TNFL6_PIG
ID TNFL6_PIG Reviewed; 282 AA.
AC Q9BEA8; Q95M04; Q95N10;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Tumor necrosis factor ligand superfamily member 6;
DE AltName: Full=CD95 ligand;
DE Short=CD95-L;
DE AltName: Full=Fas antigen ligand;
DE Short=Fas ligand;
DE Short=FasL;
DE AltName: CD_antigen=CD178;
DE Contains:
DE RecName: Full=Tumor necrosis factor ligand superfamily member 6, membrane form;
DE Contains:
DE RecName: Full=Tumor necrosis factor ligand superfamily member 6, soluble form;
DE AltName: Full=Receptor-binding FasL ectodomain;
DE AltName: Full=Soluble Fas ligand;
DE Short=sFasL;
DE Contains:
DE RecName: Full=ADAM10-processed FasL form;
DE Short=APL;
DE Contains:
DE RecName: Full=FasL intracellular domain;
DE Short=FasL ICD;
DE AltName: Full=SPPL2A-processed FasL form;
DE Short=SPA;
GN Name=FASLG; Synonyms=CD95L, FASL, TNFSF6;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=11429161; DOI=10.1089/107999001300177493;
RA Muneta Y., Shimoji Y., Inumaru S., Mori Y.;
RT "Molecular cloning, characterization, and expression of porcine Fas ligand
RT (CD95 ligand).";
RL J. Interferon Cytokine Res. 21:305-312(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Landrace X Large Yorkshire white; TISSUE=Thymocyte;
RX PubMed=11792426; DOI=10.1016/s0161-5890(01)00098-0;
RA Motegi-Ishiyama Y., Nakajima Y., Hoka S., Takagaki Y.;
RT "Porcine Fas-ligand gene: genomic sequence analysis and comparison with
RT human gene.";
RL Mol. Immunol. 38:581-586(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Lymphoid tissue;
RX PubMed=12371937; DOI=10.1034/j.1399-3089.2002.01114.x;
RA Tsuyuki S., Kono M., Bloom E.T.;
RT "Cloning and potential utility of porcine Fas ligand: overexpression in
RT porcine endothelial cells protects them from attack by human cytolytic
RT cells.";
RL Xenotransplantation 9:410-421(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Guanxi bama miniature pig;
RA Zhu N., Young Y.;
RT "Molecular cloning and characterization of porcine Fas ligand cDNA.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Cytokine that binds to TNFRSF6/FAS, a receptor that
CC transduces the apoptotic signal into cells (PubMed:11429161,
CC PubMed:12371937). Involved in cytotoxic T-cell-mediated apoptosis,
CC natural killer cell-mediated apoptosis and in T-cell development
CC (PubMed:11429161, PubMed:12371937). Initiates fratricidal/suicidal
CC activation-induced cell death (AICD) in antigen-activated T-cells
CC contributing to the termination of immune responses (By similarity).
CC TNFRSF6/FAS-mediated apoptosis has also a role in the induction of
CC peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy
CC receptor that blocks apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:P41047, ECO:0000250|UniProtKB:P48023,
CC ECO:0000269|PubMed:11429161, ECO:0000269|PubMed:12371937}.
CC -!- FUNCTION: [Tumor necrosis factor ligand superfamily member 6, soluble
CC form]: Induces FAS-mediated activation of NF-kappa-B, initiating non-
CC apoptotic signaling pathways. Can induce apoptosis but does not appear
CC to be essential for this process. {ECO:0000250|UniProtKB:P41047}.
CC -!- FUNCTION: [FasL intracellular domain]: Cytoplasmic form induces gene
CC transcription inhibition. {ECO:0000250|UniProtKB:P48023}.
CC -!- SUBUNIT: Homotrimer. Interacts with ARHGAP9, BAIAP2L1, BTK, CACNB3,
CC CACNB4, CRK, DLG2, DNMBP, DOCK4, EPS8L3, FGR, FYB1, FYN, HCK, ITK,
CC ITSN2, KALRN, LYN, MACC1, MIA, MPP4, MYO15A, NCF1, NCK1, NCK2, NCKIPSD,
CC OSTF1, PIK3R1, PSTPIP1, RIMBP3C, SAMSN1, SH3GL3, SH3PXD2B, SH3PXD2A,
CC SH3RF2, SKAP2, SNX33, SNX9, SORBS3, SPTA1, SRC, SRGAP1, SRGAP2, SRGAP3,
CC TEC, TJP3 and YES1. {ECO:0000250|UniProtKB:P48023}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P48023};
CC Single-pass type II membrane protein {ECO:0000255}. Cytoplasmic vesicle
CC lumen {ECO:0000250|UniProtKB:P48023}. Lysosome lumen
CC {ECO:0000250|UniProtKB:P48023}. Note=Colocalizes with the SPPL2A
CC protease at the cell membrane. Is internalized into multivesicular
CC bodies of secretory lysosomes after phosphorylation by FGR and
CC monoubiquitination. {ECO:0000250|UniProtKB:P48023}.
CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor ligand superfamily member
CC 6, soluble form]: Secreted {ECO:0000269|PubMed:11429161}. Note=May be
CC released into the extracellular fluid by cleavage from the cell
CC surface. {ECO:0000250|UniProtKB:P48023}.
CC -!- SUBCELLULAR LOCATION: [FasL intracellular domain]: Nucleus
CC {ECO:0000250|UniProtKB:P48023}. Note=The FasL ICD cytoplasmic form is
CC translocated into the nucleus. {ECO:0000250|UniProtKB:P48023}.
CC -!- INDUCTION: By IL-18. {ECO:0000269|PubMed:11429161}.
CC -!- PTM: The soluble form derives from the membrane form by proteolytic
CC processing. The membrane-bound form undergoes two successive
CC intramembrane proteolytic cleavages. The first one is processed by
CC ADAM10 producing an N-terminal fragment, which lacks the receptor-
CC binding extracellular domain. This ADAM10-processed FasL (FasL APL)
CC remnant form is still membrane anchored and further processed by SPPL2A
CC that liberates the FasL intracellular domain (FasL ICD). FasL shedding
CC by ADAM10 is a prerequisite for subsequent intramembrane cleavage by
CC SPPL2A in T-cells. {ECO:0000250|UniProtKB:P48023}.
CC -!- PTM: Phosphorylated by FGR on tyrosine residues; this is required for
CC ubiquitination and subsequent internalization.
CC {ECO:0000250|UniProtKB:P48023}.
CC -!- PTM: N-glycosylated. Glycosylation enhances apoptotic activity.
CC {ECO:0000250|UniProtKB:P48023}.
CC -!- PTM: Monoubiquitinated. {ECO:0000250|UniProtKB:P48023}.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB027297; BAB40919.1; -; mRNA.
DR EMBL; AB069764; BAB64291.1; -; Genomic_DNA.
DR EMBL; AF397407; AAK84408.1; -; mRNA.
DR EMBL; AY033634; AAK56449.1; -; mRNA.
DR RefSeq; NP_998971.1; NM_213806.1.
DR AlphaFoldDB; Q9BEA8; -.
DR SMR; Q9BEA8; -.
DR STRING; 9823.ENSSSCP00000019767; -.
DR PaxDb; Q9BEA8; -.
DR GeneID; 396726; -.
DR KEGG; ssc:396726; -.
DR CTD; 356; -.
DR eggNOG; ENOG502RXC1; Eukaryota.
DR InParanoid; Q9BEA8; -.
DR OrthoDB; 1029363at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0060205; C:cytoplasmic vesicle lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR CDD; cd00184; TNF; 1.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR028326; FASL.
DR InterPro; IPR006053; TNF.
DR InterPro; IPR021184; TNF_CS.
DR InterPro; IPR006052; TNF_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00229; TNF; 1.
DR PRINTS; PR01681; FASLIGAND.
DR PRINTS; PR01234; TNECROSISFCT.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS00251; TNF_1; 1.
DR PROSITE; PS50049; TNF_2; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cell membrane; Cytokine; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Lysosome; Membrane; Nucleus; Reference proteome; Repressor;
KW Secreted; Signal-anchor; Transcription; Transcription regulation;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..282
FT /note="Tumor necrosis factor ligand superfamily member 6,
FT membrane form"
FT /id="PRO_0000034510"
FT CHAIN 1..130
FT /note="ADAM10-processed FasL form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417161"
FT CHAIN 1..83
FT /note="FasL intracellular domain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417162"
FT CHAIN 131..282
FT /note="Tumor necrosis factor ligand superfamily member 6,
FT soluble form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000034511"
FT TOPO_DOM 1..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 83..103
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..282
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 30..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..70
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 82..83
FT /note="Cleavage; by SPPL2A"
FT /evidence="ECO:0000250"
FT SITE 130..131
FT /note="Cleavage; by ADAM10"
FT /evidence="ECO:0000250"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 203..234
FT /evidence="ECO:0000250|UniProtKB:P48023"
FT CONFLICT 5
FT /note="F -> L (in Ref. 2; BAB64291)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="T -> P (in Ref. 4; AAK56449)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 282 AA; 31756 MW; 6743DAA1145671FB CRC64;
MQQPFNYPYP QIFWVDSSAT SPWASPGSVF PCPASVPGRP GQRRPPPPPP PPPPPPTLLP
SRPLPPLPPP SLKKKRDHNA GLCLLVMFFM VLVALVGLGL GMFQLFHLQK ELTELRESAS
QRHTESSLEK QIGHPNLPSE KKELRKVAHL TGKPNSRSIP LEWEDTYGIA LVSGVKYMKG
SLVINDTGLY FVYSKVYFRG QYCNNQPLSH KVYTRNSRYP QDLVLMEGKM MNYCTTGQMW
ARSSYLGAVF NLTSADHLYV NVSELSLVNF EESKTFFGLY KL
