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TNF (tumor necrosis factor (TNF superfamily, member 2))

Identity

Other namesTNFa (Tumor Necrosis Factor-a)
Cachectin
TNF superfamily member 2
DIF
HGNC (Hugo) TNF
LocusID (NCBI) 7124
Location 6p21.33
Location_base_pair Starts at 31543344 and ends at 31546112 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description The human TNFa gene has 4 exons spanning 2,762bp on the region of chromosome 6p21.3. The expression of TNFa gene generates a TNFa mRNA with size of 1,669nt. The 3'-UTR region of TNFa mRNA contains a cluster of "AUUUA" elements that can be seen among many mRNAs with a short half-life, (AUUAUUUAUUAUUUAUUUAUUUAUUUAUUUAUUUA). A multiple NF-kB binding elements have been identified in the promoter region of TNFa gene.

Protein

 
  The phylogenetic tree of TNF superfamily members.
Description The human TNFa protein contains 233 amino acids with a predicated molecular weight of 25.6 kDa. The TNFa is produced initially in a membrane-associated form, which is then subjected to enzymatic remove of the N-terminal 76 amino acids by TACE/ADAM17, a TNFa converting enzyme, to generate the soluble 17kDa TNFa molecule that forms homotrimer. TNFa is the first prototypic member identified in the TNF superfamily (TNFSF, Fig.1 and Table 1). The human TNF superfamily currently has 19 well-characterized members. Other members, such as TNFSF19, TNFSF21, and TNFSF22 have not been well-established. Although each member has its own receptor preference, a functional overlapping, such as induction of apoptosis and NF-kB activation, has been observed among the majority of these members. In addition, as indicated in the phylogenetic tree in Figure 1, all of these members exhibit an evolutional conservation in their amino acid sequences, many of which show characteristics of type II membrane proteins. These features of TNF superfamily suggest that the members in this family may derived from the same ancestral gene. Several members contain a C-terminal conserved domain, named the TNF-homology domain that shares 20-30% of sequence identity. Except TNFSF1 (lymphotoxin a) and TNFSF3 (lymphotoxin b) that can form either homotrimer or heterotrimer, the active form of other members in this family is homotrimer.
Expression TNFa is expressed virtually in every type of cells in response to inflammatory signals.
Localisation membrane (type II membrane protein), extracellular soluble form, blood stream, and biological fluids.
Function The most abundant cellular sources of TNFa are macrophage and monocyte. In response to inflammatory stimulation, macrophage or monocyte secretes TNFa that can induce apoptotic or necrotic cell death of certain tumor cell lines. In addition, TNFa is also capable of inducing cell proliferation and differentiation in many types of cells under certain circumstances. TNFa can be a pyrogen that causes fever by its direct action or by stimulation of interleukin 1 secretion. Sustained generation of TNFa in a variety of human diseases, especially cancer and severe infection, can cause cachexia-like syndrome. The increased expression of TNFa in adipose tissue was considered to be responsible for the development of obesity or diabetes due to the induction of insulin resistance by TNFa. All of above functional characteristics of TNFa are executed through specific members of the TNF receptor (TNFR) superfamily, mainly TNFR1, the primary receptor for soluble TNFa, and TNFR2, the predominant receptor for membrane-associated TNFa. These receptors trigger several intracellular signaling pathways, most importantly, the IkB kinase (IKK) and mitogen-activated protein kinase (MAPK) cascades, which govern gene expression through NF-kBNF-kB and AP-1 transcription factors, respectively.

Implicated in

Disease Arthritis, asthma, cancer, cardiovascular disorders, diabetes, HIV infection and AIDS, inflammatory bowel disease, lung fibrosis, obesity, septic shock, etc..
Cytogenetics Mutations or polymorphisms in the promoter or coding region of TNFa gene have been associated with asthma, celiac, septic shock susceptibility, silicosis, Psoriasis, GVHD, Leprosy, etc..
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias t0817q24q22ID1494 t1119q23p13ID1540

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors ProstateOverviewID5041

External links

Nomenclature
HGNC (Hugo)TNF   11892
Cards
AtlasTNFaID319
Entrez_Gene (NCBI)TNF  7124  tumor necrosis factor
GeneCards (Weizmann)TNF
Ensembl (Hinxton)ENSG00000232810 [Gene_View]  chr6:31543344-31546112 [Contig_View]  TNF [Vega]
ICGC DataPortalENSG00000232810
cBioPortalTNF
AceView (NCBI)TNF
Genatlas (Paris)TNF
WikiGenes7124
SOURCE (Princeton)NM_000594
Genomic and cartography
GoldenPath (UCSC)TNF  -  6p21.33   chr6:31543344-31546112 +  6p21.3   [Description]    (hg19-Feb_2009)
EnsemblTNF - 6p21.3 [CytoView]
Mapping of homologs : NCBITNF [Mapview]
OMIM157300   191160   248310   600807   611162   
Gene and transcription
Genbank (Entrez)AB451492 AF043342 AF098751 AJ227911 AJ251878
RefSeq transcript (Entrez)NM_000594
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_007462 NT_007592 NT_113891 NT_167244 NT_167245 NT_167246 NT_167247 NT_167248 NT_167249 NW_001838980 NW_004929326
Consensus coding sequences : CCDS (NCBI)TNF
Cluster EST : UnigeneHs.241570 [ NCBI ]
CGAP (NCI)Hs.241570
Alternative Splicing : Fast-db (Paris)GSHG0025610
Alternative Splicing GalleryENSG00000232810
Gene ExpressionTNF [ NCBI-GEO ]     TNF [ SEEK ]   TNF [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01375 (Uniprot)
NextProtP01375  [Medical]
With graphics : InterProP01375
Splice isoforms : SwissVarP01375 (Swissvar)
Domaine pattern : Prosite (Expaxy)TNF_1 (PS00251)    TNF_2 (PS50049)   
Domains : Interpro (EBI)TNF [organisation]   TNF_alpha [organisation]   TNF_CS [organisation]   TNF_dom [organisation]   TNFalpha/TNFSF15 [organisation]   Tumour_necrosis_fac-like_dom [organisation]  
Related proteins : CluSTrP01375
Domain families : Pfam (Sanger)TNF (PF00229)   
Domain families : Pfam (NCBI)pfam00229   
Domain families : Smart (EMBL)TNF (SM00207)  
DMDM Disease mutations7124
Blocks (Seattle)P01375
PDB (SRS)1A8M    1TNF    2AZ5    2E7A    2TUN    2ZJC    2ZPX    3ALQ    3IT8    3L9J    4G3Y    4TSV    5TSW   
PDB (PDBSum)1A8M    1TNF    2AZ5    2E7A    2TUN    2ZJC    2ZPX    3ALQ    3IT8    3L9J    4G3Y    4TSV    5TSW   
PDB (IMB)1A8M    1TNF    2AZ5    2E7A    2TUN    2ZJC    2ZPX    3ALQ    3IT8    3L9J    4G3Y    4TSV    5TSW   
PDB (RSDB)1A8M    1TNF    2AZ5    2E7A    2TUN    2ZJC    2ZPX    3ALQ    3IT8    3L9J    4G3Y    4TSV    5TSW   
Human Protein AtlasENSG00000232810 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP01375
HPRD01855
IPIIPI00001671   IPI00894294   
Protein Interaction databases
DIP (DOE-UCLA)P01375
IntAct (EBI)P01375
FunCoupENSG00000232810
BioGRIDTNF
InParanoidP01375
Interologous Interaction database P01375
IntegromeDBTNF
STRING (EMBL)TNF
Ontologies - Pathways
Ontology : AmiGOprotein import into nucleus, translocation  negative regulation of transcription from RNA polymerase II promoter  MAPK cascade  activation of MAPKKK activity  activation of MAPK activity  response to hypoxia  cell activation  positive regulation of cytokine production  phagocytic cup  positive regulation of protein phosphorylation  protease binding  negative regulation of L-glutamate transport  chronic inflammatory response to antigenic stimulus  negative regulation of cytokine secretion involved in immune response  positive regulation of chronic inflammatory response to antigenic stimulus  positive regulation of humoral immune response mediated by circulating immunoglobulin  skeletal muscle contraction  cytokine activity  tumor necrosis factor receptor binding  protein binding  extracellular region  extracellular space  plasma membrane  integral to plasma membrane  glucose metabolic process  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  transformed cell apoptotic process  inflammatory response  humoral immune response  JNK cascade  negative regulation of cell proliferation  extrinsic apoptotic signaling pathway via death domain receptors  extrinsic apoptotic signaling pathway via death domain receptors  response to mechanical stimulus  response to virus  response to salt stress  organ morphogenesis  external side of plasma membrane  cell surface  negative regulation of gene expression  negative regulation of alkaline phosphatase activity  negative regulation of lipid storage  positive regulation of necrotic cell death  response to activity  calcium-mediated signaling  extracellular matrix organization  osteoclast differentiation  sequestering of triglyceride  positive regulation of protein complex assembly  positive regulation of fever generation  lipopolysaccharide-mediated signaling pathway  negative regulation of interleukin-6 production  positive regulation of chemokine production  positive regulation of interferon-gamma production  positive regulation of interleukin-6 production  receptor biosynthetic process  positive regulation of peptidyl-serine phosphorylation  tumor necrosis factor-mediated signaling pathway  positive regulation of heterotypic cell-cell adhesion  positive regulation of NF-kappaB import into nucleus  response to drug  identical protein binding  positive regulation of apoptotic process  positive regulation of programmed cell death  regulation of I-kappaB kinase/NF-kappaB cascade  positive regulation of I-kappaB kinase/NF-kappaB cascade  negative regulation of protein complex disassembly  positive regulation of protein complex disassembly  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  positive regulation of MAP kinase activity  protein kinase B signaling cascade  positive regulation of JUN kinase activity  positive regulation of neuron apoptotic process  negative regulation of growth of symbiont in host  transcription regulatory region DNA binding  negative regulation of viral genome replication  positive regulation of chemokine biosynthetic process  membrane raft  positive regulation of interleukin-8 biosynthetic process  positive regulation of nitric oxide biosynthetic process  negative regulation of fat cell differentiation  negative regulation of osteoblast differentiation  positive regulation of osteoclast differentiation  positive regulation of mitosis  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of translational initiation by iron  negative regulation of glucose import  positive regulation of JNK cascade  embryonic digestive tract development  positive regulation of smooth muscle cell proliferation  positive regulation of cytokine secretion  regulation of insulin secretion  positive regulation of synaptic transmission  defense response to Gram-positive bacterium  leukocyte tethering or rolling  negative regulation of lipid catabolic process  regulation of immunoglobulin secretion  positive regulation of membrane protein ectodomain proteolysis  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  positive regulation of protein transport  response to glucocorticoid  positive regulation of NFAT protein import into nucleus  positive regulation of hair follicle development  positive regulation of protein kinase B signaling cascade  recycling endosome  positive regulation of vitamin D biosynthetic process  positive regulation of calcidiol 1-monooxygenase activity  epithelial cell proliferation involved in salivary gland morphogenesis  regulation of branching involved in salivary gland morphogenesis  negative regulation of branching involved in lung morphogenesis  necrotic cell death  positive regulation of ERK1 and ERK2 cascade  cellular response to amino acid stimulus  cellular response to nicotine  cellular response to organic cyclic compound  positive regulation of mononuclear cell migration  positive regulation of podosome assembly  apoptotic signaling pathway  extrinsic apoptotic signaling pathway  positive regulation of protein localization to cell surface  positive regulation of chemokine (C-X-C motif) ligand 2 production  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Ontology : EGO-EBIprotein import into nucleus, translocation  negative regulation of transcription from RNA polymerase II promoter  MAPK cascade  activation of MAPKKK activity  activation of MAPK activity  response to hypoxia  cell activation  positive regulation of cytokine production  phagocytic cup  positive regulation of protein phosphorylation  protease binding  negative regulation of L-glutamate transport  chronic inflammatory response to antigenic stimulus  negative regulation of cytokine secretion involved in immune response  positive regulation of chronic inflammatory response to antigenic stimulus  positive regulation of humoral immune response mediated by circulating immunoglobulin  skeletal muscle contraction  cytokine activity  tumor necrosis factor receptor binding  protein binding  extracellular region  extracellular space  plasma membrane  integral to plasma membrane  glucose metabolic process  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  transformed cell apoptotic process  inflammatory response  humoral immune response  JNK cascade  negative regulation of cell proliferation  extrinsic apoptotic signaling pathway via death domain receptors  extrinsic apoptotic signaling pathway via death domain receptors  response to mechanical stimulus  response to virus  response to salt stress  organ morphogenesis  external side of plasma membrane  cell surface  negative regulation of gene expression  negative regulation of alkaline phosphatase activity  negative regulation of lipid storage  positive regulation of necrotic cell death  response to activity  calcium-mediated signaling  extracellular matrix organization  osteoclast differentiation  sequestering of triglyceride  positive regulation of protein complex assembly  positive regulation of fever generation  lipopolysaccharide-mediated signaling pathway  negative regulation of interleukin-6 production  positive regulation of chemokine production  positive regulation of interferon-gamma production  positive regulation of interleukin-6 production  receptor biosynthetic process  positive regulation of peptidyl-serine phosphorylation  tumor necrosis factor-mediated signaling pathway  positive regulation of heterotypic cell-cell adhesion  positive regulation of NF-kappaB import into nucleus  response to drug  identical protein binding  positive regulation of apoptotic process  positive regulation of programmed cell death  regulation of I-kappaB kinase/NF-kappaB cascade  positive regulation of I-kappaB kinase/NF-kappaB cascade  negative regulation of protein complex disassembly  positive regulation of protein complex disassembly  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  positive regulation of MAP kinase activity  protein kinase B signaling cascade  positive regulation of JUN kinase activity  positive regulation of neuron apoptotic process  negative regulation of growth of symbiont in host  transcription regulatory region DNA binding  negative regulation of viral genome replication  positive regulation of chemokine biosynthetic process  membrane raft  positive regulation of interleukin-8 biosynthetic process  positive regulation of nitric oxide biosynthetic process  negative regulation of fat cell differentiation  negative regulation of osteoblast differentiation  positive regulation of osteoclast differentiation  positive regulation of mitosis  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of translational initiation by iron  negative regulation of glucose import  positive regulation of JNK cascade  embryonic digestive tract development  positive regulation of smooth muscle cell proliferation  positive regulation of cytokine secretion  regulation of insulin secretion  positive regulation of synaptic transmission  defense response to Gram-positive bacterium  leukocyte tethering or rolling  negative regulation of lipid catabolic process  regulation of immunoglobulin secretion  positive regulation of membrane protein ectodomain proteolysis  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  positive regulation of protein transport  response to glucocorticoid  positive regulation of NFAT protein import into nucleus  positive regulation of hair follicle development  positive regulation of protein kinase B signaling cascade  recycling endosome  positive regulation of vitamin D biosynthetic process  positive regulation of calcidiol 1-monooxygenase activity  epithelial cell proliferation involved in salivary gland morphogenesis  regulation of branching involved in salivary gland morphogenesis  negative regulation of branching involved in lung morphogenesis  necrotic cell death  positive regulation of ERK1 and ERK2 cascade  cellular response to amino acid stimulus  cellular response to nicotine  cellular response to organic cyclic compound  positive regulation of mononuclear cell migration  positive regulation of podosome assembly  apoptotic signaling pathway  extrinsic apoptotic signaling pathway  positive regulation of protein localization to cell surface  positive regulation of chemokine (C-X-C motif) ligand 2 production  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Pathways : BIOCARTACytokines and Inflammatory Response [Genes]    Msp/Ron Receptor Signaling Pathway [Genes]    NF-kB Signaling Pathway [Genes]    Free Radical Induced Apoptosis [Genes]    Chaperones modulate interferon Signaling Pathway [Genes]    TNFR1 Signaling Pathway [Genes]    Acetylation and Deacetylation of RelA in The Nucleus [Genes]    Cytokine Network [Genes]    SODD/TNFR1 Signaling Pathway [Genes]    TNF/Stress Related Signaling [Genes]    Cadmium induces DNA synthesis and proliferation in macrophages [Genes]    Adhesion and Diapedesis of Granulocytes [Genes]    Stress Induction of HSP Regulation [Genes]    IL-10 Anti-inflammatory Signaling Pathway [Genes]    Keratinocyte Differentiation [Genes]    Regulation of transcriptional activity by PML [Genes]    Visceral Fat Deposits and the Metabolic Syndrome [Genes]    HIV-I Nef: negative effector of Fas and TNF [Genes]    Signal transduction through IL1R [Genes]    Cells and Molecules involved in local acute inflammatory response [Genes]    NFkB activation by Nontypeable Hemophilus influenzae [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]   
Pathways : KEGGMAPK signaling pathway    Cytokine-cytokine receptor interaction    NF-kappa B signaling pathway    mTOR signaling pathway    Apoptosis    TGF-beta signaling pathway    Osteoclast differentiation    Antigen processing and presentation    Toll-like receptor signaling pathway    NOD-like receptor signaling pathway    RIG-I-like receptor signaling pathway    Hematopoietic cell lineage    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    Fc epsilon RI signaling pathway    TNF signaling pathway    Adipocytokine signaling pathway    Type II diabetes mellitus    Non-alcoholic fatty liver disease (NAFLD)    Type I diabetes mellitus    Alzheimer's disease    Amyotrophic lateral sclerosis (ALS)    Pertussis    Legionellosis    Leishmaniasis    Chagas disease (American trypanosomiasis)    African trypanosomiasis    Malaria    Toxoplasmosis    Amoebiasis    Tuberculosis    Hepatitis C    Hepatitis B    Influenza A    HTLV-I infection    Herpes simplex infection    Proteoglycans in cancer    Asthma    Inflammatory bowel disease (IBD)    Systemic lupus erythematosus    Rheumatoid arthritis    Allograft rejection    Graft-versus-host disease    Hypertrophic cardiomyopathy (HCM)    Dilated cardiomyopathy   
Protein Interaction DatabaseTNF
Wikipedia pathwaysTNF
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TNF
snp3D : Map Gene to Disease7124
SNP (GeneSNP Utah)TNF
SNP : HGBaseTNF
Genetic variants : HAPMAPTNF
Exome VariantTNF
1000_GenomesTNF 
ICGC programENSG00000232810 
Somatic Mutations in Cancer : COSMICTNF 
CONAN: Copy Number AnalysisTNF 
Mutations and Diseases : HGMDTNF
Genomic VariantsTNF  TNF [DGVbeta]
dbVarTNF
ClinVarTNF
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM157300    191160    248310    600807    611162   
MedgenTNF
GENETestsTNF
Disease Genetic AssociationTNF
Huge Navigator TNF [HugePedia]  TNF [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneTNF
Homology/Alignments : Family Browser (UCSC)TNF
Phylogenetic Trees/Animal Genes : TreeFamTNF
Chemical/Protein Interactions : CTD7124
Chemical/Pharm GKB GenePA435
Clinical trialTNF
Cancer Resource (Charite)ENSG00000232810
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=TNF
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineTNF
iHOPTNF

Bibliography

The role of TNF and its family members in inflammation and cancer: lessons from gene deletion.
Aggarwal BB, Shishodia S, Ashikawa K, Bharti AC
Current drug targets. Inflammation and allergy. 2002 ; 1 (4) : 327-341.
PMID 14561180
 
Luberculous spondylitis: epidemiologic and clinical study in non-HIV patients from northwest Spain.
Rodriguez-Gomez M, Willisch A, Fernandez-Dominguez L, Lopez-Barros G, Garcˆ‚a-Porrˆ†a C, Gonzalez-Gay MA
Clinical and experimental rheumatology. 2002 ; 20 (3) : 327-333.
PMID 12102468
 
Signalling pathways of the TNF superfamily: a double-edged sword.
Aggarwal BB
Nature reviews. Immunology. 2003 ; 3 (9) : 745-756.
PMID 12949498
 
A co-evolution perspective of the TNFSF and TNFRSF families in the immune system.
Collette Y, Gilles A, Pontarotti P, Olive D
Trends in immunology. 2003 ; 24 (7) : 387-394.
PMID 12860530
 
The signaling adaptors and pathways activated by TNF superfamily.
Dempsey PW, Doyle SE, He JQ, Cheng G
Cytokine & growth factor reviews. 2003 ; 14 (3-4) : 193-209.
PMID 12787559
 
Adding facets to TNF signaling. The JNK angle.
Liu ZG
Molecular cell. 2003 ; 12 (4) : 795-796.
PMID 14580328
 
Anti-TNF-alpha therapies: the next generation.
Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL
Nature reviews. Drug discovery. 2003 ; 2 (9) : 736-746.
PMID 12951580
 
Tumour necrosis factor alpha: a potential target for the therapy of solid tumours.
Szlosarek PW, Balkwill FR
The lancet oncology. 2003 ; 4 (9) : 565-573.
PMID 12965278
 
The TNF superfamily.
Ware CF
Cytokine & growth factor reviews. 2003 ; 14 (3-4) : 181-184.
PMID 12787557
 
Inflammation: the link between insulin resistance, obesity and diabetes.
Dandona P, Aljada A, Bandyopadhyay A
Trends in immunology. 2004 ; 25 (1) : 4-7.
PMID 14698276
 
Tumor necrosis factor: an apoptosis JuNKie?
Varfolomeev EE, Ashkenazi A
Cell. 2004 ; 116 (4) : 491-497.
PMID 14980217
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written06-2004Fei Chen

Citation

This paper should be referenced as such :
Chen, F
TNF (tumor necrosis factor (TNF superfamily, member 2))
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):223-225.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/TNFaID319.html

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