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P41047

- TNFL6_MOUSE

UniProt

P41047 - TNFL6_MOUSE

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Protein
Tumor necrosis factor ligand superfamily member 6
Gene
Faslg, Apt1lg1, Cd95l, Fasl, gld, Tnfsf6
Organism
Mus musculus (Mouse)
Status
Reviewed - 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. 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei79 – 802Cleavage; by SPPL2A By similarity
Sitei127 – 1282Cleavage; by ADAM10 By similarity

GO - Biological processi

  1. T cell apoptotic process Source: Ensembl
  2. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  3. apoptotic signaling pathway Source: MGI
  4. cellular chloride ion homeostasis Source: Ensembl
  5. endosomal lumen acidification Source: Ensembl
  6. extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  7. immune response Source: InterPro
  8. inflammatory cell apoptotic process Source: Ensembl
  9. necroptotic signaling pathway Source: Ensembl
  10. negative regulation of angiogenesis Source: Ensembl
  11. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  12. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  13. positive regulation of apoptotic process Source: MGI
  14. positive regulation of cell proliferation Source: Ensembl
  15. positive regulation of endothelial cell apoptotic process Source: Ensembl
  16. positive regulation of epidermal growth factor receptor signaling pathway Source: Ensembl
  17. positive regulation of neuron apoptotic process Source: Ensembl
  18. response to growth factor Source: Ensembl
  19. response to lipopolysaccharide Source: Ensembl
  20. retinal cell programmed cell death Source: MGI
  21. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Repressor

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiREACT_215122. Regulation by c-FLIP.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:99255. Fasl.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7878Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei79 – 10022Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini101 – 279179Extracellular Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. caveola Source: Ensembl
  2. cytoplasmic membrane-bounded vesicle lumen Source: UniProtKB-SubCell
  3. external side of plasma membrane Source: MGI
  4. extracellular space Source: UniProtKB-KW
  5. extracellular vesicular exosome Source: Ensembl
  6. integral component of membrane Source: UniProtKB-KW
  7. lysosomal lumen Source: UniProtKB-SubCell
  8. nucleus Source: UniProtKB
  9. perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

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.

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 279279Tumor necrosis factor ligand superfamily member 6, membrane form
PRO_0000034508Add
BLAST
Chaini1 – 127127ADAM10-processed FasL form By similarity
PRO_0000417159Add
BLAST
Chaini1 – 8080FasL intracellular domain By similarity
PRO_0000417160Add
BLAST
Chaini128 – 279152Tumor necrosis factor ligand superfamily member 6, soluble form By similarity
PRO_0000034509Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi117 – 1171N-linked (GlcNAc...) Reviewed prediction
Glycosylationi182 – 1821N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi200 ↔ 231 Reviewed prediction
Glycosylationi248 – 2481N-linked (GlcNAc...) Reviewed prediction
Glycosylationi258 – 2581N-linked (GlcNAc...) Reviewed prediction

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 By similarity.
Monoubiquitinated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PRIDEiP41047.

Miscellaneous databases

PMAP-CutDBP41047.

Expressioni

Gene expression databases

ArrayExpressiP41047.
BgeeiP41047.
CleanExiMM_FASL.
GenevestigatoriP41047.

Interactioni

Subunit structurei

Homotrimer Inferred. 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.

Protein-protein interaction databases

BioGridi199595. 1 interaction.
MINTiMINT-1486494.

Structurei

3D structure databases

ProteinModelPortaliP41047.
SMRiP41047. Positions 142-279.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 6966Pro-rich
Add
BLAST
Compositional biasi45 – 517Poly-Pro

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42315.
HOGENOMiHOG000290680.
HOVERGENiHBG055128.
InParanoidiP41047.
KOiK04389.
OMAiHLTGKPN.
OrthoDBiEOG7V4B0Q.
PhylomeDBiP41047.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR028326. FASL.
IPR006053. TNF.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01681. FASLIGAND.
PR01234. TNECROSISFCT.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

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. Align

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

MQQPMNYPCP QIFWVDSSAT SSWAPPGSVF PCPSCGPRGP DQRRPPPPPP    50
PVSPLPPPSQ PLPLPPLTPL KKKDHNTNLW LPVVFFMVLV ALVGMGLGMY 100
QLFHLQKELA ELREFTNQSL KVSSFEKQIA NPSTPSEKKE PRSVAHLTGN 150
PHSRSIPLEW EDTYGTALIS GVKYKKGGLV INETGLYFVY SKVYFRGQSC 200
NNQPLNHKVY MRNSKYPEDL VLMEEKRLNY CTTGQIWAHS SYLGAVFNLT 250
SADHLYVNIS QLSLINFEES KTFFGLYKL 279
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti184 – 1841T → A in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. 1 Publication
Natural varianti218 – 2181E → G in strain: BALB/c, DBA/1 and DBA/2; enhances cytotoxicity. 1 Publication
Natural varianti273 – 2731F → L in gld; abolishes binding of FASL to its receptor.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 210210Missing in isoform FasLS.
VSP_006445Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
XP_006496716.1. XM_006496653.1. [P41047-1]
XP_006496717.1. XM_006496654.1. [P41047-1]
UniGeneiMm.3355.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS15418.1. [P41047-1 ]
PIRi A53062.
RefSeqi NP_034307.1. NM_010177.4. [P41047-1 ]
XP_006496716.1. XM_006496653.1. [P41047-1 ]
XP_006496717.1. XM_006496654.1. [P41047-1 ]
UniGenei Mm.3355.

3D structure databases

ProteinModelPortali P41047.
SMRi P41047. Positions 142-279.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199595. 1 interaction.
MINTi MINT-1486494.

Proteomic databases

PRIDEi P41047.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000000834 ; ENSMUSP00000000834 ; ENSMUSG00000000817 . [P41047-1 ]
GeneIDi 14103.
KEGGi mmu:14103.
UCSCi uc007dfr.2. mouse. [P41047-1 ]

Organism-specific databases

CTDi 14103.
MGIi MGI:99255. Fasl.

Phylogenomic databases

eggNOGi NOG42315.
HOGENOMi HOG000290680.
HOVERGENi HBG055128.
InParanoidi P41047.
KOi K04389.
OMAi HLTGKPN.
OrthoDBi EOG7V4B0Q.
PhylomeDBi P41047.
TreeFami TF332169.

Enzyme and pathway databases

Reactomei REACT_215122. Regulation by c-FLIP.

Miscellaneous databases

NextBioi 285134.
PMAP-CutDB P41047.
PROi P41047.
SOURCEi Search...

Gene expression databases

ArrayExpressi P41047.
Bgeei P41047.
CleanExi MM_FASL.
Genevestigatori P41047.

Family and domain databases

Gene3Di 2.60.120.40. 1 hit.
InterProi IPR028326. FASL.
IPR006053. TNF.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
PRINTSi PR01681. FASLIGAND.
PR01234. TNECROSISFCT.
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiTNFL6_MOUSE
AccessioniPrimary (citable) accession number: P41047
Secondary accession number(s): Q61217, Q9R1F2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: September 3, 2014
This is version 146 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi