TNF Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1A8M , 1TNF , 2AZ5 , 2E7A , 2TUN , 2ZJC , 2ZPX , 3ALQ , 3IT8 , 3L9J , 3WD5 , 4G3Y , 4TSV , 4TWT , 5TSW
Identifikatori Aliasi TNF Vanjski ID-jevi OMIM : 191160 MGI : 104798 HomoloGene : 496 GeneCards : TNF Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • protease binding • tumor necrosis factor receptor binding • cytokine activity • vezivanje identičnih proteina Ćelijska komponenta • membrana • cell surface • integral component of membrane • reciklirajući endosom • intracellular anatomical structure • integral component of plasma membrane • phagocytic cup • external side of plasma membrane • extracellular region • ćelijska membrana • Lipidni splav • Vanćelijsko Biološki proces • regulation of protein phosphorylation • positive regulation of protein phosphorylation • positive regulation of MAP kinase activity • response to salt stress • positive regulation of calcidiol 1-monooxygenase activity • positive regulation of programmed cell death • positive regulation of JNK cascade • response to organic substance • negative regulation of osteoblast differentiation • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • negative regulation of viral genome replication • humoral immune response • positive regulation of interleukin-8 production • intrinsic apoptotic signaling pathway in response to DNA damage • positive regulation of protein localization to cell surface • positive regulation of ERK1 and ERK2 cascade • glucose metabolic process • animal organ morphogenesis • apoptotic signaling pathway • negative regulation of alkaline phosphatase activity • regulation of I-kappaB kinase/NF-kappaB signaling • GO:0051637 defense response to Gram-positive bacterium • regulation of branching involved in salivary gland morphogenesis • positive regulation of phagocytosis • negative regulation of fat cell differentiation • negative regulation of myoblast differentiation • positive regulation of protein kinase B signaling • regulation of insulin secretion • osteoclast differentiation • regulation of tumor necrosis factor-mediated signaling pathway • response to virus • positive regulation of osteoclast differentiation • GO:0002719 negative regulation of cytokine production involved in immune response • positive regulation of peptidyl-serine phosphorylation • negative regulation of branching involved in lung morphogenesis • JNK cascade • death-inducing signaling complex assembly • regulation of osteoclast differentiation • defense response to bacterium • positive regulation of interleukin-6 production • I-kappaB kinase/NF-kappaB signaling • positive regulation of translational initiation by iron • sequestering of triglyceride • positive regulation of chronic inflammatory response to antigenic stimulus • positive regulation of chemokine (C-X-C motif) ligand 2 production • positive regulation of JUN kinase activity • positive regulation of hair follicle development • chronic inflammatory response to antigenic stimulus • GO:1904579 cellular response to organic cyclic compound • positive regulation of fever generation • extracellular matrix organization • positive regulation of DNA-binding transcription factor activity • cellular response to nicotine • positive regulation of podosome assembly • GO:1904489 regulation of reactive oxygen species metabolic process • positive regulation of protein transport • negative regulation of glucose import • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor • leukocyte tethering or rolling • positive regulation of chemokine production • cellular extravasation • negative regulation of lipid storage • negative regulation of myosin-light-chain-phosphatase activity • GO:0045996 negative regulation of transcription, DNA-templated • GO:0033109 cortical actin cytoskeleton organization • embryonic digestive tract development • leukocyte migration • lipopolysaccharide-mediated signaling pathway • positive regulation of smooth muscle cell proliferation • positive regulation of protein kinase activity • positive regulation of superoxide dismutase activity • defense response • positive regulation of ceramide biosynthetic process • positive regulation of protein-containing complex assembly • protein kinase B signaling • GO:0032737 positive regulation of cytokine production • epithelial cell proliferation involved in salivary gland morphogenesis • positive regulation of nitric oxide biosynthetic process • negative regulation of interleukin-6 production • positive regulation of membrane protein ectodomain proteolysis • positive regulation of humoral immune response mediated by circulating immunoglobulin • positive regulation of interferon-gamma production • response to glucocorticoid • positive regulation of vitamin D biosynthetic process • positive regulation of mononuclear cell migration • MAPK cascade • negative regulation of protein-containing complex disassembly • multicellular organism development • negative regulation of bicellular tight junction assembly • positive regulation of protein-containing complex disassembly • regulation of cell population proliferation • cellular response to amino acid stimulus • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • cellular response to lipopolysaccharide • negative regulation of lipid catabolic process • regulation of establishment of endothelial barrier • positive regulation of cell adhesion • regulation of protein secretion • positive regulation of apoptotic process • inflammatory response • activation of cysteine-type endopeptidase activity involved in apoptotic process • tumor necrosis factor-mediated signaling pathway • positive regulation of I-kappaB kinase/NF-kappaB signaling • necroptotic signaling pathway • GO:1901313 positive regulation of gene expression • extrinsic apoptotic signaling pathway • extrinsic apoptotic signaling pathway via death domain receptors • GO:1901227 negative regulation of transcription by RNA polymerase II • positive regulation of NF-kappaB transcription factor activity • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • positive regulation of leukocyte adhesion to arterial endothelial cell • positive regulation of leukocyte adhesion to vascular endothelial cell • positive regulation of blood microparticle formation • negative regulation of endothelial cell proliferation • positive regulation of heterotypic cell-cell adhesion • negative regulation of mitotic cell cycle • endothelial cell apoptotic process • positive regulation of vascular associated smooth muscle cell proliferation • negative regulation of gene expression • protein localization to plasma membrane • GO:1903364 positive regulation of protein catabolic process • regulation of signaling receptor activity • regulation of inflammatory response • cytokine-mediated signaling pathway • positive regulation of calcineurin-NFAT signaling cascade • positive regulation of NIK/NF-kappaB signaling Izvori:Amigo / QuickGO
Ortolozi Vrste Čovjek Miš Entrez Ensembl UniProt RefSeq (mRNK) RefSeq (bjelančevina) Lokacija (UCSC) Chr 6: 31.58 – 31.58 Mb Chr 17: 35.42 – 35.42 Mb PubMed pretraga[ 3] [ 4] Wikipodaci
Tumorski faktor nekroze (TNF , kaheksin ili kahektin , zvani i tumorski faktor nekroze alfa ili TNF-α ) citokinski mali protein koji koristi imunski sistem za ćelijsku signalizaciju . Ako makrofazi (određena bijela krvna zrnca ) otkriju infekciju, oslobađaju TNF, kako bi upozorili druge ćelije imunskog sistema kao dio upalnog odgovora . TNF je član superporodica TNF , koja se sastoji od različitih transmembranskih proteina s homolognim domenom TNF.
TNF signalizacija javlja se putem dva receptora: TNFR1 i TNFR2.[ 5] [ 6] konstitutivno eksprimiran na većini tipova ćelija, dok je TNFR2 ograničen prvenstveno na endotelne , epitelne i podskupine imunskih ćelija.[ 5] [ 6] apoptotska , dok je signalizacija TNFR2 protivupalna i podstiče ćelijsku proliferaciju .[ 5] [ 6] autoimunske bolesti ,[ 7] zacjeljivanje rana .[ 6]
TNF-α postoji kao transmembranski oblik (mTNF-α) i kao topljivi oblik (sTNF-α). sTNF-α je rezultat enzimskog cijepanja mTNF-α.[ 8] [ 8] [ 9] [ 10]
Primarna uloga TNF-a je u regulaciji imunskih ćelija . TNF, kao endogeni pirogen, može izazvati groznicu , apoptotsku ćelijsku smrt , kaheksiju , upalu i inhibirati tumorigenezu , replikaciju virusa , a i reagiraju na sepsu putem ćelijskih IL-1 i IL-6 . Disregulacija proizvodnje TNF-a uključena je u različite ljudske bolesti , uključujući Alzheimerovu ,[ 11] kancer ,[ 12] glavnu depresiju ,[ 13] psorijazu [ 14] upalnu bolest crijeva (IBD).[ 15] [ 16] [ 17]
Pod imenom tasonermin , TNF se koristi kao imunostimulacijski lijek u liječenju određenih karcinoma. Lijekovi koji se suprotstavljaju djelovanju TNF-a koriste se u liječenju različitih upalnih bolesti, naprimjer reumatoidnog artritisa .
Određeni karcinomi mogu uzrokovati hiperprodukciju TNF-a. TNFsu paralele paratireoidnih hormona i u izazivanju sekundarne hiperkalcemije i u raku s kojim je povezana prekomerna proizvodnja.
^ a b c ENSG00000230108, ENSG00000223952, ENSG00000204490, ENSG00000228321, ENSG00000232810, ENSG00000228849, ENSG00000206439 GRCh38: Ensembl release 89: ENSG00000228978, ENSG00000230108, ENSG00000223952, ENSG00000204490, ENSG00000228321, ENSG00000232810, ENSG00000228849, ENSG00000206439 - Ensembl , maj 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024401 - Ensembl , maj 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b c Heir R, Stellwagen D (2020). "TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models" . Frontiers in Cellular Neuroscience . 14 : 565841. doi :10.3389/fncel.2020.565841 . PMC 7556297 PMID 33192311 . ^ a b c d Gough P, Myles IA (2020). "Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects" . Frontiers in Immunology . 11 : 585880. doi :10.3389/fimmu.2020.585880 . PMC 7723893 PMID 33324405 . ^ Rolski F, Błyszczuk P (2020). "Complexity of TNF-α Signaling in Heart Disease" . Journal of Clinical Medicine 9 (10): 3267. doi :10.3390/jcm9103267 . PMC 7601316 PMID 33053859 . ^ a b Probert L (2017). "Forward and Reverse Signaling Mediated by Transmembrane Tumor Necrosis Factor-Alpha and TNF Receptor 2: Potential Roles in an Immunosuppressive Tumor Microenvironment" . Frontiers in Immunology 8 : 1675. doi :10.3389/fimmu.2017.01675 . PMC 5712345 PMID 29234328 . ^ Rolski F, Błyszczuk P (2015). "TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects" . Neuroscience . 302 : 2–22. doi :10.1016/j.neuroscience.2015.06.038 PMID 26117714 . ^ Szondy Z, Pallai A (2017). "Transmembrane TNF-alpha reverse signaling leading to TGF-beta production is selectively activated by TNF targeting molecules: Therapeutic implications". Pharmacological Research . 115 : 124–132. doi :10.1016/j.phrs.2016.11.025 . PMID 27888159 . ^ Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010). "A meta-analysis of cytokines in Alzheimer's disease". Biol Psychiatry . 68 (10): 930–941. doi :10.1016/j.biopsych.2010.06.012 . PMID 20692646 . S2CID 6544784 . ^ Locksley RM, Killeen N, Lenardo MJ (2001). "The TNF and TNF receptor superfamilies: integrating mammalian biology" . Cell . 104 (4): 487–501. doi :10.1016/S0092-8674(01)00237-9 PMID 11239407 . S2CID 7657797 . ^ Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010). "A meta-analysis of cytokines in major depression". Biol Psychiatry . 67 (5): 446–457. doi :10.1016/j.biopsych.2009.09.033 . PMID 20015486 . S2CID 230209 . ^ Victor FC, Gottlieb AB (2002). "TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis". J Drugs Dermatol . 1 (3): 264–75. PMID 12851985 . ^ Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T (2002). "Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease" . Gut . 51 (1): 37–43. doi :10.1136/gut.51.1.37 . PMC 1773288 PMID 12077089 . ^ Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Andrews JM, Holtmann GJ (2007). "Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review" . Inflammatory Bowel Diseases . 13 (2): 225–234. doi :10.1002/ibd.20062 PMID 17206706 . ^ Bobińska K, Gałecka E, Szemraj J, Gałecki P, Talarowska M (2017). "Is there a link between TNF gene expression and cognitive deficits in depression?" . Acta Biochim. Pol . 64 (1): 65–73. doi :10.18388/abp.2016_1276 PMID 27991935 .
