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P19438 (TNR1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 184. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:TNFRSF1A
Synonyms:TNFAR, TNFR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length455 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21

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.22

Isoform 4: Secreted. Note: Lacks a Golgi-retention motif, is not membrane bound and therefore is secreted. Ref.22

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.25 Ref.26 Ref.27 Ref.28 Ref.29

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 sheath, 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.22

Sequence similarities

Contains 1 death domain.

Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
   Biological processApoptosis
Host-virus interaction
   Cellular componentCell membrane
Golgi apparatus
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAmyloidosis
Disease mutation
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cellular response to estradiol stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

cytokine-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

defense response to bacterium

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Traceable author statement PubMed 8612133. Source: BHF-UCL

inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from mutant phenotype Ref.28. Source: BHF-UCL

negative regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern PubMed 12761501. Source: UniProtKB

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

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: Ensembl

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: Ensembl

response to alkaloid

Inferred from electronic annotation. Source: Ensembl

response to amino acid

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

tetrapyrrole metabolic process

Inferred from electronic annotation. Source: Ensembl

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi membrane

Inferred from direct assay Ref.22. Source: UniProtKB

axon

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from electronic annotation. Source: Ensembl

extracellular region

Non-traceable author statement PubMed 12189246. Source: UniProtKB

extracellular space

Inferred from direct assay Ref.28. Source: BHF-UCL

integral component of 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: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functiontumor necrosis factor-activated receptor activity

Traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 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.
Isoform 5 (identifier: P19438-5)

The sequence of this isoform differs from the canonical sequence as follows:
     184-218: NCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVI → KVLLCRPGWNAVARSRLTATSASQIQAILLLQPPK
     219-455: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Chain22 – 455434Tumor necrosis factor receptor superfamily member 1A, membrane form
PRO_0000034543
Chain41 – 201161Tumor necrosis factor-binding protein 1
PRO_0000034544

Regions

Topological domain22 – 211190Extracellular Potential
Transmembrane212 – 23423Helical; Potential
Topological domain235 – 455221Cytoplasmic Potential
Repeat43 – 8240TNFR-Cys 1
Repeat83 – 12543TNFR-Cys 2
Repeat126 – 16641TNFR-Cys 3
Repeat167 – 19630TNFR-Cys 4
Domain356 – 44186Death
Region338 – 34811N-SMase activation domain (NSD)

Amino acid modifications

Glycosylation541N-linked (GlcNAc...) Potential
Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Disulfide bond44 ↔ 58
Disulfide bond59 ↔ 72
Disulfide bond62 ↔ 81
Disulfide bond84 ↔ 99
Disulfide bond102 ↔ 117
Disulfide bond105 ↔ 125
Disulfide bond127 ↔ 143
Disulfide bond146 ↔ 158
Disulfide bond149 ↔ 166
Disulfide bond168 ↔ 179
Disulfide bond182 ↔ 195
Disulfide bond185 ↔ 191

Natural variations

Alternative sequence1 – 232232Missing in isoform 3.
VSP_037154
Alternative sequence1 – 108108Missing in isoform 2.
VSP_037153
Alternative sequence184 – 455272NCKKS…PSLLR → KHHSAVAPGHFLWSLPFIPP LHWFNVSLPTVEVQALLHCL WEIDT in isoform 4.
VSP_044949
Alternative sequence184 – 21835NCKKS…LPLVI → KVLLCRPGWNAVARSRLTAT SASQIQAILLLQPPK in isoform 5.
VSP_047613
Alternative sequence219 – 455237Missing in isoform 5.
VSP_047614
Natural variant511H → Q in FHF. Ref.27
VAR_019329
Natural variant591C → R in FHF. Ref.25
VAR_013410
Natural variant591C → S in FHF. Ref.26 Ref.27
VAR_019302
Natural variant621C → G in FHF. Ref.27
VAR_019303
Natural variant621C → Y in FHF. Ref.25
VAR_013411
Natural variant751P → L in FHF; may be a polymorphism. Ref.7 Ref.27
Corresponds to variant rs4149637 [ dbSNP | Ensembl ].
VAR_019330
Natural variant791T → M in FHF. Ref.25
VAR_013412
Natural variant811C → F in FHF. Ref.25
VAR_013413
Natural variant991C → S in FHF. Ref.28 Ref.29
VAR_019304
Natural variant1151S → G in FHF. Ref.27
VAR_019331
Natural variant1171C → R in FHF. Ref.25
VAR_013414
Natural variant1171C → Y in FHF. Ref.25
VAR_013415
Natural variant1211R → P in FHF. Ref.28
Corresponds to variant rs4149584 [ dbSNP | Ensembl ].
VAR_019305
Natural variant1211R → Q in FHF; may be a polymorphism. Ref.7 Ref.27
Corresponds to variant rs4149584 [ dbSNP | Ensembl ].
VAR_019332
Natural variant3051P → T.
Corresponds to variant rs1804532 [ dbSNP | Ensembl ].
VAR_011813

Experimental info

Sequence conflict131L → LILPQ in BAG51763. Ref.8
Sequence conflict2551K → E in BAG37891. Ref.8
Sequence conflict2861S → G in BAG51763. Ref.8
Sequence conflict3941R → L in BAF83777. Ref.8
Sequence conflict4121Missing in AAA36756. Ref.5
Sequence conflict443 – 4464GPAA → APP in AAA36756. Ref.5

Secondary structure

................................................ 455
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FL-TNFR1) [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: 4CEFBA96D03B8225

FASTA45550,495
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 8C629DAF8D7BA515
Show »

FASTA34738,651
Isoform 4 (Delta6-TNFR1) [UniParc].

Checksum: A67C489AF6DDBFEC
Show »

FASTA22825,577
Isoform 3 [UniParc].

Checksum: 31BDA9ACAEF12FC3
Show »

FASTA22324,794
Isoform 5 [UniParc].

Checksum: FBDD906CEF26F405
Show »

FASTA21824,194

References

« Hide '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. expand/collapse author list , 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]"Discovery of novel human transcript variants by analysis of intronic single-block EST with polyadenylation site."
Wang P., Yu P., Gao P., Shi T., Ma D.
BMC Genomics 10:518-518(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
[10]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]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. expand/collapse author list , 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].
[12]"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.
[13]"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.
[14]"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).
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.
[20]"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.
[21]"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.
[22]"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. expand/collapse author list , 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).
[23]"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.
[24]"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.
[25]"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. expand/collapse author list , 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.
[26]"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.
[27]"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.
[28]"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. expand/collapse author list , 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.
[29]"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.
EU927389 mRNA. Translation: ACH57451.1.
AC006057 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88805.1.
CH471116 Genomic DNA. Translation: EAW88806.1.
BC010140 mRNA. Translation: AAH10140.1.
PIRGQHUT1. A38208.
RefSeqNP_001056.1. NM_001065.3.
UniGeneHs.279594.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EXTX-ray1.85A/B41-201[»]
1FT4X-ray2.90A/B41-201[»]
1ICHNMR-A345-455[»]
1NCFX-ray2.25A/B41-201[»]
1TNRX-ray2.85R44-182[»]
ProteinModelPortalP19438.
SMRP19438. Positions 42-201, 356-442.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112986. 92 interactions.
DIPDIP-407N.
IntActP19438. 25 interactions.
MINTMINT-135026.
STRING9606.ENSP00000162749.

Chemistry

BindingDBP19438.
ChEMBLCHEMBL3378.
GuidetoPHARMACOLOGY1870.

PTM databases

PhosphoSiteP19438.

Polymorphism databases

DMDM135959.

Proteomic databases

PaxDbP19438.
PRIDEP19438.

Protocols and materials databases

DNASU7132.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000162749; ENSP00000162749; ENSG00000067182. [P19438-1]
ENST00000366159; ENSP00000380389; ENSG00000067182. [P19438-5]
GeneID7132.
KEGGhsa:7132.
UCSCuc001qnt.3. human. [P19438-1]
uc010sey.2. human. [P19438-3]

Organism-specific databases

CTD7132.
GeneCardsGC12M006412.
HGNCHGNC:11916. TNFRSF1A.
HPACAB010309.
HPA004102.
MIM142680. phenotype.
191190. gene.
614810. phenotype.
neXtProtNX_P19438.
Orphanet329967. Intermittent hydrarthrosis.
802. Multiple sclerosis.
32960. TRAPS syndrome.
PharmGKBPA36609.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39168.
HOVERGENHBG058842.
InParanoidP19438.
KOK03158.
OMACLREAHY.
PhylomeDBP19438.
TreeFamTF333916.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressP19438.
BgeeP19438.
CleanExHS_TNFRSF1A.
GenevestigatorP19438.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020419. TNFR_1A.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSPR01918. TNFACTORR1A.
SMARTSM00005. DEATH. 1 hit.
SM00208. TNFR. 4 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS50017. DEATH_DOMAIN. 1 hit.
PS00652. TNFR_NGFR_1. 3 hits.
PS50050. TNFR_NGFR_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNFRSF1A. human.
EvolutionaryTraceP19438.
GeneWikiTNFRSF1A.
GenomeRNAi7132.
NextBio27905.
PMAP-CutDBP19438.
PROP19438.
SOURCESearch...

Entry information

Entry nameTNR1A_HUMAN
AccessionPrimary (citable) accession number: P19438
Secondary accession number(s): A8K4X3 expand/collapse secondary AC list , B2RDE4, B3KPQ1, B4DQB7, B4E309, B5M0B5, D3DUR1, Q9UCA4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 184 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries