SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000481 
UniProt Accession
Theoretical PI
8.79  
Molecular Weight
31485 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
FASLG 
Gene Synonyms/Alias
APT1LG1, CD95L, FASL, TNFSF6 
Protein Name
Tumor necrosis factor ligand superfamily member 6 Tumor necrosis factor ligand superfamily member 6, membrane form Tumor necrosis factor ligand superfamily member 6, soluble form ADAM10-processed FasL form FasL intracellular domain 
Protein Synonyms/Alias
Apoptosis antigen ligand;APTL CD95 ligand;CD95-L Fas antigen ligand;Fas ligandFasL CD_antigen=CD178;Contains:Contains: Receptor-binding FasL ectodomain; Soluble Fas ligand;sFasLContains:APLContains:FasL ICD SPPL2A-processed FasL form;SPA 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:1;172628154-172636014;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Fas/FasL system may be involved in the quality control mechanism of the produced gametes. FASLG -844C/T SNP may be a genetic predisposing factor of idiopathic azoospermia or severe oligozoospermia among Han Chinese men. 
The information of related literatures
1. S. Francavilla, P. D'Abrizio, N. Rucci, G. Silvano, G. Properzi, E. Straface, G. Cordeschi, S. Necozione, L. Gnessi, M. Arizzi and S. Ulisse (2000) Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J Clin Endocrinol Metab 85(8): 2692-700. 

Abstract
In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ cell apoptosis. In the present study we evaluated the expression of Fas and Fas ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and immunohistochemistry experiments on adult human testis demonstrated the expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig cells, whereas the expression of Fas was confined to the Leydig cells and sporadic degenerating spermatocytes. The number of Fas-positive germ cells per 100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/- 0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean, 1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL expression in the human testis is developmentally regulated and under gonadotropin control. The increased germ cell expression of Fas in patients with postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in the quality control mechanism of the produced gametes. PMID: [10946867] 

2. S. K. Kim, Y. D. Yoon, Y. S. Park, J. T. Seo and J. H. Kim (2007) Involvement of the Fas-Fas ligand system and active caspase-3 in abnormal apoptosis in human testes with maturation arrest and Sertoli cell-only syndrome. Fertil Steril 87(3): 547-53. 

Abstract
OBJECTIVE PMID: [17123522] 

3. W. Wang, N. Lu, Y. Xia, A. Gu, B. Wu, J. Liang, W. Zhang, Z. Wang, J. Su and X. Wang (2009) FAS and FASLG polymorphisms and susceptibility to idiopathic azoospermia or severe oligozoospermia. Reprod Biomed Online 18(1): 141-7. 

Abstract
FAS, together with FASLG, triggers germ cell apoptosis, which occurs in various stages of mammalian testicular development. Single nucleotide polymorphisms (SNP) in the promoter regions of these two genes can influence their transcriptional activities and result in abnormal cell apoptosis, thus leading to spermatogenesis impairment. Therefore, it is reasonable to postulate that FAS and FASLG SNP may be associated with idiopathic azoospermia or severe oligozoospermia. To test this hypothesis, the distributions of FAS -1377G/A and -670A/G SNP and FASLG -844C/T SNP were studied in Han Chinese men. These SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 203 infertile men with idiopathic azoospermia or severe oligozoospermia and in 246 proven fertile controls. Frequencies of FASLG -844CC, CT and TT genotypes among infertile men were significantly different from those among controls (P = 0.024). Men with FASLG -844TT genotype had an increased risk of idiopathic azoospermia or severe oligozoospermia compared with those with CC and CT genotype (odds ratio 2.72, 95% confidence interval 1.25-5.93). The results suggest that FASLG -844C/T SNP may be a genetic predisposing factor of idiopathic azoospermia or severe oligozoospermia among Han Chinese men. PMID: [19146781] 

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Figures for illustrating the function of this protein/gene
Ref: S. Francavilla, P. D'Abrizio, N. Rucci, G. Silvano, G. Properzi, E. Straface, G. Cordeschi, S. Necozione, L. Gnessi, M. Arizzi and S. Ulisse (2000) Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J Clin Endocrinol Metab 85(8): 2692-700. PMID: [10946867]
Ref: S. Francavilla, P. D'Abrizio, N. Rucci, G. Silvano, G. Properzi, E. Straface, G. Cordeschi, S. Necozione, L. Gnessi, M. Arizzi and S. Ulisse (2000) Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J Clin Endocrinol Metab 85(8): 2692-700. PMID: [10946867]
Ref: S. Francavilla, P. D'Abrizio, N. Rucci, G. Silvano, G. Properzi, E. Straface, G. Cordeschi, S. Necozione, L. Gnessi, M. Arizzi and S. Ulisse (2000) Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J Clin Endocrinol Metab 85(8): 2692-700. PMID: [10946867]
Function
The FasL intracellular domain (FasL ICD) cytoplasmicform induces gene transcription inhibition. 
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Subcellular Location
FasL intracellular domain: Nucleus. Note=TheFasL ICD cytoplasmic form is translocated into the nucleus. 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0005901 C:caveola IEA:Compara.
GO:0060205 C:cytoplasmic membrane-bounded vesicle lumen IEA:UniProtKB-SubCell.
GO:0009897 C:external side of plasma membrane IEA:Compara.
GO:0005615 C:extracellular space IDA:BHF-UCL.
GO:0005887 C:integral to plasma membrane TAS:ProtInc.
GO:0043202 C:lysosomal lumen IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus IDA:UniProtKB.
GO:0048471 C:perinuclear region of cytoplasm IEA:Compara.
GO:0006919 P:activation of cysteine-type endopeptidase activity involved in apoptotic process IMP:BHF-UCL.
GO:0008633 P:activation of pro-apoptotic gene products TAS:Reactome.
GO:0007267 P:cell-cell signaling TAS:ProtInc.
GO:0030644 P:cellular chloride ion homeostasis IEA:Compara.
GO:0033554 P:cellular response to stress IEA:Compara.
GO:0048388 P:endosomal lumen acidification IEA:Compara.
GO:0006955 P:immune response IEA:InterPro.
GO:0008624 P:induction of apoptosis by extracellular signals IDA:BHF-UCL.
GO:0008625 P:induction of apoptosis via death domain receptors IEA:Compara.
GO:0060555 P:induction of necroptosis by extracellular signals IDA:BHF-UCL.
GO:0060554 P:induction of necroptosis of activated-T cells IDA:BHF-UCL.
GO:0006925 P:inflammatory cell apoptotic process IEA:Compara.
GO:0070265 P:necrotic cell death IDA:BHF-UCL.
GO:0016525 P:negative regulation of angiogenesis IDA:BHF-UCL.
GO:0000122 P:negative regulation of transcription from RNA polymerase II promoter IDA:UniProtKB.
GO:0008284 P:positive regulation of cell proliferation IEA:Compara.
GO:0045742 P:positive regulation of epidermal growth factor receptor signaling pathway IEA:Compara.
GO:0043123 P:positive regulation of I-kappaB kinase/NF-kappaB cascade IEP:UniProtKB.
GO:0043525 P:positive regulation of neuron apoptotic process IEA:Compara.
GO:0070848 P:response to growth factor stimulus IEA:Compara.
GO:0032496 P:response to lipopolysaccharide IEA:Compara.
GO:0046666 P:retinal cell programmed cell death IEA:Compara.
GO:0007165 P:signal transduction TAS:ProtInc.
GO:0006351 P:transcription, DNA-dependent IEA:UniProtKB-KW.
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Interpro
IPR008064;    Fas_ligand.
IPR006052;    TNF.
IPR006053;    TNF_a/b/c.
IPR021184;    TNF_CS.
IPR008983;    Tumour_necrosis_fac-like.
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Pfam
PF00229;    TNF;    1.
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SMART
SM00207;    TNF;    1.
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PROSITE
PS00251;    TNF_1;    1.
PS50049;    TNF_2;    1.
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PRINTS
PR01681;    FASLIGAND.;   
PR01234;    TNECROSISFCT.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    281       Tumor necrosis factor ligand superfamily
                             member 6, membrane form.
                             /FTId=PRO_0000034500.
CHAIN         1    129       ADAM10-processed FasL form.
                             /FTId=PRO_0000417152.
CHAIN         1     81       FasL intracellular domain.
                             /FTId=PRO_0000416842.
CHAIN       130    281       Tumor necrosis factor ligand superfamily
                             member 6, soluble form.
                             /FTId=PRO_0000034501.
TOPO_DOM      1     80       Cytoplasmic (Potential).
TRANSMEM     81    102       Helical; Signal-anchor for type II
                             membrane protein; (Potential).
TOPO_DOM    103    281       Extracellular (Potential).
COMPBIAS      4     70       Pro-rich.
COMPBIAS     45     65       Poly-Pro.
SITE         81     82       Cleavage; by SPPL2A (Probable).
SITE        129    130       Cleavage; by ADAM10 (Probable).
CARBOHYD    184    184       N-linked (GlcNAc...) (Potential).
CARBOHYD    250    250       N-linked (GlcNAc...) (Potential).
CARBOHYD    260    260       N-linked (GlcNAc...) (Potential).
DISULFID    202    233       Potential.
VAR_SEQ     117    127       STSQMHTASSL -> ATPVHPLKKRS (in isoform
                             2).
                             /FTId=VSP_006443.
VAR_SEQ     128    281       Missing (in isoform 2).
                             /FTId=VSP_006444.
VARIANT     189    189       Y -> S (in dbSNP:rs12079514).
                             /FTId=VAR_052583.
MUTAGEN     206    206       P->D,F,R: Lowers binding to TNFRSF6 and
                             reduces cytotoxicity more than 100-fold.
MUTAGEN     218    218       Y->F,R: Lowers binding to TNFRSF6 and
                             abolishes cytotoxicity.
MUTAGEN     275    275       F->L: Abolishes binding to TNRFSF6 and
                             cytotoxicity.
STRAND      146    148
STRAND      175    177
STRAND      180    182
STRAND      187    191
STRAND      194    198
STRAND      208    214
STRAND      216    220
STRAND      222    228
STRAND      240    244
STRAND      247    251
STRAND      259    263
HELIX       264    266
STRAND      278    280
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Nucleotide Sequence
Length: 1790 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 281 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
MAPK8BioGRID 
BIDBioGRID 
SUMO1BioGRID 
APBB1HPRD 
GRB2BioGRID 
BIDBioGRID 
_BioGRID 
_BioGRID 
_HPRD 
_BioGRID 
BAIAP2L1IntAct 
BIDBioGRID 
BTKIntAct 
CACNB3IntAct 
CASP8BioGRID 
CASP10BioGRID 
TRIP10MINT 
CRKIntAct 
DLG2IntAct 
DMDHPRD 
FYNBioGRID 
PRPF40AHPRD 
EZRBioGRID 
FADDHPRD 
FGRBioGRID 
FN1HPRD 
FNBP1BioGRID 
SRGAP2MINT 
FYNHPRD 
ARHGDIABioGRID 
GRAP2HPRD 
GRAPHPRD 
GRB2BioGRID 
ITKIntAct 
ITSN2IntAct 
LCKHPRD 
LYNBioGRID 
MIAIntAct 
MAPK8BioGRID 
MLLHPRD 
MMP7HPRD 
MSNBioGRID 
NCF1HPRD 
NCK1HPRD 
NCK2IntAct 
OSTF1IntAct 
c-fgrBioGRID 
PIK3R1HPRD 
PACSIN1MINT 
PACSIN2HPRD 
PACSIN3MINT 
PDCD6HPRD 
PSTPIP1MINT 
PRPF40AHPRD 
PTPN13HPRD 
PRPF40AHPRD 
_HPRD 
FASBioGRID 
GRAP2HPRD 
PACSIN2BioGRID 
DKFZp686O12165HPRD 
LYNBioGRID 
DMDHPRD 
ARHABioGRID 
_HPRD 
ARHGAP4MINT 
RHOABioGRID 
Snx18MINT 
SNX33IntAct 
SNX9IntAct 
SH3PXD2AIntAct 
SH3PXD2BIntAct 
SPTA1IntAct 
SRCHPRD 
SRGAP1IntAct 
SUMO1HPRD 
TECIntAct 
TNFRSF6BBioGRID 
Ap2b1MINT 
GRB2HPRD 
CACNB4IntAct 
CASP8BioGRID 
CASP10MINT 
TRIP10MINT 
DNMBPIntAct 
DOCK4IntAct 
FYNBioGRID 
FN1BioGRID 
EPS8L3IntAct 
EZRHPRD 
FADDBioGRID 
FN1BioGRID 
FNBP1HPRD 
SRGAP2IntAct 
FYBIntAct 
FYNBioGRID 
GRB2HPRD 
HCKIntAct 
ITKIntAct 
KALRNIntAct 
LCKBioGRID 
LYNIntAct 
MACC1IntAct 
MPP4IntAct 
MYO15AIntAct 
PACSIN1MINT 
PACSIN2BioGRID 
PACSIN3MINT 
PIN1HPRD 
PSTPIP1HPRD 
FASBioGRID 
PACSIN2BioGRID 
DKFZp686K139BioGRID 
DKFZp686O12165BioGRID 
DKFZp686L11144BioGRID 
DKFZp686A24188BioGRID 
_IntAct 
CASP10IntAct 
CASP10IntAct 
_BioGRID 
ARHGAP9IntAct 
RIMBP3CIntAct 
SAMSN1IntAct 
SH3GL3IntAct 
SH3RF2IntAct 
SKAP2IntAct 
SNX18IntAct 
Snx18MINT 
SNX9IntAct 
NCKIPSDIntAct 
SRCIntAct 
SRGAP3IntAct 
TNFRSF1ABioGRID 
FASHPRD 
TNFRSF10BBioGRID 
UBCBioGRID 
YES1IntAct 
FASBioGRID 
SORBS3IntAct 
TJP3IntAct 
Other Protein-Protein interaction resources
String database  
View Microarray data
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