Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tumor necrosis factor ligand superfamily member 6

Gene

Faslg

Organism
Rattus norvegicus (Rat)
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 - Molecular functioni

  • death receptor binding Source: RGD
  • tumor necrosis factor receptor binding Source: RGD

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • cellular chloride ion homeostasis Source: RGD
  • endosomal lumen acidification Source: RGD
  • extrinsic apoptotic signaling pathway via death domain receptors Source: RGD
  • immune response Source: InterPro
  • inflammatory cell apoptotic process Source: RGD
  • necroptotic signaling pathway Source: Ensembl
  • negative regulation of angiogenesis Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of endothelial cell apoptotic process Source: Ensembl
  • positive regulation of epidermal growth factor receptor signaling pathway Source: RGD
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of neuron apoptotic process Source: RGD
  • response to growth factor Source: RGD
  • response to lipopolysaccharide Source: RGD
  • retinal cell programmed cell death Source: Ensembl
  • T cell apoptotic process Source: Ensembl
  • 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

ReactomeiR-RNO-3371378. Regulation by c-FLIP.
R-RNO-5213460. RIPK1-mediated regulated necrosis.
R-RNO-5218900. CASP8 activity is inhibited.
R-RNO-69416. Dimerization of procaspase-8.
R-RNO-75157. FasL/ CD95L signaling.

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, Tnfsf6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi3880. Faslg.

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 – 7777CytoplasmicSequence analysisAdd
BLAST
Transmembranei78 – 9922Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini100 – 278179ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

  • caveola Source: RGD
  • cytoplasmic, membrane-bounded vesicle Source: RGD
  • cytoplasmic membrane-bounded vesicle lumen Source: UniProtKB-SubCell
  • external side of plasma membrane Source: Ensembl
  • extracellular exosome Source: Ensembl
  • extracellular space Source: UniProtKB-KW
  • integral component of membrane Source: UniProtKB-KW
  • lysosomal lumen Source: UniProtKB-SubCell
  • membrane raft Source: RGD
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: RGD
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 – 278278Tumor necrosis factor ligand superfamily member 6, membrane formPRO_0000034512Add
BLAST
Chaini1 – 126126ADAM10-processed FasL formBy similarityPRO_0000417163Add
BLAST
Chaini1 – 7979FasL intracellular domainBy similarityPRO_0000417164Add
BLAST
Chaini127 – 278152Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityPRO_0000034513Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi116 – 1161N-linked (GlcNAc...)Sequence analysis
Disulfide bondi199 ↔ 230Sequence analysis
Glycosylationi247 – 2471N-linked (GlcNAc...)Sequence analysis
Glycosylationi257 – 2571N-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
Sitei78 – 792Cleavage; by SPPL2ABy similarity
Sitei126 – 1272Cleavage; by ADAM10By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP36940.
PRIDEiP36940.

Expressioni

Tissue specificityi

Expressed in activated splenocytes and thymocytes. Moderate or weak expression found in small intestines, kidney and lung.

Inductioni

By PMA/ionomycin and concanavalin/interleukin-2.

Gene expression databases

GenevisibleiP36940. RN.

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

GO - Molecular functioni

  • death receptor binding Source: RGD
  • tumor necrosis factor receptor binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003998.

Structurei

3D structure databases

ProteinModelPortaliP36940.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi4 – 6966Pro-richAdd
BLAST
Compositional biasi45 – 5814Poly-ProAdd
BLAST

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHZF. Eukaryota.
ENOG4112D9R. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000290680.
HOVERGENiHBG055128.
InParanoidiP36940.
KOiK04389.
OMAiWEDTYGI.
OrthoDBiEOG7V4B0Q.
PhylomeDBiP36940.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR028326. FASL.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01681. FASLIGAND.
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.

P36940-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQQPVNYPCP QIYWVDSSAT SPWAPPGSVF SCPSSGPRGP GQRRPPPPPP
60 70 80 90 100
PPSPLPPPSQ PPPLPPLSPL KKKDNIELWL PVIFFMVLVA LVGMGLGMYQ
110 120 130 140 150
LFHLQKELAE LREFTNHSLR VSSFEKQIAN PSTPSETKKP RSVAHLTGNP
160 170 180 190 200
RSRSIPLEWE DTYGTALISG VKYKKGGLVI NEAGLYFVYS KVYFRGQSCN
210 220 230 240 250
SQPLSHKVYM RNFKYPGDLV LMEEKKLNYC TTGQIWAHSS YLGAVFNLTV
260 270
ADHLYVNISQ LSLINFEESK TFFGLYKL
Length:278
Mass (Da):31,140
Last modified:June 1, 1994 - v1
Checksum:i2898E18A862CEAC6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U03470 mRNA. Translation: AAC52129.1.
PIRiA49266.
RefSeqiNP_037040.1. NM_012908.1.
XP_006250210.1. XM_006250148.2.
XP_008767829.1. XM_008769607.1.
UniGeneiRn.9725.

Genome annotation databases

EnsembliENSRNOT00000003998; ENSRNOP00000003998; ENSRNOG00000002978.
GeneIDi25385.
KEGGirno:25385.
UCSCiRGD:3880. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U03470 mRNA. Translation: AAC52129.1.
PIRiA49266.
RefSeqiNP_037040.1. NM_012908.1.
XP_006250210.1. XM_006250148.2.
XP_008767829.1. XM_008769607.1.
UniGeneiRn.9725.

3D structure databases

ProteinModelPortaliP36940.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003998.

Proteomic databases

PaxDbiP36940.
PRIDEiP36940.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000003998; ENSRNOP00000003998; ENSRNOG00000002978.
GeneIDi25385.
KEGGirno:25385.
UCSCiRGD:3880. rat.

Organism-specific databases

CTDi356.
RGDi3880. Faslg.

Phylogenomic databases

eggNOGiENOG410IHZF. Eukaryota.
ENOG4112D9R. LUCA.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000290680.
HOVERGENiHBG055128.
InParanoidiP36940.
KOiK04389.
OMAiWEDTYGI.
OrthoDBiEOG7V4B0Q.
PhylomeDBiP36940.
TreeFamiTF332169.

Enzyme and pathway databases

ReactomeiR-RNO-3371378. Regulation by c-FLIP.
R-RNO-5213460. RIPK1-mediated regulated necrosis.
R-RNO-5218900. CASP8 activity is inhibited.
R-RNO-69416. Dimerization of procaspase-8.
R-RNO-75157. FasL/ CD95L signaling.

Miscellaneous databases

PROiP36940.

Gene expression databases

GenevisibleiP36940. RN.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR028326. FASL.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01681. FASLIGAND.
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. "Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family."
    Suda T., Takahashi T., Golstein P., Nagata S.
    Cell 75:1169-1178(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiTNFL6_RAT
AccessioniPrimary (citable) accession number: P36940
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 8, 2016
This is version 135 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. 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.