Reviewed,
UniProtKB/Swiss-Prot P48023 (TNFL6_HUMAN)
Last modified
November 25, 2008.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Tumor necrosis factor ligand superfamily member 6 Alternative name(s): Fas antigen ligand Short name=Fas ligand CD95L protein Apoptosis antigen ligand Short name=APTL CD_antigen=CD178 Cleaved into the following 2 chains: 1- Recommended name: Tumor necrosis factor ligand superfamily member 6, membrane form 2- Recommended name: Tumor necrosis factor ligand superfamily member 6, soluble form | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 281 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. May be involved in cytotoxic T-cell mediated apoptosis and in T-cell development. TNFRSF6/FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. Binding to the decoy receptor TNFRSF6B/DcR3 modulates its effects. |
| Subunit structure | Homotrimer Probable. |
| Subcellular location | Cell membrane; Single-pass type II membrane protein. Secreted. Note= May be released into the extracellular fluid, probably by cleavage form the cell surface. |
| Post-translational modification | N-glycosylated. The soluble form derives from the membrane form by proteolytic processing. |
| Involvement in disease | Defects in FASLG are the cause of autoimmune lymphoproliferative syndrome type 1B (ALPS1B) [MIM:601859]; also known as Canale-Smith syndrome (CSS). ALPS is a childhood syndrome involving hemolytic anemia and thrombocytopenia with massive lymphadenopathy and splenomegaly. |
| Sequence similarities | Belongs to the tumor necrosis factor family. |
Ontologies
Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Cell membrane Membrane Secreted |
| Coding sequence diversity | Alternative splicing |
| Domain | Signal-anchor Transmembrane |
| Molecular function | Cytokine |
| PTM | Glycoprotein |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | activation of pro-apoptotic gene products Inferred from Experiment. Source: Reactome cell-cell signaling Ref.2Traceable author statement. Source: ProtInc immune responseInferred from electronic annotation. Source: InterPro induction of apoptosis by extracellular signalsInferred from Experiment. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascadeInferred from expression pattern. Source: UniProtKB |
| Cellular component | extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.2Traceable author statement. Source: ProtInc |
| Molecular function | tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P48023-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P48023-2) The sequence of this isoform differs from the canonical sequence as follows: 117-127: STSQMHTASSL → ATPVHPLKKRS 128-281: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 281 | 281 | Tumor necrosis factor ligand superfamily member 6, membrane form | PRO_0000034500 | ||||||||||||||||||||||||||||||
| Chain | 130 – 281 | 152 | Tumor necrosis factor ligand superfamily member 6, soluble form | PRO_0000034501 | ||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||
| Topological domain | 1 – 80 | 80 | Cytoplasmic Potential | |||||||||||||||||||||||||||||||
| Transmembrane | 81 – 102 | 22 | Signal-anchor for type II membrane protein Potential | |||||||||||||||||||||||||||||||
| Topological domain | 103 – 281 | 179 | Extracellular Potential | |||||||||||||||||||||||||||||||
| Compositional bias | 4 – 70 | 67 | Pro-rich | |||||||||||||||||||||||||||||||
| Compositional bias | 45 – 65 | 21 | Poly-Pro | |||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||
| Site | 129 – 130 | 2 | Cleavage | |||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||
| Glycosylation | 184 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||
| Glycosylation | 250 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||
| Glycosylation | 260 | 1 | N-linked (GlcNAc...) Potential | |||||||||||||||||||||||||||||||
| Disulfide bond | 202 ↔ 233 | Potential | ||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||
| Alternative sequence | 117 – 127 | 11 | STSQMHTASSL → ATPVHPLKKRS in isoform 2. | VSP_006443 | ||||||||||||||||||||||||||||||
| Alternative sequence | 128 – 281 | 154 | Missing in isoform 2. | VSP_006444 | ||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||
| Mutagenesis | 206 | 1 | P → D, F or R: Lowers binding to TNFRSF6 and reduces cytotoxity more than 100-fold | |||||||||||||||||||||||||||||||
| Mutagenesis | 218 | 1 | Y → F or R: Lowers binding to TNFRSF6 and abolishes cytotoxity | |||||||||||||||||||||||||||||||
| Mutagenesis | 275 | 1 | F → L: Abolishes binding to TNRFSF6 and cytotoxicity | |||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||
| Beta strand | 146 – 148 | 3 | ||||||||||||||||||||||||||||||||
| Beta strand | 175 – 177 | 3 | ||||||||||||||||||||||||||||||||
| Beta strand | 180 – 182 | 3 | ||||||||||||||||||||||||||||||||
| Beta strand | 187 – 191 | 5 | ||||||||||||||||||||||||||||||||
| Beta strand | 194 – 198 | 5 | ||||||||||||||||||||||||||||||||
| Beta strand | 208 – 214 | 7 | ||||||||||||||||||||||||||||||||
| Beta strand | 216 – 220 | 5 | ||||||||||||||||||||||||||||||||
| Beta strand | 222 – 228 | 7 | ||||||||||||||||||||||||||||||||
| Beta strand | 240 – 244 | 5 | ||||||||||||||||||||||||||||||||
| Beta strand | 247 – 251 | 5 | ||||||||||||||||||||||||||||||||
| Beta strand | 259 – 263 | 5 | ||||||||||||||||||||||||||||||||
| Helix | 264 – 266 | 3 | ||||||||||||||||||||||||||||||||
| Beta strand | 278 – 280 | 3 | ||||||||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Fas ligand mediates activation-induced cell death in human T lymphocytes." Alderson M. J. Exp. Med. 181:71-77(1995) [PubMed: 7528780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Human Fas ligand: gene structure, chromosomal location and species specificity." Takahashi T., Tanaka M., Inazawa J., Abe T., Suda T., Nagata S. Int. Immunol. 6:1567-1574(1994) [PubMed: 7826947] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [3] | Schaetzlein C.E., Poehlmann R., Philippsen P., Eibel H. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [4] | "Role of Fas ligand in apoptosis induced by hepatitis C virus infection." Mita E., Hayashi N., Iio S., Takehara T., Hijioka T., Kasahara A., Fusamoto H., Kamada T. Biochem. Biophys. Res. Commun. 204:468-474(1994) [PubMed: 7980502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [5] | "Isolation and characterization of a new naturally occuring variant of human Fas ligand that is expressed only in membrane bound form." Zeytun A., Nagarkatti M., Nagarkatti P.S. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Leukocyte. |
| [6] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Blood. |
| [8] | Matsumura M., Nakanishi Y., Ohba Y. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-10. Tissue: Blood. |
| [9] | "Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease." Wu J., Wilson J., He J., Xiang L., Schur P.H., Mountz J.D. J. Clin. Invest. 98:1107-1113(1996) [PubMed: 8787672] [Abstract] Cited for: INVOLVEMENT IN ALPS1B. |
| [10] | "Characterization of Fas (Apo-1, CD95)-Fas ligand interaction." Schneider P., Bodmer J.-L., Holler N., Mattmann C., Scuderi P., Terskikh A., Peitsch M.C., Tschopp J. J. Biol. Chem. 272:18827-18833(1997) [PubMed: 9228058] [Abstract] Cited for: CHARACTERIZATION, MUTAGENESIS OF PRO-206; TYR-218 AND PHE-275. |
| [11] | "Downregulation of Fas ligand by shedding." Tanaka M., Itai T., Adachi M., Nagata S. Nat. Med. 4:31-36(1998) [PubMed: 9427603] [Abstract] Cited for: PROTEOLYTIC PROCESSING. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. Translation: CAB09424.1. BC017502 mRNA. Translation: AAH17502.1. AB013303 Genomic DNA. Translation: BAA32542.1. | |||||||||||||
| PIR | I38707. | ||||||||||||
| RefSeq | NP_000630.1. | ||||||||||||
| UniGene | Hs.2007 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP:2997N. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000117560. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 356. | ||||||||||||
| KEGG | hsa:356. | ||||||||||||
Organism-specific databases | |||||||||||||
| H-InvDB | HIX0001337. | ||||||||||||
| HGNC | HGNC:11936. FASLG. | ||||||||||||
| HPA | CAB011435. | ||||||||||||
| MIM | 134638. gene. 601859. phenotype. | ||||||||||||
| Orphanet | 3261. Autoimmune lymphoproliferative syndrome. | ||||||||||||
| PharmGKB | PA56. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
| GeneCards | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | P48023. | ||||||||||||
| HOVERGEN | P48023. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Reactome | REACT_578. Apoptosis. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P48023. | ||||||||||||
| CleanEx | HS_FASLG. | ||||||||||||
| GermOnline | ENSG00000117560. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR008064. Fas_ligand. IPR006053. TNF_abc. IPR002961. TNF_C. IPR006052. TNF_family. IPR008983. Tumour_necrosis_fac-like. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit. | ||||||||||||
| PANTHER | PTHR11471:SF7. Fas_ligand. 1 hit. | ||||||||||||
| Pfam | PF00229. TNF. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR01681. FASLIGAND. PR01234. TNECROSISFCT. PR01237. TNFC. | ||||||||||||
| ProDom | PD002012. TNF_subf. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||
| SMART | SM00207. TNF. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS00251. TNF_1. 1 hit. PS50049. TNF_2. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 1489. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | TNFL6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P48023 Secondary accession number(s): Q9BZP9 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| 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 |
| 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 |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


