Human Gene TNF (uc003nui.4)
  Description: Homo sapiens tumor necrosis factor (TNF), mRNA.
RefSeq Summary (NM_000594): This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr6:31,543,344-31,546,112 Size: 2,769 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg19 chr6:31,543,519-31,545,314 Size: 1,796 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:31,543,344-31,546,112)mRNA (may differ from genome)Protein (233 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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MGIneXtProtOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TNFA_HUMAN
DESCRIPTION: RecName: Full=Tumor necrosis factor; AltName: Full=Cachectin; AltName: Full=TNF-alpha; AltName: Full=Tumor necrosis factor ligand superfamily member 2; Short=TNF-a; Contains: RecName: Full=Tumor necrosis factor, membrane form; AltName: Full=N-terminal fragment; Short=NTF; Contains: RecName: Full=Intracellular domain 1; Short=ICD1; Contains: RecName: Full=Intracellular domain 2; Short=ICD2; Contains: RecName: Full=C-domain 1; Contains: RecName: Full=C-domain 2; Contains: RecName: Full=Tumor necrosis factor, soluble form; Flags: Precursor;
FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.
FUNCTION: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
SUBUNIT: Homotrimer. Interacts with SPPL2B.
INTERACTION: P19438:TNFRSF1A; NbExp=6; IntAct=EBI-359977, EBI-299451;
SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.
SUBCELLULAR LOCATION: Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein.
SUBCELLULAR LOCATION: Tumor necrosis factor, soluble form: Secreted.
SUBCELLULAR LOCATION: C-domain 1: Secreted.
SUBCELLULAR LOCATION: C-domain 2: Secreted.
PTM: The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C- domain 2 secreted into the extracellular space.
PTM: The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
PTM: O-glycosylated; glycans contain galactose, N- acetylgalactosamine and N-acetylneuraminic acid.
POLYMORPHISM: Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424].
POLYMORPHISM: Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162].
DISEASE: Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
SIMILARITY: Belongs to the tumor necrosis factor family.
SEQUENCE CAUTION: Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Sequence=CAA75070.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha entry; URL="http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha";
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TNFaID319.html";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/tnf/";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/tnf/";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TNF
CDC HuGE Published Literature: TNF
Positive Disease Associations: acute renal allograft rejection , alcohol abuse , allergic rhinitis , allograft dysfunction, renal , allograft outcome , Alzheimer's Disease , Alzheimer's disease; dementia , ankylosing spondylitis , Arthritis, Rheumatoid| , asthma , asthma, aspirin-intolerant , Asthma. Allergy. , Asthma| , atherosclerosis, coronary , beta-Thalassemia , bone mineral density , Bone mineral mass , breast cancer , brucellosis , C-reactive protein , Carbamazepine hypersensitivity , Carcinoma, Hepatocellular|Liver Neoplasms , celiac , celiac disease , cerebral malaria , chemotherapy-induced pulmonary fibrosis , chorioamnionitis , chronic active hepatitis C infection. , chronic bronchitis , chronic GVHD , chronic obstructive pulmonary disease/COPD; bronchiectatic disease , cirrhosis , cirrhosis, alcoholic , cirrhosis, biliary primary; hepatitis, autoimmune , coal workers' pneumoconiosis (CWP) , contact hypersensitivity , COPD , Crohn's disease , Crohn's disease inflammatory bowel disease ulcerative colitis , Crohn's disease ulcerative colitis , Crohn's disease; ulcerative colitis , Delayed Graft Function|Inflammation , dermatitis herpetiformis. , Diabetes mellitus type II|Diabetes Mellitus, Type 2|Glucose Intolerance|Overweight , diabetes, type 1 , diabetes, type 2 , emphysema , endometriosis , Excessive fat accumulation , fibrosing alveolitis , graft-versus-host disease , Graves' disease , GVHD , head and neck cancer , Helicobacter pylori cagA subtype infection , hematopoietic stem cell transplantation , hepatitis B , HIV disease , human narcolepsy. , Hypertension/complications* , hypertension; cirrhosis , hypothyroidism , increased cardiopulmonary morbidity , increased development of adult T-cell leukemia/lymphoma , inflammatory bowel disease , insulin resistance in obesity , interleukin-1 beta (IL-1 beta) synthesis capacity , irritant contact dermatitis , kawasaki disease , kidney failure, chronic , kidney transplant , kidney transplant complications , Leishmania chagasi infection , lep. Leprosy , limb deficiency anomalies , lipodystrophy , Longevity , lung function , Lupus , lupus erythematosus; rheumatoid arthritis; Sjogren's syndrome; tuberculosis , malaria , malarial anemia and cerebral malaria , meliodosis , meningococcal disease. , Meningococcal Infections|Sepsis , migraine , Migraine Disorders , mucocutaneous leishmaniasis , multiple sclerosis , myasthenia gravis , myelopathy, HTLV-1 associated , Natural Menopause|Obesity|POF - Premature ovarian failure|POLYCYSTIC OVARIAN SYNDROME|Polycystic Ovary Syndrome|Primary Ovarian Insufficiency|Puberty, Delayed|Puberty, Precocious|Thrombophilia|Tobacco Use Disorder , noncardia gastric cancer , Obesity ????????? , Obesity- associated hypertension ??????? , oral cancer , pancreatitis , parvovirus B19 infection , periodontitis , Plasmodium falciparum reinfections , Polyendocrinopathies, Autoimmune , pre-term delivery infant mortality and malaria morbidity , preterm delivery , Primary Billiary Cirrosis , primary sclerosing cholangitis , psoriasis , recurrent pregnancy loss , rheumatoid arthritis , Scarring trachoma , schizophrenia , sclerosis, systemic , sepsis , sepsis; systemic inflammatory response syndrome , Silicosis , stomach cancer , stomach cancer; gastritis , stroke, hemorrhagic stroke, ischemic , subarachnoid hemorrhage , synthetic hemodialysis graft failure , testicular cancer , thyroid-associated ophthalmopathy , tuberculosis , Typhoid Fever , ulcerative colitis and Crohn's disease , Uveitis , Wounds and Injuries
Related Studies:
  1. acute renal allograft rejection
    Lee H 2004, Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the incidence of acute renal allograft rejection., Journal of clinical pathology. 2004 Jan;57(1):101-3. [PubMed 14693849]
    This finding argues for prospective TNFA genotyping of renal donors, with avoidance of allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR mismatched recipients.
  2. alcohol abuse
    Gonzalez-Quintela, A. et al. 2004, Relation of tumor necrosis factor (TNF) gene polymorphisms with serum concentrations and in vitro production of TNF-alpha and interleukin-8 in heavy drinkers., Alcohol (Fayetteville, NY). 2004 Oct-Nov;34(3-Feb):273-7. [PubMed 15902922]
    In comparison with findings for control subjects, heavy drinkers showed higher TNF-alpha production, higher IL-8 production, and higher serum IL-8 concentrations. Increased serum TNF-alpha concentrations were specifically found in heavy drinkers with the -857 (C-->T) substitution (CT heterozygotes), therefore indicating an interaction between alcohol consumption and that polymorphism on serum TNF-alpha concentrations.
  3. allergic rhinitis
    Gentile, D. A. et al. 2004, Association between TNF-alpha and TGF-beta genotypes in infants and parental history of allergic rhinitis and asthma., Human immunology. 2004 Apr;65(4):347-51. [PubMed 15120189]
    These results suggest a role for TNF-alpha and TGF-beta1 genotypes in the pathogenesis of allergic rhinitis and asthma, respectively. If confirmed by future studies, cytokine genotyping may be a useful tool for identifying at-risk infants who may benefit from the selective use of preventative and/or early intervention treatments for these disorders.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TNF
Diseases sorted by gene-association score: migraine with or without aura 1* (395), asthma* (362), malaria* (273), asthma susceptibility, tnf-related* (100), arthritis (79), psoriatic arthritis (42), toxic shock syndrome (42), chorioamnionitis (36), synovitis (33), rheumatic disease (33), pulmonary sarcoidosis (31), cardiac sarcoidosis (30), colitis (28), alcoholic hepatitis (27), spondylarthropathy (25), lymphadenitis (24), listeriosis (24), chagas disease (23), mucocutaneous leishmaniasis (23), louse-borne relapsing fever (23), mycobacterium avium complex disease (23), scleritis (23), ileocolitis (22), inflammatory bowel disease (22), miller fisher syndrome (22), blau syndrome (20), spondyloarthropathy 1 (20), spondylitis (20), rheumatoid arthritis (20), trypanosomiasis (19), vasculitis (19), kashin-beck disease (19), systemic onset juvenile idiopathic arthritis (19), acute graft versus host disease (18), acute respiratory distress syndrome (18), staphylococcal toxic shock syndrome (18), new daily-persistent headache (18), actinic prurigo (18), leukomalacia (18), lymphangiosarcoma (18), spondyloarthropathy (17), pneumoconiosis (17), tonsil cancer (17), leishmaniasis (17), dengue hemorrhagic fever (17), panuveitis (17), pyoderma (17), pulmonary edema (17), hemorrhagic fever with renal syndrome (16), ileitis (16), nephropathia epidemica (16), crohn's colitis (16), sialadenitis (16), diverticulitis (16), monoclonal gammopathy of uncertain significance (16), spotted fever (15), granulomatous dermatitis (15), microscopic colitis (15), cellulitis (15), inner ear disease (15), swine influenza (15), erysipelas (15), uveitis (15), tuberculosis (15), nervous system disease (15), adult dermatomyositis (15), poliomyelitis (15), hepatitis b (15), ulcerative colitis (15), periodontal disease (15), psoriasis (15), clonorchiasis (15), pneumonia (15), adult respiratory distress syndrome (14), dry eye syndrome (14), hidradenitis suppurativa (14), aggressive periodontitis (14), pustular psoriasis (14), hidradenitis (14), rheumatic heart disease (13), plasmodium vivax malaria (13), progressive multifocal leukoencephalopathy (13), aseptic meningitis (13), punctate inner choroidopathy (13), cytomegalovirus infection (13), tuberculous meningitis (13), crimean-congo hemorrhagic fever (13), idiopathic neutropenia (13), beryllium disease (13), autoimmune inner ear disease (13), stromal keratitis (13), farmer's lung (12), fatty liver disease (12), trachoma (12), periodic fever, familial (12), hepatitis (12), sarcoidosis 1 (12), monocytic leukemia (12), paracoccidioidomycosis (12), trichuriasis (12), tympanosclerosis (12), atherosclerosis (12), brucellosis (12), peritonitis (12), pleurisy (12), primary systemic mycosis (12), aphthous stomatitis (12), complex regional pain syndrome (12), pleural tuberculosis (12), posterior uveitis (12), bone inflammation disease (11), hypersensitivity reaction type ii disease (11), retinitis pigmentosa 55 (11), endocarditis (11), retinitis pigmentosa 75 (11), connective tissue disease (11), erythema multiforme (11), dengue shock syndrome (11), myasthenia gravis (11), endometritis (11), acquired immunodeficiency syndrome (11), proctitis (11), aids dementia complex (11), pyoderma gangrenosum (11), spinal cord injury (11), multidrug-resistant tuberculosis (11), appendicitis (11), rheumatoid arthritis, systemic juvenile (11), relapsing fever (11), takayasu arteritis (11), lepromatous leprosy (11), primary bacterial infectious disease (11), subacute cutaneous lupus erythematosus (11), scorpion envenomation (11), arthropathy (11), melkersson-rosenthal syndrome (11), streptococcal toxic-shock syndrome (11), skin disease (11), choroiditis (10), microscopic polyangiitis (10), tropical endomyocardial fibrosis (10), sleep apnea (10), autoimmune myocarditis (10), periventricular leukomalacia (10), typhoid fever (10), primary progressive multiple sclerosis (10), radiation proctitis (10), q fever (10), endomyocardial fibrosis (10), granulocytopenia (10), melioidosis (10), acute gonococcal salpingitis (10), periodontitis (10), liver disease (10), arthus reaction (10), silicosis (10), avian influenza (10), skin conditions (10), joint disorders (10), pulpitis (10), viral encephalitis (10), adult-onset still's disease (10), meconium aspiration syndrome (10), guillain-barre syndrome (10), rheumatoid lung disease (10), fasciitis (10), oral tuberculosis (10), poems syndrome (10), neuritis (10), autoinflammation, lipodystrophy, and dermatosis syndrome (10), hematopoietic stem cell transplantation (9), bacterial meningitis (9), alveolar echinococcosis (9), reactive arthritis (9), hepatitis a (9), contact dermatitis (9), rheumatic fever (9), burns (9), angioimmunoblastic lymphadenopathy with dysproteinemia (9), chronic beryllium disease (9), hemorrhagic fever (9), critical limb ischemia (9), leptospirosis (9), scrub typhus (9), obstructive sleep apnea (9), cutaneous lupus erythematosus (9), lung disease (9), bronchiolitis obliterans (9), headache (9), skin sarcoidosis (9), intracranial hypertension (9), intermediate uveitis (9), sympathetic ophthalmia (9), visceral leishmaniasis (9), narcolepsy (9), cytomegalovirus retinitis (9), soft tissue sarcoma (9), allergic contact dermatitis (8), meningitis (8), compartment syndrome (8), alopecia areata (8), extrinsic cardiomyopathy (8), otitis media (8), lacrimal apparatus disease (8), demyelinating disease (8), obstructive jaundice (8), bacterial vaginosis (8), optic neuritis (8), retinal ischemia (8), autoinflammation, panniculitis, and dermatosis syndrome (8), eales disease (8), rosacea (8), fibrosarcoma (8), rheumatoid vasculitis (8), systemic lupus erythematosus (8), autoimmune pancreatitis (8), actinic cheilitis (8), mixed connective tissue disease (8), multifocal choroiditis (8), chronic pulmonary heart disease (8), localized scleroderma (8), pertussis (8), pyelonephritis (8), myelitis (8), cutaneous leishmaniasis (8), hepatopulmonary syndrome (8), pericarditis (8), burning mouth syndrome (8), tinea profunda (8), leprosy (8), anthracosis (8), haemophilus influenzae (8), prostatitis (7), commensal bacterial infectious disease (7), churg-strauss syndrome (7), chikungunya (7), parasitic protozoa infectious disease (7), keratitis (7), japanese encephalitis (7), multiple sclerosis, disease progression, modifier of (7), intestinal disease (7), hepatitis e (7), breast disease (7), transient hypogammaglobulinemia (7), idiopathic achalasia (7), viral infectious disease (7), kawasaki disease (7), laryngitis (7), respiratory system disease (7), schistosomiasis (7), lichen disease (7), infective endocarditis (7), macrophage activation syndrome (7), smallpox (7), tonsillitis (7), familial mediterranean fever, ar (7), systolic heart failure (7), osteomyelitis (7), sickle cell anemia (7), lichen planus (7), relapsing-remitting multiple sclerosis (7), gingivitis (7), pustulosis of palm and sole (7), protein-energy malnutrition (7), marburg hemorrhagic fever (7), trichosporonosis (7), scleral disease (7), tungiasis (7), post-transplant lymphoproliferative disease (7), irritable bowel syndrome (7), toxoplasmosis (7), bronchitis (7), melancholia (7), trench fever (7), chronic fatigue syndrome (7), dystrophinopathies (7), peptic ulcer disease (7), wegener granulomatosis (7), cystitis (7), ischemic heart disease (6), echinococcosis (6), chlamydia (6), weill-marchesani syndrome (6), anca-associated vasculitis (6), epstein-barr virus-associated gastric carcinoma (6), lichen sclerosus (6), lyme disease (6), vulvar vestibulitis syndrome (6), respiratory failure (6), alopecia universalis (6), legionellosis (6), filariasis (6), palindromic rheumatism (6), hypersensitivity reaction disease (6), gastroenteritis (6), congenital hydrocephalus (6), glossitis (6), interstitial lung disease (6), gastrointestinal system disease (6), irritant dermatitis (6), cholangitis (6), severe acute respiratory syndrome (6), duodenal ulcer (6), eye disease (6), limb ischemia (6), pleural disease (6), viral hepatitis (6), hepatitis c (6), end stage renal failure (6), carotid stenosis (6), anterior uveitis (6), bronchiolitis (6), sclerosing cholangitis (6), hepatic encephalopathy (6), gastric ulcer (6), mumps (6), listeria meningitis (6), hemophagocytic lymphohistiocytosis (6), cerebral palsy (6), plasmodium falciparum malaria (6), rubella (6), myocarditis (6), portal hypertension (6), cholesteatoma (6), purpura (6), pulmonary tuberculosis (6), stachybotrys chartarum (6), nontuberculous mycobacterial lung disease (6), posterior urethral valves (6), jejunoileitis (6), atrophic gastritis (6), hypersensitivity reaction type iv disease (6), immune system disease (6), chronic gonococcal salpingitis (6), human immunodeficiency virus infectious disease (6), familial tumoral calcinosis (6), rectal disease (6), behcet syndrome (6), retinitis pigmentosa 60 (6), early-onset schizophrenia (6), posterior scleritis (6), null-cell leukemia (5), keratoconjunctivitis (5), transverse myelitis (5), mycobacterium abscessus (5), osteoarthritis (5), orofacial granulomatosis (5), breast adenocarcinoma (5), oligoarticular juvenile idiopathic arthritis (5), pulmonary disease, chronic obstructive (5), penicilliosis (5), peroneal neuropathy (5), middle ear disease (5), severe hemophilia a (5), central nervous system vasculitis (5), pustulosis palmaris et plantaris (5), rasmussen encephalitis (5), coccidiosis (5), acute vascular insufficiency of intestine (5), inflammatory bowel disease 3 (5), osteosclerotic myeloma (5), keratoconjunctivitis sicca (5), dental pulp disease (5), bronchial disease (5), pneumocystosis (5), traumatic brain injury (5), sweat gland disease (5), acute proliferative glomerulonephritis (5), spinal cord disease (4), lupus erythematosus (4), acquired metabolic disease (4), critical illness polyneuropathy (4), acute salpingitis (4), heart disease (4), streptococcal meningitis (4), uterine disease (4), opportunistic mycosis (4), upper respiratory tract disease (4), spermatocele (4), lymph node disease (4), kaposi sarcoma (4), dilated cardiomyopathy (4), hypersensitivity reaction type iii disease (4), omenn syndrome (4), tuberculous peritonitis (4), exanthem (4), atopic dermatitis (4), osteoporosis (4), chronic salpingitis (4), perinatal necrotizing enterocolitis (4), crohn's disease (4), suppurative cholangitis (4), sudden infant death syndrome (4), geographic tongue (3), cogan syndrome (3), pre-eclampsia (3), kidney cancer (3), cerebrovascular disease (3), colorectal cancer (3), primary immunodeficiency disease (3), lateral sclerosis (3), obesity (3), alzheimer disease (3), artery disease (3), stomatitis (2), diarrhea (2), common variable immunodeficiency (2), celiac disease (2), aplastic anemia (2), chronic granulomatous disease (2), urinary bladder cancer (2), stomach cancer (2), multiple myeloma (2), tooth agenesis (2), cardiomyopathy (2), overnutrition (2), motor neuron disease (2), diabetes mellitus, noninsulin-dependent (2), breast cancer (2), myocardial infarction (2), leukocyte disease (2), glucose metabolism disease (1), mouth disease (1), female reproductive system disease (1), parasitic helminthiasis infectious disease (1), diabetes mellitus, insulin-dependent (1), nose disease (1), urinary system disease (1), macular degeneration, age-related, 1 (1), reproductive system disease (1), gastrointestinal system cancer (1), leigh syndrome (1), pulmonary fibrosis, idiopathic (1), leukemia, acute myeloid (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 58.12 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 74.58 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -42.70175-0.244 Picture PostScript Text
3' UTR -253.92798-0.318 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006052 - TNF
IPR006053 - TNF_a/b/c
IPR002959 - TNF_alpha
IPR021184 - TNF_CS
IPR008983 - Tumour_necrosis_fac-like

Pfam Domains:
PF00229 - TNF(Tumour Necrosis Factor) family

SCOP Domains:
49842 - TNF-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1A8M - X-ray MuPIT 1TNF - X-ray MuPIT 2AZ5 - X-ray MuPIT 2E7A - X-ray MuPIT 2TUN - X-ray MuPIT 2ZJC - X-ray MuPIT 2ZPX - X-ray MuPIT 3ALQ - X-ray MuPIT 3IT8 - X-ray MuPIT 3L9J - X-ray MuPIT 4TSV - X-ray MuPIT 5TSW - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P01375
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002020 protease binding
GO:0005125 cytokine activity
GO:0005164 tumor necrosis factor receptor binding
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0044212 transcription regulatory region DNA binding

Biological Process:
GO:0000060 protein import into nucleus, translocation
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000165 MAPK cascade
GO:0000185 activation of MAPKKK activity
GO:0000187 activation of MAPK activity
GO:0001819 positive regulation of cytokine production
GO:0001932 regulation of protein phosphorylation
GO:0001934 positive regulation of protein phosphorylation
GO:0001937 negative regulation of endothelial cell proliferation
GO:0002439 chronic inflammatory response to antigenic stimulus
GO:0002740 negative regulation of cytokine secretion involved in immune response
GO:0002876 positive regulation of chronic inflammatory response to antigenic stimulus
GO:0002925 positive regulation of humoral immune response mediated by circulating immunoglobulin
GO:0006006 glucose metabolic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006952 defense response
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0006959 humoral immune response
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007254 JNK cascade
GO:0007275 multicellular organism development
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009615 response to virus
GO:0009651 response to salt stress
GO:0009887 animal organ morphogenesis
GO:0010033 response to organic substance
GO:0010469 regulation of receptor activity
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010693 negative regulation of alkaline phosphatase activity
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0010888 negative regulation of lipid storage
GO:0019221 cytokine-mediated signaling pathway
GO:0030198 extracellular matrix organization
GO:0030316 osteoclast differentiation
GO:0030730 sequestering of triglyceride
GO:0030866 cortical actin cytoskeleton organization
GO:0031334 positive regulation of protein complex assembly
GO:0031622 positive regulation of fever generation
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032715 negative regulation of interleukin-6 production
GO:0032722 positive regulation of chemokine production
GO:0032729 positive regulation of interferon-gamma production
GO:0032755 positive regulation of interleukin-6 production
GO:0032757 positive regulation of interleukin-8 production
GO:0032800 receptor biosynthetic process
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034116 positive regulation of heterotypic cell-cell adhesion
GO:0035509 negative regulation of myosin-light-chain-phosphatase activity
GO:0042127 regulation of cell proliferation
GO:0042742 defense response to bacterium
GO:0043065 positive regulation of apoptotic process
GO:0043068 positive regulation of programmed cell death
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043242 negative regulation of protein complex disassembly
GO:0043243 positive regulation of protein complex disassembly
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043406 positive regulation of MAP kinase activity
GO:0043491 protein kinase B signaling
GO:0043507 positive regulation of JUN kinase activity
GO:0044130 negative regulation of growth of symbiont in host
GO:0045071 negative regulation of viral genome replication
GO:0045080 positive regulation of chemokine biosynthetic process
GO:0045123 cellular extravasation
GO:0045416 positive regulation of interleukin-8 biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045599 negative regulation of fat cell differentiation
GO:0045662 negative regulation of myoblast differentiation
GO:0045668 negative regulation of osteoblast differentiation
GO:0045670 regulation of osteoclast differentiation
GO:0045672 positive regulation of osteoclast differentiation
GO:0045732 positive regulation of protein catabolic process
GO:0045785 positive regulation of cell adhesion
GO:0045860 positive regulation of protein kinase activity
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045930 negative regulation of mitotic cell cycle
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0045994 positive regulation of translational initiation by iron
GO:0046325 negative regulation of glucose import
GO:0046330 positive regulation of JNK cascade
GO:0048566 embryonic digestive tract development
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050708 regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050727 regulation of inflammatory response
GO:0050766 positive regulation of phagocytosis
GO:0050796 regulation of insulin secretion
GO:0050830 defense response to Gram-positive bacterium
GO:0050900 leukocyte migration
GO:0050901 leukocyte tethering or rolling
GO:0050995 negative regulation of lipid catabolic process
GO:0051023 regulation of immunoglobulin secretion
GO:0051044 positive regulation of membrane protein ectodomain proteolysis
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051222 positive regulation of protein transport
GO:0051384 response to glucocorticoid
GO:0051798 positive regulation of hair follicle development
GO:0051897 positive regulation of protein kinase B signaling
GO:0060557 positive regulation of vitamin D biosynthetic process
GO:0060559 positive regulation of calcidiol 1-monooxygenase activity
GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis
GO:0060693 regulation of branching involved in salivary gland morphogenesis
GO:0061048 negative regulation of branching involved in lung morphogenesis
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070886 positive regulation of calcineurin-NFAT signaling cascade
GO:0071222 cellular response to lipopolysaccharide
GO:0071230 cellular response to amino acid stimulus
GO:0071316 cellular response to nicotine
GO:0071407 cellular response to organic cyclic compound
GO:0071550 death-inducing signaling complex assembly
GO:0071677 positive regulation of mononuclear cell migration
GO:0071803 positive regulation of podosome assembly
GO:0072577 endothelial cell apoptotic process
GO:0072659 protein localization to plasma membrane
GO:0097190 apoptotic signaling pathway
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097527 necroptotic signaling pathway
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1901671 positive regulation of superoxide dismutase activity
GO:1903140 regulation of establishment of endothelial barrier
GO:1903347 negative regulation of bicellular tight junction assembly
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:1904996 positive regulation of leukocyte adhesion to vascular endothelial cell
GO:1904999 positive regulation of leukocyte adhesion to arterial endothelial cell
GO:2000010 positive regulation of protein localization to cell surface
GO:2000304 positive regulation of ceramide biosynthetic process
GO:2000334 positive regulation of blood microparticle formation
GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component:
GO:0001891 phagocytic cup
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009897 external side of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0045121 membrane raft
GO:0055037 recycling endosome


-  Descriptions from all associated GenBank mRNAs
  AK314960 - Homo sapiens cDNA, FLJ95875, Homo sapiens tumor necrosis factor (TNF superfamily, member 2)(TNF), mRNA.
BC028148 - Homo sapiens tumor necrosis factor (TNF superfamily, member 2), mRNA (cDNA clone MGC:39905 IMAGE:5217636), complete cds.
X01394 - Human mRNA for tumor necrosis factor.
M10988 - Human tumor necrosis factor (TNF) mRNA.
E00423 - cDNA encoding human TNF gene and flanking sequence.
E00514 - cDNA coding human tumor necrosis factor.
E01053 - cDNA encoding human TNF precursor.
E01128 - DNA encoding human TNF precursor.
E01590 - cDNA encoding human tumor necrosis factor.
E02008 - cDNA encoding precursor of human tumor necrosis factor.
JD464028 - Sequence 445052 from Patent EP1572962.
DQ891662 - Synthetic construct clone IMAGE:100004292; FLH179071.01X; RZPDo839C06130D tumor necrosis factor (TNF superfamily, member 2) (TNF) gene, encodes complete protein.
DQ894849 - Synthetic construct Homo sapiens clone IMAGE:100009309; FLH179067.01L; RZPDo839C06129D tumor necrosis factor (TNF superfamily, member 2) (TNF) gene, encodes complete protein.
AB464327 - Synthetic construct DNA, clone: pF1KB7595, Homo sapiens TNF gene for tumor necrosis factor, without stop codon, in Flexi system.
KJ892290 - Synthetic construct Homo sapiens clone ccsbBroadEn_01684 TNF gene, encodes complete protein.
E00884 - DNA sequence of human pro-TNF.
E08302 - cDNA encoding precursor of human tumor necrosis factor.
HQ201306 - Homo sapiens tumor necrosis factor-alpha mRNA, complete cds.
E00712 - cDNA encoding human tumor necrosis factor.
FJ795028 - Homo sapiens tumor necrosis factor alpha (TNF) mRNA, partial cds.
E00702 - cDNA encoding human tumor necrosis factor.
E01153 - cDNA encoding human TNF.
AB451492 - Homo sapiens TNF mRNA for tumor necrosis factor alpha, partial cds, clone: FLJ80001DABN.
AF043342 - Homo sapiens tumor necrosis factor alpha (TNFa) mRNA, partial cds.
AJ251878 - Homo sapiens partial mRNA for tumor necrosis factor alpha (TNF-alpha gene), isolate B10, exon 3.
AJ251879 - Homo sapiens partial mRNA for tumor necrosis factor alpha (TNF-alpha gene),isolate B19, exon 3.
E01052 - DNA encoding human mature TNF.
E01127 - DNA encoding protein which has TNF-like anti tumor activity.
E02672 - cDNA encoding human tumor necrosis factor-like poly peptide.
E01641 - cDNA encoding modified human tumor necrosis factor (hTNF).
E01642 - cDNA encoding modified human tumor necrosis factor (hTNF).
E01647 - cDNA endoding modified human tumor necrosis factor (hTNF).
E04591 - cDNA encoding human TNF.
AF098751 - Homo sapiens APC1 protein mRNA, partial cds.
E01925 - cDNA encoding new TNF polypeptide.
JD380278 - Sequence 361302 from Patent EP1572962.
JD054693 - Sequence 35717 from Patent EP1572962.
FW573317 - JP 2010529847-A/38: Oligonucleotides for modulation of target RNA activity.
JD184985 - Sequence 166009 from Patent EP1572962.
FW573321 - JP 2010529847-A/42: Oligonucleotides for modulation of target RNA activity.
JD495115 - Sequence 476139 from Patent EP1572962.
JD061975 - Sequence 42999 from Patent EP1572962.
JD086132 - Sequence 67156 from Patent EP1572962.
FW573319 - JP 2010529847-A/40: Oligonucleotides for modulation of target RNA activity.
FW573318 - JP 2010529847-A/39: Oligonucleotides for modulation of target RNA activity.
JD346852 - Sequence 327876 from Patent EP1572962.
FW573313 - JP 2010529847-A/34: Oligonucleotides for modulation of target RNA activity.
FW573315 - JP 2010529847-A/36: Oligonucleotides for modulation of target RNA activity.
AJ227911 - Homo sapiens partial mRNA; ID YG39-2, YG53, EE2-16F2.
FW573316 - JP 2010529847-A/37: Oligonucleotides for modulation of target RNA activity.
JD226145 - Sequence 207169 from Patent EP1572962.
JD351270 - Sequence 332294 from Patent EP1572962.
FW573322 - JP 2010529847-A/43: Oligonucleotides for modulation of target RNA activity.
JD391029 - Sequence 372053 from Patent EP1572962.
JD313727 - Sequence 294751 from Patent EP1572962.
FW573320 - JP 2010529847-A/41: Oligonucleotides for modulation of target RNA activity.
JD328621 - Sequence 309645 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04060 - Cytokine-cytokine receptor interaction
hsa04210 - Apoptosis
hsa04350 - TGF-beta signaling pathway
hsa04612 - Antigen processing and presentation
hsa04620 - Toll-like receptor signaling pathway
hsa04621 - NOD-like receptor signaling pathway
hsa04622 - RIG-I-like receptor signaling pathway
hsa04640 - Hematopoietic cell lineage
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04660 - T cell receptor signaling pathway
hsa04664 - Fc epsilon RI signaling pathway
hsa04920 - Adipocytokine signaling pathway
hsa04930 - Type II diabetes mellitus
hsa04940 - Type I diabetes mellitus
hsa05010 - Alzheimer's disease
hsa05014 - Amyotrophic lateral sclerosis (ALS)
hsa05140 - Leishmaniasis
hsa05142 - Chagas disease
hsa05310 - Asthma
hsa05322 - Systemic lupus erythematosus
hsa05330 - Allograft rejection
hsa05332 - Graft-versus-host disease
hsa05410 - Hypertrophic cardiomyopathy (HCM)
hsa05414 - Dilated cardiomyopathy

BioCarta from NCI Cancer Genome Anatomy Project
h_inflamPathway - Cytokines and Inflammatory Response
h_mspPathway - Msp/Ron Receptor Signaling Pathway
h_nfkbPathway - NF-kB Signaling Pathway
h_freePathway - Free Radical Induced Apoptosis
h_tidPathway - Chaperones modulate interferon Signaling Pathway
h_tnfr1Pathway - TNFR1 Signaling Pathway
h_RELAPathway - Acetylation and Deacetylation of RelA in The Nucleus
h_cytokinePathway - Cytokine Network
h_soddPathway - SODD/TNFR1 Signaling Pathway
h_stressPathway - TNF/Stress Related Signaling
h_cdMacPathway - Cadmium induces DNA synthesis and proliferation in macrophages
h_granulocytesPathway - Adhesion and Diapedesis of Granulocytes
h_hsp27Pathway - Stress Induction of HSP Regulation
h_il10Pathway - IL-10 Anti-inflammatory Signaling Pathway
h_keratinocytePathway - Keratinocyte Differentiation
h_pmlPathway - Regulation of transcriptional activity by PML
h_vobesityPathway - Visceral Fat Deposits and the Metabolic Syndrome
h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF
h_il1rPathway - Signal transduction through IL1R
h_LairPathway - Cells and Molecules involved in local acute inflammatory response
h_nthiPathway - NFkB activation by Nontypeable Hemophilus influenzae
h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)

Reactome (by CSHL, EBI, and GO)

Protein P01375 (Reactome details) participates in the following event(s):

R-HSA-83660 Membrane-anchored TNF-alpha binds TNFR1
R-HSA-3371385 TNF-alpha is cleaved by ADAM17 (TACE)
R-HSA-5668404 TNFA binds TNFR2
R-HSA-3371353 Soluble TNF-alpha binds TNFR1
R-HSA-5668417 cIAP1,2:TRAF2:TRAF3:NIK complex binds TNFR2 trimer
R-HSA-5668467 2xTNFR2 binds TNFA trimer:TNFR2
R-HSA-83656 TNF:TNFR1 binds TRADD, TRAF2 and RIPK1
R-HSA-5626953 TNF-alpha:TNFR1 binds DENN/MADD
R-HSA-5626988 TNF-alpha:TNFR1 binds NSMAF
R-HSA-5634221 TRAF1 binds TRAF2 within TNFR1 signaling complex
R-HSA-83582 TRADD:TRAF2:RIP1 complex dissociates from the TNF-alpha:TNF-R1 complex.
R-HSA-5357780 TNF:TNFR1:TRADD:TRAF2:RIPK1 recruits BIRC2/3 (cIAP1/2)
R-HSA-5357860 TNF:TNFR1:TRADD:TRAF2:K63polyUb-RIPK1:BIRC2/3 recruits TAK1 complex
R-HSA-5357904 TNF:TNFR1:TRADD:TRAF2:RIPK1 binds LUBAC
R-HSA-5357928 CLIP3 and CYLD bind TNF signaling complex
R-HSA-5693055 TAX1BP1:TNFAIP3(A20) binds RIPK1-containing complexes
R-HSA-5357757 BIRC(cIAP1/2) ubiquitinates RIPK1
R-HSA-5626982 TNF-alpha:TNFR1:NSMAF binds GNB2L1
R-HSA-5693108 TNFAIP3 (A20) ubiquitinates RIPK1 with K48-linked Ub chains
R-HSA-5357776 TNF:TNFR1:TRADD:TRAF2:K63polyUb-RIPK1:BIRC2,3:LUBAC recruits IKKA:IKBKB:IKBKG
R-HSA-5626981 TNF-alpha:TNFR1:NSMAF:GNB2L1 associates with SMPD2,3
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-75893 TNF signaling
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-73887 Death Receptor Signalling
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-449147 Signaling by Interleukins
R-HSA-5626978 TNFR1-mediated ceramide production
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-162582 Signal Transduction
R-HSA-168256 Immune System
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway

-  Other Names for This Gene
  Alternate Gene Symbols: NM_000594, NP_000585, O43647, P01375, Q9P1Q2, Q9UIV3, TNFA, TNFA_HUMAN, TNFSF2, uc003nui.3
UCSC ID: uc003nui.4
RefSeq Accession: NM_000594
Protein: P01375 (aka TNFA_HUMAN)
CCDS: CCDS4702.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000594.3
exon count: 4CDS single in 3' UTR: no RNA size: 1686
ORF size: 702CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1604.00frame shift in genome: no % Coverage: 99.35
has start codon: yes stop codon in genome: no # of Alignments: 8
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.