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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 (PubMed:7505205). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:7505205). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (By similarity).By similarity1 Publication
Tumor necrosis factor ligand superfamily member 6, soluble form: Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways. Can induce apoptosis but does not appear to be essential for this process.By similarity
FasL intracellular domain: Cytoplasmic form induces gene transcription inhibition.By similarity

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • death receptor binding Source: RGD
  • tumor necrosis factor receptor binding Source: RGD

GO - Biological processi

Keywordsi

Molecular functionCytokine, Repressor
Biological processApoptosis, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi3880. Faslg.

Subcellular locationi

  • Cell membrane 1 Publication; Single-pass type II membrane protein Sequence analysis
  • Cytoplasmic vesicle lumen By similarity
  • Lysosome lumen By similarity

  • Note: Colocalizes with the SPPL2A protease at the cell membrane. Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination.By similarity
Tumor necrosis factor ligand superfamily member 6, soluble form :
  • Secreted By similarity

  • Note: May be released into the extracellular fluid by cleavage from 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)DescriptionActionsGraphical viewLength
Topological domaini1 – 77CytoplasmicSequence analysisAdd BLAST77
Transmembranei78 – 99Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini100 – 278ExtracellularSequence analysisAdd BLAST179

GO - Cellular componenti

  • caveola Source: RGD
  • cytoplasmic vesicle Source: RGD
  • cytoplasmic vesicle lumen Source: UniProtKB-SubCell
  • external side of plasma membrane Source: Ensembl
  • extracellular exosome Source: Ensembl
  • 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

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000345121 – 278Tumor necrosis factor ligand superfamily member 6, membrane formAdd BLAST278
ChainiPRO_00004171631 – 126ADAM10-processed FasL formBy similarityAdd BLAST126
ChainiPRO_00004171641 – 79FasL intracellular domainBy similarityAdd BLAST79
ChainiPRO_0000034513127 – 278Tumor necrosis factor ligand superfamily member 6, soluble formBy similarityAdd BLAST152

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi116N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi199 ↔ 230By similarity
Glycosylationi247N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi257N-linked (GlcNAc...) asparagineSequence analysis1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei78 – 79Cleavage; by SPPL2ABy similarity2
Sitei126 – 127Cleavage; by ADAM10By similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP36940.
PRIDEiP36940.

PTM databases

PhosphoSitePlusiP36940.

Expressioni

Tissue specificityi

Expressed in activated splenocytes and thymocytes. Moderate or weak expression found in small intestines, kidney and lung.1 Publication

Inductioni

By PMA/ionomycin and concanavalin/interleukin-2.1 Publication

Gene expression databases

BgeeiENSRNOG00000002978.
ExpressionAtlasiP36940. baseline.
GenevisibleiP36940. RN.

Interactioni

Subunit structurei

Homotrimer. 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

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • death receptor binding Source: RGD
  • tumor necrosis factor receptor binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003998.

Structurei

3D structure databases

ProteinModelPortaliP36940.
SMRiP36940.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 69Pro-richAdd BLAST66
Compositional biasi45 – 58Poly-ProAdd BLAST14

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.
OrthoDBiEOG091G0MFC.
PhylomeDBiP36940.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiView protein in InterPro
IPR028326. FASL.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
PfamiView protein in Pfam
PF00229. TNF. 1 hit.
PRINTSiPR01681. FASLIGAND.
SMARTiView protein in SMART
SM00207. TNF. 1 hit.
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiView protein in PROSITE
PS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.

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_006250148.3.
XP_008767829.1. XM_008769607.2.
XP_017454164.1. XM_017598675.1.
UniGeneiRn.9725.

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiTNFL6_RAT
AccessioniPrimary (citable) accession number: P36940
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: August 30, 2017
This is version 144 of the entry and version 1 of the sequence. See 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