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Protein

Tumor necrosis factor ligand superfamily member 6

Gene

FASLG

Organism
Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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).By similarity
The FasL intracellular domain (FasL ICD) cytoplasmic form induces gene transcription inhibition.By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Repressor

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

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:CD95L, FASL, TNFSF6
OrganismiCercocebus atys (Sooty mangabey) (Cercocebus torquatus atys)
Taxonomic identifieri9531 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeCercocebus

Subcellular locationi

Tumor necrosis factor ligand superfamily member 6, soluble form :
  • Secreted By similarity

  • Note: May be released into the extracellular fluid, probably by cleavage form the cell surface.By similarity
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 – 8080CytoplasmicSequence analysisAdd
BLAST
Transmembranei81 – 10121Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini102 – 280179ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 280280Tumor necrosis factor ligand superfamily member 6, membrane formPRO_0000034498Add
BLAST
Chaini1 – 128128ADAM10-processed FasL formBy similarityPRO_0000417148Add
BLAST
Chaini1 – 8181FasL intracellular domainBy similarityPRO_0000417149Add
BLAST
Chaini129 – 280152Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityPRO_0000034499Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi183 – 1831N-linked (GlcNAc...)Sequence analysis
Disulfide bondi201 ↔ 232Sequence analysis
Glycosylationi249 – 2491N-linked (GlcNAc...)Sequence analysis
Glycosylationi259 – 2591N-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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei80 – 812Cleavage; by SPPL2ABy similarity
Sitei128 – 1292Cleavage; by ADAM10By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

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

Structurei

3D structure databases

ProteinModelPortaliQ9BDN1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 6966Pro-richAdd
BLAST
Compositional biasi45 – 6420Poly-ProAdd
BLAST

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG055128.

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]

Sequencei

Sequence statusi: Complete.

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

Q9BDN1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQQPFNYPYP QIYWVDSSAS SPWAPPGTVL PCPTSVPRRP GQRRPPPPPP
60 70 80 90 100
PPPLPPPPPP PLPPLPLPPL KKRGNHSTGL CLLVMFFMVL VALVGLGLGM
110 120 130 140 150
FQLFHLQKEL AELRESTSQK HTASSLEKQI GHPSPPPEKK EQRKVAHLTG
160 170 180 190 200
KPNSRSMPLE WEDTYGIVLL SGVKYKKGGL VINETGLYFV YSKVYFRGQS
210 220 230 240 250
CTNLPLSHKV YMRNSKYPQD LVMMEGKMMS YCTTGQMWAH SSYLGAVFNL
260 270 280
TSTDHLYVNV SELSLVNFEE SQTFFGLYKL
Length:280
Mass (Da):31,408
Last modified:June 1, 2001 - v1
Checksum:i729EA60067B7D398
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF344847 mRNA. Translation: AAK37606.1.
RefSeqiNP_001292889.1. NM_001305960.1.

Genome annotation databases

GeneIDi105597557.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF344847 mRNA. Translation: AAK37606.1.
RefSeqiNP_001292889.1. NM_001305960.1.

3D structure databases

ProteinModelPortaliQ9BDN1.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi105597557.

Organism-specific databases

CTDi356.

Phylogenomic databases

HOVERGENiHBG055128.

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]
ProtoNetiSearch...

Publicationsi

  1. "Cloning, sequencing, and homology analysis of nonhuman primate Fas/Fas-ligand and co-stimulatory molecules."
    Villinger F.J., Bostik P., Mayne A.E., King C.L., Genain C.P., Weiss W.R., Ansari A.A.
    Immunogenetics 53:315-328(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lymphocyte.

Entry informationi

Entry nameiTNFL6_CERAT
AccessioniPrimary (citable) accession number: Q9BDN1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: June 1, 2001
Last modified: May 11, 2016
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.