FSTL1

Follistatin-related protein 1 is a protein that in humans is encoded by the FSTL1 gene.[5][6][7]

FSTL1
Identifiers
Aliases	FSTL1, FRP, FSL1, MIR198, follistatin like 1, OCC-1, OCC1, tsc36
External IDs	OMIM: 605547 MGI: 102793 HomoloGene: 5144 GeneCards: FSTL1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q13.33 Start 120,392,293 bp[1] End 120,450,993 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 B3|16 26.48 cM Start 37,776,873 bp[2] End 37,836,514 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • calcium ion binding • heparin binding Cellular component • extracellular region • extracellular exosome • extracellular • endoplasmic reticulum lumen Biological process • response to starvation • BMP signaling pathway • post-translational modification • cellular protein metabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	11167	14314
Ensembl	ENSG00000163430	ENSMUSG00000022816
UniProt	Q12841	Q62356
RefSeq (mRNA)	NM_007085	NM_008047
RefSeq (protein)	NP_009016	NP_032073
Location (UCSC)	Chr 3: 120.39 – 120.45 Mb	Chr 16: 37.78 – 37.84 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

This gene encodes a protein with similarity to follistatin, an BMP-4-binding protein.[8] It binds to BMP-4 and TGF-β1, but not Activin A.[8] It contains an FS module (a follistatin-like sequence containing 10 conserved cysteine residues), a Kazal-type serine protease inhibitor domain, 2 EF hand domains, and a Von Willebrand factor type C domain.[7]

Clinical significance

Development

FSTL1 has a role in development,[9][10] such as lung development,[8][11] ureter development,[12] central nervous system development,[13] and skeletal development.[11]

Arthritis

This gene product is thought to be an autoantigen associated with rheumatoid arthritis.[7]

FSTL1 up-regulates proinflammatory mediators important in the pathology of arthritis, and serum levels of FSTL1 correlate with severity of arthritis.[14][15][16]

Cardiovascular diseases

FSTL1 protein seems to have a cardioprotective role. FSTL1 attenuated hypertrophy following pressure overload[17] and prevented myocardial ischemia/reperfusion injury in a mouse or pig model of ischemia/reperfusion.[18] Muscle-derived Fstl1 modulates vascular remodelling in response to injury.[19]

FSTL1 has been shown to have a pronounced ability as a possible therapeutic to stimulate regeneration following myocardial infarction. Treating experimental animals (mouse and pig) with FSTL1 after myocardial infarction progressively restored heart function, at least in part by stimulating replication of normally non-dividing heart muscle cells[20]

References

1. GRCh38: Ensembl release 89: ENSG00000163430 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022816 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Zwijsen A, Blockx H, Van Arnhem W, Willems J, Fransen L, Devos K, Raymackers J, Van de Voorde A, Slegers H (Nov 1994). "Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue". European Journal of Biochemistry / FEBS. 225 (3): 937–46. doi:10.1111/j.1432-1033.1994.0937b.x. PMID 7957230.
6. Tanaka M, Ozaki S, Osakada F, Mori K, Okubo M, Nakao K (Sep 1998). "Cloning of follistatin-related protein as a novel autoantigen in systemic rheumatic diseases". International Immunology. 10 (9): 1305–14. doi:10.1093/intimm/10.9.1305. PMID 9786430.
7. "Entrez Gene: FSTL1 follistatin-like 1".
8. Geng Y, Dong Y, Yu M, Zhang L, Yan X, Sun J, Qiao L, Geng H, Nakajima M, Furuichi T, Ikegawa S, Gao X, Chen YG, Jiang D, Ning W (Apr 2011). "Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development". Proceedings of the National Academy of Sciences of the United States of America. 108 (17): 7058–63. doi:10.1073/pnas.1007293108. PMC 3084141. PMID 21482757.
9. Umezu T, Yamanouchi H, Iida Y, Miura M, Tomooka Y (Mar 2010). "Follistatin-like-1, a diffusible mesenchymal factor determines the fate of epithelium". Proceedings of the National Academy of Sciences of the United States of America. 107 (10): 4601–6. doi:10.1073/pnas.0909501107. PMC 2842048. PMID 20176958.
10. Sylva M, Moorman AF, van den Hoff MJ (Mar 2013). "Follistatin-like 1 in vertebrate development". Birth Defects Research. Part C, Embryo Today. 99 (1): 61–9. doi:10.1002/bdrc.21030. PMID 23723173.
11. Sylva M, Li VS, Buffing AA, van Es JH, van den Born M, van der Velden S, Gunst Q, Koolstra JH, Moorman AF, Clevers H, van den Hoff MJ (3 August 2011). "The BMP antagonist follistatin-like 1 is required for skeletal and lung organogenesis". PLOS ONE. 6 (8): e22616. doi:10.1371/journal.pone.0022616. PMC 3149603. PMID 21826198.
12. Xu J, Qi X, Gong J, Yu M, Zhang F, Sha H, Gao X (2012). "Fstl1 antagonizes BMP signaling and regulates ureter development". PLOS ONE. 7 (4): e32554. doi:10.1371/journal.pone.0032554. PMC 3317656. PMID 22485132.
13. Yang Y, Liu J, Mao H, Hu YA, Yan Y, Zhao C (Oct 2009). "The expression pattern of Follistatin-like 1 in mouse central nervous system development". Gene Expression Patterns. 9 (7): 532–40. doi:10.1016/j.gep.2009.07.001. PMID 19595790.
14. Chaly Y, Marinov AD, Oxburgh L, Bushnell DS, Hirsch R (Apr 2012). "FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression". Arthritis and Rheumatism. 64 (4): 1082–8. doi:10.1002/art.33422. PMC 3276726. PMID 22006268.
15. Chaly Y, Blair HC, Smith SM, Bushnell DS, Marinov AD, Campfield BT, Hirsch R (Jul 2015). "Follistatin-like protein 1 regulates chondrocyte proliferation and chondrogenic differentiation of mesenchymal stem cells". Annals of the Rheumatic Diseases. 74 (7): 1467–73. doi:10.1136/annrheumdis-2013-204822. PMID 24641944. S2CID 31184311.
16. Chaly Y, Fu Y, Marinov A, Hostager B, Yan W, Campfield B, Kellum JA, Bushnell D, Wang Y, Vockley J, Hirsch R (May 2014). "Follistatin-like protein 1 enhances NLRP3 inflammasome-mediated IL-1β secretion from monocytes and macrophages". European Journal of Immunology. 44 (5): 1467–79. doi:10.1002/eji.201344063. PMC 4004659. PMID 24470197.
17. Shimano M, Ouchi N, Nakamura K, van Wijk B, Ohashi K, Asaumi Y, Higuchi A, Pimentel DR, Sam F, Murohara T, van den Hoff MJ, Walsh K (Oct 2011). "Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload". Proceedings of the National Academy of Sciences of the United States of America. 108 (43): E899–906. doi:10.1073/pnas.1108559108. PMC 3203781. PMID 21987816.
18. Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T (Oct 2012). "Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models". Circulation. 126 (14): 1728–38. doi:10.1161/CIRCULATIONAHA.112.115089. PMC 3548325. PMID 22929303.
19. Miyabe M, Ohashi K, Shibata R, Uemura Y, Ogura Y, Yuasa D, Kambara T, Kataoka Y, Yamamoto T, Matsuo K, Joki Y, Enomoto T, Hayakawa S, Hiramatsu-Ito M, Ito M, Van Den Hoff MJ, Walsh K, Murohara T, Ouchi N (Jul 2014). "Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury". Cardiovascular Research. 103 (1): 111–20. doi:10.1093/cvr/cvu105. PMC 4834864. PMID 24743592.
20. Wei K, Serpooshan V, Hurtado C, Diez-Cuñado M, Zhao M, Maruyama S, Zhu W, Fajardo G, Noseda M, Nakamura K, Tian X, Liu Q, Wang A, Matsuura Y, Bushway P, Cai W, Savchenko A, Mahmoudi M, Schneider MD, van den Hoff MJ, Butte MJ, Yang PC, Walsh K, Zhou B, Bernstein D, Mercola M, Ruiz-Lozano P (Sep 2015). "Epicardial FSTL1 reconstitution regenerates the adult mammalian heart". Nature. 525 (7570): 479–85. doi:10.1038/nature15372. PMC 4762253. PMID 26375005.

Further reading

• Vertegaal AC, Kuiperij HB, van Laar T, Scharnhorst V, van der Eb AJ, Zantema A (Dec 2000). "cDNA micro array identification of a gene differentially expressed in adenovirus type 5- versus type 12-transformed cells". FEBS Letters. 487 (2): 151–5. doi:10.1016/S0014-5793(00)02339-5. PMID 11150499. S2CID 44781190.
• Ciarmela P, Florio P, Sigurdardottir M, Toti P, Maguer-Satta V, Rimokh R, Altomare A, Tosi P, Petraglia F (Aug 2004). "Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma". European Journal of Endocrinology. 151 (2): 251–7. doi:10.1530/eje.0.1510251. PMID 15296481.
• Zhang Z, Henzel WJ (Oct 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
• Ehara Y, Sakurai D, Tsuchiya N, Nakano K, Tanaka Y, Yamaguchi A, Tokunaga K (2005). "Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility". Clinical and Experimental Rheumatology. 22 (6): 707–12. PMID 15638044.
• Liu S, Wang L, Wang W, Lin J, Han J, Sun H, Guo H, Sun R, Wu Q (Apr 2006). "TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration". Experimental and Molecular Pathology. 80 (2): 132–40. doi:10.1016/j.yexmp.2005.07.005. PMID 16256108.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.

External links

• Overview of all the structural information available in the PDB for UniProt: Q62356 (Mouse Follistatin-related protein 1) at the PDBe-KB.