SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000912 
UniProt Accession
Theoretical PI
7.75  
Molecular Weight
27271 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Fstl3 
Gene Synonyms/Alias
Flrg 
Protein Name
Follistatin-related protein 3 
Protein Synonyms/Alias
Follistatin-like protein 3; Follistatin-related gene protein;Flags: Precursor 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:10;79240017-79245375;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Follistatin-like 3 (FSTL3; also known as FLRG and FSRP) is a recently described member of the FST family having an overall structure and activity profile similar to that of FST, including binding and neutralization of activin. FSTL3 is most highly expressed in the placenta and testis, whereas FST is highest in the ovary and kidney. FSTL3 is likely to be a local regulator of activin action in gonadal development and gametogenesis and, further, that activin appears to have important actions in gonadal development and function that are critical for normal reproduction. 
The information of related literatures
1. Y. Xia, Y. Sidis and A. Schneyer (2004) Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice. Mol Endocrinol 18(4): 979-94. 

Abstract
Activin has numerous biological activities including regulation of follicular development, spermatogenesis, and steroidogenesis within the gonads. Activities of activin are regulated by follistatin (FST), an activin binding protein, and perhaps follistatin-like 3 (FSTL3; also known as FLRG and FSRP). FSTL3 is a recently described member of the FST family having an overall structure and activity profile similar to that of FST, including binding and neutralization of activin. FSTL3 is most highly expressed in the placenta and testis, whereas FST is highest in the ovary and kidney, suggesting that FSTL3 has biological actions that do not entirely overlap those of FST. To investigate the role of local FSTL3 as a potential regulator of activin action in gonad development and function, we examined FSTL3 expression in the mouse testis. FSTL3 protein was localized to Leydig cells, spermatagonia, and mature spermatids in normal male mice. We then created transgenic mice using a human FSTL3 cDNA driven by the mouse alpha-inhibin promoter. Three of five transgenic founders were fertile and were bred to establish lines. In the highest expressing line 3, transgene expression was largely restricted to gonads, with pituitary, adrenal, brain, and uterine expression being substantially lower. Gonad weights, sperm counts, and fertility were significantly reduced in transgenic males, and reduced litter size was evident in line 3 females. Within the testis, highest transgene expression was observed in Sertoli cells, and although most tubules showed evidence of normal spermatogenic development, degenerating tubules devoid of germ cells and Leydig cell hyperplasia were also evident in every line 3 animal examined. Ovaries from line 3 females contained fewer antral follicles and more apparent follicular atresia. Although circulating human FSTL3 levels were undetectable, FSH and LH levels in adult transgenic mice were not significantly different from wild-type animals. However, testosterone levels were significantly increased at d 21 and significantly reduced at d 60 compared with wild-type males. These results suggest that FSTL3 is likely to be a local regulator of activin action in gonadal development and gametogenesis and, further, that activin appears to have important actions in gonadal development and function that are critical for normal reproduction. PMID: [14739256] 

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Figures for illustrating the function of this protein/gene
Ref: Y. Xia, Y. Sidis and A. Schneyer (2004) Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice. Mol Endocrinol 18(4): 979-94. PMID: [14739256]
Ref: Y. Xia, Y. Sidis and A. Schneyer (2004) Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice. Mol Endocrinol 18(4): 979-94. PMID: [14739256]
Ref: Y. Xia, Y. Sidis and A. Schneyer (2004) Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice. Mol Endocrinol 18(4): 979-94. PMID: [14739256]
Ref: Y. Xia, Y. Sidis and A. Schneyer (2004) Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice. Mol Endocrinol 18(4): 979-94. PMID: [14739256]
Function
The secreted form is a binding and antagonizing proteinfor members of the TGF-beta family, such us activin, BMP2 andMSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-inducedcellular signaling; more effective on activin A than on activin B.Involved in bone formation; inhibits osteoclast differentiation.Involved in hematopoiesis; involved in differentiation ofhemopoietic progenitor cells, increases hematopoietic celladhesion to fibronectin and seems to contribute to the adhesion ofhematopoietic precursor cells to the bone marrow stroma. Thenuclear form is probably involved in transcriptional regulationvia interaction with MLLT10 (By similarity). 
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Subcellular Location
Secreted (By similarity). Nucleus (Bysimilarity). 
Tissue Specificity
Abundantly expressed in heart, lung, kidneyand testis. Continuously expressed in embryonic heart. 
Gene Ontology
GO IDGO termEvidence
GO:0005615 C:extracellular space IDA:MGI.
GO:0044306 C:neuron projection terminus IEA:Compara.
GO:0005634 C:nucleus IEA:UniProtKB-SubCell.
GO:0048471 C:perinuclear region of cytoplasm IEA:Compara.
GO:0030141 C:secretory granule IEA:Compara.
GO:0030325 P:adrenal gland development IEA:Compara.
GO:0071248 P:cellular response to metal ion IEA:Compara.
GO:0002244 P:hemopoietic progenitor cell differentiation IEA:Compara.
GO:0001822 P:kidney development IEA:Compara.
GO:0030324 P:lung development IEA:Compara.
GO:0008584 P:male gonad development IEA:Compara.
GO:0032926 P:negative regulation of activin receptor signaling pathway IEA:Compara.
GO:0030514 P:negative regulation of BMP signaling pathway IDA:MGI.
GO:0045671 P:negative regulation of osteoclast differentiation IEA:Compara.
GO:0001503 P:ossification IEA:UniProtKB-KW.
GO:0022409 P:positive regulation of cell-cell adhesion IEA:Compara.
GO:0045944 P:positive regulation of transcription from RNA polymerase II promoter IEA:Compara.
GO:0007283 P:spermatogenesis IEA:Compara.
GO:0006351 P:transcription, DNA-dependent IEA:UniProtKB-KW.
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Interpro
IPR003645;    Fol_N.
IPR015369;    Follistatin/Osteonectin_EGF.
IPR011497;    Kazal-type_dom.
IPR002350;    Prot_inh_Kazal.
IPR017878;    TB_dom.
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Pfam
PF09289;    FOLN;    1.
PF07648;    Kazal_2;    2.
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SMART
SM00274;    FOLN;    2.
SM00280;    KAZAL;    2.
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PROSITE
PS00282;    KAZAL_1;    FALSE_NEG.
PS51465;    KAZAL_2;    2.
PS51364;    TB;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
SIGNAL        1     23       Potential.
CHAIN        24    256       Follistatin-related protein 3.
                             /FTId=PRO_0000010116.
DOMAIN       34    105       TB.
DOMAIN       97    117       Follistatin-like 1.
DOMAIN      111    167       Kazal-like 1.
DOMAIN      168    191       Follistatin-like 2.
DOMAIN      187    243       Kazal-like 2.
CARBOHYD     71     71       N-linked (GlcNAc...) (Potential).
CARBOHYD    213    213       N-linked (GlcNAc...) (Potential).
DISULFID     36     59       By similarity.
DISULFID     46     90       By similarity.
DISULFID     60     93       By similarity.
DISULFID     97    108       By similarity.
DISULFID    102    117       By similarity.
DISULFID    119    151       By similarity.
DISULFID    123    144       By similarity.
DISULFID    133    165       By similarity.
DISULFID    193    227       By similarity.
DISULFID    198    220       By similarity.
DISULFID    209    241       By similarity.
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Nucleotide Sequence
Length: 1626 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 256 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
Other Protein-Protein interaction resources
String database  
View Microarray data
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