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Protein

Tumor necrosis factor ligand superfamily member 6

Gene

Faslg

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publications
Tumor necrosis factor ligand superfamily member 6, soluble form: Induces 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 Publication
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

Enzyme and pathway databases

ReactomeiR-MMU-3371378. Regulation by c-FLIP.
R-MMU-5213460. RIPK1-mediated regulated necrosis.
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 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:Apt1lg1, Cd95l, Fasl, gld, Tnfsf6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:99255. Fasl.

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 – 78CytoplasmicSequence analysisAdd BLAST78
Transmembranei79 – 100Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini101 – 279ExtracellularSequence analysisAdd BLAST179

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

A deficiency in this protein is the cause of generalized lymphoproliferation disease phenotype (gld). Gld mice present lymphadenopathy and autoantibody production. The phenotype is recessively inherited.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000345081 – 279Tumor necrosis factor ligand superfamily member 6, membrane formAdd BLAST279
ChainiPRO_00004171591 – 127ADAM10-processed FasL formBy similarityAdd BLAST127
ChainiPRO_00004171601 – 80FasL intracellular domainBy similarityAdd BLAST80
ChainiPRO_0000034509128 – 279Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityAdd BLAST152

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi182N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi200 ↔ 231By similarity
Glycosylationi248N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi258N-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
Sitei79 – 80Cleavage; by SPPL2ABy similarity2
Sitei127 – 128Cleavage; by ADAM10By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP41047.
PRIDEiP41047.

PTM databases

PhosphoSitePlusiP41047.

Miscellaneous databases

PMAP-CutDBiP41047.

Expressioni

Tissue specificityi

Expressed in T-cells (PubMed:19794494). Expressed in natural killer cells (PubMed:7532682).2 Publications

Gene expression databases

BgeeiENSMUSG00000000817.
CleanExiMM_FASL.
ExpressionAtlasiP41047. baseline and differential.
GenevisibleiP41047. 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 similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Pstpip1P978144EBI-7833717,EBI-7484574

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199595. 1 interactor.
IntActiP41047. 2 interactors.
MINTiMINT-1486494.
STRINGi10090.ENSMUSP00000000834.

Structurei

3D structure databases

ProteinModelPortaliP41047.
SMRiP41047.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 69Pro-richAdd BLAST66
Compositional biasi45 – 51Poly-Pro7

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHZF. Eukaryota.
ENOG4112D9R. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000290680.
HOVERGENiHBG055128.
InParanoidiP41047.
KOiK04389.
OMAiWEDTYGI.
OrthoDBiEOG091G0MFC.
PhylomeDBiP41047.
TreeFamiTF332169.

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.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform FasL (identifier: P41047-1) [UniParc]FASTAAdd to basket

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.

« Hide

        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
Length:279
Mass (Da):31,442
Last modified:February 1, 1995 - v1
Checksum:i37972E2728E0A1CA
GO
Isoform FasLS (identifier: P41047-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-210: Missing.

Show »
Length:69
Mass (Da):8,040
Checksum:i9BA6F24DD120A482
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti184T → A in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. 1 Publication1
Natural varianti218E → G in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. 1 Publication1
Natural varianti273F → L in gld; abolishes binding of FASL to its receptor. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0064451 – 210Missing in isoform FasLS. 1 PublicationAdd BLAST210

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.
CCDSiCCDS15418.1. [P41047-1]
PIRiA53062.
RefSeqiNP_034307.1. NM_010177.4. [P41047-1]
UniGeneiMm.3355.

Genome annotation databases

EnsembliENSMUST00000000834; ENSMUSP00000000834; ENSMUSG00000000817. [P41047-1]
ENSMUST00000193648; ENSMUSP00000141422; ENSMUSG00000000817. [P41047-2]
GeneIDi14103.
KEGGimmu:14103.
UCSCiuc007dfr.2. mouse. [P41047-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNFL6_MOUSE
AccessioniPrimary (citable) accession number: P41047
Secondary accession number(s): Q61217, Q9R1F2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: September 27, 2017
This is version 172 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families