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P25446

- TNR6_MOUSE

UniProt

P25446 - TNR6_MOUSE

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Protein
Tumor necrosis factor receptor superfamily member 6
Gene
Fas, Apt1, Tnfrsf6
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. protein binding Source: UniProtKB
  2. transmembrane signaling receptor activity Source: InterPro

GO - Biological processi

  1. B cell mediated immunity Source: MGI
  2. T cell homeostasis Source: MGI
  3. activation-induced cell death of T cells Source: MGI
  4. apoptotic process Source: MGI
  5. apoptotic signaling pathway Source: MGI
  6. cellular response to hyperoxia Source: Ensembl
  7. cellular response to lithium ion Source: MGI
  8. cellular response to mechanical stimulus Source: Ensembl
  9. circadian rhythm Source: UniProtKB
  10. extrinsic apoptotic signaling pathway Source: MGI
  11. extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  12. extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  13. gene expression Source: MGI
  14. immunoglobulin production Source: MGI
  15. inflammatory cell apoptotic process Source: MGI
  16. motor neuron apoptotic process Source: MGI
  17. necroptotic signaling pathway Source: MGI
  18. negative regulation of B cell activation Source: MGI
  19. negative regulation of apoptotic process Source: MGI
  20. negative thymic T cell selection Source: MGI
  21. neuron apoptotic process Source: MGI
  22. positive regulation of apoptotic process Source: Ensembl
  23. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  24. positive regulation of necrotic cell death Source: Ensembl
  25. positive regulation of protein homooligomerization Source: BHF-UCL
  26. positive regulation of release of cytochrome c from mitochondria Source: BHF-UCL
  27. protein homooligomerization Source: MGI
  28. regulation of lymphocyte differentiation Source: MGI
  29. regulation of myeloid cell differentiation Source: MGI
  30. renal system process Source: MGI
  31. response to glucocorticoid Source: MGI
  32. response to toxic substance Source: MGI
  33. spleen development Source: MGI
  34. transformed cell apoptotic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_215122. Regulation by c-FLIP.

Names & Taxonomyi

Protein namesi
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 namesi
Name:Fas
Synonyms:Apt1, Tnfrsf6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 19

Organism-specific databases

MGIiMGI:95484. Fas.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 169148Extracellular Reviewed prediction
Add
BLAST
Transmembranei170 – 18617Helical; Reviewed prediction
Add
BLAST
Topological domaini187 – 327141Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. CD95 death-inducing signaling complex Source: UniProtKB
  2. cell surface Source: MGI
  3. cytoplasm Source: Ensembl
  4. external side of plasma membrane Source: MGI
  5. extracellular region Source: MGI
  6. integral component of membrane Source: UniProtKB-KW
  7. membrane raft Source: Ensembl
  8. nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

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

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121 Reviewed prediction
Add
BLAST
Chaini22 – 327306Tumor necrosis factor receptor superfamily member 6
PRO_0000034567Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi43 – 431N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi44 ↔ 55 By similarity
Disulfide bondi56 ↔ 69 By similarity
Disulfide bondi59 ↔ 78 By similarity
Disulfide bondi81 ↔ 97 By similarity
Disulfide bondi100 ↔ 115 By similarity
Disulfide bondi103 ↔ 123 By similarity
Glycosylationi114 – 1141N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi125 ↔ 139 By similarity
Disulfide bondi142 ↔ 153 By similarity
Disulfide bondi145 ↔ 161 By similarity
Modified residuei220 – 2201Phosphoserine1 Publication
Modified residuei314 – 3141Phosphothreonine1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP25446.
PRIDEiP25446.

PTM databases

PhosphoSiteiP25446.

Expressioni

Tissue specificityi

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

Inductioni

Expression oscillates in a circadian manner in the liver with peak levels seen at CT12.1 Publication

Gene expression databases

ArrayExpressiP25446.
BgeeiP25446.
CleanExiMM_FAS.
GenevestigatoriP25446.

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Casp8O891103EBI-296206,EBI-851690
DAXXQ9UER74EBI-296206,EBI-77321From a different organism.
DaxxO356132EBI-296206,EBI-77304
FADDQ131585EBI-296206,EBI-494804From a different organism.
FaddQ611603EBI-296206,EBI-524415
Hipk3Q9ERH73EBI-296206,EBI-524356
PmlQ609536EBI-296206,EBI-3895605

Protein-protein interaction databases

BioGridi199594. 6 interactions.
DIPiDIP-31093N.
IntActiP25446. 11 interactions.
MINTiMINT-144559.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3OQ9X-ray6.80A/B/C/D/E223-308[»]
ProteinModelPortaliP25446.
SMRiP25446. Positions 48-159, 223-308.

Miscellaneous databases

EvolutionaryTraceiP25446.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati43 – 7937TNFR-Cys 1
Add
BLAST
Repeati80 – 12344TNFR-Cys 2
Add
BLAST
Repeati124 – 16239TNFR-Cys 3
Add
BLAST
Domaini222 – 30685Death
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni204 – 309106Interaction with HIPK3
Add
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 death domain.
Contains 3 TNFR-Cys repeats.

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG45364.
GeneTreeiENSGT00730000111280.
HOGENOMiHOG000139681.
HOVERGENiHBG004091.
InParanoidiQ6GT31.
KOiK04390.
OMAiCEHCNPC.
OrthoDBiEOG7DVDC8.
TreeFamiTF333916.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR008063. Fas_rcpt.
IPR001368. TNFR/NGFR_Cys_rich_reg.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSiPR01680. TNFACTORR6.
SMARTiSM00005. DEATH. 1 hit.
SM00208. TNFR. 3 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P25446-1 [UniParc]FASTAAdd to Basket

« Hide

MLWIWAVLPL VLAGSQLRVH TQGTNSISES LKLRRRVRET DKNCSEGLYQ    50
GGPFCCQPCQ PGKKKVEDCK MNGGTPTCAP CTEGKEYMDK NHYADKCRRC 100
TLCDEEHGLE VETNCTLTQN TKCKCKPDFY CDSPGCEHCV RCASCEHGTL 150
EPCTATSNTN CRKQSPRNRL WLLTILVLLI PLVFIYRKYR KRKCWKRRQD 200
DPESRTSSRE TIPMNASNLS LSKYIPRIAE DMTIQEAKKF ARENNIKEGK 250
IDEIMHDSIQ DTAEQKVQLL LCWYQSHGKS DAYQDLIKGL KKAECRRTLD 300
KFQDMVQKDL GKSTPDTGNE NEGQCLE 327
Length:327
Mass (Da):37,437
Last modified:July 27, 2011 - v2
Checksum:iD8DA95CA525CED56
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti246 – 2461I → N in lpr. 1 Publication

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti38 – 381R → H in AAA37593. 1 Publication
Sequence conflicti38 – 381R → H in CAC00638. 1 Publication
Sequence conflicti38 – 381R → H in AAB25700. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS29758.1.
PIRiA46484.
RefSeqiNP_032013.2. NM_007987.2.
UniGeneiMm.1626.

Genome annotation databases

EnsembliENSMUST00000025691; ENSMUSP00000025691; ENSMUSG00000024778.
GeneIDi14102.
KEGGimmu:14102.
UCSCiuc008hgi.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS29758.1.
PIRi A46484.
RefSeqi NP_032013.2. NM_007987.2.
UniGenei Mm.1626.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3OQ9 X-ray 6.80 A/B/C/D/E 223-308 [» ]
ProteinModelPortali P25446.
SMRi P25446. Positions 48-159, 223-308.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199594. 6 interactions.
DIPi DIP-31093N.
IntActi P25446. 11 interactions.
MINTi MINT-144559.

PTM databases

PhosphoSitei P25446.

Proteomic databases

PaxDbi P25446.
PRIDEi P25446.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000025691 ; ENSMUSP00000025691 ; ENSMUSG00000024778 .
GeneIDi 14102.
KEGGi mmu:14102.
UCSCi uc008hgi.2. mouse.

Organism-specific databases

CTDi 355.
MGIi MGI:95484. Fas.

Phylogenomic databases

eggNOGi NOG45364.
GeneTreei ENSGT00730000111280.
HOGENOMi HOG000139681.
HOVERGENi HBG004091.
InParanoidi Q6GT31.
KOi K04390.
OMAi CEHCNPC.
OrthoDBi EOG7DVDC8.
TreeFami TF333916.

Enzyme and pathway databases

Reactomei REACT_215122. Regulation by c-FLIP.

Miscellaneous databases

ChiTaRSi FAS. mouse.
EvolutionaryTracei P25446.
NextBioi 285130.
PROi P25446.
SOURCEi Search...

Gene expression databases

ArrayExpressi P25446.
Bgeei P25446.
CleanExi MM_FAS.
Genevestigatori P25446.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
InterProi IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR008063. Fas_rcpt.
IPR001368. TNFR/NGFR_Cys_rich_reg.
[Graphical view ]
Pfami PF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view ]
PRINTSi PR01680. TNFACTORR6.
SMARTi SM00005. DEATH. 1 hit.
SM00208. TNFR. 3 hits.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
PROSITEi PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiTNR6_MOUSE
AccessioniPrimary (citable) accession number: P25446
Secondary accession number(s): Q6GT31, Q9DCQ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: July 27, 2011
Last modified: September 3, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi