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P41047

- TNFL6_MOUSE

UniProt

P41047 - TNFL6_MOUSE

Protein

Tumor necrosis factor ligand superfamily member 6

Gene

Faslg

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 147 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    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.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 SPPL2ABy similarity
    Sitei127 – 1282Cleavage; by ADAM10By similarity

    GO - Biological processi

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

    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.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

    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

    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 formPRO_0000034508Add
    BLAST
    Chaini1 – 127127ADAM10-processed FasL formBy similarityPRO_0000417159Add
    BLAST
    Chaini1 – 8080FasL intracellular domainBy similarityPRO_0000417160Add
    BLAST
    Chaini128 – 279152Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityPRO_0000034509Add
    BLAST

    Amino acid modifications

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

    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.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 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.By similarityCurated

    Protein-protein interaction databases

    BioGridi199595. 1 interaction.
    MINTiMINT-1486494.

    Structurei

    3D structure databases

    ProteinModelPortaliP41047.
    SMRiP41047. Positions 142-279.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 7878CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini101 – 279179ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei79 – 10022Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Compositional bias

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

    Sequence similaritiesi

    Belongs to the tumor necrosis factor family.Curated

    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. 1 PublicationVSP_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: October 1, 2014
    This is version 147 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