P19438 (TNR1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 1A

Alternative name(s):
Tumor necrosis factor receptor 1
Short name=TNF-R1
Tumor necrosis factor receptor type I
Short name=TNF-RI
Short name=TNFR-I
p55
p60
CD_antigen=CD120a

Cleaved into the following 2 chains:

1. Tumor necrosis factor receptor superfamily member 1A, membrane form
2. Tumor necrosis factor-binding protein 1
   Short name=TBPI

Gene names

Name:	TNFRSF1A
Synonyms:	TNFAR, TNFR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	455 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 TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. 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. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
Subunit structure	Binding of TNF to the extracellular domain leads to homotrimerization. The aggregated death domains provide a novel molecular interface that interacts specifically with the death domain of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and possibly FADD, are recruited to the complex by their association with TRADD. This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4, BRE, FEM1B, GRB2, SQSTM1 and TRPC4AP. Interacts with HCV core protein. Interacts with human cytomegalovirus/HHV-5 protein UL138. Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Subcellular location	Cell membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Secreted. Note: A secreted form is produced through proteolytic processing. Ref.20 Isoform 4: Secreted. Note: Lacks a Golgi-retention motif, is not membrane bound and therefore is secreted. Ref.20
Domain	The domain that induces A-SMASE is probably identical to the death domain. The N-SMASE activation domain (NSD) is both necessary and sufficient for activation of N-SMASE. Both the cytoplasmic membrane-proximal region and the C-terminal region containing the death domain are involved in the interaction with TRPC4AP By similarity.
Post-translational modification	The soluble form is produced from the membrane form by proteolytic processing.
Involvement in disease	Familial hibernian fever (FHF) [MIM:142680]: A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Multiple sclerosis 5 (MS5) [MIM:614810]: A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist. Ref.20
Sequence similarities	Contains 1 death domain. Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction
Cellular component	Cell membrane Golgi apparatus Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Amyloidosis Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement. Source: Reactome cellular response to estradiol stimulus Inferred from electronic annotation. Source: Compara cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB defense response to bacterium Inferred from electronic annotation. Source: Compara diterpenoid metabolic process Inferred from electronic annotation. Source: Compara flavonoid metabolic process Inferred from electronic annotation. Source: Compara inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from mutant phenotype Ref.26. Source: BHF-UCL negative regulation of interleukin-6 production Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern PubMed 12761501. Source: UniProtKB positive regulation of angiogenesis Inferred from electronic annotation. Source: Compara positive regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein import into nucleus, translocation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from mutant phenotype PubMed 21410936. Source: BHF-UCL prostaglandin metabolic process Inferred from electronic annotation. Source: InterPro protein heterooligomerization Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from electronic annotation. Source: Compara response to alkaloid Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara tetrapyrrole metabolic process Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi membrane Inferred from direct assay Ref.20. Source: UniProtKB axon Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay Ref.26. Source: BHF-UCL integral to plasma membrane Traceable author statement Ref.4. Source: ProtInc membrane raft Inferred from direct assay PubMed 17010968. Source: BHF-UCL nucleus Inferred from electronic annotation. Source: Compara protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	tumor necrosis factor-activated receptor activity Traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RIPK1	Q13546	6	EBI-299451,EBI-358507
TNF	P01375	6	EBI-299451,EBI-359977
TRADD	Q15628	10	EBI-299451,EBI-359215

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P19438-1)

Also known as: FL-TNFR1;

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: P19438-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: P19438-4)

Also known as: Delta6-TNFR1;

The sequence of this isoform differs from the canonical sequence as follows:
     184-455: NCKKSLECTK...ALPPAPSLLR → KHHSAVAPGH...LLHCLWEIDT

Note: Disease-associated isoform. Isoform 4 splicing pattern is driven by a variation in the exon 6/intron 6 boundary region that alters exon 6 splicing. Exon 6 skipping introduces a frameshift and the translation of a protein lacking the intracellular, the transmembrane and part of the extracellular domain.

Isoform 3 (identifier: P19438-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-232: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 455

434

Tumor necrosis factor receptor superfamily member 1A, membrane form

PRO_0000034543

Chain

41 – 291

251

Tumor necrosis factor-binding protein 1

PRO_0000034544

Regions

Topological domain

22 – 211

190

Extracellular Potential

Transmembrane

212 – 234

23

Helical; Potential

Topological domain

235 – 455

221

Cytoplasmic Potential

Repeat

43 – 82

40

TNFR-Cys 1

Repeat

83 – 125

43

TNFR-Cys 2

Repeat

126 – 166

41

TNFR-Cys 3

Repeat

167 – 196

30

TNFR-Cys 4

Domain

356 – 441

86

Death

Region

338 – 348

11

N-SMase activation domain (NSD)

Amino acid modifications

Glycosylation

54

1

N-linked (GlcNAc...) Potential

Glycosylation

145

1

N-linked (GlcNAc...) Potential

Glycosylation

151

1

N-linked (GlcNAc...) Potential

Disulfide bond

44 ↔ 58

Disulfide bond

59 ↔ 72

Disulfide bond

62 ↔ 81

Disulfide bond

84 ↔ 99

Disulfide bond

102 ↔ 117

Disulfide bond

105 ↔ 125

Disulfide bond

127 ↔ 143

Disulfide bond

146 ↔ 158

Disulfide bond

149 ↔ 166

Disulfide bond

168 ↔ 179

Disulfide bond

182 ↔ 195

Disulfide bond

185 ↔ 191

Natural variations

Alternative sequence

1 – 232

232

Missing in isoform 3.

VSP_037154

Alternative sequence

1 – 108

108

Missing in isoform 2.

VSP_037153

Alternative sequence

184 – 455

272

NCKKS…PSLLR → KHHSAVAPGHFLWSLPFIPP LHWFNVSLPTVEVQALLHCL WEIDT in isoform 4.

VSP_044949

Natural variant

51

1

H → Q in FHF. Ref.25

VAR_019329

Natural variant

59

1

C → R in FHF. Ref.23

VAR_013410

Natural variant

59

1

C → S in FHF. Ref.24 Ref.25

VAR_019302

Natural variant

62

1

C → G in FHF. Ref.25

VAR_019303

Natural variant

62

1

C → Y in FHF. Ref.23

VAR_013411

Natural variant

75

1

P → L in FHF; may be a polymorphism. Ref.7 Ref.25
Corresponds to variant rs4149637 [ dbSNP | Ensembl ].

VAR_019330

Natural variant

79

1

T → M in FHF. Ref.23

VAR_013412

Natural variant

81

1

C → F in FHF. Ref.23

VAR_013413

Natural variant

99

1

C → S in FHF. Ref.26 Ref.27

VAR_019304

Natural variant

115

1

S → G in FHF. Ref.25

VAR_019331

Natural variant

117

1

C → R in FHF. Ref.23

VAR_013414

Natural variant

117

1

C → Y in FHF. Ref.23

VAR_013415

Natural variant

121

1

R → P in FHF. Ref.26

VAR_019305

Natural variant

121

1

R → Q in FHF; may be a polymorphism. Ref.7 Ref.25
Corresponds to variant rs4149584 [ dbSNP | Ensembl ].

VAR_019332

Natural variant

305

1

P → T.
Corresponds to variant rs1804532 [ dbSNP | Ensembl ].

VAR_011813

Experimental info

Sequence conflict

13

1

L → LILPQ in BAG51763. Ref.8

Sequence conflict

255

1

K → E in BAG37891. Ref.8

Sequence conflict

286

1

S → G in BAG51763. Ref.8

Sequence conflict

394

1

R → L in BAF83777. Ref.8

Sequence conflict

412

1

Missing in AAA36756. Ref.5

Sequence conflict

443 – 446

4

GPAA → APP in AAA36756. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

455

Helix Strand Turn

Details...

Beta strand

48 – 50

3

Beta strand

52 – 54

3

Beta strand

58 – 60

3

Beta strand

66 – 70

5

Beta strand

80 – 83

4

Beta strand

92 – 94

3

Helix

107 – 109

3

Beta strand

112 – 115

4

Beta strand

124 – 126

3

Beta strand

131 – 137

7

Beta strand

140 – 145

6

Beta strand

152 – 156

5

Beta strand

160 – 162

3

Beta strand

165 – 168

4

Beta strand

172 – 175

4

Beta strand

178 – 181

4

Helix

182 – 184

3

Helix

192 – 195

4

Helix

357 – 365

9

Helix

371 – 378

8

Helix

382 – 391

10

Helix

396 – 410

15

Helix

417 – 427

11

Helix

431 – 441

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (FL-TNFR1) [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 4CEFBA96D03B8225	FASTA	455	50,495
	10 20 30 40 50 60 MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI HPQNNSICCT 70 80 90 100 110 120 KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL SCSKCRKEMG QVEISSCTVD 130 140 150 160 170 180 RDTVCGCRKN QYRHYWSENL FQCFNCSLCL NGTVHLSCQE KQNTVCTCHA GFFLRENECV 190 200 210 220 230 240 SCSNCKKSLE CTKLCLPQIE NVKGTEDSGT TVLLPLVIFF GLCLLSLLFI GLMYRYQRWK 250 260 270 280 290 300 SKLYSIVCGK STPEKEGELE GTTTKPLAPN PSFSPTPGFT PTLGFSPVPS STFTSSSTYT 310 320 330 340 350 360 PGDCPNFAAP RREVAPPYQG ADPILATALA SDPIPNPLQK WEDSAHKPQS LDTDDPATLY 370 380 390 400 410 420 AVVENVPPLR WKEFVRRLGL SDHEIDRLEL QNGRCLREAQ YSMLATWRRR TPRREATLEL 430 440 450 LGRVLRDMDL LGCLEDIEEA LCGPAALPPA PSLLR
	Isoform 2 [UniParc]. Checksum: 8C629DAF8D7BA515	FASTA	347	38,651
	10 20 30 40 50 60 MGQVEISSCT VDRDTVCGCR KNQYRHYWSE NLFQCFNCSL CLNGTVHLSC QEKQNTVCTC 70 80 90 100 110 120 HAGFFLRENE CVSCSNCKKS LECTKLCLPQ IENVKGTEDS GTTVLLPLVI FFGLCLLSLL 130 140 150 160 170 180 FIGLMYRYQR WKSKLYSIVC GKSTPEKEGE LEGTTTKPLA PNPSFSPTPG FTPTLGFSPV 190 200 210 220 230 240 PSSTFTSSST YTPGDCPNFA APRREVAPPY QGADPILATA LASDPIPNPL QKWEDSAHKP 250 260 270 280 290 300 QSLDTDDPAT LYAVVENVPP LRWKEFVRRL GLSDHEIDRL ELQNGRCLRE AQYSMLATWR 310 320 330 340 RRTPRREATL ELLGRVLRDM DLLGCLEDIE EALCGPAALP PAPSLLR
	Isoform 4 (Delta6-TNFR1) [UniParc]. Checksum: A67C489AF6DDBFEC	FASTA	228	25,577
	10 20 30 40 50 60 MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI HPQNNSICCT 70 80 90 100 110 120 KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL SCSKCRKEMG QVEISSCTVD 130 140 150 160 170 180 RDTVCGCRKN QYRHYWSENL FQCFNCSLCL NGTVHLSCQE KQNTVCTCHA GFFLRENECV 190 200 210 220 SCSKHHSAVA PGHFLWSLPF IPPLHWFNVS LPTVEVQALL HCLWEIDT
	Isoform 3 [UniParc]. Checksum: 31BDA9ACAEF12FC3	FASTA	223	24,794
	10 20 30 40 50 60 MYRYQRWKSK LYSIVCGKST PEKEGELEGT TTKPLAPNPS FSPTPGFTPT LGFSPVPSST 70 80 90 100 110 120 FTSSSTYTPG DCPNFAAPRR EVAPPYQGAD PILATALASD PIPNPLQKWE DSAHKPQSLD 130 140 150 160 170 180 TDDPATLYAV VENVPPLRWK EFVRRLGLSD HEIDRLELQN GRCLREAQYS MLATWRRRTP 190 200 210 220 RREATLELLG RVLRDMDLLG CLEDIEEALC GPAALPPAPS LLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor." Loetscher H., Pan Y.-C.E., Lahm H.-W., Gentz R., Brockhaus M., Tabuchi H., Lesslauer W. Cell 61:351-359(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning and expression of a receptor for human tumor necrosis factor." Schall T.J., Lewis M., Koller K.J., Lee A., Rice G.C., Wong G.H.W., Getanaga T., Granger G.A., Lentz R., Raab H., Kohr W.J., Goeddel D.V. Cell 61:361-370(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[3]	"Molecular cloning and expression of human and rat tumor necrosis factor receptor chain (p60) and its soluble derivative, tumor necrosis factor-binding protein." Himmler A., Maurer-Fogy I., Kroenke M., Scheurich P., Pfizenmaier K., Lantz M., Olsson I., Hauptmann R., Stratowa C., Adolf G.R. DNA Cell Biol. 9:705-715(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor." Nophar Y., Kemper O., Brakebusch C., Engelmann H., Zwang R., Aderka D., Holtmann H., Wallach D. EMBO J. 9:3269-3278(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 41-53; 110-124 AND 199-201 (ISOFORM 1).
[5]	"Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein." Gray P.W., Barrett K., Chantry D., Turner M., Feldman M. Proc. Natl. Acad. Sci. U.S.A. 87:7380-7384(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[6]	"Structure of the human TNF receptor 1 (p60) gene (TNFR1) and localization to chromosome 12p13." Fuchs P., Strehl S., Dworzak M., Himmler A., Ambros P.F. Genomics 13:219-224(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	SeattleSNPs variation discovery resource Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-75 AND GLN-121.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Neutrophil, Teratocarcinoma, Tongue and Uterus.
[9]	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].
[10]	"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] (ISOFORM 1). Tissue: Muscle.
[11]	"Purification of two types of TNF inhibitors in the urine of the patient with chronic glomerulonephritis." Suzuki J., Tomizawa S., Arai H., Seki Y., Maruyama K., Kuroume T. Nephron 66:386-390(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-57 (ISOFORM 1). Tissue: Urine.
[12]	"Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors." Engelmann H., Novick D., Wallach D. J. Biol. Chem. 265:1531-1536(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-45 (ISOFORM 1).
[13]	"Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis." Zhu N., Khoshnan A., Schneider R., Matsumoto M., Dennert G., Ware C.F., Lai M.M.C. J. Virol. 72:3691-3697(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCV CORE PROTEIN.
[14]	"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation." Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. EMBO J. 18:3044-3053(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RIPK1 AND SQSTM1.
[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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FEM1B.
[16]	"Identification of Grb2 as a novel binding partner of tumor necrosis factor (TNF) receptor I." Hildt E., Oess S. J. Exp. Med. 189:1707-1714(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB2.
[17]	"Prevention of constitutive TNF receptor 1 signaling by silencer of death domains." Jiang Y., Woronicz J.D., Liu W., Goeddel D.V. Science 283:543-546(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BAG4.
[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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BRE.
[19]	"The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb'-encoded modulation of TNF-alpha signaling." Le V.T., Trilling M., Hengel H. J. Virol. 85:13260-13270(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HHV-5 PROTEIN UL138.
[20]	"TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis." Gregory A.P., Dendrou C.A., Attfield K.E., Haghikia A., Xifara D.K., Butter F., Poschmann G., Kaur G., Lambert L., Leach O.A., Promel S., Punwani D., Felce J.H., Davis S.J., Gold R., Nielsen F.C., Siegel R.M., Mann M. , Bell J.I., McVean G., Fugger L. Nature 488:508-511(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MS5, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORM 4).
[21]	"Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation." Banner D.W., D'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C., Loetscher H., Lesslauer W. Cell 73:431-445(1993) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 30-211 IN COMPLEX WITH TNFB.
[22]	"Structures of the extracellular domain of the type I tumor necrosis factor receptor." Naismith J.H., Devine T.Q., Khono H., Sprang S.R. Structure 4:1251-1262(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 41-202.
[23]	"Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes." McDermott M.F., Aksentijevich I., Galon J., McDermott E.M., Ogunkolade B.W., Centola M., Mansfield E., Gadina M., Karenko L., Pettersson T., McCarthy J., Frucht D.M., Aringer M., Torosyan Y., Teppo A.-M., Wilson M., Karaarslan H.M., Wan Y. , Todd I., Wood G., Schlimgen R., Kumarajeewa T.R., Cooper S.M., Vella J.P., Amos C.I., Mulley J., Quane K.A., Molloy M.G., Rnaki A., Powell R.J., Hitman G.A., O'Shea J., Kastner D.L. Cell 97:133-144(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FHF ARG-59; TYR-62; MET-79; PHE-81; ARG-117 AND TYR-117.
[24]	"A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family." Dode C., Papo T., Fieschi C., Pecheux C., Dion E., Picard F., Godeau P., Bienvenu J., Piette J.-C., Delpech M., Grateau G. Arthritis Rheum. 43:1535-1542(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FHF SER-59.
[25]	"The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers." Aksentijevich I., Galon J., Soares M., Mansfield E., Hull K., Oh H.-H., Goldbach-Mansky R., Dean J., Athreya B., Reginato A.J., Henrickson M., Pons-Estel B., O'Shea J.J., Kastner D.L. Am. J. Hum. Genet. 69:301-314(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FHF GLN-51; SER-59; GLY-62; LEU-75; GLY-115 AND GLN-121.
[26]	"Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes." Aganna E., Hammond L., Hawkins P.N., Aldea A., McKee S.A., Ploos van Amstel H.K., Mischung C., Kusuhara K., Saulsbury F.T., Lachmann H.J., Bybee A., McDermott E.M., La Regina M., Arostegui J.I., Campistol J.M., Worthington S., High K.P., Molloy M.G. , Baker N., Bidwell J.L., Castaner J.L., Whiteford M.L., Janssens-Korpola P.L., Manna R., Powell R.J., Woo P., Solis P., Minden K., Frenkel J., Yague J., Mirakian R.M., Hitman G.A., McDermott M.F. Arthritis Rheum. 48:2632-2644(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FHF SER-99 AND PRO-121.
[27]	"Tumour necrosis factor receptor-associated periodic syndrome with a novel mutation in the TNFRSF1A gene in a Japanese family." Kusuhara K., Nomura A., Nakao F., Hara T. Eur. J. Pediatr. 163:30-32(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FHF SER-99.
+	Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M58286 mRNA. Translation: AAA36753.1.
M33294 mRNA. Translation: AAA03210.1.
M63121 mRNA. Translation: AAA36754.1.
X55313 mRNA. Translation: CAA39021.1.
M60275 mRNA. Translation: AAA36756.1.
M75866, M75864, M75865 Genomic DNA. Translation: AAA61201.1.
AY131997 Genomic DNA. Translation: AAM77802.1.
AK056611 mRNA. Translation: BAG51763.1.
AK291088 mRNA. Translation: BAF83777.1.
AK298729 mRNA. Translation: BAG60879.1.
AK304517 mRNA. Translation: BAG65321.1.
AK315509 mRNA. Translation: BAG37891.1.
CH471116 Genomic DNA. Translation: EAW88805.1.
CH471116 Genomic DNA. Translation: EAW88806.1.
BC010140 mRNA. Translation: AAH10140.1.

IPI

IPI00018880.
IPI00795875.
IPI00929211.

PIR

GQHUT1. A38208.

RefSeq

NP_001056.1. NM_001065.3.

UniGene

Hs.279594.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EXT	X-ray	1.85	A/B	41-201	[»]
1FT4	X-ray	2.90	A/B	41-201	[»]
1ICH	NMR	-	A	345-455	[»]
1NCF	X-ray	2.25	A/B	41-201	[»]
1TNR	X-ray	2.85	R	44-182	[»]

ProteinModelPortal

P19438.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-407N.

IntAct

P19438. 16 interactions.

MINT

MINT-135026.

STRING

9606.ENSP00000162749.

PTM databases

PhosphoSite

P19438.

Polymorphism databases

DMDM

135959.

Proteomic databases

PaxDb

P19438.

PRIDE

P19438.

Protocols and materials databases

DNASU

7132.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000162749; ENSP00000162749; ENSG00000067182.

GeneID

7132.

KEGG

hsa:7132.

UCSC

uc001qnt.3. human.
uc010sey.2. human.

Organism-specific databases

CTD

7132.

GeneCards

GC12M006412.

HGNC

HGNC:11916. TNFRSF1A.

HPA

CAB010309.
HPA004102.

MIM

142680. phenotype.
191190. gene.
614810. phenotype.

neXtProt

NX_P19438.

Orphanet

32960. TRAPS syndrome.

PharmGKB

PA36609.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39168.

HOVERGEN

HBG058842.

InParanoid

P19438.

KO

K03158.

OMA

LCPQGKY.

OrthoDB

EOG4Z8XWT.

PhylomeDB

P19438.

Enzyme and pathway databases

Pathway_Interaction_DB

nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
caspase_pathway. Caspase cascade in apoptosis.
ceramidepathway. Ceramide signaling pathway.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P19438.

Bgee

P19438.

CleanEx

HS_TNFRSF1A.

Genevestigator

P19438.

GermOnline

ENSG00000067182. Homo sapiens.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.

InterPro

IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020419. TNFR_1A.
[Graphical view]

Pfam

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

PRINTS

PR01918. TNFACTORR1A.

SMART

SM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 3 hits.
PS50050. TNFR_NGFR_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P19438.

ChEMBL

CHEMBL3378.

ChiTaRS

TNFRSF1A. human.

EvolutionaryTrace

P19438.

GenomeRNAi

7132.

NextBio

27905.

PMAP-CutDB

P19438.

SOURCE

Search...

Entry information

Entry name

TNR1A_HUMAN

Accession

Primary (citable) accession number: P19438
Secondary accession number(s): A8K4X3 , B2RDE4, B3KPQ1, B4DQB7, B4E309, D3DUR1, Q9UCA4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 173 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.