ID B3GDZ6_PIG Unreviewed; 232 AA. AC B3GDZ6; DT 22-JUL-2008, integrated into UniProtKB/TrEMBL. DT 22-JUL-2008, sequence version 1. DT 02-SEP-2026, entry version 110. 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}; GN Name=TNFa {ECO:0000313|EMBL:ACD81655.1}; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823 {ECO:0000313|EMBL:ACD81655.1}; RN [1] {ECO:0000313|EMBL:ACD81655.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=PBMC {ECO:0000313|EMBL:ACD81655.1}; RA Boyd P., Tompkins D., Hudgens T., Baldwin C., Lunney J.; RT "U.S. Veterinary Immune Reagent Network: Expressed Swine Gene Sequences."; RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:AEP25618.1} RP NUCLEOTIDE SEQUENCE. RA Huo J.L., Zhao Y., Zeng Y.Z.; RT "cDNA Cloning, Sequence Analysis and Tissue Expression Profile of TNF-alpha RT in Banna Mini-pig Inbred Line (BMI)."; RL Submitted (APR-2011) to the EMBL/GenBank/DDBJ databases. 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|ARBA:ARBA00025967, 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|PROSITE-ProRule:PRU01387, CC ECO:0000256|RuleBase:RU368112}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU01387}. 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; EU682384; ACD81655.1; -; mRNA. DR EMBL; JF831365; AEP25618.1; -; mRNA. DR RefSeq; NP_999187.1; NM_214022.1. DR AlphaFoldDB; B3GDZ6; -. DR SMR; B3GDZ6; -. DR GeneID; 397086; -. DR KEGG; ssc:397086; -. DR CTD; 7124; -. DR HOGENOM; CLU_070352_3_1_1; -. DR OMA; GATMLFC; -. DR OrthoDB; 9940698at2759; -. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0001891; C:phagocytic cup; IEA:Ensembl. DR GO; GO:0055037; C:recycling endosome; IEA:Ensembl. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-UniRule. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:Ensembl. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:UniProtKB-UniRule. DR GO; GO:0140374; P:antiviral innate immune response; IEA:Ensembl. DR GO; GO:0071479; P:cellular response to ionizing radiation; IEA:Ensembl. DR GO; GO:0071316; P:cellular response to nicotine; IEA:Ensembl. DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl. DR GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEA:Ensembl. DR GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl. DR GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl. DR GO; GO:0090594; P:inflammatory response to wounding; IEA:Ensembl. DR GO; GO:0050901; P:leukocyte tethering or rolling; IEA:Ensembl. DR GO; GO:0002281; P:macrophage activation involved in immune response; IEA:Ensembl. DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl. DR GO; GO:0097527; P:necroptotic signaling pathway; IEA:UniProtKB-UniRule. DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; IEA:Ensembl. DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; IEA:Ensembl. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IEA:Ensembl. DR GO; GO:0061048; P:negative regulation of branching involved in lung morphogenesis; IEA:Ensembl. DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; IEA:Ensembl. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl. DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0061044; P:negative regulation of vascular wound healing; IEA:Ensembl. DR GO; GO:0045071; P:negative regulation of viral genome replication; IEA:Ensembl. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IEA:Ensembl. DR GO; GO:2000334; P:positive regulation of blood microparticle formation; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:AgBase. DR GO; GO:0031622; P:positive regulation of fever generation; IEA:Ensembl. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl. DR GO; GO:0051798; P:positive regulation of hair follicle development; IEA:Ensembl. DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IEA:Ensembl. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; IEA:Ensembl. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IEA:Ensembl. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0051222; P:positive regulation of protein transport; IEA:Ensembl. DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IEA:Ensembl. DR GO; GO:0050806; P:positive regulation of synaptic transmission; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; IEA:Ensembl. DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IEA:Ensembl. DR GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl. DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0050807; P:regulation of synapse organization; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0010573; P:vascular endothelial growth factor production; IEA:UniProtKB-UniRule. DR CDD; cd00184; TNF; 1. DR FunFam; 2.60.120.40:FF:000007; Tumor necrosis factor; 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; THD_1; 1. DR PROSITE; PS50049; THD_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|PROSITE- KW ProRule:PRU01387}; 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, ECO:0000256|RuleBase:RU368112}; 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-anchor {ECO:0000256|ARBA:ARBA00022968, KW ECO:0000256|RuleBase:RU368112}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, KW ECO:0000256|RuleBase:RU368112}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|RuleBase:RU368112}. FT TRANSMEM 30..53 FT /note="Helical" FT /evidence="ECO:0000256|RuleBase:RU368112" FT DOMAIN 87..232 FT /note="THD" FT /evidence="ECO:0000259|PROSITE:PS50049" SQ SEQUENCE 232 AA; 25254 MW; 65B28F702D99C8BE CRC64; MSTESMIRDV ELAEEALAKK AGGPQGSRRC LCLSLFSFLL VAGATTLFCL LHFEVIGPQK EEFPAGPLSI NPLAQGLRSS SQTSDKPVAH VVANVKAEGQ LQWQSGYANA LLANGVKLKD NQLVVPTDGL YLIYSQVLFR GQGCPSTNVF LTHTISRIAV SYQTKVNLLS AIKSPCQRET PEGAEAKPWY EPIYLGGVFQ LEKDDRLSAE INLPDYLDFA ESGQVYFGII AL //