SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000412 
UniProt Accession
Theoretical PI
8.43  
Molecular Weight
37732 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
FAS 
Gene Synonyms/Alias
APT1, FAS1, TNFRSF6 
Protein Name
Tumor necrosis factor receptor superfamily member 6 
Protein Synonyms/Alias
Apo-1 antigen; Apoptosis-mediating surface antigen FAS; FASLG receptor; CD_antigen=CD95;Flags: Precursor 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:10;90729553-90775542;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Altered meiotic and post-meiotic germ cell maturation might be associated with an up-regulation of Fas gene expression capable of triggering apoptotic elimination of defective germ cells 
The information of related literatures
1.  


2. 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] 

3. S. Francavilla, P. D'Abrizio, G. Cordeschi, F. Pelliccione, S. Necozione, S. Ulisse, G. Properzi and F. Francavilla (2002) Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis. Mol Hum Reprod 8(3): 213-20. 

Abstract
Degeneration of human male germ cells was analysed by means of light (LM) and transmission electron (TEM) microscopy. The frequency of degenerating cells was correlated with that of Fas-expressing germ cells in human testes with normal spermatogenesis (n = 10), complete early maturation arrest (EMA) (n = 10) or incomplete late maturation arrest (LMA; n = 10) of spermatogenesis. LM analysis of testis sections with normal spermatogenesis indicated that degenerating germ cells were localized in the adluminal compartment of the seminiferous epithelium. TEM showed that apoptotic cells were mostly primary spermatocytes and, to a lesser extent, round or early elongating spermatids. Apoptotic germ cells appeared to be eliminated either in the seminiferous lumen or by Sertoli cell phagocytosis. An increased number of degenerating cells was observed in testes with LMA as compared with normal testes and testes with EMA of spermatogenesis (P < 0.001, Wilcoxon's rank sum test). Comparison of these results with those obtained from immunohistochemistry experiments demonstrated a tight correlation between the number of apoptotic cells and the number of Fas-expressing germ cells (P = 0.001, Spearman's rank = 0.69). These findings suggest that altered meiotic and post-meiotic germ cell maturation might be associated with an up-regulation of Fas gene expression capable of triggering apoptotic elimination of defective germ cells. PMID: [11870228] 

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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
Receptor for TNFSF6/FASLG. The adapter molecule FADDrecruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolyticactivation which initiates the subsequent cascade of caspases(aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheraltolerance, in the antigen-stimulated suicide of mature T-cells, orboth. The secreted isoforms 2 to 6 block apoptosis (in vitro). 
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Subcellular Location
Isoform 6: Secreted. 
Tissue Specificity
Isoform 1 and isoform 6 are expressed at equallevels in resting peripheral blood mononuclear cells. Afteractivation there is an increase in isoform 1 and decrease in thelevels of isoform 6. 
Gene Ontology
GO IDGO termEvidence
GO:0031265 C:CD95 death-inducing signaling complex IDA:UniProtKB.
GO:0005829 C:cytosol NAS:UniProtKB.
GO:0009897 C:external side of plasma membrane IEA:Compara.
GO:0005576 C:extracellular region IEA:UniProtKB-SubCell.
GO:0016021 C:integral to membrane IEA:UniProtKB-KW.
GO:0045121 C:membrane raft IDA:UniProtKB.
GO:0005634 C:nucleus IDA:HPA.
GO:0048471 C:perinuclear region of cytoplasm IEA:Compara.
GO:0004872 F:receptor activity NAS:UniProtKB.
GO:0004871 F:signal transducer activity TAS:ProtInc.
GO:0005031 F:tumor necrosis factor-activated receptor activity IEA:Compara.
GO:0006919 P:activation of cysteine-type endopeptidase activity involved in apoptotic process TAS:Reactome.
GO:0008633 P:activation of pro-apoptotic gene products TAS:Reactome.
GO:0006924 P:activation-induced cell death of T cells IEA:Compara.
GO:0007568 P:aging IEA:Compara.
GO:0006916 P:anti-apoptosis TAS:ProtInc.
GO:0019724 P:B cell mediated immunity IEA:Compara.
GO:0071455 P:cellular response to hyperoxia IMP:UniProtKB.
GO:0071285 P:cellular response to lithium ion IEA:Compara.
GO:0071260 P:cellular response to mechanical stimulus IEP:UniProtKB.
GO:0031104 P:dendrite regeneration IEA:Compara.
GO:0010467 P:gene expression IEA:Compara.
GO:0002377 P:immunoglobulin production IEA:Compara.
GO:0008624 P:induction of apoptosis by extracellular signals TAS:Reactome.
GO:0008625 P:induction of apoptosis via death domain receptors IEA:Compara.
GO:0006925 P:inflammatory cell apoptotic process IEA:Compara.
GO:0050869 P:negative regulation of B cell activation IEA:Compara.
GO:0045060 P:negative thymic T cell selection IEA:Compara.
GO:0051402 P:neuron apoptotic process IEA:Compara.
GO:0042698 P:ovulation cycle IEA:Compara.
GO:0010940 P:positive regulation of necrotic cell death IMP:BHF-UCL.
GO:0032464 P:positive regulation of protein homooligomerization IEA:Compara.
GO:0006461 P:protein complex assembly TAS:ProtInc.
GO:0051260 P:protein homooligomerization IEA:Compara.
GO:0042127 P:regulation of cell proliferation IEA:Compara.
GO:0045619 P:regulation of lymphocyte differentiation IEA:Compara.
GO:0045637 P:regulation of myeloid cell differentiation IEA:Compara.
GO:0003014 P:renal system process IEA:Compara.
GO:0042493 P:response to drug IEA:Compara.
GO:0043627 P:response to estrogen stimulus IEA:Compara.
GO:0051384 P:response to glucocorticoid stimulus IEA:Compara.
GO:0070848 P:response to growth factor stimulus IEA:Compara.
GO:0001666 P:response to hypoxia IEA:Compara.
GO:0032496 P:response to lipopolysaccharide IEA:Compara.
GO:0043434 P:response to peptide hormone stimulus IEA:Compara.
GO:0009636 P:response to toxin IEA:Compara.
GO:0007283 P:spermatogenesis IEA:Compara.
GO:0048536 P:spleen development IEA:Compara.
GO:0006927 P:transformed cell apoptotic process IEA:Compara.
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Interpro
IPR000488;    Death.
IPR011029;    DEATH-like.
IPR008063;    Fas_rcpt.
IPR001368;    TNFR/NGFR_Cys_rich_reg.
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Pfam
PF00531;    Death;    1.
PF00020;    TNFR_c6;    2.
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SMART
SM00005;    DEATH;    1.
SM00208;    TNFR;    3.
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PROSITE
PS50017;    DEATH_DOMAIN;    1.
PS00652;    TNFR_NGFR_1;    2.
PS50050;    TNFR_NGFR_2;    2.
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PRINTS
PR01680;    TNFACTORR6.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
SIGNAL        1     25       Potential.
CHAIN        26    335       Tumor necrosis factor receptor
                             superfamily member 6.
                             /FTId=PRO_0000034563.
TOPO_DOM     26    173       Extracellular (Potential).
TRANSMEM    174    190       Helical; (Potential).
TOPO_DOM    191    335       Cytoplasmic (Potential).
REPEAT       47     83       TNFR-Cys 1.
REPEAT       84    127       TNFR-Cys 2.
REPEAT      128    166       TNFR-Cys 3.
DOMAIN      230    314       Death.
REGION      212    317       Interaction with HIPK3 (By similarity).
MOD_RES     209    209       Phosphoserine.
MOD_RES     214    214       Phosphothreonine.
MOD_RES     225    225       Phosphoserine (By similarity).
MOD_RES     230    230       Phosphoserine (By similarity).
CARBOHYD     28     28       O-linked (GalNAc...).
CARBOHYD    118    118       N-linked (GlcNAc...).
CARBOHYD    136    136       N-linked (GlcNAc...) (Potential).
DISULFID     59     73       By similarity.
DISULFID     63     82       By similarity.
DISULFID     85    101       By similarity.
DISULFID    104    119       By similarity.
DISULFID    107    127       By similarity.
DISULFID    129    143       By similarity.
DISULFID    146    157       By similarity.
DISULFID    149    165       By similarity.
VAR_SEQ      66    103       GERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRR ->
                             DVNMESSRNAHSPATPSAKRKDPDLTWGGFVFFFCQFH
                             (in isoform 2).
                             /FTId=VSP_006481.
VAR_SEQ      66     86       GERKARDCTVNGDEPDCVPCQ -> DVNMESSRNAHSPATP
                             SAKRK (in isoform 3).
                             /FTId=VSP_006483.
VAR_SEQ      87    335       Missing (in isoform 3).
                             /FTId=VSP_006484.
VAR_SEQ     104    335       Missing (in isoform 2).
                             /FTId=VSP_006482.
VAR_SEQ     112    149       GLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKC ->
                             DVNMESSRNAHSPATPSAKRKDPDLTWGGFVFFFCQFH
                             (in isoform 4).
                             /FTId=VSP_006485.
VAR_SEQ     112    132       GLEVEINCTRTQNTKCRCKPN -> DVNMESSRNAHSPATP
                             SAKRK (in isoform 5).
                             /FTId=VSP_006487.
VAR_SEQ     133    335       Missing (in isoform 5).
                             /FTId=VSP_006488.
VAR_SEQ     150    335       Missing (in isoform 4).
                             /FTId=VSP_006486.
VAR_SEQ     169    189       Missing (in isoform 6).
                             /FTId=VSP_006489.
VARIANT      16     16       A -> T (in dbSNP:rs3218619).
                             /FTId=VAR_020008.
VARIANT      25     25       A -> T (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013416.
VARIANT      28     28       T -> A (in ALPS1A; associated with
                             autoimmune hepatitis type 2).
                             /FTId=VAR_013417.
VARIANT      82     82       C -> R (in ALPS1A).
                             /FTId=VAR_013418.
VARIANT     118    118       N -> S (in squamous cell carcinoma; burn-
                             scar related; somatic mutation).
                             /FTId=VAR_018321.
VARIANT     121    121       R -> W (in ALPS1A).
                             /FTId=VAR_013419.
VARIANT     122    122       T -> I (in dbSNP:rs3218614).
                             /FTId=VAR_020009.
VARIANT     178    178       C -> R (in squamous cell carcinoma; burn-
                             scar related; somatic mutation).
                             /FTId=VAR_018322.
VARIANT     180    180       L -> F (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013420.
VARIANT     183    183       P -> L (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013421.
VARIANT     184    184       I -> V (in dbSNP:rs28362322).
                             /FTId=VAR_052347.
VARIANT     198    198       T -> I (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013422.
VARIANT     232    232       Y -> C (in ALPS1A; no effect on
                             interaction with FADD).
                             /FTId=VAR_013423.
VARIANT     241    241       T -> K (in ALPS1A).
                             /FTId=VAR_013424.
VARIANT     241    241       T -> P (in ALPS1A).
                             /FTId=VAR_013425.
VARIANT     249    249       V -> L (in ALPS1A).
                             /FTId=VAR_065128.
VARIANT     250    250       R -> P (in ALPS1A).
                             /FTId=VAR_013426.
VARIANT     250    250       R -> Q (in ALPS1A; no effect on
                             interaction with FADD).
                             /FTId=VAR_013427.
VARIANT     253    253       G -> D (in ALPS1A).
                             /FTId=VAR_065129.
VARIANT     253    253       G -> S (in ALPS1A).
                             /FTId=VAR_065130.
VARIANT     255    255       N -> D (in squamous cell carcinoma; burn-
                             scar related; somatic mutation).
                             /FTId=VAR_018323.
VARIANT     257    257       A -> D (in ALPS1A; loss of interaction
                             with FADD).
                             /FTId=VAR_013428.
VARIANT     259    259       I -> R (in ALPS1A).
                             /FTId=VAR_065131.
VARIANT     260    260       D -> G (in ALPS1A).
                             /FTId=VAR_013429.
VARIANT     260    260       D -> V (in ALPS1A; also found in non-
                             Hodgkin lymphoma; somatic mutation; loss
                             of interaction with FADD;
                             dbSNP:rs28929498).
                             /FTId=VAR_013431.
VARIANT     260    260       D -> Y (in ALPS1A; loss of interaction
                             with FADD).
                             /FTId=VAR_013430.
VARIANT     262    262       I -> S (in ALPS1A).
                             /FTId=VAR_058910.
VARIANT     264    264       N -> K (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013432.
VARIANT     270    270       T -> I (in ALPS1A).
                             /FTId=VAR_013433.
VARIANT     270    270       T -> K (in ALPS1A; loss of interaction
                             with FADD).
                             /FTId=VAR_065132.
VARIANT     272    272       E -> G (in ALPS1A).
                             /FTId=VAR_013434.
VARIANT     272    272       E -> K (in ALPS1A; also found in non-
                             Hodgkin lymphoma; somatic mutation; loss
                             of interaction with FADD).
                             /FTId=VAR_013435.
VARIANT     278    278       L -> F (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013436.
VARIANT     299    299       K -> N (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_013437.
VARIANT     305    305       T -> I (in dbSNP:rs3218611).
                             /FTId=VAR_020942.
VARIANT     310    310       I -> S (in ALPS1A).
                             /FTId=VAR_013438.
MUTAGEN     250    250       R->E: Strongly decreased interaction with
                             FADD.
MUTAGEN     261    261       E->K: Loss of interaction with FADD.
MUTAGEN     283    283       Q->K: Loss of interaction with FADD.
MUTAGEN     287    287       K->D: Strongly decreased interaction with
                             FADD.
MUTAGEN     291    291       Y->D: Decreased interaction with FADD.
MUTAGEN     313    313       I->D: Constitutive activation. Promotes
                             apoptosis, both in the presence and in
                             the absence of stimulation by a ligand.
CONFLICT    224    224       L -> F (in Ref. 10; AAR08906).
CONFLICT    242    242       L -> P (in Ref. 8; CAR92543).
STRAND       67     71
STRAND       75     77
STRAND       82     84
TURN         87     89
HELIX       109    111
STRAND      113    117
STRAND      126    129
STRAND      137    139
HELIX       232    242
TURN        251    253
HELIX       256    265
HELIX       270    282
HELIX       287    319
HELIX       327    334
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Nucleotide Sequence
Length: 2534 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 335 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
FBF1HPRD 
SUMO1BioGRID 
TNFSF13BioGRID 
ADIPOQString 
ADIPOR1String 
ANK3HPRD 
hCG_2045906BioGRID 
_BioGRID 
_HPRD 
BREBioGRID 
BTKHPRD 
TNFBioGRID 
CASP8AP2HPRD 
CALM1IntAct 
CASP8HPRD 
CD47HPRD 
DAXXIntAct 
CRMP1IntAct 
FYNBioGRID 
EEF1A1HPRD 
EGFRHPRD 
C14orf1IntAct 
FADDHPRD 
FAF1HPRD 
FAIM2HPRD 
FEM1BHPRD 
FYNHPRD 
HIPK3HPRD 
LCKHPRD 
MAP3K5IntAct 
PDCD6HPRD 
Pdcd6IntAct 
PTPN13HPRD 
TNFSF13BioGRID 
_HPRD 
FASLGHPRD 
TNFSF13HPRD 
FAF1HPRD 
BTKHPRD 
TNFBioGRID 
FASBioGRID 
EEF1A1HPRD 
RIF1IntAct 
RIPK1HPRD 
SRCIntAct 
SUMO1HPRD 
TNFSF13HPRD 
TNFBioGRID 
FASLGHPRD 
_HPRD 
METHPRD 
MAPK8BioGRID 
FBF1BioGRID 
BIDBioGRID 
RAP1AHPRD 
ADIPOQString 
ADIPOR1String 
APAF1HPRD 
BIDBioGRID 
CRMP1HPRD 
_BioGRID 
NOL3BioGRID 
CALM1HPRD 
_BioGRID 
_BioGRID 
_BioGRID 
_BioGRID 
PRKCAHPRD 
BIDBioGRID 
BREBioGRID 
CALM1HPRD 
CASP8BioGRID 
CASP10BioGRID 
CFLARBioGRID 
DAXXBioGRID 
CRMP1BioGRID 
EEF1A1BioGRID 
C14orf1HPRD 
EZRHPRD 
FADDBioGRID 
FAF1BioGRID 
ARHGDIABioGRID 
PRKCAHPRD 
C1orf103HPRD 
METHPRD 
MAPK8BioGRID 
MSNBioGRID 
NOL3BioGRID 
PDCD6BioGRID 
PTPN6HPRD 
_BioGRID 
_BioGRID 
FASLGBioGRID 
FAF1BioGRID 
FASBioGRID 
NOL3BioGRID 
C14orf1HPRD 
EEF1A1BioGRID 
DKFZp686A24188BioGRID 
PRKCAHPRD 
_HPRD 
CRMP1HPRD 
ARHABioGRID 
_HPRD 
RAP1AHPRD 
RHOABioGRID 
RIPK1BioGRID 
INPP5DMINT 
SUMO1IntAct 
FASLGBioGRID 
TNFRSF1ABioGRID 
FASHPRD 
FASHPRD 
TNFRSF10BBioGRID 
UBE2IBioGRID 
YES1IntAct 
FasIntAct 
TRADDHPRD 
UBA7HPRD 
UBE2IHPRD 
Other Protein-Protein interaction resources
String database  
View Microarray data
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