UniProtKB - P48023 (TNFL6_HUMAN)
Tumor necrosis factor ligand superfamily member 6
FASLG
Functioni
GO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- death receptor binding Source: Ensembl
- signaling receptor binding Source: ProtInc
- tumor necrosis factor receptor binding Source: Ensembl
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
- apoptotic process Source: ProtInc
- apoptotic signaling pathway Source: BHF-UCL
- cell-cell signaling Source: ProtInc
- cellular chloride ion homeostasis Source: Ensembl
- cellular response to interferon-gamma Source: Ensembl
- cytokine-mediated signaling pathway Source: Reactome
- endosomal lumen acidification Source: Ensembl
- extrinsic apoptotic signaling pathway Source: UniProtKB
- extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
- inflammatory cell apoptotic process Source: Ensembl
- necroptotic process Source: BHF-UCL
- necroptotic signaling pathway Source: BHF-UCL
- negative regulation of angiogenesis Source: BHF-UCL
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of cell population proliferation Source: Ensembl
- positive regulation of endothelial cell apoptotic process Source: BHF-UCL
- positive regulation of epidermal growth factor receptor signaling pathway Source: Ensembl
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of neuron apoptotic process Source: Ensembl
- regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
- 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: Ensembl
- signal transduction Source: ProtInc
- T cell apoptotic process Source: UniProtKB
Keywordsi
Molecular function | Cytokine, Repressor |
Biological process | Apoptosis, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P48023 |
Reactomei | R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand R-HSA-3371378, Regulation by c-FLIP R-HSA-5213460, RIPK1-mediated regulated necrosis R-HSA-5218900, CASP8 activity is inhibited R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-69416, Dimerization of procaspase-8 R-HSA-75157, FasL/ CD95L signaling R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-9614657, FOXO-mediated transcription of cell death genes |
SIGNORi | P48023 |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor necrosis factor ligand superfamily member 6Alternative name(s): Apoptosis antigen ligand Short name: APTL 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, TNFSF6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11936, FASLG |
MIMi | 134638, gene |
neXtProti | NX_P48023 |
VEuPathDBi | HostDB:ENSG00000117560.7 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Single-pass type II membrane protein Sequence analysis
Lysosome
- Lysosome lumen 1 Publication
Other locations
- Cytoplasmic vesicle lumen 1 Publication
Note: Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination (PubMed:17164290). Colocalizes with the SPPL2A protease at the cell membrane (PubMed:17557115).2 Publications
Extracellular region or secreted
- Secreted 1 Publication
Note: May be released into the extracellular fluid by cleavage from the cell surface.1 Publication
Nucleus
- Nucleus 1 Publication
Note: The FasL ICD cytoplasmic form is translocated into the nucleus.1 Publication
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: BHF-UCL
Lysosome
- lysosomal lumen Source: UniProtKB-SubCell
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- caveola Source: Ensembl
- external side of plasma membrane Source: Ensembl
- integral component of plasma membrane Source: ProtInc
- plasma membrane Source: AgBase
Other locations
- cytoplasmic vesicle lumen Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 80 | CytoplasmicSequence analysisAdd BLAST | 80 | |
Transmembranei | 81 – 102 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 22 | |
Topological domaini | 103 – 281 | ExtracellularSequence analysisAdd BLAST | 179 |
Keywords - Cellular componenti
Cell membrane, Cytoplasmic vesicle, Lysosome, Membrane, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Autoimmune lymphoproliferative syndrome 1B (ALPS1B)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075568 | 202 | C → S in ALPS1B; significant reduction in cytotoxicity and apoptosis and inhibition of the shedding of the soluble form. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 206 | P → D, F or R: Lowers binding to TNFRSF6 and reduces cytotoxicity more than 100-fold. 1 Publication | 1 | |
Mutagenesisi | 218 | Y → F or R: Lowers binding to TNFRSF6 and abolishes cytotoxicity. 1 Publication | 1 | |
Mutagenesisi | 275 | F → L: Abolishes binding to TNRFSF6 and cytotoxicity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 356 |
GeneReviewsi | FASLG |
MalaCardsi | FASLG |
MIMi | 601859, phenotype |
OpenTargetsi | ENSG00000117560 |
Orphaneti | 3261, Autoimmune lymphoproliferative syndrome |
PharmGKBi | PA56 |
Miscellaneous databases
Pharosi | P48023, Tbio |
Chemistry databases
ChEMBLi | CHEMBL5714 |
Genetic variation databases
BioMutai | FASLG |
DMDMi | 1345957 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000034500 | 1 – 281 | Tumor necrosis factor ligand superfamily member 6, membrane formAdd BLAST | 281 | |
ChainiPRO_0000417152 | 1 – 129 | ADAM10-processed FasL formAdd BLAST | 129 | |
ChainiPRO_0000416842 | 1 – 81 | FasL intracellular domainAdd BLAST | 81 | |
ChainiPRO_0000034501 | 130 – 281 | Tumor necrosis factor ligand superfamily member 6, soluble formAdd BLAST | 152 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 184 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 202 ↔ 233 | Combined sources1 Publication | ||
Glycosylationi | 250 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 260 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 81 – 82 | Cleavage; by SPPL2ACurated | 2 | |
Sitei | 129 – 130 | Cleavage; by ADAM10Curated | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Ubl conjugationProteomic databases
MassIVEi | P48023 |
PaxDbi | P48023 |
PeptideAtlasi | P48023 |
PRIDEi | P48023 |
ProteomicsDBi | 55831 [P48023-1] 55832 [P48023-2] |
PTM databases
GlyGeni | P48023, 3 sites |
iPTMneti | P48023 |
PhosphoSitePlusi | P48023 |
SwissPalmi | P48023 |
Expressioni
Gene expression databases
Bgeei | ENSG00000117560, Expressed in granulocyte and 82 other tissues |
ExpressionAtlasi | P48023, baseline and differential |
Genevisiblei | P48023, HS |
Organism-specific databases
HPAi | ENSG00000117560, Tissue enhanced (blood, lymphoid tissue) |
Interactioni
Subunit structurei
Homotrimer (PubMed:27806260).
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.
Curated3 PublicationsBinary interactionsi
Hide detailsP48023
GO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- death receptor binding Source: Ensembl
- signaling receptor binding Source: ProtInc
- tumor necrosis factor receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 106852, 91 interactors |
DIPi | DIP-2997N |
ELMi | P48023 |
IntActi | P48023, 83 interactors |
MINTi | P48023 |
STRINGi | 9606.ENSP00000356694 |
Miscellaneous databases
RNActi | P48023, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P48023 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 4 – 70 | Pro-richAdd BLAST | 67 | |
Compositional biasi | 45 – 65 | Poly-ProAdd BLAST | 21 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502S09I, Eukaryota |
GeneTreei | ENSGT01010000222306 |
HOGENOMi | CLU_070352_2_0_1 |
InParanoidi | P48023 |
OMAi | PQIFWVD |
PhylomeDBi | P48023 |
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
MQQPFNYPYP QIYWVDSSAS SPWAPPGTVL PCPTSVPRRP GQRRPPPPPP
60 70 80 90 100
PPPLPPPPPP PPLPPLPLPP LKKRGNHSTG LCLLVMFFMV LVALVGLGLG
110 120 130 140 150
MFQLFHLQKE LAELRESTSQ MHTASSLEKQ IGHPSPPPEK KELRKVAHLT
160 170 180 190 200
GKSNSRSMPL EWEDTYGIVL LSGVKYKKGG LVINETGLYF VYSKVYFRGQ
210 220 230 240 250
SCNNLPLSHK VYMRNSKYPQ DLVMMEGKMM SYCTTGQMWA RSSYLGAVFN
260 270 280
LTSADHLYVN VSELSLVNFE ESQTFFGLYK L
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052583 | 189 | Y → S. Corresponds to variant dbSNP:rs12079514Ensembl. | 1 | |
Natural variantiVAR_075568 | 202 | C → S in ALPS1B; significant reduction in cytotoxicity and apoptosis and inhibition of the shedding of the soluble form. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006443 | 117 – 127 | STSQMHTASSL → ATPVHPLKKRS in isoform 2. 1 PublicationAdd BLAST | 11 | |
Alternative sequenceiVSP_006444 | 128 – 281 | Missing in isoform 2. 1 PublicationAdd BLAST | 154 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U08137 mRNA Translation: AAC50071.1 U11821 mRNA Translation: AAC50124.1 X89102 mRNA Translation: CAA61474.1 D38122 mRNA Translation: BAA07320.1 AF288573 mRNA Translation: AAG60017.1 Z96050 Genomic DNA No translation available. BC017502 mRNA Translation: AAH17502.1 AB013303 Genomic DNA Translation: BAA32542.1 |
CCDSi | CCDS1304.1 [P48023-1] CCDS76243.1 [P48023-2] |
PIRi | I38707 |
RefSeqi | NP_000630.1, NM_000639.2 [P48023-1] NP_001289675.1, NM_001302746.1 [P48023-2] |
Genome annotation databases
Ensembli | ENST00000340030; ENSP00000344739; ENSG00000117560 [P48023-2] ENST00000367721; ENSP00000356694; ENSG00000117560 [P48023-1] |
GeneIDi | 356 |
KEGGi | hsa:356 |
UCSCi | uc001git.4, human [P48023-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
FASLGbase FASLG mutation db |
Wikipedia FAS-ligand entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U08137 mRNA Translation: AAC50071.1 U11821 mRNA Translation: AAC50124.1 X89102 mRNA Translation: CAA61474.1 D38122 mRNA Translation: BAA07320.1 AF288573 mRNA Translation: AAG60017.1 Z96050 Genomic DNA No translation available. BC017502 mRNA Translation: AAH17502.1 AB013303 Genomic DNA Translation: BAA32542.1 |
CCDSi | CCDS1304.1 [P48023-1] CCDS76243.1 [P48023-2] |
PIRi | I38707 |
RefSeqi | NP_000630.1, NM_000639.2 [P48023-1] NP_001289675.1, NM_001302746.1 [P48023-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BZI | model | - | B/C | 1-281 | [»] | |
4MSV | X-ray | 2.50 | A | 130-281 | [»] | |
5L19 | X-ray | 2.00 | A | 130-281 | [»] | |
5L36 | X-ray | 3.10 | A | 130-281 | [»] | |
SMRi | P48023 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106852, 91 interactors |
DIPi | DIP-2997N |
ELMi | P48023 |
IntActi | P48023, 83 interactors |
MINTi | P48023 |
STRINGi | 9606.ENSP00000356694 |
Chemistry databases
ChEMBLi | CHEMBL5714 |
PTM databases
GlyGeni | P48023, 3 sites |
iPTMneti | P48023 |
PhosphoSitePlusi | P48023 |
SwissPalmi | P48023 |
Genetic variation databases
BioMutai | FASLG |
DMDMi | 1345957 |
Proteomic databases
MassIVEi | P48023 |
PaxDbi | P48023 |
PeptideAtlasi | P48023 |
PRIDEi | P48023 |
ProteomicsDBi | 55831 [P48023-1] 55832 [P48023-2] |
Protocols and materials databases
ABCDi | P48023, 4 sequenced antibodies |
Antibodypediai | 4418, 1314 antibodies |
DNASUi | 356 |
Genome annotation databases
Ensembli | ENST00000340030; ENSP00000344739; ENSG00000117560 [P48023-2] ENST00000367721; ENSP00000356694; ENSG00000117560 [P48023-1] |
GeneIDi | 356 |
KEGGi | hsa:356 |
UCSCi | uc001git.4, human [P48023-1] |
Organism-specific databases
CTDi | 356 |
DisGeNETi | 356 |
GeneCardsi | FASLG |
GeneReviewsi | FASLG |
HGNCi | HGNC:11936, FASLG |
HPAi | ENSG00000117560, Tissue enhanced (blood, lymphoid tissue) |
MalaCardsi | FASLG |
MIMi | 134638, gene 601859, phenotype |
neXtProti | NX_P48023 |
OpenTargetsi | ENSG00000117560 |
Orphaneti | 3261, Autoimmune lymphoproliferative syndrome |
PharmGKBi | PA56 |
VEuPathDBi | HostDB:ENSG00000117560.7 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S09I, Eukaryota |
GeneTreei | ENSGT01010000222306 |
HOGENOMi | CLU_070352_2_0_1 |
InParanoidi | P48023 |
OMAi | PQIFWVD |
PhylomeDBi | P48023 |
TreeFami | TF332169 |
Enzyme and pathway databases
PathwayCommonsi | P48023 |
Reactomei | R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand R-HSA-3371378, Regulation by c-FLIP R-HSA-5213460, RIPK1-mediated regulated necrosis R-HSA-5218900, CASP8 activity is inhibited R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-69416, Dimerization of procaspase-8 R-HSA-75157, FasL/ CD95L signaling R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-9614657, FOXO-mediated transcription of cell death genes |
SIGNORi | P48023 |
Miscellaneous databases
BioGRID-ORCSi | 356, 5 hits in 879 CRISPR screens |
ChiTaRSi | FASLG, human |
GeneWikii | Fas_ligand |
GenomeRNAii | 356 |
Pharosi | P48023, Tbio |
PROi | PR:P48023 |
RNActi | P48023, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000117560, Expressed in granulocyte and 82 other tissues |
ExpressionAtlasi | P48023, baseline and differential |
Genevisiblei | P48023, HS |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TNFL6_HUMAN | |
Accessioni | P48023Primary (citable) accession number: P48023 Secondary accession number(s): Q9BZP9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1996 |
Last sequence update: | February 1, 1996 | |
Last modified: | February 10, 2021 | |
This is version 219 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families