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P41047 (TNFL6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Tumor necrosis factor ligand superfamily member 6, membrane form
  2. Tumor necrosis factor ligand superfamily member 6, soluble form
    Alternative name(s):
    Receptor-binding FasL ectodomain
    Soluble Fas ligand
    Short name=sFasL
  3. ADAM10-processed FasL form
    Short name=APL
  4. FasL intracellular domain
    Short name=FasL ICD
    Alternative name(s):
    SPPL2A-processed FasL form
    Short name=SPA
Gene names
Name:Faslg
Synonyms:Apt1lg1, Cd95l, Fasl, gld, Tnfsf6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length279 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 By similarity.

The FasL intracellular domain (FasL ICD) cytoplasmic form induces gene transcription inhibition By similarity.

Subunit structure

Homotrimer Probable. Interacts with ARHGAP9, BAIAP2L1, BTK, CACNB3, CACNB4, CRK, DLG2, DNMBP, DOCK4, EPS8L3, FGR, FYB, 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.

Subcellular location

Isoform FasL: Cell membrane; Single-pass type II membrane protein. Cytoplasmic vesicle lumen By similarity. Lysosome 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.

Isoform FasLS: Secreted.

Tumor necrosis factor ligand superfamily member 6, soluble form: Secreted. Note: May be released into the extracellular fluid, probably by cleavage form the cell surface.

FasL intracellular domain: Nucleus By similarity. Note: The FasL ICD cytoplasmic form is translocated into the nucleus By similarity.

Post-translational modification

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 By similarity.

Monoubiquitinated By similarity.

Involvement in disease

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.

Sequence similarities

Belongs to the tumor necrosis factor family.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCell membrane
Cytoplasmic vesicle
Lysosome
Membrane
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionCytokine
Repressor
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

apoptotic signaling pathway

Inferred from direct assay PubMed 15629131Ref.1. Source: MGI

cellular chloride ion homeostasis

Inferred from electronic annotation. Source: Ensembl

endosomal lumen acidification

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay PubMed 10588860PubMed 15039234. Source: MGI

immune response

Inferred from electronic annotation. Source: InterPro

inflammatory cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

necrotic cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from sequence orthology PubMed 14749367. Source: MGI

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of epidermal growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

response to growth factor

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

retinal cell programmed cell death

Inferred from mutant phenotype PubMed 14517994. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcaveola

Inferred from electronic annotation. Source: Ensembl

cytoplasmic membrane-bounded vesicle lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

external side of plasma membrane

Inferred from direct assay PubMed 16973387. Source: MGI

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular vesicular exosome

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lysosomal lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform FasL (identifier: P41047-1)

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 FasLS (identifier: P41047-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 279279Tumor necrosis factor ligand superfamily member 6, membrane form
PRO_0000034508
Chain1 – 127127ADAM10-processed FasL form By similarity
PRO_0000417159
Chain1 – 8080FasL intracellular domain By similarity
PRO_0000417160
Chain128 – 279152Tumor necrosis factor ligand superfamily member 6, soluble form By similarity
PRO_0000034509

Regions

Topological domain1 – 7878Cytoplasmic Potential
Transmembrane79 – 10022Helical; Signal-anchor for type II membrane protein; Potential
Topological domain101 – 279179Extracellular Potential
Compositional bias4 – 6966Pro-rich
Compositional bias45 – 517Poly-Pro

Sites

Site79 – 802Cleavage; by SPPL2A By similarity
Site127 – 1282Cleavage; by ADAM10 By similarity

Amino acid modifications

Glycosylation1171N-linked (GlcNAc...) Potential
Glycosylation1821N-linked (GlcNAc...) Potential
Glycosylation2481N-linked (GlcNAc...) Potential
Glycosylation2581N-linked (GlcNAc...) Potential
Disulfide bond200 ↔ 231 Potential

Natural variations

Alternative sequence1 – 210210Missing in isoform FasLS.
VSP_006445
Natural variant1841T → A in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. Ref.7
Natural variant2181E → G in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. Ref.7
Natural variant2731F → L in gld; abolishes binding of FASL to its receptor.

Sequences

Sequence LengthMass (Da)Tools
Isoform FasL [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 37972E2728E0A1CA

FASTA27931,442
        10         20         30         40         50         60 
MQQPMNYPCP QIFWVDSSAT SSWAPPGSVF PCPSCGPRGP DQRRPPPPPP PVSPLPPPSQ 

        70         80         90        100        110        120 
PLPLPPLTPL KKKDHNTNLW LPVVFFMVLV ALVGMGLGMY QLFHLQKELA ELREFTNQSL 

       130        140        150        160        170        180 
KVSSFEKQIA NPSTPSEKKE PRSVAHLTGN PHSRSIPLEW EDTYGTALIS GVKYKKGGLV 

       190        200        210        220        230        240 
INETGLYFVY SKVYFRGQSC NNQPLNHKVY MRNSKYPEDL VLMEEKRLNY CTTGQIWAHS 

       250        260        270 
SYLGAVFNLT SADHLYVNIS QLSLINFEES KTFFGLYKL 

« Hide

Isoform FasLS [UniParc].

Checksum: 9BA6F24DD120A482
Show »

FASTA698,040

References

[1]"Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand."
Takahashi T., Tanaka M., Brannan C.I., Jenkins N.A., Copeland N.G., Suda T., Nagata S.
Cell 76:969-976(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FASL).
[2]"Comparative molecular modelling of the Fas-ligand and other members of the TNF family."
Peitsch M.C., Tschopp J.
Mol. Immunol. 32:761-772(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FASL), 3D-STRUCTURE MODELING.
Strain: C57BL/6.
[3]"The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster."
Lynch D.H., Watson M.L., Alderson M.R., Baum P.R., Miller R.E., Tough T., Gibson M., Davis-Smith T., Smith C.A., Hunter K.
Immunity 1:131-136(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FASL).
[4]"Mus musculus Balb/c Fas ligand differs from 129/SV Fas ligand in two amino acids."
Fenner M.H., Shioda T., Isselbacher K.J.
Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FASL).
Strain: BALB/c.
[5]"Cloning and expression of a short Fas ligand: a new alternatively spliced product of the mouse Fas ligand gene."
Ayroldi E., D'Adamio F., Zollo O., Agostini M., Moraca R., Cannarile L., Migliorati G., Delfino D.V., Riccardi C.
Blood 94:3456-3467(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FASLS).
Strain: C3H.
Tissue: Spleen.
[6]"Characterization of the non-functional Fas ligand of gld mice."
Hahne M., Peitsch M.C., Irmler M., Schroeter M., Lowin B., Rousseau M., Bron C., Renno T., French L., Tschopp J.
Int. Immunol. 7:1381-1386(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT GLD.
[7]"Polymorphism of murine Fas ligand that affects the biological activity."
Kayagaki N., Yamaguchi N., Nagao F., Matsuo S., Maeda H., Okumura K., Yagita H.
Proc. Natl. Acad. Sci. U.S.A. 94:3914-3919(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-184 AND GLY-218.
Strain: BALB/c, C3H, C57BL/6, DBA/1, DBA/2, MRL, NOD, NZB, NZW and SJL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA53062.
RefSeqNP_034307.1. NM_010177.4.
XP_006496716.1. XM_006496653.1.
XP_006496717.1. XM_006496654.1.
UniGeneMm.3355.

3D structure databases

ProteinModelPortalP41047.
SMRP41047. Positions 158-279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199595. 1 interaction.
MINTMINT-1486494.

Proteomic databases

PRIDEP41047.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000000834; ENSMUSP00000000834; ENSMUSG00000000817. [P41047-1]
GeneID14103.
KEGGmmu:14103.
UCSCuc007dfr.2. mouse. [P41047-1]

Organism-specific databases

CTD14103.
MGIMGI:99255. Fasl.

Phylogenomic databases

eggNOGNOG42315.
HOGENOMHOG000290680.
HOVERGENHBG055128.
InParanoidP41047.
KOK04389.
OMAWEDTYGI.
OrthoDBEOG7V4B0Q.
PhylomeDBP41047.
TreeFamTF332169.

Gene expression databases

ArrayExpressP41047.
BgeeP41047.
CleanExMM_FASL.
GenevestigatorP41047.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR028326. FASL.
IPR006053. TNF.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
PRINTSPR01681. FASLIGAND.
PR01234. TNECROSISFCT.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio285134.
PMAP-CutDBP41047.
PROP41047.
SOURCESearch...

Entry information

Entry nameTNFL6_MOUSE
AccessionPrimary (citable) accession number: P41047
Secondary accession number(s): Q61217, Q9R1F2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot