ID Q09H18_MACMU Unreviewed; 182 AA. AC Q09H18; DT 17-OCT-2006, integrated into UniProtKB/TrEMBL. DT 17-OCT-2006, sequence version 1. DT 29-MAY-2024, entry version 92. DE RecName: Full=Tumor necrosis factor {ECO:0000256|RuleBase:RU368112}; DE Short=TNF-a {ECO:0000256|RuleBase:RU368112}; DE AltName: Full=Cachectin {ECO:0000256|RuleBase:RU368112}; DE AltName: Full=TNF-alpha {ECO:0000256|RuleBase:RU368112}; DE AltName: Full=Tumor necrosis factor ligand superfamily member 2 {ECO:0000256|RuleBase:RU368112}; DE Contains: DE RecName: Full=Intracellular domain 1 {ECO:0000256|RuleBase:RU368112}; DE Short=ICD1 {ECO:0000256|RuleBase:RU368112}; DE Contains: DE RecName: Full=Intracellular domain 2 {ECO:0000256|RuleBase:RU368112}; DE Short=ICD2 {ECO:0000256|RuleBase:RU368112}; DE Contains: DE RecName: Full=C-domain 1 {ECO:0000256|RuleBase:RU368112}; DE Contains: DE RecName: Full=C-domain 2 {ECO:0000256|RuleBase:RU368112}; DE Contains: DE RecName: Full=Tumor necrosis factor, soluble form {ECO:0000256|RuleBase:RU368112}; DE Flags: Fragment; GN Name=TNF-alpha {ECO:0000313|EMBL:ABI63795.1}; OS Macaca mulatta (Rhesus macaque). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; OC Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9544 {ECO:0000313|EMBL:ABI63795.1}; RN [1] {ECO:0000313|EMBL:ABI63795.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=95027 {ECO:0000313|EMBL:ABI63789.1}, and 95114 RC {ECO:0000313|EMBL:ABI63795.1}; RX PubMed=17106666; DOI=10.1007/s00251-006-0166-6; RA Weiler A., May G.E., Qi Y., Wilson N., Watkins D.I.; RT "Polymorphisms in eight host genes associated with control of HIV RT replication do not mediate elite control of viral replication in SIV- RT infected Indian rhesus macaques."; RL Immunogenetics 58:1003-1009(2006). CC -!- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It CC is mainly secreted by macrophages and can induce cell death of certain CC tumor cell lines. It is potent pyrogen causing fever by direct action CC or by stimulation of interleukin-1 secretion and is implicated in the CC induction of cachexia, Under certain conditions it can stimulate cell CC proliferation and induce cell differentiation. Induces insulin CC resistance in adipocytes via inhibition of insulin-induced IRS1 CC tyrosine phosphorylation and insulin-induced glucose uptake. Induces CC GKAP42 protein degradation in adipocytes which is partially responsible CC for TNF-induced insulin resistance. Plays a role in angiogenesis by CC inducing VEGF production synergistically with IL1B and IL6. CC {ECO:0000256|RuleBase:RU368112}. CC -!- FUNCTION: The TNF intracellular domain (ICD) form induces IL12 CC production in dendritic cells. {ECO:0000256|ARBA:ARBA00003559, CC ECO:0000256|RuleBase:RU368112}. CC -!- SUBUNIT: Homotrimer. Interacts with SPPL2B. CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004401, CC ECO:0000256|RuleBase:RU368112}; Single-pass type II membrane protein CC {ECO:0000256|ARBA:ARBA00004401, ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [C-domain 2]: Secreted CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, soluble form]: Secreted CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, membrane form]: Membrane CC {ECO:0000256|RuleBase:RU368112}; Single-pass type II membrane protein CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [C-domain 1]: Secreted CC {ECO:0000256|RuleBase:RU368112}. CC -!- PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine CC and N-acetylneuraminic acid. {ECO:0000256|RuleBase:RU368112}. CC -!- PTM: The membrane form, but not the soluble form, is phosphorylated on CC serine residues. Dephosphorylation of the membrane form occurs by CC binding to soluble TNFRSF1A/TNFR1. {ECO:0000256|RuleBase:RU368112}. CC -!- PTM: The soluble form derives from the membrane form by proteolytic CC processing. The membrane-bound form is further proteolytically CC processed by SPPL2A or SPPL2B through regulated intramembrane CC proteolysis producing TNF intracellular domains (ICD1 and ICD2) CC released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into CC the extracellular space. {ECO:0000256|RuleBase:RU368112}. CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. CC {ECO:0000256|ARBA:ARBA00008670, ECO:0000256|RuleBase:RU368112}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; DQ902456; ABI63789.1; -; mRNA. DR EMBL; DQ902462; ABI63795.1; -; mRNA. DR AlphaFoldDB; Q09H18; -. DR HOGENOM; CLU_070352_3_1_1; -. DR GO; GO:0009986; C:cell surface; IEA:TreeGrafter. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-UniRule. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-UniRule. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:UniProtKB-UniRule. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:TreeGrafter. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0097527; P:necroptotic signaling pathway; IEA:UniProtKB-UniRule. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:TreeGrafter. DR GO; GO:0065008; P:regulation of biological quality; IEA:UniProt. DR GO; GO:0050793; P:regulation of developmental process; IEA:UniProt. DR GO; GO:0051239; P:regulation of multicellular organismal process; IEA:UniProt. DR GO; GO:0051046; P:regulation of secretion; IEA:UniProt. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:TreeGrafter. DR GO; GO:0010573; P:vascular endothelial growth factor production; IEA:UniProtKB-UniRule. DR CDD; cd00184; TNF; 1. DR Gene3D; 2.60.120.40; -; 1. DR InterPro; IPR006053; TNF. DR InterPro; IPR002959; TNF_alpha. DR InterPro; IPR021184; TNF_CS. DR InterPro; IPR006052; TNF_dom. DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom. DR PANTHER; PTHR11471:SF23; TUMOR NECROSIS FACTOR; 1. DR PANTHER; PTHR11471; TUMOR NECROSIS FACTOR FAMILY MEMBER; 1. DR Pfam; PF00229; TNF; 1. DR PRINTS; PR01234; TNECROSISFCT. DR PRINTS; PR01235; TNFALPHA. DR SMART; SM00207; TNF; 1. DR SUPFAM; SSF49842; TNF-like; 1. DR PROSITE; PS00251; TNF_1; 1. DR PROSITE; PS50049; TNF_2; 1. PE 2: Evidence at transcript level; KW Cell membrane {ECO:0000256|ARBA:ARBA00022475, KW ECO:0000256|RuleBase:RU368112}; KW Cytokine {ECO:0000256|ARBA:ARBA00022514, ECO:0000256|RuleBase:RU368112}; KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, KW ECO:0000256|RuleBase:RU368112}; KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180}; KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288, ECO:0000256|RuleBase:RU368112}; KW Membrane {ECO:0000256|ARBA:ARBA00023136}; KW Myristate {ECO:0000256|ARBA:ARBA00022707, ECO:0000256|RuleBase:RU368112}; KW Phosphoprotein {ECO:0000256|RuleBase:RU368112}; KW Secreted {ECO:0000256|ARBA:ARBA00022525, ECO:0000256|RuleBase:RU368112}; KW Signal {ECO:0000256|SAM:SignalP}; KW Signal-anchor {ECO:0000256|ARBA:ARBA00022968, KW ECO:0000256|RuleBase:RU368112}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989}. FT SIGNAL 1..23 FT /evidence="ECO:0000256|SAM:SignalP" FT CHAIN 24..182 FT /note="Tumor necrosis factor" FT /evidence="ECO:0000256|SAM:SignalP" FT /id="PRO_5010133584" FT DOMAIN 54..182 FT /note="TNF family profile" FT /evidence="ECO:0000259|PROSITE:PS50049" FT NON_TER 1 FT /evidence="ECO:0000313|EMBL:ABI63795.1" FT NON_TER 182 FT /evidence="ECO:0000313|EMBL:ABI63795.1" SQ SEQUENCE 182 AA; 19957 MW; C0DDC5B18CA83FA8 CRC64; FSFLLVAGAT TLFCLLHFGV IGPQREEFPK DPSLISPLAQ AVRSSSRTPS DKPVAHVVAN PQAEGQLQWL NRRANALLAN GVELTDNQLV VPSEGLYLIY SQVLFKGQGC PSNHVLLTHT ISRIAVSYQT KVNLLSAIKS PCQRETPEGA EAKPWYEPIY LGGVFQLEKG DRLSAEINLP DY //