P25446 (TNR6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › 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. 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.
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 Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell mediated immunity Inferred from mutant phenotype PubMed 18199416. Source: MGI activation-induced cell death of T cells Inferred from direct assay PubMed 12702495. Source: MGI cellular response to hyperoxia Inferred from electronic annotation. Source: Compara cellular response to lithium ion Inferred from mutant phenotype PubMed 20530871. Source: MGI cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara extrinsic apoptotic signaling pathway via death domain receptors Inferred from mutant phenotype PubMed 10429671PubMed 12801066PubMed 8524870. Source: MGI 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 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 direct assay PubMed 10950869. Source: BHF-UCL positive regulation of necrotic cell death Inferred from electronic annotation. Source: Compara 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 stimulus Inferred from mutant phenotype PubMed 7602121PubMed 8640868. Source: MGI response to toxin 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_component	CD95 death-inducing signaling complex Inferred from direct assay PubMed 20935634. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from direct assay PubMed 12801066PubMed 16365167PubMed 16493007PubMed 8788039. Source: MGI extracellular region Inferred from direct assay PubMed 7595210. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro
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	5	EBI-296206,EBI-494804	From a different organism.
Hipk3	Q9ERH7	3	EBI-296206,EBI-524356
Pml	Q60953	6	EBI-296206,EBI-3895605

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	Helical; 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	206	1	Phosphothreonine Ref.11
	Modified residue	217	1	Phosphoserine Ref.11
	Modified residue	220	1	Phosphoserine Ref.10
	Modified residue	222	1	Phosphoserine Ref.11
	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. Ref.12
Experimental info
	Sequence conflict	38	1	R → H in AAA37593. Ref.1
	Sequence conflict	38	1	R → H in CAC00638. Ref.2
	Sequence conflict	38	1	R → H in AAB25700. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P25446 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: D8DA95CA525CED56	FASTA	327	37,437
	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

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] [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. , 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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-220, MASS SPECTROMETRY. 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 THR-206; SER-217 AND SER-222, MASS SPECTROMETRY. Tissue: Macrophage.
[12]	"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.

IPI

IPI00110896.

PIR

A46484.

RefSeq

NP_032013.2. NM_007987.2.

UniGene

Mm.1626.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3OQ9	X-ray	6.80	A/B/C/D/E	223-308	[»]

ProteinModelPortal

P25446.

SMR

P25446. Positions 48-159, 223-308.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31093N.

IntAct

P25446. 9 interactions.

MINT

MINT-144559.

PTM databases

PhosphoSite

P25446.

Proteomic databases

PaxDb

P25446.

PRIDE

P25446.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000025691; ENSMUSP00000025691; ENSMUSG00000024778.

GeneID

14102.

KEGG

mmu:14102.

Organism-specific databases

CTD

355.

MGI

MGI:95484. Fas.

Phylogenomic databases

eggNOG

NOG45364.

GeneTree

ENSGT00530000063703.

HOGENOM

HOG000139681.

HOVERGEN

HBG004091.

InParanoid

Q6GT31.

KO

K04390.

OMA

CVPCQEG.

OrthoDB

EOG4K6G53.

Gene expression databases

ArrayExpress

P25446.

Bgee

P25446.

CleanEx

MM_FAS.

Genevestigator

P25446.

GermOnline

ENSMUSG00000024778. Mus musculus.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.

InterPro

IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR008063. Fas_rcpt.
IPR001368. TNFR/NGFR_Cys_rich_reg.
[Graphical view]

Pfam

PF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]

PRINTS

PR01680. TNFACTORR6.

SMART

SM00005. DEATH. 1 hit.
SM00208. TNFR. 3 hits.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

FAS. mouse.

EvolutionaryTrace

P25446.

NextBio

285130.

SOURCE

Search...

Entry information

Entry name

TNR6_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program