P25445 (TNR6_HUMAN) 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, FAS1, TNFRSF6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	335 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. The secreted isoforms 2 to 6 block apoptosis (in vitro). Ref.4 Ref.23
Subunit structure	Binds DAXX. Interacts with HIPK3. Part of a complex containing HIPK3 and FADD By similarity. Binds RIPK1 and FAIM2. Interacts with BRE and FEM1B. Interacts with FADD. Ref.14 Ref.15 Ref.16 Ref.18 Ref.21 Ref.23
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.23. Isoform 2: Secreted Ref.23. Isoform 3: Secreted Ref.23. Isoform 4: Secreted Ref.23. Isoform 5: Secreted Ref.23. Isoform 6: Secreted Ref.23.
Tissue specificity	Isoform 1 and isoform 6 are expressed at equal levels in resting peripheral blood mononuclear cells. After activation there is an increase in isoform 1 and decrease in the levels of isoform 6. Ref.3
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 autoimmune lymphoproliferative syndrome type 1A (ALPS1A) [MIM:601859]; also known as Canale-Smith syndrome (CSS). ALPS is a childhood syndrome involving hemolytic anemia and thrombocytopenia with massive lymphadenopathy and splenomegaly. Ref.6 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37
Sequence similarities	Contains 1 death domain. Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	activation of cysteine-type endopeptidase activity involved in apoptotic process Traceable author statement. Source: Reactome activation of pro-apoptotic gene products Traceable author statement. Source: Reactome anti-apoptosis Traceable author statement. Source: ProtInc cellular response to hyperoxia Inferred from mutant phenotype. Source: UniProtKB cellular response to mechanical stimulus Inferred from expression pattern. Source: UniProtKB positive regulation of necrotic cell death Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	CD95 death-inducing signaling complex Inferred from direct assay Ref.37. Source: UniProtKB cytosol Non-traceable author statement Ref.4. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA soluble fraction Traceable author statement. Source: ProtInc
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct kinase binding Inferred from physical interaction Ref.14. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-494743,EBI-494743
CALM1	P62158	4	EBI-494743,EBI-397435
CASP8	Q14790	10	EBI-494743,EBI-78060
CAV1	Q03135	3	EBI-494743,EBI-603614
DAXX	Q9UER7	2	EBI-494743,EBI-77321
FADD	Q13158	28	EBI-494743,EBI-494804
Pdcd6	P12815	2	EBI-494743,EBI-309164	From a different organism.
SRC	P12931	2	EBI-494743,EBI-621482

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P25445-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P25445-2)

Also known as: del2; D;

The sequence of this isoform differs from the canonical sequence as follows:
     66-103: GERKARDCTV...KAHFSSKCRR → DVNMESSRNA...GFVFFFCQFH
     104-335: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: P25445-3)

Also known as: del3; E;

The sequence of this isoform differs from the canonical sequence as follows:
     66-86: GERKARDCTVNGDEPDCVPCQ → DVNMESSRNAHSPATPSAKRK
     87-335: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 4 (identifier: P25445-4)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     112-149: GLEVEINCTR...CEHCDPCTKC → DVNMESSRNA...GFVFFFCQFH
     150-335: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 5 (identifier: P25445-5)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     112-132: GLEVEINCTRTQNTKCRCKPN → DVNMESSRNAHSPATPSAKRK
     133-335: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 6 (identifier: P25445-6)

Also known as: TMdel; A;

The sequence of this isoform differs from the canonical sequence as follows:
     169-189: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Chain

26 – 335

310

Tumor necrosis factor receptor superfamily member 6

PRO_0000034563

Regions

Topological domain

26 – 173

148

Extracellular Potential

Transmembrane

174 – 190

17

Helical; Potential

Topological domain

191 – 335

145

Cytoplasmic Potential

Repeat

47 – 83

37

TNFR-Cys 1

Repeat

84 – 127

44

TNFR-Cys 2

Repeat

128 – 166

39

TNFR-Cys 3

Domain

230 – 314

85

Death

Region

212 – 317

106

Interaction with HIPK3 By similarity

Amino acid modifications

Modified residue

209

1

Phosphoserine Ref.19

Modified residue

214

1

Phosphothreonine Ref.19

Modified residue

225

1

Phosphoserine By similarity

Modified residue

230

1

Phosphoserine By similarity

Glycosylation

118

1

N-linked (GlcNAc...) Ref.20

Glycosylation

136

1

N-linked (GlcNAc...) Potential

Disulfide bond

59 ↔ 73

By similarity

Disulfide bond

63 ↔ 82

By similarity

Disulfide bond

85 ↔ 101

By similarity

Disulfide bond

104 ↔ 119

By similarity

Disulfide bond

107 ↔ 127

By similarity

Disulfide bond

129 ↔ 143

By similarity

Disulfide bond

146 ↔ 157

By similarity

Disulfide bond

149 ↔ 165

By similarity

Natural variations

Alternative sequence

66 – 103

38

GERKA…SKCRR → DVNMESSRNAHSPATPSAKR KDPDLTWGGFVFFFCQFH in isoform 2.

VSP_006481

Alternative sequence

66 – 86

21

GERKA…CVPCQ → DVNMESSRNAHSPATPSAKR K in isoform 3.

VSP_006483

Alternative sequence

87 – 335

249

Missing in isoform 3.

VSP_006484

Alternative sequence

104 – 335

232

Missing in isoform 2.

VSP_006482

Alternative sequence

112 – 149

38

GLEVE…PCTKC → DVNMESSRNAHSPATPSAKR KDPDLTWGGFVFFFCQFH in isoform 4.

VSP_006485

Alternative sequence

112 – 132

21

GLEVE…RCKPN → DVNMESSRNAHSPATPSAKR K in isoform 5.

VSP_006487

Alternative sequence

133 – 335

203

Missing in isoform 5.

VSP_006488

Alternative sequence

150 – 335

186

Missing in isoform 4.

VSP_006486

Alternative sequence

169 – 189

21

Missing in isoform 6.

VSP_006489

Natural variant

16

1

A → T. Ref.10
Corresponds to variant rs3218619 [ dbSNP | Ensembl ].

VAR_020008

Natural variant

25

1

A → T in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013416

Natural variant

28

1

T → A in ALPS1A; associated with autoimmune hepatitis type 2. Ref.28

VAR_013417

Natural variant

82

1

C → R in ALPS1A. Ref.34

VAR_013418

Natural variant

118

1

N → S in squamous cell carcinoma; burn-scar related; somatic mutation. Ref.35

VAR_018321

Natural variant

121

1

R → W in ALPS1A. Ref.26

VAR_013419

Natural variant

122

1

T → I. Ref.10
Corresponds to variant rs3218614 [ dbSNP | Ensembl ].

VAR_020009

Natural variant

178

1

C → R in squamous cell carcinoma; burn-scar related; somatic mutation. Ref.35

VAR_018322

Natural variant

180

1

L → F in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013420

Natural variant

183

1

P → L in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013421

Natural variant

184

1

I → V.
Corresponds to variant rs28362322 [ dbSNP | Ensembl ].

VAR_052347

Natural variant

198

1

T → I in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013422

Natural variant

232

1

Y → C in ALPS1A; no effect on interaction with FADD. Ref.26 Ref.37

VAR_013423

Natural variant

241

1

T → K in ALPS1A. Ref.31

VAR_013424

Natural variant

241

1

T → P in ALPS1A. Ref.24 Ref.36

VAR_013425

Natural variant

249

1

V → L in ALPS1A. Ref.32

VAR_065128

Natural variant

250

1

R → P in ALPS1A. Ref.32 Ref.34

VAR_013426

Natural variant

250

1

R → Q in ALPS1A; no effect on interaction with FADD. Ref.31 Ref.37

VAR_013427

Natural variant

253

1

G → D in ALPS1A. Ref.32

VAR_065129

Natural variant

253

1

G → S in ALPS1A. Ref.32

VAR_065130

Natural variant

255

1

N → D in squamous cell carcinoma; burn-scar related; somatic mutation. Ref.35

VAR_018323

Natural variant

257

1

A → D in ALPS1A; loss of interaction with FADD. Ref.27 Ref.37

VAR_013428

Natural variant

259

1

I → R in ALPS1A. Ref.32

VAR_065131

Natural variant

260

1

D → G in ALPS1A. Ref.34

VAR_013429

Natural variant

260

1

D → V in ALPS1A; also found in non-Hodgkin lymphoma; somatic mutation; loss of interaction with FADD. Ref.29 Ref.30 Ref.36 Ref.37
Corresponds to variant rs28929498 [ dbSNP | Ensembl ].

VAR_013431

Natural variant

260

1

D → Y in ALPS1A; loss of interaction with FADD. Ref.25 Ref.37

VAR_013430

Natural variant

262

1

I → S in ALPS1A. Ref.6

VAR_058910

Natural variant

264

1

N → K in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013432

Natural variant

270

1

T → I in ALPS1A. Ref.34 Ref.36

VAR_013433

Natural variant

270

1

T → K in ALPS1A; loss of interaction with FADD. Ref.32 Ref.37

VAR_065132

Natural variant

272

1

E → G in ALPS1A. Ref.33 Ref.36

VAR_013434

Natural variant

272

1

E → K in ALPS1A; also found in non-Hodgkin lymphoma; somatic mutation; loss of interaction with FADD. Ref.29 Ref.32 Ref.37

VAR_013435

Natural variant

278

1

L → F in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013436

Natural variant

299

1

K → N in non-Hodgkin lymphoma; somatic mutation. Ref.29

VAR_013437

Natural variant

305

1

T → I. Ref.10
Corresponds to variant rs3218611 [ dbSNP | Ensembl ].

VAR_020942

Natural variant

310

1

I → S in ALPS1A. Ref.27

VAR_013438

Experimental info

Mutagenesis

250

1

R → E: Strongly decreased interaction with FADD. Ref.37

Mutagenesis

261

1

E → K: Loss of interaction with FADD. Ref.37

Mutagenesis

283

1

Q → K: Loss of interaction with FADD. Ref.37

Mutagenesis

287

1

K → D: Strongly decreased interaction with FADD. Ref.37

Mutagenesis

291

1

Y → D: Decreased interaction with FADD. Ref.23

Mutagenesis

313

1

I → D: Constitutive activation. Promotes apoptosis, both in the presence and in the absence of stimulation by a ligand. Ref.23

Sequence conflict

224

1

L → F in AAR08906. Ref.10

Sequence conflict

242

1

L → P in CAR92543. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

335

Helix Strand Turn

Details...

Helix

232 – 239

8

Helix

242 – 250

9

Turn

251 – 253

3

Helix

256 – 264

9

Turn

265 – 268

4

Helix

273 – 284

12

Beta strand

287 – 289

3

Helix

290 – 300

11

Helix

306 – 318

13

Turn

319 – 322

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 0139942535111410	FASTA	335	37,732
	10 20 30 40 50 60 MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH 70 80 90 100 110 120 KPCPPGERKA RDCTVNGDEP DCVPCQEGKE YTDKAHFSSK CRRCRLCDEG HGLEVEINCT 130 140 150 160 170 180 RTQNTKCRCK PNFFCNSTVC EHCDPCTKCE HGIIKECTLT SNTKCKEEGS RSNLGWLCLL 190 200 210 220 230 240 LLPIPLIVWV KRKEVQKTCR KHRKENQGSH ESPTLNPETV AINLSDVDLS KYITTIAGVM 250 260 270 280 290 300 TLSQVKGFVR KNGVNEAKID EIKNDNVQDT AEQKVQLLRN WHQLHGKKEA YDTLIKDLKK 310 320 330 ANLCTLAEKI QTIILKDITS DSENSNFRNE IQSLV
	Isoform 2 (del2) (D) [UniParc]. Checksum: F0DEA7F598AFBB00	FASTA	103	11,435
	10 20 30 40 50 60 MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH 70 80 90 100 KPCPPDVNME SSRNAHSPAT PSAKRKDPDL TWGGFVFFFC QFH
	Isoform 3 (del3) (E) [UniParc]. Checksum: D55B05CA4C2D1D49	FASTA	86	9,390
	10 20 30 40 50 60 MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH 70 80 KPCPPDVNME SSRNAHSPAT PSAKRK
	Isoform 4 (B) [UniParc]. Checksum: 5061E69484678FC0	FASTA	149	16,648
	10 20 30 40 50 60 MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH 70 80 90 100 110 120 KPCPPGERKA RDCTVNGDEP DCVPCQEGKE YTDKAHFSSK CRRCRLCDEG HDVNMESSRN 130 140 AHSPATPSAK RKDPDLTWGG FVFFFCQFH
	Isoform 5 (C) [UniParc]. Checksum: B10B6F86DE5E8690	FASTA	132	14,602
	10 20 30 40 50 60 MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH 70 80 90 100 110 120 KPCPPGERKA RDCTVNGDEP DCVPCQEGKE YTDKAHFSSK CRRCRLCDEG HDVNMESSRN 130 AHSPATPSAK RK
	Isoform 6 (TMdel) (A) [UniParc]. Checksum: 83F8FAC62DB8B457	FASTA	314	35,386
	10 20 30 40 50 60 MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH 70 80 90 100 110 120 KPCPPGERKA RDCTVNGDEP DCVPCQEGKE YTDKAHFSSK CRRCRLCDEG HGLEVEINCT 130 140 150 160 170 180 RTQNTKCRCK PNFFCNSTVC EHCDPCTKCE HGIIKECTLT SNTKCKEEVK RKEVQKTCRK 190 200 210 220 230 240 HRKENQGSHE SPTLNPETVA INLSDVDLSK YITTIAGVMT LSQVKGFVRK NGVNEAKIDE 250 260 270 280 290 300 IKNDNVQDTA EQKVQLLRNW HQLHGKKEAY DTLIKDLKKA NLCTLAEKIQ TIILKDITSD 310 SENSNFRNEI QSLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis." Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. Cell 66:233-243(1991) [PubMed: 1713127] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen." Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B.C., Ponstingl H., Krammer P.H. J. Biol. Chem. 267:10709-10715(1992) [PubMed: 1375228] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 226-240; 269-291 AND 321-335.
[3]	"Differential expression of human Fas mRNA species upon peripheral blood mononuclear cell activation." Liu C., Cheng J., Mountz J.D. Biochem. J. 310:957-963(1995) [PubMed: 7575433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 6), TISSUE SPECIFICITY.
[4]	"Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing." Cascino I., Fiucci G., Papoff G., Ruberti G. J. Immunol. 154:2706-2713(1995) [PubMed: 7533181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 6), FUNCTION.
[5]	"An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents cell death in vitro." Papoff G., Cascino I., Eramo A., Starace G., Lynch D.H., Ruberti G. J. Immunol. 156:4622-4630(1996) [PubMed: 8648105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5).
[6]	"Autoimmune lymphoproliferative syndrome (ALPS) in a patient with a new germline Fas gene mutation." Del-Rey M.J., Manzanares J., Bosque A., Aguilo J.I., Gomez-Rial J., Roldan E., Serrano A., Anel A., Paz-Artal E., Allende L.M. Immunobiology 212:73-83(2007) [PubMed: 17336828] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALPS1A SER-262.
[7]	Schaetzlein C.E., Poehlmann R., Philippsen P., Eibel H. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). Tissue: Peripheral blood lymphocyte.
[8]	De La Calle-Martin O. Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[9]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-16; ILE-122 AND ILE-305.
[11]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Urinary bladder.
[14]	"RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death." Stanger B.Z., Leder P., Lee T.-H., Kim E., Seed B. Cell 81:513-523(1995) [PubMed: 7538908] [Abstract] Cited for: INTERACTION WITH RIPK1.
[15]	"F1Aalpha, a death receptor-binding protein homologous to the Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase substrate that mediates apoptosis." Chan S.-L., Tan K.-O., Zhang L., Yee K.S.Y., Ronca F., Chan M.-Y., Yu V.C. J. Biol. Chem. 274:32461-32468(1999) [PubMed: 10542291] [Abstract] Cited for: INTERACTION WITH FEM1B.
[16]	"LFG: an anti-apoptotic gene that provides protection from fas-mediated cell death." Somia N.V., Schmitt M.J., Vetter D.E., Van Antwerp D., Heinemann S.F., Verma I.M. Proc. Natl. Acad. Sci. U.S.A. 96:12667-12672(1999) [PubMed: 10535980] [Abstract] Cited for: INTERACTION WITH FAIM2.
[17]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[18]	"A death receptor-associated anti-apoptotic protein, BRE, inhibits mitochondrial apoptotic pathway." Li Q., Ching A.K.-K., Chan B.C.-L., Chow S.K.-Y., Lim P.-L., Ho T.C.-Y., Ip W.-K., Wong C.-K., Lam C.W.-K., Lee K.K.-H., Chan J.Y.-H., Chui Y.-L. J. Biol. Chem. 279:52106-52116(2004) [PubMed: 15465831] [Abstract] Cited for: INTERACTION WITH BRE.
[19]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209 AND THR-214, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-118, MASS SPECTROMETRY. Tissue: Liver.
[21]	"Whole-exome-sequencing-based discovery of human FADD deficiency." Bolze A., Byun M., McDonald D., Morgan N.V., Abhyankar A., Premkumar L., Puel A., Bacon C.M., Rieux-Laucat F., Pang K., Britland A., Abel L., Cant A., Maher E.R., Riedl S.J., Hambleton S., Casanova J.L. Am. J. Hum. Genet. 87:873-881(2010) [PubMed: 21109225] [Abstract] Cited for: INTERACTION WITH FADD.
[22]	"NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain." Huang B., Eberstadt M., Olejniczak E.T., Meadows R.P., Fesik S.W. Nature 384:638-641(1996) [PubMed: 8967952] [Abstract] Cited for: STRUCTURE BY NMR OF 218-335.
[23]	"The Fas-FADD death domain complex structure unravels signalling by receptor clustering." Scott F.L., Stec B., Pop C., Dobaczewska M.K., Lee J.J., Monosov E., Robinson H., Salvesen G.S., Schwarzenbacher R., Riedl S.J. Nature 457:1019-1022(2009) [PubMed: 19118384] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS) OF 223-335 IN COMPLEX WITH FADD, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-291 AND ILE-313.
[24]	"Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome." Fisher G.H., Rosenberg F.J., Straus S.E., Dale J.K., Middleton L.A., Lin A.Y., Strober W., Lenardo M.J., Puck J.M. Cell 81:935-946(1995) [PubMed: 7540117] [Abstract] Cited for: VARIANT ALPS1A PRO-241.
[25]	"Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity." Drappa J., Vaishnaw A.K., Sullivan K.E., Chu J.-L., Elkon K.B. N. Engl. J. Med. 335:1643-1649(1996) [PubMed: 8929361] [Abstract] Cited for: VARIANT ALPS1A TYR-260.
[26]	"Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis." Bettinardi A., Brugnoni D., Quiros-Roldan E., Malagoli A., La Grutta S., Correra A., Notarangelo L.D. Blood 89:902-909(1997) [PubMed: 9028321] [Abstract] Cited for: VARIANTS ALPS1A TRP-121 AND CYS-232.
[27]	"Clincial, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis." Sneller M.C., Wang J., Dale J.K., Strober W., Middelton L.A., Choi Y., Fleisher T.A., Lim M.S., Jaffe E.S., Puck J.M., Lenardo M.J., Straus S.E. Blood 89:1341-1348(1997) [PubMed: 9028957] [Abstract] Cited for: VARIANTS ALPS1A ASP-257 AND SER-310.
[28]	"Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis." Pensati L., Costanzo A., Ianni A., Accapezzato D., Iorio R., Natoli G., Nisini R., Almerighi C., Balsano C., Vajro P., Vegnente A., Levrero M. Gastroenterology 113:1384-1389(1997) [PubMed: 9322534] [Abstract] Cited for: VARIANT ALPS1A ALA-28.
[29]	"Somatic Fas mutations in non-Hodgkin's lymphoma: association with extranodal disease and autoimmunity." Groenbaek K., Straten P.T., Ralfkiaer E., Ahrenkiel V., Andersen M.K., Hansen N.E., Zeuthen J., Hou-Jensen K., Guldberg P. Blood 92:3018-3024(1998) [PubMed: 9787134] [Abstract] Cited for: VARIANTS NON-HODGKIN LYMPHOMA THR-25; PHE-180; LEU-183; ILE-198; VAL-260; LYS-264; LYS-272; PHE-278 AND ASN-299.
[30]	"The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis." Infante A.J., Britton H.A., DeNapoli T., Middelton L.A., Lenardo M.J., Jackson C.E., Wang J., Fleisher T., Straus S.E., Puck J.M. J. Pediatr. 133:629-633(1998) [PubMed: 9821419] [Abstract] Cited for: VARIANT ALPS1A VAL-260.
[31]	"Autoimmune lymphoproliferative syndrome with defective Fas: genotype influences penetrance." Jackson C.E., Fischer R.E., Hsu A.P., Anderson S.M., Choi Y., Wang J., Dale J.K., Fleisher T.A., Middelton L.A., Sneller M.C., Lenardo M.J., Straus S.E., Puck J.M. Am. J. Hum. Genet. 64:1002-1014(1999) [PubMed: 10090885] [Abstract] Cited for: VARIANTS ALPS1A LYS-241 AND GLN-250.
[32]	"Lymphoproliferative syndrome with autoimmunity: A possible genetic basis for dominant expression of the clinical manifestations." Rieux-Laucat F., Blachere S., Danielan S., De Villartay J.P., Oleastro M., Solary E., Bader-Meunier B., Arkwright P., Pondare C., Bernaudin F., Chapel H., Nielsen S., Berrah M., Fischer A., Le Deist F. Blood 94:2575-2582(1999) [PubMed: 10515860] [Abstract] Cited for: VARIANTS ALPS1A LEU-249; PRO-250; ASP-253; SER-253; ARG-259; LYS-270 AND LYS-272.
[33]	"Defective apoptosis due to a point mutation in the death domain of CD95 associated with autoimmune lymphoproliferative syndrome, T-cell lymphoma, and Hodgkin's disease." Peters A.M., Kohfink B., Martin H., Griesinger F., Wormann B., Gahr M., Roesler J. Exp. Hematol. 27:868-874(1999) [PubMed: 10340403] [Abstract] Cited for: VARIANT ALPS1A GLY-272.
[34]	"The molecular basis for apoptotic defects in patients with CD95 (Fas/Apo-1) mutations." Vaishnaw A.K., Orlinick J.R., Chu J.-L., Krammer P.H., Chao M.V., Elkon K.B. J. Clin. Invest. 103:355-363(1999) [PubMed: 9927496] [Abstract] Cited for: VARIANTS ALPS1A ARG-82; PRO-250; GLY-260 AND ILE-270.
[35]	"Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell carcinoma arising from a burn scar." Lee S.H., Shin M.S., Kim H.S., Park W.S., Kim S.Y., Jang J.J., Rhim K.J., Jang J., Lee H.K., Park J.Y., Oh R.R., Han S.Y., Lee J.H., Lee J.Y., Yoo N.J. J. Invest. Dermatol. 114:122-126(2000) [PubMed: 10620127] [Abstract] Cited for: VARIANTS SQUAMOUS CELL CARCINOMA SER-118; ARG-178 AND ASP-255.
[36]	"The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis." Straus S.E., Jaffe E.S., Puck J.M., Dale J.K., Elkon K.B., Roesen-Wolff A., Peters A.M.J., Sneller M.C., Hallahan C.W., Wang J., Fischer R.E., Jackson C.M., Lin A.Y., Baeumler C., Siegert E., Marx A., Vaishnaw A.K., Grodzicky T., Fleisher T.A., Lenardo M.J. Blood 98:194-200(2001) [PubMed: 11418480] [Abstract] Cited for: VARIANTS ALPS1A PRO-241; VAL-260; ILE-270 AND GLY-272.
[37]	"The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations." Wang L., Yang J.K., Kabaleeswaran V., Rice A.J., Cruz A.C., Park A.Y., Yin Q., Damko E., Jang S.B., Raunser S., Robinson C.V., Siegel R.M., Walz T., Wu H. Nat. Struct. Mol. Biol. 17:1324-1329(2010) [PubMed: 20935634] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ALPS1A CYS-232; GLN-250; ASP-257; TYR-260; VAL-260; LYS-270 AND LYS-272, MUTAGENESIS OF ARG-250; GLU-261; GLN-283 AND LYS-287.
+	Additional computationally mapped references.

Web resources

Autoimmune Lymphoproliferative Syndrome Database (ALPSbase)

Mutations in TNFRSF6 causing ALPS type Ia

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M67454 mRNA. Translation: AAA63174.1.
X63717 mRNA. Translation: CAA45250.1.
X83490 mRNA. No translation available.
X83491 mRNA. No translation available.
X83492 mRNA. No translation available.
X83493 mRNA. No translation available.
Z47993 mRNA. Translation: CAA88031.1.
Z47994 mRNA. Translation: CAA88032.1.
Z47995 mRNA. Translation: CAA88033.1.
Z70519 mRNA. Translation: CAA94430.1.
Z70520 mRNA. Translation: CAA94431.1.
AY495076 mRNA. Translation: AAS76663.1.
X89101 mRNA. Translation: CAA61473.1.
FM246458 mRNA. Translation: CAR92543.1.
AK290978 mRNA. Translation: BAF83667.1.
AY450925 Genomic DNA. Translation: AAR08906.1.
AL157394 Genomic DNA. Translation: CAI13871.1.
AL157394 Genomic DNA. Translation: CAI13872.1.
CH471066 Genomic DNA. Translation: EAW50151.1.
BC012479 mRNA. Translation: AAH12479.1.

IPI

IPI00170811.
IPI00216357.
IPI00216358.
IPI00216359.
IPI00291314.
IPI00744894.

PIR

A40036.
I37383.
I37384.
S58662.

RefSeq

NP_000034.1. NM_000043.4.
NP_690610.1. NM_152871.2.
NP_690611.1. NM_152872.2.

UniGene

Hs.244139.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BZI	model	-	A	1-335	[»]
1DDF	NMR	-	A	218-335	[»]
3EWT	X-ray	2.40	E	230-254	[»]
3EZQ	X-ray	2.73	A/C/E/G/I/K/M/O	223-335	[»]

ProteinModelPortal

P25445.

SMR

P25445. Positions 48-148, 218-335.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-924N.

IntAct

P25445. 34 interactions.

MINT

MINT-146256.

STRING

P25445.

PTM databases

PhosphoSite

P25445.

Polymorphism databases

DMDM

119833.

Proteomic databases

PRIDE

P25445.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355740; ENSP00000347979; ENSG00000026103.

GeneID

355.

KEGG

hsa:355.

UCSC

uc001kfr.1. human.
uc001kfu.1. human.
uc001kfv.1. human.
uc001kfx.1. human.
uc001kfy.1. human.

Organism-specific databases

CTD

355.

GeneCards

GC10P090741.

H-InvDB

HIX0009017.

HGNC

HGNC:11920. FAS.

HPA

HPA027444.

MIM

134637. gene.
601859. phenotype.

neXtProt

NX_P25445.

Orphanet

3261. Autoimmune lymphoproliferative syndrome.

PharmGKB

PA36613.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13680.

HOVERGEN

HBG004091.

OrthoDB

EOG4K6G53.

PhylomeDB

P25445.

Enzyme and pathway databases

Pathway_Interaction_DB

faspathway. FAS signaling pathway (CD95).
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P25445.

Bgee

P25445.

CleanEx

HS_FAS.

Genevestigator

P25445.

GermOnline

ENSG00000026103. Homo sapiens.

Family and domain databases

InterPro

IPR000488. Death.
IPR011029. DEATH-like.
IPR008063. Fas_rcpt.
IPR001368. TNFR_Cys_rich_reg.
[Graphical view]

Gene3D

G3DSA:1.10.533.10. DEATH_like. 1 hit.

KO

K04390.

Pfam

PF00531. Death. 1 hit.
PF00020. TNFR_c6. 2 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

NextBio

1471.

PMAP-CutDB

P25445.

SOURCE

Search...

Entry information

Entry name

TNR6_HUMAN

Accession

Primary (citable) accession number: P25445
Secondary accession number(s): A9UJX4 , B6VNV4, Q14292, Q14293, Q14294, Q14295, Q16652, Q5T9P1, Q5T9P2, Q6SSE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	January 25, 2012
This is version 157 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.