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Protein

Tumor necrosis factor ligand superfamily member 6

Gene

FASLG

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:11429161, PubMed:12371937). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:11429161, PubMed:12371937). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (By similarity).By similarity2 Publications
Tumor necrosis factor ligand superfamily member 6, soluble form: Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways. Can induce apoptosis but does not appear to be essential for this process.By similarity
FasL intracellular domain: Cytoplasmic form induces gene transcription inhibition.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine, Repressor
Biological processApoptosis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 6
Alternative 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
FasL intracellular domain
Short name:
FasL ICD
Alternative name(s):
SPPL2A-processed FasL form
Short name:
SPA
Gene namesi
Name:FASLG
Synonyms:CD95L, FASL, TNFSF6
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 82CytoplasmicSequence analysisAdd BLAST82
Transmembranei83 – 103Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini104 – 282ExtracellularSequence analysisAdd BLAST179

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Lysosome, Membrane, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000345101 – 282Tumor necrosis factor ligand superfamily member 6, membrane formAdd BLAST282
ChainiPRO_00004171611 – 130ADAM10-processed FasL formBy similarityAdd BLAST130
ChainiPRO_00004171621 – 83FasL intracellular domainBy similarityAdd BLAST83
ChainiPRO_0000034511131 – 282Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityAdd BLAST152

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi185N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi203 ↔ 234By similarity
Glycosylationi251N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi261N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form undergoes two successive intramembrane proteolytic cleavages. The first one is processed by ADAM10 producing an N-terminal fragment, which lacks the receptor-binding extracellular domain. This ADAM10-processed FasL (FasL APL) remnant form is still membrane anchored and further processed by SPPL2A that liberates the FasL intracellular domain (FasL ICD). FasL shedding by ADAM10 is a prerequisite for subsequent intramembrane cleavage by SPPL2A in T-cells.By similarity
Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization.By similarity
N-glycosylated. Glycosylation enhances apoptotic activity.By similarity
Monoubiquitinated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei82 – 83Cleavage; by SPPL2ABy similarity2
Sitei130 – 131Cleavage; by ADAM10By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9BEA8
PRIDEiQ9BEA8

Expressioni

Inductioni

By IL-18.1 Publication

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 similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000019767

Structurei

3D structure databases

ProteinModelPortaliQ9BEA8
SMRiQ9BEA8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 70Pro-richAdd BLAST67
Compositional biasi45 – 56Poly-ProAdd BLAST12

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHZF Eukaryota
ENOG4112D9R LUCA
HOVERGENiHBG055128
InParanoidiQ9BEA8
KOiK04389

Family and domain databases

Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR028326 FASL
IPR006053 TNF
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01681 FASLIGAND
PR01234 TNECROSISFCT
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9BEA8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQQPFNYPYP QIFWVDSSAT SPWASPGSVF PCPASVPGRP GQRRPPPPPP
60 70 80 90 100
PPPPPPTLLP SRPLPPLPPP SLKKKRDHNA GLCLLVMFFM VLVALVGLGL
110 120 130 140 150
GMFQLFHLQK ELTELRESAS QRHTESSLEK QIGHPNLPSE KKELRKVAHL
160 170 180 190 200
TGKPNSRSIP LEWEDTYGIA LVSGVKYMKG SLVINDTGLY FVYSKVYFRG
210 220 230 240 250
QYCNNQPLSH KVYTRNSRYP QDLVLMEGKM MNYCTTGQMW ARSSYLGAVF
260 270 280
NLTSADHLYV NVSELSLVNF EESKTFFGLY KL
Length:282
Mass (Da):31,756
Last modified:June 1, 2001 - v1
Checksum:i6743DAA1145671FB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5F → L in BAB64291 (PubMed:11792426).Curated1
Sequence conflicti57T → P in AAK56449 (Ref. 4) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB027297 mRNA Translation: BAB40919.1
AB069764 Genomic DNA Translation: BAB64291.1
AF397407 mRNA Translation: AAK84408.1
AY033634 mRNA Translation: AAK56449.1
RefSeqiNP_998971.1, NM_213806.1
UniGeneiSsc.15870

Genome annotation databases

GeneIDi396726
KEGGissc:396726

Similar proteinsi

Entry informationi

Entry nameiTNFL6_PIG
AccessioniPrimary (citable) accession number: Q9BEA8
Secondary accession number(s): Q95M04, Q95N10
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: June 1, 2001
Last modified: March 28, 2018
This is version 102 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health