Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P25446 (TNR6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tumor necrosis factor receptor superfamily member 6
Alternative name(s):
Apo-1 antigen
Apoptosis-mediating surface antigen FAS
FASLG receptor
CD_antigen=CD95
Gene names
Name:Fas
Synonyms:Apt1, Tnfrsf6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length327 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both By similarity.

Subunit structure

Binds DAXX and RIPK1. Interacts with BRE and FEM1B By similarity. Interacts with HIPK3. Part of a complex containing HIPK3 and FADD. Interacts with FADD By similarity. Ref.8 Ref.9

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Detected in various tissues including thymus, liver, lung, heart, and adult ovary.

Induction

Expression oscillates in a circadian manner in the liver with peak levels seen at CT12. Ref.12

Domain

Contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins.

Involvement in disease

Defects in Fas are the cause of the lymphoproliferation phenotype (lpr). Lpr mice show lymphadenopathy and autoantibody production.

Sequence similarities

Contains 1 death domain.

Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentMembrane
   DiseaseDisease mutation
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell mediated immunity

Inferred from mutant phenotype PubMed 18199416. Source: MGI

T cell homeostasis

Inferred from mutant phenotype PubMed 8640868. Source: MGI

activation-induced cell death of T cells

Inferred from direct assay PubMed 12702495. Source: MGI

apoptotic process

Inferred from mutant phenotype PubMed 8700551. Source: MGI

apoptotic signaling pathway

Inferred from direct assay PubMed 7511063PubMed 8666928. Source: MGI

cellular response to hyperoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to lithium ion

Inferred from mutant phenotype PubMed 20530871. Source: MGI

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

circadian rhythm

Inferred from expression pattern Ref.12. Source: UniProtKB

extrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 17980593. Source: MGI

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 13679421. Source: MGI

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay PubMed 10950869. Source: BHF-UCL

gene expression

Inferred from mutant phenotype PubMed 7602121. Source: MGI

immunoglobulin production

Inferred from mutant phenotype PubMed 18199416. Source: MGI

inflammatory cell apoptotic process

Inferred from direct assay PubMed 12801066. Source: MGI

motor neuron apoptotic process

Inferred from mutant phenotype PubMed 13679421. Source: MGI

necroptotic signaling pathway

Inferred from genetic interaction PubMed 21052097. Source: MGI

negative regulation of B cell activation

Inferred from mutant phenotype PubMed 6610701. Source: MGI

negative regulation of apoptotic process

Inferred from direct assay PubMed 7595210. Source: MGI

negative thymic T cell selection

Inferred from mutant phenotype PubMed 10429671. Source: MGI

neuron apoptotic process

Inferred from mutant phenotype PubMed 20530871. Source: MGI

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 15039234. Source: MGI

positive regulation of necrotic cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein homooligomerization

Inferred from direct assay PubMed 10950869. Source: BHF-UCL

positive regulation of release of cytochrome c from mitochondria

Inferred by curator PubMed 10950869. Source: BHF-UCL

protein homooligomerization

Inferred from direct assay PubMed 8524870. Source: MGI

regulation of lymphocyte differentiation

Inferred from mutant phenotype PubMed 6610701. Source: MGI

regulation of myeloid cell differentiation

Inferred from mutant phenotype PubMed 9697835. Source: MGI

renal system process

Inferred from mutant phenotype PubMed 8640868. Source: MGI

response to glucocorticoid

Inferred from mutant phenotype PubMed 7602121PubMed 8640868. Source: MGI

response to toxic substance

Inferred from mutant phenotype PubMed 8557033. Source: MGI

spleen development

Inferred from mutant phenotype PubMed 18199416. Source: MGI

transformed cell apoptotic process

Inferred from direct assay PubMed 12801066. Source: MGI

   Cellular_componentCD95 death-inducing signaling complex

Inferred from direct assay PubMed 20935634. Source: UniProtKB

cell surface

Inferred from direct assay PubMed 7595210. Source: MGI

cytoplasm

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from direct assay PubMed 12801066PubMed 16365167PubMed 16493007PubMed 23583643PubMed 8788039. Source: MGI

extracellular region

Inferred from direct assay PubMed 7595210. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane raft

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

transmembrane signaling receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 327306Tumor necrosis factor receptor superfamily member 6
PRO_0000034567

Regions

Topological domain22 – 169148Extracellular Potential
Transmembrane170 – 18617Helical; Potential
Topological domain187 – 327141Cytoplasmic Potential
Repeat43 – 7937TNFR-Cys 1
Repeat80 – 12344TNFR-Cys 2
Repeat124 – 16239TNFR-Cys 3
Domain222 – 30685Death
Region204 – 309106Interaction with HIPK3

Amino acid modifications

Modified residue2201Phosphoserine Ref.11
Modified residue3141Phosphothreonine Ref.11
Glycosylation431N-linked (GlcNAc...) Potential
Glycosylation1141N-linked (GlcNAc...) Potential
Disulfide bond44 ↔ 55 By similarity
Disulfide bond56 ↔ 69 By similarity
Disulfide bond59 ↔ 78 By similarity
Disulfide bond81 ↔ 97 By similarity
Disulfide bond100 ↔ 115 By similarity
Disulfide bond103 ↔ 123 By similarity
Disulfide bond125 ↔ 139 By similarity
Disulfide bond142 ↔ 153 By similarity
Disulfide bond145 ↔ 161 By similarity

Natural variations

Natural variant2461I → N in lpr. Ref.13

Experimental info

Sequence conflict381R → H in AAA37593. Ref.1
Sequence conflict381R → H in CAC00638. Ref.2
Sequence conflict381R → H in AAB25700. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P25446 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: D8DA95CA525CED56

FASTA32737,437
        10         20         30         40         50         60 
MLWIWAVLPL VLAGSQLRVH TQGTNSISES LKLRRRVRET DKNCSEGLYQ GGPFCCQPCQ 

        70         80         90        100        110        120 
PGKKKVEDCK MNGGTPTCAP CTEGKEYMDK NHYADKCRRC TLCDEEHGLE VETNCTLTQN 

       130        140        150        160        170        180 
TKCKCKPDFY CDSPGCEHCV RCASCEHGTL EPCTATSNTN CRKQSPRNRL WLLTILVLLI 

       190        200        210        220        230        240 
PLVFIYRKYR KRKCWKRRQD DPESRTSSRE TIPMNASNLS LSKYIPRIAE DMTIQEAKKF 

       250        260        270        280        290        300 
ARENNIKEGK IDEIMHDSIQ DTAEQKVQLL LCWYQSHGKS DAYQDLIKGL KKAECRRTLD 

       310        320 
KFQDMVQKDL GKSTPDTGNE NEGQCLE 

« Hide

References

« Hide 'large scale' references
[1]"The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen."
Watanabe-Fukunaga R., Brannan C.I., Itoh N., Yonehara S., Copeland N.G., Jenkins N.A., Nagata S.
J. Immunol. 148:1274-1279(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Role of a mutant fas receptor in a transgenic mouse."
Koczan D., Ibrahim S.M., Thiesen H.J.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/Sv.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Kidney.
[4]"A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas."
Villa-Morales M., Santos J., Perez-Gomez E., Quintanilla M., Fernandez-Piqueras J.
Cancer Res. 67:5107-5116(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6J.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[7]"Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice."
Adachi M., Watanabe-Fukunaga R., Nagata S.
Proc. Natl. Acad. Sci. U.S.A. 90:1756-1760(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
[8]"Daxx, a novel Fas-binding protein that activates JNK and apoptosis."
Yang X., Khosravi-Far R., Chang H.Y., Baltimore D.
Cell 89:1067-1076(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAXX.
[9]"FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase activation."
Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K., Tschopp J.
J. Exp. Med. 192:1165-1174(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIPK3.
[10]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[11]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-220 AND THR-314, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"p75 neurotrophin receptor is a clock gene that regulates oscillatory components of circadian and metabolic networks."
Baeza-Raja B., Eckel-Mahan K., Zhang L., Vagena E., Tsigelny I.F., Sassone-Corsi P., Ptacek L.J., Akassoglou K.
J. Neurosci. 33:10221-10234(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[13]"Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis."
Watanabe-Fukunaga R., Brannan C.I., Copeland N.G., Jenkins N.A., Nagata S.
Nature 356:314-317(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LPR ASN-246.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M83649 mRNA. Translation: AAA37593.1.
AK002590 mRNA. Translation: BAB22211.1.
AJ295702, AJ295703, AJ295704 Genomic DNA. Translation: CAC00638.1.
DQ846748 mRNA. Translation: ABI24112.1.
CH466534 Genomic DNA. Translation: EDL41748.1.
BC061160 mRNA. Translation: AAH61160.1.
S56490, S56485, S56486 Genomic DNA. Translation: AAB25700.1.
CCDSCCDS29758.1.
PIRA46484.
RefSeqNP_032013.2. NM_007987.2.
UniGeneMm.1626.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3OQ9X-ray6.80A/B/C/D/E223-308[»]
ProteinModelPortalP25446.
SMRP25446. Positions 48-159, 223-308.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199594. 6 interactions.
DIPDIP-31093N.
IntActP25446. 11 interactions.
MINTMINT-144559.

PTM databases

PhosphoSiteP25446.

Proteomic databases

PaxDbP25446.
PRIDEP25446.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025691; ENSMUSP00000025691; ENSMUSG00000024778.
GeneID14102.
KEGGmmu:14102.
UCSCuc008hgi.2. mouse.

Organism-specific databases

CTD355.
MGIMGI:95484. Fas.

Phylogenomic databases

eggNOGNOG45364.
GeneTreeENSGT00730000111280.
HOGENOMHOG000139681.
HOVERGENHBG004091.
InParanoidQ6GT31.
KOK04390.
OMACEHCNPC.
OrthoDBEOG7DVDC8.
TreeFamTF333916.

Gene expression databases

ArrayExpressP25446.
BgeeP25446.
CleanExMM_FAS.
GenevestigatorP25446.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR008063. Fas_rcpt.
IPR001368. TNFR/NGFR_Cys_rich_reg.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSPR01680. TNFACTORR6.
SMARTSM00005. DEATH. 1 hit.
SM00208. TNFR. 3 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFAS. mouse.
EvolutionaryTraceP25446.
NextBio285130.
PROP25446.
SOURCESearch...

Entry information

Entry nameTNR6_MOUSE
AccessionPrimary (citable) accession number: P25446
Secondary accession number(s): Q6GT31, Q9DCQ1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot