Reviewed, UniProtKB/Swiss-Prot P25446 (TNR6_MOUSE)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 6
Alternative name(s):
    FASLG receptor
    Apoptosis-mediating surface antigen FAS
    Apo-1 antigen
    CD_antigen=CD95

Gene names

Name:	Fas
Synonyms:	Apt1, Tnfrsf6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	327 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Detected in various tissues including thymus, liver, lung, heart, and adult ovary.
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 process	Apoptosis
Cellular component	Membrane
Disease	Disease mutation
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	B cell mediated immunity Inferred from mutant phenotype. Source: MGI activated T cell apoptosis Inferred from direct assay. Source: MGI gene expression Inferred from mutant phenotype. Source: MGI immunoglobulin production Inferred from mutant phenotype. Source: MGI induction of apoptosis via death domain receptors Inferred from direct assay. Source: MGI inflammatory cell apoptosis Inferred from direct assay. Source: MGI negative regulation of B cell activation Inferred from mutant phenotype. Source: MGI negative regulation of apoptosis Inferred from direct assay. Source: MGI negative thymic T cell selection Inferred from mutant phenotype. Source: MGI protein homooligomerization Inferred from direct assay. Source: MGI regulation of lymphocyte differentiation Inferred from mutant phenotype. Source: MGI regulation of myeloid cell differentiation Inferred from mutant phenotype. Source: MGI renal system process Inferred from mutant phenotype. Source: MGI response to glucocorticoid stimulus Inferred from mutant phenotype. Source: MGI response to protein stimulus Inferred from mutant phenotype. Source: MGI response to toxin Inferred from mutant phenotype. Source: MGI spleen development Inferred from mutant phenotype. Source: MGI transformed cell apoptosis Inferred from direct assay. Source: MGI
Cellular component	external side of plasma membrane Inferred from direct assay. Source: MGI extracellular region Inferred from direct assay. Source: MGI
Molecular function	protein binding Ref.5 Ref.6 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	4	EBI-296206,EBI-77321	From a different organism.
Daxx	O35613	2	EBI-296206,EBI-77304
FADD	Q13158	1	EBI-296206,EBI-494804	From a different organism.
Hipk3	Q9ERH7	3	EBI-296206,EBI-524356

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 327	306	Tumor necrosis factor receptor superfamily member 6		PRO_0000034567
Regions
	Topological domain	22 – 169	148	Extracellular Potential
	Transmembrane	170 – 186	17	Potential
	Topological domain	187 – 327	141	Cytoplasmic Potential
	Repeat	43 – 79	37	TNFR-Cys 1
	Repeat	80 – 123	44	TNFR-Cys 2
	Repeat	124 – 162	39	TNFR-Cys 3
	Domain	222 – 306	85	Death
	Region	204 – 309	106	Interaction with HIPK3
Amino acid modifications
	Modified residue	220	1	Phosphoserine
	Glycosylation	43	1	N-linked (GlcNAc...) Potential
	Glycosylation	114	1	N-linked (GlcNAc...) Potential
	Disulfide bond	44 ↔ 55		By similarity
	Disulfide bond	56 ↔ 69		By similarity
	Disulfide bond	59 ↔ 78		By similarity
	Disulfide bond	81 ↔ 97		By similarity
	Disulfide bond	100 ↔ 115		By similarity
	Disulfide bond	103 ↔ 123		By similarity
	Disulfide bond	125 ↔ 139		By similarity
	Disulfide bond	142 ↔ 153		By similarity
	Disulfide bond	145 ↔ 161		By similarity
Natural variations
	Natural variant	246	1	I → N in lpr.
Experimental info
	Sequence conflict	38	1	H → R in BAB22211. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P25446-1 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: F6BFFC5ACE356EEE	FASTA	327	37,418
	10 20 30 40 50 60 MLWIWAVLPL VLAGSQLRVH TQGTNSISES LKLRRRVHET 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

References

	« Hide 'large scale' referencesShow '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: 1371136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[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. , 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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Kidney.
[4]	"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: 7680478] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
[5]	"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: 9215629] [Abstract] Cited for: INTERACTION WITH DAXX.
[6]	"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: 11034606] [Abstract] Cited for: INTERACTION WITH HIPK3.
[7]	"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: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-220, MASS SPECTROMETRY. Tissue: Liver.
[8]	"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: 1372394] [Abstract] Cited for: VARIANT LPR ASN-246.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M83649 mRNA. Translation: AAA37593.1. AK002590 mRNA. Translation: BAB22211.1. AJ295702, AJ295703, AJ295704 Genomic DNA. Translation: CAC00638.1. S56490, S56485, S56486 Genomic DNA. Translation: AAB25700.1.
PIR	A46484.
RefSeq	NP_032013.1.
UniGene	Mm.1626
3D structure databases
HSSP	HSSP built from PDB template 1DDF based on UniProtKB P25445.
ModBase	Search...
Protein-protein interaction databases
IntAct	P25446.
PTM databases
PhosphoSite	P25446.
Genome annotation databases
Ensembl	ENSMUSG00000024778. Mus musculus. [Contig view]
GeneID	14102.
KEGG	mmu:14102.
Organism-specific databases
MGI	MGI:95484. Fas.
Phylogenomic databases
HOGENOM	P25446.
HOVERGEN	P25446.
Gene expression databases
ArrayExpress	P25446.
CleanEx	MM_FAS.
GermOnline	ENSMUSG00000024778. Mus musculus.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH_like. IPR008063. Fas_rcpt. IPR001368. TNFR_c6. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
Pfam	PF00531. Death. 1 hit. PF00020. TNFR_c6. 3 hits. [Graphical view]
PRINTS	PR01680. FASRECEPTOR.
SMART	SM00005. DEATH. 1 hit. SM00208. TNFR. 3 hits. [Graphical view]
PROSITE	PS50017. DEATH_DOMAIN. 1 hit. PS00652. TNFR_NGFR_1. 2 hits. PS50050. TNFR_NGFR_2. 2 hits. [Graphical view]
BLOCKS	Search...
ProtoNet	Search...
Other Resources
NextBio	285130.
SOURCE	Search...

Entry information

Entry name

TNR6_MOUSE

Accession

Primary (citable) accession number: P25446
Secondary accession number(s): Q9DCQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	November 4, 2008
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)