Q925I7 (PDGFD_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Platelet-derived growth factor D
Short name=PDGF-D

Alternative name(s):
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:	Scdgfb

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	370 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 By similarity. Has oncogenic potential and can induce tumor formation. 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. Ref.6 Ref.8 Ref.10
Subunit structure	Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB By similarity.
Subcellular location	Secreted By similarity. Note: Released by platelets upon wounding By similarity.
Tissue specificity	Expressed at high levels in developing heart, lung, kidney and some muscle derivatives. Moderately expressed in liver, brain and testis. In the kidney, localized to glomerular mesangial cells and vascular smooth muscle cells. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, expressed in interstitial cells at day 4, with an increased to maximal expression at day 14. Ref.2 Ref.5 Ref.8 Ref.9
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 By similarity.
Sequence similarities	Belongs to the PDGF/VEGF growth factor family. Contains 1 CUB domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Signal
Molecular function	Developmental protein Growth factor Mitogen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to amino acid stimulus Inferred from direct assay PubMed 20548288. Source: MGI multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 11940581. Source: MGI
Cellular_component	extracellular space Inferred from sequence orthology Ref.1. Source: MGI membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	platelet-derived growth factor receptor binding Inferred from sequence orthology Ref.1. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q925I7-1)

Also known as: Long;

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: Q925I7-2)

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

Isoform 3 (identifier: Q925I7-3)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     258-261: VDLD → GIEV
     262-370: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 370	347	Platelet-derived growth factor D, latent form		PRO_0000250190
	Chain	250 – 370	121	Platelet-derived growth factor D, receptor-binding form Potential		PRO_0000250191
Regions
	Domain	52 – 170	119	CUB
Sites
	Site	247 – 248	2	Cleavage Potential
	Site	249 – 250	2	Cleavage Potential
Amino acid modifications
	Glycosylation	276	1	N-linked (GlcNAc...) Potential
	Disulfide bond	109 ↔ 131		By similarity
	Disulfide bond	296		Interchain By similarity
	Disulfide bond	302 ↔ 360		By similarity
	Disulfide bond	306 ↔ 362		By similarity
Natural variations
	Alternative sequence	42 – 47	6	Missing in isoform 2.		VSP_020616
	Alternative sequence	258 – 261	4	VDLD → GIEV in isoform 3.		VSP_020617
	Alternative sequence	262 – 370	109	Missing in isoform 3.		VSP_020618
Experimental info
	Sequence conflict	173	1	F → S in AAH30896. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 9E80B4CF6813BFBE	FASTA	370	42,809
	10 20 30 40 50 60 MQRLVLVSIL LCANFSCYPD TFATPQRASI KALRNANLRR DESNHLTDLY QREENIQVTS 70 80 90 100 110 120 NGHVQSPRFP NSYPRNLLLT WWLRSQEKTR IQLSFDHQFG LEEAENDICR YDFVEVEEVS 130 140 150 160 170 180 ESSTVVRGRW CGHKEIPPRI TSRTNQIKIT FKSDDYFVAK PGFKIYYSFV EDFQPEAASE 190 200 210 220 230 240 TNWESVTSSF SGVSYHSPSI TDPTLTADAL DKTVAEFDTV EDLLKHFNPV SWQDDLENLY 250 260 270 280 290 300 LDTPHYRGRS YHDRKSKVDL DRLNDDVKRY SCTPRNHSVN LREELKLTNA VFFPRCLLVQ 310 320 330 340 350 360 RCGGNCGCGT VNWKSCTCSS GKTVKKYHEV LKFEPGHFKR RGKAKNMALV DIQLDHHERC 370 DCICSSRPPR
	Isoform 2 [UniParc]. Checksum: 4273B8715A7DBC97	FASTA	364	42,127
	10 20 30 40 50 60 MQRLVLVSIL LCANFSCYPD TFATPQRASI KALRNANLRR DDLYQREENI QVTSNGHVQS 70 80 90 100 110 120 PRFPNSYPRN LLLTWWLRSQ EKTRIQLSFD HQFGLEEAEN DICRYDFVEV EEVSESSTVV 130 140 150 160 170 180 RGRWCGHKEI PPRITSRTNQ IKITFKSDDY FVAKPGFKIY YSFVEDFQPE AASETNWESV 190 200 210 220 230 240 TSSFSGVSYH SPSITDPTLT ADALDKTVAE FDTVEDLLKH FNPVSWQDDL ENLYLDTPHY 250 260 270 280 290 300 RGRSYHDRKS KVDLDRLNDD VKRYSCTPRN HSVNLREELK LTNAVFFPRC LLVQRCGGNC 310 320 330 340 350 360 GCGTVNWKSC TCSSGKTVKK YHEVLKFEPG HFKRRGKAKN MALVDIQLDH HERCDCICSS RPPR
	Isoform 3 (Short) [UniParc]. Checksum: 3AA92B3236B16809	FASTA	261	30,289
	10 20 30 40 50 60 MQRLVLVSIL LCANFSCYPD TFATPQRASI KALRNANLRR DESNHLTDLY QREENIQVTS 70 80 90 100 110 120 NGHVQSPRFP NSYPRNLLLT WWLRSQEKTR IQLSFDHQFG LEEAENDICR YDFVEVEEVS 130 140 150 160 170 180 ESSTVVRGRW CGHKEIPPRI TSRTNQIKIT FKSDDYFVAK PGFKIYYSFV EDFQPEAASE 190 200 210 220 230 240 TNWESVTSSF SGVSYHSPSI TDPTLTADAL DKTVAEFDTV EDLLKHFNPV SWQDDLENLY 250 260 LDTPHYRGRS YHDRKSKGIE V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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). Strain: BALB/c.
[2]	"A novel murine PDGF-D splicing variant results in significant differences in peptide expression and function." Zhuo Y., Hoyle G.W., Zhang J., Morris G., Lasky J.A. Biochem. Biophys. Res. Commun. 308:126-132(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Hippocampus.
[4]	"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 3). Strain: FVB/N. Tissue: Mammary gland.
[5]	"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: TISSUE SPECIFICITY.
[6]	"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: FUNCTION.
[7]	"PDGF signaling in cells and mice." Tallquist M., Kazlauskas A. Cytokine Growth Factor Rev. 15:205-213(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[8]	"Exogenous PDGF-D is a potent mesangial cell mitogen and causes a severe mesangial proliferative glomerulopathy." Hudkins K.L., Gilbertson D.G., Carling M., Taneda S., Hughes S.D., Holdren M.S., Palmer T.E., Topouzis S., Haran A.C., Feldhaus A.L., Alpers C.E. J. Am. Soc. Nephrol. 15:286-298(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[9]	"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.
[10]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF335583 mRNA. Translation: AAK38839.1. AK003359 mRNA. Translation: BAB22735.2. AK141551 mRNA. Translation: BAE24732.1. BC030896 mRNA. Translation: AAH30896.1.
IPI	IPI00126922. IPI00788343. IPI00788435.
RefSeq	NP_082200.1. NM_027924.2.
UniGene	Mm.390122.
3D structure databases
HSSP	HSSP built from PDB template 1NT0 based on UniProtKB Q9QX89.
ProteinModelPortal	Q925I7.
SMR	Q925I7. Positions 62-206, 253-363.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000056240.
PTM databases
PhosphoSite	Q925I7.
Proteomic databases
PaxDb	Q925I7.
PRIDE	Q925I7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000058692; ENSMUSP00000056240; ENSMUSG00000032006. ENSMUST00000168039; ENSMUSP00000128388; ENSMUSG00000032006.
GeneID	71785.
KEGG	mmu:71785.
UCSC	uc009oby.1. mouse. uc009obz.1. mouse. uc012gnq.1. mouse.
Organism-specific databases
CTD	80310.
MGI	MGI:1919035. Pdgfd.
Phylogenomic databases
eggNOG	NOG148355.
GeneTree	ENSGT00390000005171.
HOGENOM	HOG000261610.
HOVERGEN	HBG057324.
InParanoid	Q925I7.
KO	K05450.
OMA	LYLDTPH.
OrthoDB	EOG4NKBVN.
Gene expression databases
Bgee	Q925I7.
CleanEx	MM_PDGFD.
Genevestigator	Q925I7.
Family and domain databases
Gene3D	2.60.120.290. 1 hit.
InterPro	IPR000859. CUB_dom. IPR000072. PD_growth_factor. IPR027123. PDGFD. [Graphical view]
PANTHER	PTHR10127:SF13. PTHR10127:SF13. 1 hit.
Pfam	PF00431. CUB. 1 hit. [Graphical view]
SMART	SM00042. CUB. 1 hit. SM00141. PDGF. 1 hit. [Graphical view]
SUPFAM	SSF49854. CUB. 1 hit.
PROSITE	PS01180. CUB. 1 hit. PS00249. PDGF_1. False negative. PS50278. PDGF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	334516.
SOURCE	Search...

Entry information

Entry name

PDGFD_MOUSE

Accession

Primary (citable) accession number: Q925I7
Secondary accession number(s): Q3URF6, Q8K2L3, Q9D1L8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2006
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program