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Protein

Tumor necrosis factor receptor superfamily member 1B

Gene

TNFRSF1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity.1 Publication

GO - Molecular functioni

  • tumor necrosis factor-activated receptor activity Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-5669034 TNFs bind their physiological receptors
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695 Neutrophil degranulation
SIGNORiP20333

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 1B
Alternative name(s):
Tumor necrosis factor receptor 2
Short name:
TNF-R2
Tumor necrosis factor receptor type II
Short name:
TNF-RII
Short name:
TNFR-II
p75
p80 TNF-alpha receptor
CD_antigen: CD120b
INN: Etanercept
Cleaved into the following 2 chains:
Gene namesi
Name:TNFRSF1B
Synonyms:TNFBR, TNFR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000028137.16
HGNCiHGNC:11917 TNFRSF1B
MIMi191191 gene
neXtProtiNX_P20333

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 257ExtracellularSequence analysisAdd BLAST235
Transmembranei258 – 287HelicalSequence analysisAdd BLAST30
Topological domaini288 – 461CytoplasmicSequence analysisAdd BLAST174

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Pharmaceutical usei

Available under the name Enbrel (Immunex and Wyeth-Ayerst). Used to treat moderate to severe rheumatoid arthritis (RA). Enbrel consist of the extracellular ligand-binding portion of TNFRSF1B linked to an immunoglobulin Fc chain. It binds to TNF-alpha and blocks its interactions with receptors.

Organism-specific databases

DisGeNETi7133
MalaCardsiTNFRSF1B
OpenTargetsiENSG00000028137
PharmGKBiPA36610

Chemistry databases

ChEMBLiCHEMBL1250356
DrugBankiDB00005 Etanercept

Polymorphism and mutation databases

BioMutaiTNFRSF1B
DMDMi21264534

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000003454823 – 461Tumor necrosis factor receptor superfamily member 1b, membrane formAdd BLAST439
ChainiPRO_000003454927 – ?Tumor necrosis factor-binding protein 2

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi30O-linked (GalNAc...) threonine1 Publication1
Disulfide bondi40 ↔ 53PROSITE-ProRule annotation
Disulfide bondi54 ↔ 67PROSITE-ProRule annotation
Disulfide bondi57 ↔ 75PROSITE-ProRule annotation
Disulfide bondi78 ↔ 93PROSITE-ProRule annotation
Disulfide bondi96 ↔ 110PROSITE-ProRule annotation
Disulfide bondi100 ↔ 118PROSITE-ProRule annotation
Disulfide bondi120 ↔ 126PROSITE-ProRule annotation
Disulfide bondi134 ↔ 143PROSITE-ProRule annotation
Disulfide bondi137 ↔ 161PROSITE-ProRule annotation
Disulfide bondi164 ↔ 179PROSITE-ProRule annotation
Glycosylationi171N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi193N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi206O-linked (GalNAc...) threonine1 Publication1
Glycosylationi221O-linked (GalNAc...) serine1 Publication1
Glycosylationi222O-linked (GalNAc...) threonine1 Publication1
Modified residuei330PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated; mainly on serine residues and with a very low level on threonine residues.
A soluble form (tumor necrosis factor binding protein 2) is produced from the membrane form by proteolytic processing.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP20333
PeptideAtlasiP20333
PRIDEiP20333
ProteomicsDBi53746
53747 [P20333-2]

PTM databases

GlyConnecti705
iPTMnetiP20333
PhosphoSitePlusiP20333

Miscellaneous databases

PMAP-CutDBiP20333

Expressioni

Gene expression databases

BgeeiENSG00000028137 Expressed in 210 organ(s), highest expression level in blood
CleanExiHS_TNFRSF1B
ExpressionAtlasiP20333 baseline and differential
GenevisibleiP20333 HS

Organism-specific databases

HPAiHPA004796

Interactioni

Subunit structurei

Binds to TRAF2 (PubMed:8069916, PubMed:10206649). Interacts with BMX (PubMed:12370298). Interacts (activated form) with XPNPEP3 (PubMed:25609706).4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112987, 26 interactors
CORUMiP20333
DIPiDIP-78N
ELMiP20333
IntActiP20333, 12 interactors
MINTiP20333
STRINGi9606.ENSP00000365435

Structurei

Secondary structure

1461
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP20333
SMRiP20333
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20333

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati39 – 76TNFR-Cys 1Add BLAST38
Repeati77 – 118TNFR-Cys 2Add BLAST42
Repeati119 – 162TNFR-Cys 3Add BLAST44
Repeati163 – 201TNFR-Cys 4Add BLAST39

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IJ06 Eukaryota
ENOG410YPQW LUCA
GeneTreeiENSGT00760000119204
HOGENOMiHOG000132845
HOVERGENiHBG054237
InParanoidiP20333
KOiK05141
OMAiNCVIMTQ
OrthoDBiEOG091G03XW
PhylomeDBiP20333
TreeFamiTF331157

Family and domain databases

CDDicd10577 TNFRSF1B, 1 hit
InterProiView protein in InterPro
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR020411 TNFR_1B
IPR033996 TNFRSF1B_N
PfamiView protein in Pfam
PF00020 TNFR_c6, 3 hits
PRINTSiPR01919 TNFACTORR1B
SMARTiView protein in SMART
SM00208 TNFR, 4 hits
PROSITEiView protein in PROSITE
PS00652 TNFR_NGFR_1, 2 hits
PS50050 TNFR_NGFR_2, 3 hits

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P20333-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAPVAVWAAL AVGLELWAAA HALPAQVAFT PYAPEPGSTC RLREYYDQTA
60 70 80 90 100
QMCCSKCSPG QHAKVFCTKT SDTVCDSCED STYTQLWNWV PECLSCGSRC
110 120 130 140 150
SSDQVETQAC TREQNRICTC RPGWYCALSK QEGCRLCAPL RKCRPGFGVA
160 170 180 190 200
RPGTETSDVV CKPCAPGTFS NTTSSTDICR PHQICNVVAI PGNASMDAVC
210 220 230 240 250
TSTSPTRSMA PGAVHLPQPV STRSQHTQPT PEPSTAPSTS FLLPMGPSPP
260 270 280 290 300
AEGSTGDFAL PVGLIVGVTA LGLLIIGVVN CVIMTQVKKK PLCLQREAKV
310 320 330 340 350
PHLPADKARG TQGPEQQHLL ITAPSSSSSS LESSASALDR RAPTRNQPQA
360 370 380 390 400
PGVEASGAGE ARASTGSSDS SPGGHGTQVN VTCIVNVCSS SDHSSQCSSQ
410 420 430 440 450
ASSTMGDTDS SPSESPKDEQ VPFSKEECAF RSQLETPETL LGSTEEKPLP
460
LGVPDAGMKP S
Length:461
Mass (Da):48,291
Last modified:May 27, 2002 - v3
Checksum:i603D0AE1CD69ACBF
GO
Isoform 2 (identifier: P20333-2) [UniParc]FASTAAdd to basket
Also known as: DS-TNFR2(Delta7,8), sTNFR2

The sequence of this isoform differs from the canonical sequence as follows:
     263-268: GLIVGV → ASLACR
     269-461: Missing.

Show »
Length:268
Mass (Da):28,461
Checksum:i51A97BA5222FA444
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5A977B5A977_HUMAN
Soluble TNFR1B variant 1
TNFRSF1B TNFR1B
155Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti35 – 37EPG → APT AA sequence (PubMed:8015639).Curated3
Sequence conflicti98S → P in AAN72434 (PubMed:14688072).Curated1
Sequence conflicti102S → P in AAN72434 (PubMed:14688072).Curated1
Sequence conflicti141R → P in AAA63262 (PubMed:2166946).Curated1
Sequence conflicti363A → T in AAA63262 (PubMed:2166946).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017176187V → M1 PublicationCorresponds to variant dbSNP:rs2228494Ensembl.1
Natural variantiVAR_015434196M → R Frequent polymorphism; seems to be associated with hyperandrogenism, polycystic ovary syndrome (PCOS) and systemic lupus erythematosus. 7 PublicationsCorresponds to variant dbSNP:rs1061622Ensembl.1
Natural variantiVAR_015435232E → K4 PublicationsCorresponds to variant dbSNP:rs5746026Ensembl.1
Natural variantiVAR_017177236A → T1 PublicationCorresponds to variant dbSNP:rs5746027Ensembl.1
Natural variantiVAR_017178264L → P1 PublicationCorresponds to variant dbSNP:rs2229700Ensembl.1
Natural variantiVAR_017179269T → P1 PublicationCorresponds to variant dbSNP:rs17879042Ensembl.1
Natural variantiVAR_017180295Q → R1 PublicationCorresponds to variant dbSNP:rs5746032Ensembl.1
Natural variantiVAR_017181301P → R1 PublicationCorresponds to variant dbSNP:rs17883432Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011826263 – 268GLIVGV → ASLACR in isoform 2. 1 Publication6
Alternative sequenceiVSP_011827269 – 461Missing in isoform 2. 1 PublicationAdd BLAST193

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55994 mRNA Translation: AAA36755.1
M32315 mRNA Translation: AAA59929.1
U52165
, U52156, U52157, U52158, U52159, U52160, U52161, U52162, U52163, U52164 Genomic DNA Translation: AAC50622.1
AY148473 mRNA Translation: AAN72434.1
BT019927 mRNA Translation: AAV38730.1
AY264804 Genomic DNA Translation: AAO89076.1
AY342040 Genomic DNA Translation: AAP88939.1
AL031276 Genomic DNA No translation available.
AL357835 Genomic DNA No translation available.
CH471130 Genomic DNA Translation: EAW71733.1
BC052977 mRNA Translation: AAH52977.1
S63368 mRNA Translation: AAB19824.2
M35857 mRNA Translation: AAA63262.1
AB030950 Genomic DNA Translation: BAA89053.1
CCDSiCCDS145.1 [P20333-1]
PIRiA35356
RefSeqiNP_001057.1, NM_001066.2 [P20333-1]
UniGeneiHs.256278

Genome annotation databases

EnsembliENST00000376259; ENSP00000365435; ENSG00000028137 [P20333-1]
GeneIDi7133
KEGGihsa:7133
UCSCiuc001att.4 human [P20333-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs
NIEHS-SNPs
Enbrel

Clinical information on Enbrel

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55994 mRNA Translation: AAA36755.1
M32315 mRNA Translation: AAA59929.1
U52165
, U52156, U52157, U52158, U52159, U52160, U52161, U52162, U52163, U52164 Genomic DNA Translation: AAC50622.1
AY148473 mRNA Translation: AAN72434.1
BT019927 mRNA Translation: AAV38730.1
AY264804 Genomic DNA Translation: AAO89076.1
AY342040 Genomic DNA Translation: AAP88939.1
AL031276 Genomic DNA No translation available.
AL357835 Genomic DNA No translation available.
CH471130 Genomic DNA Translation: EAW71733.1
BC052977 mRNA Translation: AAH52977.1
S63368 mRNA Translation: AAB19824.2
M35857 mRNA Translation: AAA63262.1
AB030950 Genomic DNA Translation: BAA89053.1
CCDSiCCDS145.1 [P20333-1]
PIRiA35356
RefSeqiNP_001057.1, NM_001066.2 [P20333-1]
UniGeneiHs.256278

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CA9X-ray2.30G/H420-428[»]
3ALQX-ray3.00R/S/T/U/V/W33-205[»]
ProteinModelPortaliP20333
SMRiP20333
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112987, 26 interactors
CORUMiP20333
DIPiDIP-78N
ELMiP20333
IntActiP20333, 12 interactors
MINTiP20333
STRINGi9606.ENSP00000365435

Chemistry databases

ChEMBLiCHEMBL1250356
DrugBankiDB00005 Etanercept

PTM databases

GlyConnecti705
iPTMnetiP20333
PhosphoSitePlusiP20333

Polymorphism and mutation databases

BioMutaiTNFRSF1B
DMDMi21264534

Proteomic databases

PaxDbiP20333
PeptideAtlasiP20333
PRIDEiP20333
ProteomicsDBi53746
53747 [P20333-2]

Protocols and materials databases

DNASUi7133
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376259; ENSP00000365435; ENSG00000028137 [P20333-1]
GeneIDi7133
KEGGihsa:7133
UCSCiuc001att.4 human [P20333-1]

Organism-specific databases

CTDi7133
DisGeNETi7133
EuPathDBiHostDB:ENSG00000028137.16
GeneCardsiTNFRSF1B
HGNCiHGNC:11917 TNFRSF1B
HPAiHPA004796
MalaCardsiTNFRSF1B
MIMi191191 gene
neXtProtiNX_P20333
OpenTargetsiENSG00000028137
PharmGKBiPA36610
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJ06 Eukaryota
ENOG410YPQW LUCA
GeneTreeiENSGT00760000119204
HOGENOMiHOG000132845
HOVERGENiHBG054237
InParanoidiP20333
KOiK05141
OMAiNCVIMTQ
OrthoDBiEOG091G03XW
PhylomeDBiP20333
TreeFamiTF331157

Enzyme and pathway databases

ReactomeiR-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-5669034 TNFs bind their physiological receptors
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695 Neutrophil degranulation
SIGNORiP20333

Miscellaneous databases

ChiTaRSiTNFRSF1B human
EvolutionaryTraceiP20333
GeneWikiiTNFRSF1B
GenomeRNAii7133
PMAP-CutDBiP20333
PROiPR:P20333
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000028137 Expressed in 210 organ(s), highest expression level in blood
CleanExiHS_TNFRSF1B
ExpressionAtlasiP20333 baseline and differential
GenevisibleiP20333 HS

Family and domain databases

CDDicd10577 TNFRSF1B, 1 hit
InterProiView protein in InterPro
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR020411 TNFR_1B
IPR033996 TNFRSF1B_N
PfamiView protein in Pfam
PF00020 TNFR_c6, 3 hits
PRINTSiPR01919 TNFACTORR1B
SMARTiView protein in SMART
SM00208 TNFR, 4 hits
PROSITEiView protein in PROSITE
PS00652 TNFR_NGFR_1, 2 hits
PS50050 TNFR_NGFR_2, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTNR1B_HUMAN
AccessioniPrimary (citable) accession number: P20333
Secondary accession number(s): B1AJZ3
, Q16042, Q6YI29, Q9UIH1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: May 27, 2002
Last modified: September 12, 2018
This is version 207 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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