAF80597)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 345 AA; 39029 MW; CDE9E51F40633E78 CRC64;
MSLFGLLLLT SALAGQRQGT QAESNLSSKF QFSSNKEQNG VQDPQHERII TVSTNGSIHS
PRFPHTYPRN TVLVWRLVAV EENVWIQLTF DERFGLEDPE DDICKYDFVE VEEPSDGTIL
GRWCGSGTVP GKQISKGNQI RIRFVSDEYF PSEPGFCIHY NIVMPQFTEA VSPSVLPPSA
LPLDLLNNAI TAFSTLEDLI RYLEPERWQL DLEDLYRPTW QLLGKAFVFG RKSRVVDLNL
LTEEVRLYSC TPRNFSVSIR EELKRTDTIF WPGCLLVKRC GGNCACCLHN CNECQCVPSK
VTKKYHEVLQ LRPKTGVRGL HKSLTDVALE HHEECDCVCR GSTGG
