Tumor necrosis factor receptor 2

TNFRSF1B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CA9, 3ALQ
Identifiers
Aliases	TNFRSF1B, CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B, TNFR2, TNFR80, p75, p75TNFR, tumor necrosis factor receptor superfamily member 1B, TNF receptor superfamily member 1B
External IDs	OMIM: 191191; MGI: 1314883; HomoloGene: 829; GeneCards: TNFRSF1B; OMA:TNFRSF1B - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p36.22 Start 12,166,991 bp End 12,209,228 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4 E1|4 78.17 cM Start 144,940,033 bp End 144,973,440 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte blood spleen appendix tendon of biceps brachii right lung lymph node subcutaneous adipose tissue periodontal fiber Top expressed in decidua stroma of bone marrow aortic valve granulocyte gastrula blood mesenteric lymph nodes spleen ascending aorta internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding ubiquitin protein ligase binding tumor necrosis factor-activated receptor activity tumor necrosis factor binding Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane varicosity extracellular region axon soma perinuclear region of cytoplasm membrane raft nucleus specific granule membrane tumor necrosis factor receptor superfamily complex Biological process extrinsic apoptotic signaling pathway RNA destabilization cellular response to growth factor stimulus positive regulation of membrane protein ectodomain proteolysis ageing multicellular organism development cell surface receptor signaling pathway response to lipopolysaccharide regulation of cell population proliferation immune response intrinsic apoptotic signaling pathway in response to DNA damage apoptotic signaling pathway inflammatory response cellular response to lipopolysaccharide negative regulation of inflammatory response apoptotic process tumor necrosis factor-mediated signaling pathway neutrophil degranulation negative regulation of cysteine-type endopeptidase activity involved in apoptotic process cytokine-mediated signaling pathway aortic valve development pulmonary valve development negative regulation of extracellular matrix constituent secretion negative regulation of cardiac muscle hypertrophy positive regulation of apoptotic process involved in morphogenesis regulation of T cell cytokine production regulation of myelination regulation of T cell proliferation regulation of neuroinflammatory response cellular response to tumor necrosis factor positive regulation of myelination positive regulation of oligodendrocyte differentiation negative regulation of cell death negative regulation of neuroinflammatory response glial cell-neuron signaling negative regulation of neuron death regulation of RNA biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7133 21938 Ensembl ENSG00000028137 ENSMUSG00000028599 UniProt P20333 P25119 RefSeq (mRNA) NM_001066 NM_011610 RefSeq (protein) NP_001057 NP_035740 Location (UCSC) Chr 1: 12.17 – 12.21 Mb Chr 4: 144.94 – 144.97 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).

Function

The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1A. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2 (TRAF2), which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways.

Clinical significance

CNS

At least partly because TNFR2 has no intracellular death domain, TNFR2 is neuroprotective.

Patients with schizophrenia have increased levels of soluble tumor necrosis factor receptor 2 (sTNFR2).

Cancer

Targeting of TNRF2 in tumor cells is associated with increased tumor cell death and decreased progression of tumor cell growth.

Increased expression of TNFR2 is found in breast cancer, cervical cancer, colon cancer, and renal cancer. A link between the expression of TNRF2 in tumor cells and late-stage cancer has been discovered. TNFR2 plays a significant role in tumor cell growth as it has been found that the loss of TNFR2 expression is linked with increased death of associated tumor cells and a significant standstill of further growth. There is therapeutic potential in the targeting of TNFR2 for cancer treatments through TNFR2 inhibition.

Systemic Lupus Erythematous (SLE)

A small scale study of 289 Japanese patients suggested a minor increased predisposition from an amino acid substitution of the 196 allele at exon 6. Genomic testing of 81 SLE patients and 207 healthy patients in a Japanese study showed 37% of SLE patients had a polymorphism on position 196 of exon 6 compared to 18.8% of healthy patients. The TNFR2 196R allele polymorphism suggests that even one 196R allele results in increased risk for SLE.

Interactions

TNFRSF1B has been shown to interact with:

• TRAF2, and
• TTRAP.

Further reading

• Kollias G, Kontoyiannis D (2003). "Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments". Cytokine & Growth Factor Reviews. 13 (4–5): 315–321. doi:10.1016/S1359-6101(02)00019-9. PMID 12220546.
• Holtmann MH, Schuchmann M, Zeller G, Galle PR, Neurath MF (2003). "The emerging distinct role of TNF-receptor 2 (p80) signaling in chronic inflammatory disorders". Archivum Immunologiae et Therapiae Experimentalis. 50 (4): 279–288. PMID 12371624.
• Horiuchi T, Kiyohara C, Tsukamoto H, Sawabe T, Furugo I, Yoshizawa S, et al. (March 2007). "A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case-control study and a meta-analysis". Annals of the Rheumatic Diseases. 66 (3): 320–324. doi:10.1136/ard.2006.058917. PMC 1856025. PMID 17028114.{{cite journal}}: CS1 maint: overridden setting (link)

External links

• CD120b Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)