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Identification
HMDB Protein ID HMDBP14509
Secondary Accession Numbers None
Name Follistatin-related protein 3
Synonyms
  1. Follistatin-like protein 3
  2. Follistatin-related gene protein
Gene Name FSTL3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiationc. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
multicellular organismal development
spermatogenesis
adrenal gland development
positive regulation of cell-cell adhesion
post-translational protein modification
cellular protein metabolic process
regulation of transcription from RNA polymerase II promoter
hematopoietic progenitor cell differentiation
negative regulation of BMP signaling pathway
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
regulation of BMP signaling pathway
positive regulation of transcription from RNA polymerase II promoter
cell differentiation
negative regulation of activin receptor signaling pathway
male gonad development
ossification
cellular response to metal ion
kidney development
negative regulation of osteoclast differentiation
lung development
Cellular Component
endoplasmic reticulum lumen
Golgi apparatus
nucleus
nucleoplasm
secretory granule
extracellular region
extracellular space
neuron projection terminus
Molecular Function
activin binding
fibronectin binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 263
Molecular Weight 27663.23
Theoretical pI 6.773
Pfam Domain Function
Signals
  • 1-26;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O95633
UniProtKB/Swiss-Prot Entry Name FSTL3_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309 ]
  4. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [PubMed:15340161 ]
  5. Maguer-Satta V, Forissier S, Bartholin L, Martel S, Jeanpierre S, Bachelard E, Rimokh R: A novel role for fibronectin type I domain in the regulation of human hematopoietic cell adhesiveness through binding to follistatin domains of FLRG and follistatin. Exp Cell Res. 2006 Feb 15;312(4):434-42. Epub 2005 Dec 5. [PubMed:16336961 ]
  6. Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE: A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. [PubMed:26091039 ]
  7. Hayette S, Gadoux M, Martel S, Bertrand S, Tigaud I, Magaud JP, Rimokh R: FLRG (follistatin-related gene), a new target of chromosomal rearrangement in malignant blood disorders. Oncogene. 1998 Jun 4;16(22):2949-54. doi: 10.1038/sj.onc.1201807. [PubMed:9671416 ]
  8. Tortoriello DV, Sidis Y, Holtzman DA, Holmes WE, Schneyer AL: Human follistatin-related protein: a structural homologue of follistatin with nuclear localization. Endocrinology. 2001 Aug;142(8):3426-34. doi: 10.1210/endo.142.8.8319. [PubMed:11459787 ]
  9. Bartholin L, Maguer-Satta V, Hayette S, Martel S, Gadoux M, Corbo L, Magaud JP, Rimokh R: Transcription activation of FLRG and follistatin by activin A, through Smad proteins, participates in a negative feedback loop to modulate activin A function. Oncogene. 2002 Mar 28;21(14):2227-35. doi: 10.1038/sj.onc.1205294. [PubMed:11948405 ]
  10. Schneyer A, Schoen A, Quigg A, Sidis Y: Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG). Endocrinology. 2003 May;144(5):1671-4. doi: 10.1210/en.2002-0203. [PubMed:12697670 ]
  11. Wang HQ, Takebayashi K, Tsuchida K, Nishimura M, Noda Y: Follistatin-related gene (FLRG) expression in human endometrium: sex steroid hormones regulate the expression of FLRG in cultured human endometrial stromal cells. J Clin Endocrinol Metab. 2003 Sep;88(9):4432-9. doi: 10.1210/jc.2002-021758. [PubMed:12970321 ]
  12. Maguer-Satta V, Rimokh R: FLRG, member of the follistatin family, a new player in hematopoiesis. Mol Cell Endocrinol. 2004 Oct 15;225(1-2):109-18. doi: 10.1016/j.mce.2004.07.009. [PubMed:15451575 ]
  13. Bartholin L, Destaing O, Forissier S, Martel S, Maguer-Satta V, Jurdic P, Rimokh R: FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation. Biol Cell. 2005 Jul;97(7):577-88. doi: 10.1042/BC20040506. [PubMed:15574124 ]
  14. Saito S, Sidis Y, Mukherjee A, Xia Y, Schneyer A: Differential biosynthesis and intracellular transport of follistatin isoforms and follistatin-like-3. Endocrinology. 2005 Dec;146(12):5052-62. doi: 10.1210/en.2005-0833. Epub 2005 Sep 8. [PubMed:16150905 ]
  15. Forissier S, Razanajaona D, Ay AS, Martel S, Bartholin L, Rimokh R: AF10-dependent transcription is enhanced by its interaction with FLRG. Biol Cell. 2007 Oct;99(10):563-71. doi: 10.1042/bc20060131. [PubMed:17868029 ]
  16. Stamler R, Keutmann HT, Sidis Y, Kattamuri C, Schneyer A, Thompson TB: The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity. J Biol Chem. 2008 Nov 21;283(47):32831-8. doi: 10.1074/jbc.M801266200. Epub 2008 Sep 2. [PubMed:18768470 ]
  17. Cash JN, Angerman EB, Kattamuri C, Nolan K, Zhao H, Sidis Y, Keutmann HT, Thompson TB: Structure of myostatin.follistatin-like 3: N-terminal domains of follistatin-type molecules exhibit alternate modes of binding. J Biol Chem. 2012 Jan 6;287(2):1043-53. doi: 10.1074/jbc.M111.270801. Epub 2011 Nov 3. [PubMed:22052913 ]