UniProtKB - P41047 (TNFL6_MOUSE)
Tumor necrosis factor ligand superfamily member 6
Faslg
Functioni
Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:7511063).
Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:19794494, PubMed:7532682).
Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (PubMed:19794494).
TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (PubMed:10779162).
Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (By similarity).
By similarity3 PublicationsInduces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways (PubMed:19794494).
Can induce apoptosis but does not appear to be essential for this process (By similarity).
By similarity1 PublicationCytoplasmic form induces gene transcription inhibition.
By similarityGO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- death receptor binding Source: MGI
- tumor necrosis factor receptor binding Source: MGI
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
- apoptotic signaling pathway Source: MGI
- cellular chloride ion homeostasis Source: MGI
- cellular response to interferon-gamma Source: Ensembl
- endosomal lumen acidification Source: MGI
- extrinsic apoptotic signaling pathway Source: MGI
- extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
- inflammatory cell apoptotic process Source: MGI
- necroptotic process Source: MGI
- necroptotic signaling pathway Source: MGI
- negative regulation of angiogenesis Source: MGI
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of apoptotic process Source: MGI
- positive regulation of cell population proliferation Source: MGI
- positive regulation of endothelial cell apoptotic process Source: MGI
- positive regulation of epidermal growth factor receptor signaling pathway Source: MGI
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: GO_Central
- positive regulation of neuron apoptotic process Source: MGI
- positive regulation of phosphatidylserine exposure on apoptotic cell surface Source: MGI
- release of sequestered calcium ion into cytosol by endoplasmic reticulum Source: MGI
- response to growth factor Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- retinal cell programmed cell death Source: MGI
- T cell apoptotic process Source: MGI
Keywordsi
Molecular function | Cytokine, Repressor |
Biological process | Apoptosis, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-3371378, Regulation by c-FLIP R-MMU-5218900, CASP8 activity is inhibited R-MMU-69416, Dimerization of procaspase-8 R-MMU-75157, FasL/ CD95L signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor necrosis factor ligand superfamily member 6Alternative name(s): CD95 ligand Short name: CD95-L Fas antigen ligand Short name: Fas ligand Short name: FasL CD_antigen: CD178 Cleaved into the following 4 chains: Alternative name(s): Receptor-binding FasL ectodomain Soluble Fas ligand Short name: sFasL Alternative name(s): SPPL2A-processed FasL form Short name: SPA |
Gene namesi | Name:Faslg Synonyms:Apt1lg1, Cd95l, Fasl, gld, Tnfsf6 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:99255, Fasl |
VEuPathDBi | HostDB:ENSMUSG00000000817 |
Subcellular locationi
Lysosome
- Lysosome lumen By similarity
Plasma membrane
- Cell membrane 2 Publications; Single-pass type II membrane protein Sequence analysis
Other locations
- Cytoplasmic vesicle lumen By similarity
Note: Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination. Colocalizes with the SPPL2A protease at the cell membrane.By similarity
Extracellular region or secreted
- Secreted 2 Publications
Note: May be released into the extracellular fluid by cleavage from the cell surface.By similarity
Nucleus
- Nucleus By similarity
Note: The FasL ICD cytoplasmic form is translocated into the nucleus.By similarity
Extracellular region or secreted
- extracellular exosome Source: MGI
- extracellular space Source: MGI
Lysosome
- lysosomal lumen Source: UniProtKB-SubCell
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- caveola Source: MGI
- external side of plasma membrane Source: MGI
- plasma membrane Source: MGI
Other locations
- cell surface Source: BHF-UCL
- cytoplasmic vesicle Source: MGI
- cytoplasmic vesicle lumen Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-KW
- membrane raft Source: MGI
- perinuclear region of cytoplasm Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 78 | CytoplasmicSequence analysisAdd BLAST | 78 | |
Transmembranei | 79 – 100 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 22 | |
Topological domaini | 101 – 279 | ExtracellularSequence analysisAdd BLAST | 179 |
Keywords - Cellular componenti
Cell membrane, Cytoplasmic vesicle, Lysosome, Membrane, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Keywords - Diseasei
Disease variantPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000034508 | 1 – 279 | Tumor necrosis factor ligand superfamily member 6, membrane formAdd BLAST | 279 | |
ChainiPRO_0000417159 | 1 – 127 | ADAM10-processed FasL formBy similarityAdd BLAST | 127 | |
ChainiPRO_0000417160 | 1 – 80 | FasL intracellular domainBy similarityAdd BLAST | 80 | |
ChainiPRO_0000034509 | 128 – 279 | Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityAdd BLAST | 152 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 117 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 182 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 200 ↔ 231 | By similarity | ||
Glycosylationi | 248 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 258 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 79 – 80 | Cleavage; by SPPL2ABy similarity | 2 | |
Sitei | 127 – 128 | Cleavage; by ADAM10By similarity | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Ubl conjugationProteomic databases
PaxDbi | P41047 |
PRIDEi | P41047 |
PTM databases
GlyGeni | P41047, 4 sites |
PhosphoSitePlusi | P41047 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000000817, Expressed in ectoplacental cone and 70 other tissues |
Genevisiblei | P41047, MM |
Interactioni
Subunit structurei
Homotrimer.
Interacts with ARHGAP9, BAIAP2L1, BTK, CACNB3, CACNB4, CRK, DLG2, DNMBP, DOCK4, EPS8L3, FGR, FYB1, FYN, HCK, ITK, ITSN2, KALRN, LYN, MACC1, MIA, MPP4, MYO15A, NCF1, NCK1, NCK2, NCKIPSD, OSTF1, PIK3R1, PSTPIP1, RIMBP3C, SAMSN1, SH3GL3, SH3PXD2B, SH3PXD2A, SH3RF2, SKAP2, SNX33, SNX9, SORBS3, SPTA1, SRC, SRGAP1, SRGAP2, SRGAP3, TEC, TJP3 and YES1.
By similarityGO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- death receptor binding Source: MGI
- tumor necrosis factor receptor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 199595, 2 interactors |
MINTi | P41047 |
STRINGi | 10090.ENSMUSP00000000834 |
Miscellaneous databases
RNActi | P41047, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 30 – 70 | DisorderedSequence analysisAdd BLAST | 41 | |
Regioni | 126 – 150 | DisorderedSequence analysisAdd BLAST | 25 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 30 – 68 | Pro residuesSequence analysisAdd BLAST | 39 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502RXC1, Eukaryota |
GeneTreei | ENSGT01040000240394 |
HOGENOMi | CLU_070352_2_0_1 |
InParanoidi | P41047 |
OMAi | YPQIFWV |
PhylomeDBi | P41047 |
TreeFami | TF332169 |
Family and domain databases
CDDi | cd00184, TNF, 1 hit |
Gene3Di | 2.60.120.40, 1 hit |
InterProi | View protein in InterPro IPR028326, FASL IPR006053, TNF IPR021184, TNF_CS IPR006052, TNF_dom IPR008983, Tumour_necrosis_fac-like_dom |
Pfami | View protein in Pfam PF00229, TNF, 1 hit |
PRINTSi | PR01681, FASLIGAND PR01234, TNECROSISFCT |
SMARTi | View protein in SMART SM00207, TNF, 1 hit |
SUPFAMi | SSF49842, SSF49842, 1 hit |
PROSITEi | View protein in PROSITE PS00251, TNF_1, 1 hit PS50049, TNF_2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MQQPMNYPCP QIFWVDSSAT SSWAPPGSVF PCPSCGPRGP DQRRPPPPPP
60 70 80 90 100
PVSPLPPPSQ PLPLPPLTPL KKKDHNTNLW LPVVFFMVLV ALVGMGLGMY
110 120 130 140 150
QLFHLQKELA ELREFTNQSL KVSSFEKQIA NPSTPSEKKE PRSVAHLTGN
160 170 180 190 200
PHSRSIPLEW EDTYGTALIS GVKYKKGGLV INETGLYFVY SKVYFRGQSC
210 220 230 240 250
NNQPLNHKVY MRNSKYPEDL VLMEEKRLNY CTTGQIWAHS SYLGAVFNLT
260 270
SADHLYVNIS QLSLINFEES KTFFGLYKL
The sequence of this isoform differs from the canonical sequence as follows:
1-210: Missing.
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 184 | T → A in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. 1 Publication | 1 | |
Natural varianti | 218 | E → G in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. 1 Publication | 1 | |
Natural varianti | 273 | F → L in gld; abolishes binding of FASL to its receptor. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006445 | 1 – 210 | Missing in isoform FasLS. 1 PublicationAdd BLAST | 210 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U06948 mRNA Translation: AAA17800.1 U10984 mRNA Translation: AAA19778.1 S76752 mRNA Translation: AAB33780.1 U58995 mRNA Translation: AAB02915.1 AF119335 mRNA Translation: AAD52106.1 |
CCDSi | CCDS15418.1 [P41047-1] |
PIRi | A53062 |
RefSeqi | NP_034307.1, NM_010177.4 [P41047-1] |
Genome annotation databases
Ensembli | ENSMUST00000000834; ENSMUSP00000000834; ENSMUSG00000000817 [P41047-1] ENSMUST00000193648; ENSMUSP00000141422; ENSMUSG00000000817 [P41047-2] |
GeneIDi | 14103 |
KEGGi | mmu:14103 |
UCSCi | uc007dfr.2, mouse [P41047-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U06948 mRNA Translation: AAA17800.1 U10984 mRNA Translation: AAA19778.1 S76752 mRNA Translation: AAB33780.1 U58995 mRNA Translation: AAB02915.1 AF119335 mRNA Translation: AAD52106.1 |
CCDSi | CCDS15418.1 [P41047-1] |
PIRi | A53062 |
RefSeqi | NP_034307.1, NM_010177.4 [P41047-1] |
3D structure databases
AlphaFoldDBi | P41047 |
SMRi | P41047 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 199595, 2 interactors |
MINTi | P41047 |
STRINGi | 10090.ENSMUSP00000000834 |
PTM databases
GlyGeni | P41047, 4 sites |
PhosphoSitePlusi | P41047 |
Proteomic databases
PaxDbi | P41047 |
PRIDEi | P41047 |
Protocols and materials databases
Antibodypediai | 4418, 1368 antibodies from 45 providers |
DNASUi | 14103 |
Genome annotation databases
Ensembli | ENSMUST00000000834; ENSMUSP00000000834; ENSMUSG00000000817 [P41047-1] ENSMUST00000193648; ENSMUSP00000141422; ENSMUSG00000000817 [P41047-2] |
GeneIDi | 14103 |
KEGGi | mmu:14103 |
UCSCi | uc007dfr.2, mouse [P41047-1] |
Organism-specific databases
CTDi | 14103 |
MGIi | MGI:99255, Fasl |
VEuPathDBi | HostDB:ENSMUSG00000000817 |
Phylogenomic databases
eggNOGi | ENOG502RXC1, Eukaryota |
GeneTreei | ENSGT01040000240394 |
HOGENOMi | CLU_070352_2_0_1 |
InParanoidi | P41047 |
OMAi | YPQIFWV |
PhylomeDBi | P41047 |
TreeFami | TF332169 |
Enzyme and pathway databases
Reactomei | R-MMU-3371378, Regulation by c-FLIP R-MMU-5218900, CASP8 activity is inhibited R-MMU-69416, Dimerization of procaspase-8 R-MMU-75157, FasL/ CD95L signaling |
Miscellaneous databases
BioGRID-ORCSi | 14103, 1 hit in 74 CRISPR screens |
ChiTaRSi | Fasl, mouse |
PROi | PR:P41047 |
RNActi | P41047, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000000817, Expressed in ectoplacental cone and 70 other tissues |
Genevisiblei | P41047, MM |
Family and domain databases
CDDi | cd00184, TNF, 1 hit |
Gene3Di | 2.60.120.40, 1 hit |
InterProi | View protein in InterPro IPR028326, FASL IPR006053, TNF IPR021184, TNF_CS IPR006052, TNF_dom IPR008983, Tumour_necrosis_fac-like_dom |
Pfami | View protein in Pfam PF00229, TNF, 1 hit |
PRINTSi | PR01681, FASLIGAND PR01234, TNECROSISFCT |
SMARTi | View protein in SMART SM00207, TNF, 1 hit |
SUPFAMi | SSF49842, SSF49842, 1 hit |
PROSITEi | View protein in PROSITE PS00251, TNF_1, 1 hit PS50049, TNF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TNFL6_MOUSE | |
Accessioni | P41047Primary (citable) accession number: P41047 Secondary accession number(s): Q61217, Q9R1F2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | May 25, 2022 | |
This is version 201 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families