TNFA_RAT
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 03-AUG-2022, entry version 192.
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, and
RC 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.
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 (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). {ECO:0000250|UniProtKB:P01375,
CC ECO:0000250|UniProtKB:P06804}.
CC -!- FUNCTION: The TNF intracellular domain (ICD) form induces IL12
CC production in dendritic cells. {ECO:0000250|UniProtKB:P01375}.
CC -!- SUBUNIT: Homotrimer. Interacts with SPPL2B (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, membrane form]: Membrane
CC {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, soluble form]: Secreted
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [C-domain 1]: Secreted {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [C-domain 2]: Secreted {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine
CC and N-acetylneuraminic acid. {ECO:0000250}.
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 RefSeq; XP_008770997.1; XM_008772775.2.
DR AlphaFoldDB; P16599; -.
DR SMR; P16599; -.
DR DIP; DIP-39461N; -.
DR IntAct; P16599; 74.
DR STRING; 10116.ENSRNOP00000001110; -.
DR BindingDB; P16599; -.
DR GlyGen; P16599; 2 sites.
DR PhosphoSitePlus; P16599; -.
DR PaxDb; P16599; -.
DR Ensembl; ENSRNOT00000001110; ENSRNOP00000001110; ENSRNOG00000070745.
DR GeneID; 24835; -.
DR KEGG; rno:24835; -.
DR UCSC; RGD:3876; rat.
DR CTD; 7124; -.
DR RGD; 3876; Tnf.
DR eggNOG; ENOG502S4K8; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_070352_3_1_1; -.
DR InParanoid; P16599; -.
DR OMA; GATMLFC; -.
DR OrthoDB; 1124938at2759; -.
DR PhylomeDB; P16599; -.
DR TreeFam; TF332169; -.
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 NFkappaB 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 tissues.
DR Genevisible; P16599; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
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:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0002020; F:protease binding; 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:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0002526; P:acute inflammatory response; IEP:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IDA:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:RGD.
DR GO; GO:0001775; P:cell activation; IDA:RGD.
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:0071346; P:cellular response to interferon-gamma; IEP: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:0071407; P:cellular response to organic cyclic compound; 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:0002439; P:chronic inflammatory response to antigenic stimulus; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO: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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; 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:0002523; P:leukocyte migration involved in inflammatory response; IEP:RGD.
DR GO; GO:0050901; P:leukocyte tethering or rolling; ISO:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0000165; P:MAPK cascade; 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:0010693; P:negative regulation of alkaline phosphatase activity; ISO:RGD.
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:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; 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:0046325; P:negative regulation of glucose import; IDA: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:1903799; P:negative regulation of miRNA maturation; 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:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; 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:0043242; P:negative regulation of protein-containing complex disassembly; ISO:RGD.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; ISO: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:0045892; P:negative regulation of transcription, DNA-templated; 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:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; ISO:RGD.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
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:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:2001272; P:positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IMP: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:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IBA:GO_Central.
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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:ARUK-UCL.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:RGD.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO: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:0043507; P:positive regulation of JUN kinase activity; 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:0043406; P:positive regulation of MAP kinase activity; 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:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:ARUK-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO: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:0051173; P:positive regulation of nitrogen compound metabolic process; ISO:RGD.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; IDA:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:ARUK-UCL.
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:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
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:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:ARUK-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:1901671; P:positive regulation of superoxide dismutase activity; 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:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0045994; P:positive regulation of translational initiation by iron; ISO:RGD.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:ARUK-UCL.
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:0043491; P:protein kinase B signaling; 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: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:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; 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:0006357; P:regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
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:0009617; P:response to bacterium; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; 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:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB.
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:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; ISO:RGD.
DR GO; GO:1901554; P:response to paracetamol; IEP:RGD.
DR GO; GO:0009314; P:response to radiation; 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:0030730; P:sequestering of triglyceride; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; IDA: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; ISO:RGD.
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 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; PTHR11471:SF23; 1.
DR Pfam; PF00229; TNF; 1.
DR PRINTS; PR01234; TNECROSISFCT.
DR PRINTS; PR01235; TNFALPHA.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS00251; TNF_1; 1.
DR PROSITE; PS50049; TNF_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"
FT /id="PRO_0000417287"
FT CHAIN 1..35
FT /note="Intracellular domain 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417288"
FT CHAIN 50..?
FT /note="C-domain 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417289"
FT CHAIN 52..?
FT /note="C-domain 2"
FT /evidence="ECO:0000250"
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 SITE 34..35
FT /note="Cleavage; by SPPL2A or SPPL2B"
FT /evidence="ECO:0000250"
FT SITE 39..40
FT /note="Cleavage; by SPPL2A or SPPL2B"
FT /evidence="ECO:0000250"
FT SITE 49..50
FT /note="Cleavage; by SPPL2A or SPPL2B"
FT /evidence="ECO:0000250"
FT SITE 51..52
FT /note="Cleavage; by SPPL2A or SPPL2B"
FT /evidence="ECO:0000250"
FT SITE 79..80
FT /note="Cleavage; by ADAM17"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250"
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"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 148..179
FT /evidence="ECO:0000250"
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
