ID   TNFA_RAT                Reviewed;         235 AA.
AC   P16599; Q6EE11; Q9JI26; Q9JI27;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   04-NOV-2026, entry version 212.
DE   RecName: Full=Tumor necrosis factor;
DE   AltName: Full=Cachectin;
DE   AltName: Full=TNF-alpha;
DE   AltName: Full=Tumor necrosis factor ligand superfamily member 2;
DE            Short=TNF-a;
DE   Contains:
DE     RecName: Full=Tumor necrosis factor, membrane form;
DE     AltName: Full=N-terminal fragment;
DE              Short=NTF;
DE   Contains:
DE     RecName: Full=Intracellular domain 1;
DE              Short=ICD1;
DE   Contains:
DE     RecName: Full=Intracellular domain 2;
DE              Short=ICD2;
DE   Contains:
DE     RecName: Full=C-domain 1;
DE   Contains:
DE     RecName: Full=C-domain 2;
DE   Contains:
DE     RecName: Full=Tumor necrosis factor, soluble form;
DE   Flags: Precursor;
GN   Name=Tnf; Synonyms=Tnfa, Tnfsf2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Shirai T., Shimizu N., Horiguchi S., Ito H.;
RT   "Cloning and expression in Escherichia coli of the gene for rat tumor
RT   necrosis factor.";
RL   Agric. Biol. Chem. 53:1733-1736(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1627266; DOI=10.1515/bchm3.1992.373.1.271;
RA   Estler H.C., Grewe M., Gaussling R., Pavlovic M., Decker K.F.;
RT   "Rat tumor necrosis factor-alpha. Transcription in rat Kupffer cells and in
RT   vitro posttranslational processing based on a PCR-derived cDNA.";
RL   Biol. Chem. Hoppe-Seyler 373:271-281(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Testis;
RX   PubMed=8224868; DOI=10.1016/0378-1119(93)90200-m;
RA   Kwon J., Chung I.Y., Benveniste E.N.;
RT   "Cloning and sequence analysis of the rat tumor necrosis factor-encoding
RT   genes.";
RL   Gene 132:227-236(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ACI/SegHsd, BB(DR)/Wor, Brown Norway/SsNHsd, DA/Bkl, F344/NHsd,
RC   and LEW/NHsd;
RX   PubMed=11477479; DOI=10.1038/sj.gene.6363761;
RA   Furuya T., Joe B., Salstrom J.L., Hashiramoto A., Dobbins D.E.,
RA   Wilder R.L., Remmers E.F.;
RT   "Polymorphisms of the tumor necrosis factor alpha locus among autoimmune
RT   disease susceptible and resistant inbred rat strains.";
RL   Genes Immun. 2:229-232(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS PRO-122 AND GLU-190.
RC   STRAIN=Dark agouti;
RA   Seidel M.F., Junier M.-P., Vetter H.;
RT   "TNF-alpha polymorphism in rats with collagen-induced arthritis.";
RL   Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=AUG/OlaHsd, PVG/OlaHsd, and WF/HanHsd;
RX   PubMed=15935297; DOI=10.1016/j.trim.2005.04.002;
RA   Warle M.C., van der Laan L.J., Kusters J.G., Pot R.G., Hop W.C.,
RA   Segeren K.C., Ijzermans J.N., Metselaar H.J., Tilanus H.W.;
RT   "No association between tumor necrosis factor-alpha production and gene
RT   polymorphisms among inbred rat strains.";
RL   Transpl. Immunol. 14:77-82(2005).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15060004; DOI=10.1101/gr.1987704;
RA   Hurt P., Walter L., Sudbrak R., Klages S., Mueller I., Shiina T., Inoko H.,
RA   Lehrach H., Guenther E., Reinhardt R., Himmelbauer H.;
RT   "The genomic sequence and comparative analysis of the rat major
RT   histocompatibility complex.";
RL   Genome Res. 14:631-639(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-231.
RC   TISSUE=Tail;
RA   Kirisits M.J., Vardimon D., Kunz H.W., Gill T.J. III;
RT   "Mapping of the TNF-alpha locus in the rat.";
RL   Submitted (JUN-1993) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   INDUCTION BY LIPOPOLYSACCHARIDES.
RX   PubMed=30980393; DOI=10.1002/jcp.28614;
RA   Chao C.N., Lai C.H., Badrealam K.F., Lo J.F., Shen C.Y., Chen C.H.,
RA   Chen R.J., Viswanadha V.P., Kuo W.W., Huang C.Y.;
RT   "CHIP attenuates lipopolysaccharide-induced cardiac hypertrophy and
RT   apoptosis by promoting NFATc3 proteasomal degradation.";
RL   J. Cell. Physiol. 234:20128-20138(2019).
CC   -!- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR,
CC       activating the tumor necrosis factor-mediated (TNF) signaling pathway.
CC       The TNF signaling pathway acts as a master regulator of the immune
CC       system, which either (1) promotes cell survival and inflammation by
CC       activating the canonical NF-kappa-B pathway or (2) trigger programmed
CC       cell death (apoptosis and necroptosis). Impairs regulatory T-cells
CC       (Treg) function in individuals with rheumatoid arthritis via FOXP3
CC       dephosphorylation: acts by up-regulating the expression of protein
CC       phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue
CC       of FOXP3, thereby inactivating FOXP3 and rendering Treg cells
CC       functionally defective. Key mediator of cell death in the anticancer
CC       action of BCG-stimulated neutrophils in combination with DIABLO/SMAC
CC       mimetic in the RT4v6 bladder cancer cell line (By similarity). Induces
CC       insulin 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 (By similarity). Plays a role in
CC       angiogenesis by inducing VEGF production synergistically with IL1B and
CC       IL6 (By similarity). Promotes osteoclastogenesis and therefore mediates
CC       bone resorption (By similarity). {ECO:0000250|UniProtKB:P01375,
CC       ECO:0000250|UniProtKB:P06804}.
CC   -!- FUNCTION: [Tumor necrosis factor, soluble form]: Cytokine mainly
CC       secreted by macrophages that binds to TNFRSF1A/TNFR1 and
CC       TNFRSF1B/TNFBR, activating the tumor necrosis factor-mediated (TNF)
CC       signaling pathway. The TNF signaling pathway acts as a master regulator
CC       of the immune system, which either (1) promotes cell survival and
CC       inflammation by activating the canonical NF-kappa-B pathway or (2)
CC       trigger programmed cell death (apoptosis and necroptosis).
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- FUNCTION: [Intracellular domain 1]: The TNF intracellular domain (ICD)
CC       form induces IL12 production in dendritic cells.
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- FUNCTION: [Intracellular domain 2]: The TNF intracellular domain (ICD)
CC       form induces IL12 production in dendritic cells.
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:P01375}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01375};
CC       Single-pass type II membrane protein {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, membrane form]: Membrane
CC       {ECO:0000250|UniProtKB:P01375}; Single-pass type II membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, soluble form]: Secreted
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- SUBCELLULAR LOCATION: [C-domain 1]: Secreted
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- SUBCELLULAR LOCATION: [C-domain 2]: Secreted
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- INDUCTION: Induced by lipopolysaccharides.
CC       {ECO:0000269|PubMed:30980393}.
CC   -!- PTM: The soluble form derives from the membrane form by proteolytic
CC       processing by ADAM17. The membrane-bound form is further
CC       proteolytically processed by SPPL2A or SPPL2B through regulated
CC       intramembrane proteolysis producing TNF intracellular domains (ICD1 and
CC       ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2
CC       secreted into the extracellular space. {ECO:0000250|UniProtKB:P01375}.
CC   -!- PTM: [Tumor necrosis factor, membrane form]: The membrane form, but not
CC       the soluble form, is phosphorylated on serine residues.
CC       Dephosphorylation of the membrane form occurs by binding to soluble
CC       TNFRSF1A/TNFR1. {ECO:0000250|UniProtKB:P01375}.
CC   -!- PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine
CC       and N-acetylneuraminic acid. {ECO:0000250|UniProtKB:P01375}.
CC   -!- PTM: [Tumor necrosis factor, soluble form]: The soluble form is
CC       demyristoylated by SIRT6, promoting its secretion.
CC       {ECO:0000250|UniProtKB:P01375}.
CC   -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
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DR   EMBL; D00475; BAA00367.1; -; Genomic_DNA.
DR   EMBL; X66539; CAA47146.1; -; mRNA.
DR   EMBL; AJ002278; CAA05290.1; -; mRNA.
DR   EMBL; L00981; AAA16275.1; -; Genomic_DNA.
DR   EMBL; AF329982; AAK53568.1; -; Genomic_DNA.
DR   EMBL; AF329983; AAK53569.1; -; Genomic_DNA.
DR   EMBL; AF329984; AAK53570.1; -; Genomic_DNA.
DR   EMBL; AF329985; AAK53571.1; -; Genomic_DNA.
DR   EMBL; AF329986; AAK53572.1; -; Genomic_DNA.
DR   EMBL; AF329987; AAK53573.1; -; Genomic_DNA.
DR   EMBL; AF269159; AAF82567.1; -; mRNA.
DR   EMBL; AF269160; AAF82568.1; -; mRNA.
DR   EMBL; AY427673; AAR91624.1; -; Genomic_DNA.
DR   EMBL; AY427674; AAR91625.1; -; Genomic_DNA.
DR   EMBL; AY427675; AAR91626.1; -; Genomic_DNA.
DR   EMBL; BX883046; CAE84003.1; -; Genomic_DNA.
DR   EMBL; BC107671; AAI07672.1; -; mRNA.
DR   EMBL; L19123; AAA42255.1; -; Genomic_DNA.
DR   PIR; JU0029; JU0029.
DR   RefSeq; NP_036807.1; NM_012675.3.
DR   AlphaFoldDB; P16599; -.
DR   SMR; P16599; -.
DR   DIP; DIP-39461N; -.
DR   FunCoup; P16599; 932.
DR   IntAct; P16599; 74.
DR   STRING; 10116.ENSRNOP00000001110; -.
DR   BindingDB; P16599; -.
DR   GlyCosmos; P16599; 2 sites, No reported glycans.
DR   GlyGen; P16599; 2 sites.
DR   PhosphoSitePlus; P16599; -.
DR   PaxDb; 10116-ENSRNOP00000001110; -.
DR   Ensembl; ENSRNOT00055013522; ENSRNOP00055010843; ENSRNOG00055008022.
DR   Ensembl; ENSRNOT00060007886; ENSRNOP00060005929; ENSRNOG00060004712.
DR   Ensembl; ENSRNOT00065054848; ENSRNOP00065045113; ENSRNOG00065031842.
DR   GeneID; 24835; -.
DR   KEGG; rno:24835; -.
DR   UCSC; RGD:3876; rat.
DR   AGR; RGD:3876; -.
DR   CTD; 7124; -.
DR   RGD; 3876; Tnf.
DR   eggNOG; ENOG502S4K8; Eukaryota.
DR   HOGENOM; CLU_070352_3_1_1; -.
DR   InParanoid; P16599; -.
DR   OMA; AAIKSPC; -.
DR   OrthoDB; 9940698at2759; -.
DR   PhylomeDB; P16599; -.
DR   Reactome; R-RNO-5357786; TNFR1-induced proapoptotic signaling.
DR   Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-RNO-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR   Reactome; R-RNO-5626978; TNFR1-mediated ceramide production.
DR   Reactome; R-RNO-5668541; TNFR2 non-canonical NF-kB pathway.
DR   Reactome; R-RNO-75893; TNF signaling.
DR   PRO; PR:P16599; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   Bgee; ENSRNOG00000000837; Expressed in thymus and 4 other cell types or tissues.
DR   ExpressionAtlas; P16599; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:RGD.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR   GO; GO:0005576; C:extracellular region; IDA:ARUK-UCL.
DR   GO; GO:0045121; C:membrane raft; ISO:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0001891; C:phagocytic cup; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0055037; C:recycling endosome; ISO:RGD.
DR   GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR   GO; GO:0140072; F:histone H3K9ac reader activity; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0002020; F:protease binding; ISO:RGD.
DR   GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; IDA:RGD.
DR   GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR   GO; GO:0140374; P:antiviral innate immune response; ISO:RGD.
DR   GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:0019722; P:calcium-mediated signaling; IDA:RGD.
DR   GO; GO:0007259; P:cell surface receptor signaling pathway via JAK-STAT; IDA:ARUK-UCL.
DR   GO; GO:0045123; P:cellular extravasation; ISO:RGD.
DR   GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR   GO; GO:1904646; P:cellular response to amyloid-beta; IEP:RGD.
DR   GO; GO:0071479; P:cellular response to ionizing radiation; ISO:RGD.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:RGD.
DR   GO; GO:0071219; P:cellular response to molecule of bacterial origin; IEP:RGD.
DR   GO; GO:0071316; P:cellular response to nicotine; ISO:RGD.
DR   GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
DR   GO; GO:0097237; P:cellular response to toxic substance; IEP:RGD.
DR   GO; GO:0071346; P:cellular response to type II interferon; IEP:RGD.
DR   GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; ISO:RGD.
DR   GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR   GO; GO:0006952; P:defense response; ISO:RGD.
DR   GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
DR   GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:RGD.
DR   GO; GO:0048566; P:embryonic digestive tract development; ISO:RGD.
DR   GO; GO:0072577; P:endothelial cell apoptotic process; ISO:RGD.
DR   GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; ISO:RGD.
DR   GO; GO:0030198; P:extracellular matrix organization; ISO:RGD.
DR   GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR   GO; GO:0006006; P:glucose metabolic process; ISO:RGD.
DR   GO; GO:0006959; P:humoral immune response; ISO:RGD.
DR   GO; GO:0006955; P:immune response; IBA:GO_Central.
DR   GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR   GO; GO:0090594; P:inflammatory response to wounding; ISO:RGD.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR   GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR   GO; GO:0050900; P:leukocyte migration; ISO:RGD.
DR   GO; GO:0050901; P:leukocyte tethering or rolling; ISO:RGD.
DR   GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:RGD.
DR   GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR   GO; GO:0002281; P:macrophage activation involved in immune response; ISO:RGD.
DR   GO; GO:0001774; P:microglial cell activation; ISO:RGD.
DR   GO; GO:0097527; P:necroptotic signaling pathway; ISS:UniProtKB.
DR   GO; GO:1900222; P:negative regulation of amyloid-beta clearance; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR   GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:RGD.
DR   GO; GO:0120190; P:negative regulation of bile acid secretion; IDA:RGD.
DR   GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:RGD.
DR   GO; GO:0061048; P:negative regulation of branching involved in lung morphogenesis; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR   GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; ISO:RGD.
DR   GO; GO:0046325; P:negative regulation of D-glucose import across plasma membrane; IDA:RGD.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISO:RGD.
DR   GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:RGD.
DR   GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR   GO; GO:0010459; P:negative regulation of heart rate; IMP:RGD.
DR   GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:RGD.
DR   GO; GO:0002037; P:negative regulation of L-glutamate import across plasma membrane; IDA:RGD.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:RGD.
DR   GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:RGD.
DR   GO; GO:0031642; P:negative regulation of myelination; IMP:RGD.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:RGD.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR   GO; GO:0090324; P:negative regulation of oxidative phosphorylation; IDA:RGD.
DR   GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:RGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0061044; P:negative regulation of vascular wound healing; ISO:RGD.
DR   GO; GO:0045071; P:negative regulation of viral genome replication; ISO:RGD.
DR   GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR   GO; GO:0045760; P:positive regulation of action potential; IDA:RGD.
DR   GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISO:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:2000334; P:positive regulation of blood microparticle formation; ISO:RGD.
DR   GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:ARUK-UCL.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; ISO:RGD.
DR   GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:RGD.
DR   GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR   GO; GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; ISO:RGD.
DR   GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR   GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR   GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IDA:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:RGD.
DR   GO; GO:2000866; P:positive regulation of estradiol secretion; ISO:RGD.
DR   GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:RGD.
DR   GO; GO:0031622; P:positive regulation of fever generation; ISO:RGD.
DR   GO; GO:0032724; P:positive regulation of fractalkine production; IDA:ARUK-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR   GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:RGD.
DR   GO; GO:0051798; P:positive regulation of hair follicle development; ISO:RGD.
DR   GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IDA:RGD.
DR   GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:RGD.
DR   GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; ISO:RGD.
DR   GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:RGD.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR   GO; GO:0032741; P:positive regulation of interleukin-18 production; IMP:RGD.
DR   GO; GO:0150129; P:positive regulation of interleukin-33 production; ISO:RGD.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:ARUK-UCL.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR   GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; ISO:RGD.
DR   GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; ISO:RGD.
DR   GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISO:RGD.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:RGD.
DR   GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:RGD.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR   GO; GO:1902565; P:positive regulation of neutrophil activation; IMP:RGD.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD.
DR   GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:RGD.
DR   GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISO:RGD.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:RGD.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:ARUK-UCL.
DR   GO; GO:0071803; P:positive regulation of podosome assembly; ISO:RGD.
DR   GO; GO:0043068; P:positive regulation of programmed cell death; ISO:RGD.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:RGD.
DR   GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISO:RGD.
DR   GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:ARUK-UCL.
DR   GO; GO:0051222; P:positive regulation of protein transport; IDA:RGD.
DR   GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:RGD.
DR   GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISO:RGD.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
DR   GO; GO:0050806; P:positive regulation of synaptic transmission; IMP:RGD.
DR   GO; GO:1901647; P:positive regulation of synoviocyte proliferation; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR   GO; GO:0045994; P:positive regulation of translational initiation by iron; ISO:RGD.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; ISO:RGD.
DR   GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:RGD.
DR   GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; ISO:RGD.
DR   GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD.
DR   GO; GO:0060693; P:regulation of branching involved in salivary gland morphogenesis; ISO:RGD.
DR   GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; ISO:RGD.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IDA:RGD.
DR   GO; GO:2000351; P:regulation of endothelial cell apoptotic process; ISO:RGD.
DR   GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:RGD.
DR   GO; GO:0045598; P:regulation of fat cell differentiation; ISO:RGD.
DR   GO; GO:0002637; P:regulation of immunoglobulin production; ISO:RGD.
DR   GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
DR   GO; GO:0050796; P:regulation of insulin secretion; ISO:RGD.
DR   GO; GO:0045670; P:regulation of osteoclast differentiation; ISO:RGD.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR   GO; GO:0050708; P:regulation of protein secretion; ISO:RGD.
DR   GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:RGD.
DR   GO; GO:0050807; P:regulation of synapse organization; ISO:RGD.
DR   GO; GO:1905242; P:response to 3,3',5-triiodo-L-thyronine; IEP:RGD.
DR   GO; GO:0014823; P:response to activity; IEP:RGD.
DR   GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR   GO; GO:0046677; P:response to antibiotic; IEP:RGD.
DR   GO; GO:0009617; P:response to bacterium; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0009750; P:response to fructose; IEP:RGD.
DR   GO; GO:0051384; P:response to glucocorticoid; ISO:RGD.
DR   GO; GO:1990268; P:response to gold nanoparticle; IEP:RGD.
DR   GO; GO:0140460; P:response to Gram-negative bacterium; IEP:RGD.
DR   GO; GO:1904880; P:response to hydrogen sulfide; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0035900; P:response to isolation stress; IEP:RGD.
DR   GO; GO:1902065; P:response to L-glutamate; IDA:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB.
DR   GO; GO:0036005; P:response to macrophage colony-stimulating factor; IEP:RGD.
DR   GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR   GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR   GO; GO:1905235; P:response to quercetin; IEP:RGD.
DR   GO; GO:1904638; P:response to resveratrol; IEP:RGD.
DR   GO; GO:0009615; P:response to virus; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0003009; P:skeletal muscle contraction; IEP:RGD.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IMP:UniProtKB.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:ARUK-UCL.
DR   GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR   GO; GO:0042311; P:vasodilation; IMP:RGD.
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; Cytokine; Disulfide bond; Glycoprotein; Lipoprotein;
KW   Membrane; Myristate; Phosphoprotein; Reference proteome; Secreted;
KW   Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..235
FT                   /note="Tumor necrosis factor, membrane form"
FT                   /id="PRO_0000034451"
FT   CHAIN           1..39
FT                   /note="Intracellular domain 1"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT                   /id="PRO_0000417287"
FT   CHAIN           1..35
FT                   /note="Intracellular domain 2"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT                   /id="PRO_0000417288"
FT   CHAIN           50..?
FT                   /note="C-domain 1"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT                   /id="PRO_0000417289"
FT   CHAIN           52..?
FT                   /note="C-domain 2"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT                   /id="PRO_0000417290"
FT   CHAIN           80..235
FT                   /note="Tumor necrosis factor, soluble form"
FT                   /id="PRO_0000034452"
FT   TOPO_DOM        1..35
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        36..56
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        57..235
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          91..235
FT                   /note="THD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01387"
FT   SITE            35..36
FT                   /note="Cleavage; by SPPL2A or SPPL2B"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   SITE            39..40
FT                   /note="Cleavage; by SPPL2A or SPPL2B"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   SITE            49..50
FT                   /note="Cleavage; by SPPL2A or SPPL2B"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   SITE            51..52
FT                   /note="Cleavage; by SPPL2A or SPPL2B"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   SITE            79..80
FT                   /note="Cleavage; by ADAM17"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   MOD_RES         2
FT                   /note="Phosphoserine; by CK1"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   LIPID           19
FT                   /note="N6-myristoyl lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   LIPID           20
FT                   /note="N6-myristoyl lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   CARBOHYD        83
FT                   /note="O-linked (GalNAc...) serine; in soluble form"
FT                   /evidence="ECO:0000250|UniProtKB:P01375"
FT   CARBOHYD        86
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        148..179
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01387"
FT   VARIANT         122
FT                   /note="L -> P"
FT                   /evidence="ECO:0000269|Ref.5"
FT   VARIANT         190
FT                   /note="K -> E"
FT                   /evidence="ECO:0000269|Ref.5"
FT   CONFLICT        39
FT                   /note="L -> P (in Ref. 2; CAA05290/CAA47146)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        163
FT                   /note="I -> T (in Ref. 2; CAA05290/CAA47146)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        202
FT                   /note="F -> S (in Ref. 2; CAA05290/CAA47146)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   235 AA;  25806 MW;  B808EC6D049C2F3B CRC64;
     MSTESMIRDV ELAEEALPKK MGGLQNSRRC LCLSLFSFLL VAGATTLFCL LNFGVIGPNK
     EEKFPNGLPL ISSMAQTLTL RSSSQNSSDK PVAHVVANHQ AEEQLEWLSQ RANALLANGM
     DLKDNQLVVP ADGLYLIYSQ VLFKGQGCPD YVLLTHTVSR FAISYQEKVS LLSAIKSPCP
     KDTPEGAELK PWYEPMYLGG VFQLEKGDLL SAEVNLPKYL DITESGQVYF GVIAL
//