TNFA_MOUSE
ID TNFA_MOUSE Reviewed; 235 AA.
AC P06804; O35853; Q62326; Q91VF3;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 222.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2836146; DOI=10.1089/dna.1988.7.193;
RA Shirai T., Shimizu N., Shiojiri S., Horiguchi S., Ito H.;
RT "Cloning and expression in Escherichia coli of the gene for mouse tumor
RT necrosis factor.";
RL DNA 7:193-201(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3898078; DOI=10.1073/pnas.82.18.6060;
RA Pennica D., Hayflick J.S., Bringman T.S., Palladino M.A., Goeddel D.V.;
RT "Cloning and expression in Escherichia coli of the cDNA for murine tumor
RT necrosis factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6060-6064(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2419912; DOI=10.1073/pnas.83.6.1670;
RA Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A.;
RT "Identification of a common nucleotide sequence in the 3'-untranslated
RT region of mRNA molecules specifying inflammatory mediators.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:1670-1674(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2989794; DOI=10.1093/nar/13.12.4417;
RA Fransen L., Mueller R., Marmenout A., Tavernier J., van der Heyden J.,
RA Kawashima E., Chollet A., Tizard R., van Heuverswyn H., van Vliet A.,
RA Ruysschaert M.-R., Fiers W.;
RT "Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic
RT expression.";
RL Nucleic Acids Res. 13:4417-4429(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=3040015;
RA Shakhov A.N., Nedospasov S.A.;
RT "Molecular cloning of genes coding for tumor necrosis factor. Complete
RT nucleotide sequence of the genome copy of TNF-alpha in mice.";
RL Bioorg. Khim. 13:701-705(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3684584; DOI=10.1093/nar/15.21.9083;
RA Semon D., Kawashima E., Jongeneel C.V., Shakhov A.N., Nedospasov S.A.;
RT "Nucleotide sequence of the murine TNF locus, including the TNF-alpha
RT (tumor necrosis factor) and TNF-beta (lymphotoxin) genes.";
RL Nucleic Acids Res. 15:9083-9084(1987).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CTS, and NOD;
RX PubMed=7560085; DOI=10.1172/jci118239;
RA Ikegami H., Makino S., Yamato E., Kawaguchi Y., Ueda H., Sakamoto T.,
RA Takekawa K., Ogihara T.;
RT "Identification of a new susceptibility locus for insulin-dependent
RT diabetes mellitus by ancestral haplotype congenic mapping.";
RL J. Clin. Invest. 96:1936-1942(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-7 AND ALA-77.
RC STRAIN=A/J, BALB/cJ, and C57BL/6J;
RX PubMed=9089109; DOI=10.1007/s002510050233;
RA Iraqi F., Teale A.;
RT "Cloning and sequencing of the Tnfa genes of three inbred mouse strains.";
RL Immunogenetics 45:459-461(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129;
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE OF 1-96.
RC STRAIN=BFM/2Msf, BLG2/Msf, C57BL/10SnJ, CAST/EiJ, HMI/Msf, MSM/Msf,
RC NJL/Msf, pgn2, and SWN/Msf;
RA Liu Y., Kitano T., Koide T., Shiroishi T., Moriwaki K., Saitou N.;
RT "Conspicuous differences among gene genealogies of 21 nuclear genes of five
RT Mus musculus subspecies.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 70-87.
RX PubMed=2777790; DOI=10.1016/s0021-9258(18)71615-3;
RA Cseh K., Beutler B.;
RT "Alternative cleavage of the cachectin/tumor necrosis factor propeptide
RT results in a larger, inactive form of secreted protein.";
RL J. Biol. Chem. 264:16256-16260(1989).
RN [12]
RP PROTEIN SEQUENCE OF 80-99.
RX PubMed=2268312; DOI=10.1016/s0006-291x(05)80895-2;
RA Sherry B., Juc D.-M., Zentella A., Cerami A.;
RT "Characterization of high molecular weight glycosylated forms of murine
RT tumor necrosis factor.";
RL Biochem. Biophys. Res. Commun. 173:1072-1078(1990).
RN [13]
RP IDENTIFICATION OF MEMBRANE-BOUND FORM.
RX PubMed=3349526; DOI=10.1016/0092-8674(88)90486-2;
RA Kriegler M., Perez X., Defay K., Albert I., Lu S.D.;
RT "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane
RT protein: ramifications for the complex physiology of TNF.";
RL Cell 53:45-53(1988).
RN [14]
RP FUNCTION.
RX PubMed=25586176; DOI=10.1074/jbc.m114.624759;
RA Ando Y., Shinozawa Y., Iijima Y., Yu B.C., Sone M., Ooi Y., Watanaka Y.,
RA Chida K., Hakuno F., Takahashi S.;
RT "Tumor necrosis factor (TNF)-alpha-induced repression of GKAP42 protein
RT levels through cGMP-dependent kinase (cGK)-Ialpha causes insulin resistance
RT in 3T3-L1 adipocytes.";
RL J. Biol. Chem. 290:5881-5892(2015).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 80-235.
RX PubMed=10089307; DOI=10.1107/s0907444998018435;
RA Baeyens K.J., De Bondt H.L., Raeymaekers A., Fiers W., De Ranter C.J.;
RT "The structure of mouse tumour-necrosis factor at 1.4 A resolution: towards
RT modulation of its selectivity and trimerization.";
RL Acta Crystallogr. D 55:772-778(1999).
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 (PubMed:25586176). Plays a role in
CC angiogenesis by inducing VEGF production synergistically with IL1B and
CC IL6 (By similarity). {ECO:0000250|UniProtKB:P01375,
CC ECO:0000269|PubMed:25586176}.
CC -!- FUNCTION: The TNF intracellular domain (ICD) form induces IL12
CC production in dendritic cells. {ECO:0000250|UniProtKB:P01375}.
CC -!- SUBUNIT: Interacts with SPPL2B (By similarity). Homotrimer.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein.
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 -!- SUBCELLULAR LOCATION: [C-domain 1]: Secreted {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [C-domain 2]: Secreted {ECO:0000250}.
CC -!- PTM: The membrane-bound form is further proteolytically processed by
CC SPPL2A or SPPL2B through regulated intramembrane proteolysis producing
CC TNF intracellular domains (ICD1 and ICD2) released in the cytosol and
CC TNF C-domain 1 and C-domain 2 secreted into the extracellular space (By
CC similarity). The soluble form derives from the membrane form by
CC proteolytic processing. {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; M20155; AAA40462.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M11731; AAA40458.1; -; mRNA.
DR EMBL; M13049; AAA40457.1; -; mRNA.
DR EMBL; X02611; CAA26457.1; -; mRNA.
DR EMBL; M38296; AAA40459.1; -; Genomic_DNA.
DR EMBL; Y00467; CAA68530.1; -; Genomic_DNA.
DR EMBL; U06950; AAA18594.1; -; Unassigned_DNA.
DR EMBL; D84196; BAA19512.1; -; Genomic_DNA.
DR EMBL; D84199; BAA19513.1; -; Genomic_DNA.
DR EMBL; U68414; AAB65593.1; -; Genomic_DNA.
DR EMBL; AF109719; AAC82484.1; -; Genomic_DNA.
DR EMBL; AB039224; BAB68748.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039225; BAB68749.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039226; BAB68750.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039227; BAB68751.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039228; BAB68752.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039229; BAB68753.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039230; BAB68754.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039231; BAB68755.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB039232; BAB68756.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS28691.1; -.
DR PIR; A22908; QWMSN.
DR RefSeq; NP_001265530.1; NM_001278601.1.
DR RefSeq; NP_038721.1; NM_013693.3.
DR PDB; 2TNF; X-ray; 1.40 A; A/B/C=80-234.
DR PDB; 7KP7; X-ray; 2.65 A; A/B/C=88-235.
DR PDB; 7KP8; X-ray; 3.15 A; A/B/C=89-235.
DR PDBsum; 2TNF; -.
DR PDBsum; 7KP7; -.
DR PDBsum; 7KP8; -.
DR AlphaFoldDB; P06804; -.
DR SMR; P06804; -.
DR BioGRID; 204240; 20.
DR DIP; DIP-40029N; -.
DR IntAct; P06804; 2.
DR STRING; 10090.ENSMUSP00000025263; -.
DR BindingDB; P06804; -.
DR ChEMBL; CHEMBL4984; -.
DR GlyGen; P06804; 2 sites.
DR iPTMnet; P06804; -.
DR PhosphoSitePlus; P06804; -.
DR SwissPalm; P06804; -.
DR EPD; P06804; -.
DR PaxDb; P06804; -.
DR PRIDE; P06804; -.
DR Antibodypedia; 27196; 4706 antibodies from 56 providers.
DR DNASU; 21926; -.
DR Ensembl; ENSMUST00000025263; ENSMUSP00000025263; ENSMUSG00000024401.
DR GeneID; 21926; -.
DR KEGG; mmu:21926; -.
DR UCSC; uc008cgr.2; mouse.
DR CTD; 7124; -.
DR MGI; MGI:104798; Tnf.
DR VEuPathDB; HostDB:ENSMUSG00000024401; -.
DR eggNOG; ENOG502S4K8; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_070352_3_1_1; -.
DR InParanoid; P06804; -.
DR OMA; GATMLFC; -.
DR OrthoDB; 1124938at2759; -.
DR PhylomeDB; P06804; -.
DR TreeFam; TF332169; -.
DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5626978; TNFR1-mediated ceramide production.
DR Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-MMU-75893; TNF signaling.
DR BioGRID-ORCS; 21926; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Tnf; mouse.
DR EvolutionaryTrace; P06804; -.
DR PRO; PR:P06804; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P06804; protein.
DR Bgee; ENSMUSG00000024401; Expressed in granulocyte and 34 other tissues.
DR ExpressionAtlas; P06804; baseline and differential.
DR Genevisible; P06804; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0001891; C:phagocytic cup; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0055037; C:recycling endosome; IDA:BHF-UCL.
DR GO; GO:0030141; C:secretory granule; TAS:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IDA:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0002526; P:acute inflammatory response; IEA:Ensembl.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0045123; P:cellular extravasation; IDA:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0071316; P:cellular response to nicotine; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0097237; P:cellular response to toxic substance; IEA:Ensembl.
DR GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; ISO:MGI.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0006952; P:defense response; IMP:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IDA:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IGI:MGI.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl.
DR GO; GO:0072577; P:endothelial cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IDA:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IGI:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IDA:MGI.
DR GO; GO:0006959; P:humoral immune response; IMP:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IGI:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:MGI.
DR GO; GO:0007254; P:JNK cascade; IDA:MGI.
DR GO; GO:0050900; P:leukocyte migration; IDA:MGI.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0050901; P:leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:MGI.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0001774; P:microglial cell activation; IDA:ARUK-UCL.
DR GO; GO:0097527; P:necroptotic signaling pathway; IGI:MGI.
DR GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IDA:BHF-UCL.
DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; IGI:ARUK-UCL.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:MGI.
DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:MGI.
DR GO; GO:0120190; P:negative regulation of bile acid secretion; IEA:Ensembl.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0061048; P:negative regulation of branching involved in lung morphogenesis; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; ISO:MGI.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI.
DR GO; GO:0046325; P:negative regulation of glucose import; IDA:MGI.
DR GO; GO:0010459; P:negative regulation of heart rate; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0002037; P:negative regulation of L-glutamate import across plasma membrane; IEA:Ensembl.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:MGI.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; ISO:MGI.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:BHF-UCL.
DR GO; GO:0031642; P:negative regulation of myelination; IEA:Ensembl.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:MGI.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:BHF-UCL.
DR GO; GO:0090324; P:negative regulation of oxidative phosphorylation; IEA:Ensembl.
DR GO; GO:0043242; P:negative regulation of protein-containing complex disassembly; ISS:UniProtKB.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0061044; P:negative regulation of vascular wound healing; ISO:MGI.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISO:MGI.
DR GO; GO:0030316; P:osteoclast differentiation; IGI:MGI.
DR GO; GO:0045760; P:positive regulation of action potential; IEA:Ensembl.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IDA:ARUK-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2000334; P:positive regulation of blood microparticle formation; ISO:MGI.
DR GO; GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; ISO:MGI.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:MGI.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:MGI.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:MGI.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; IGI:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:2001272; P:positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
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; IDA:BHF-UCL.
DR GO; GO:0032724; P:positive regulation of fractalkine production; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0051798; P:positive regulation of hair follicle development; IMP:UniProtKB.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IGI:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISO:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IGI:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IEA:Ensembl.
DR GO; GO:0150129; P:positive regulation of interleukin-33 production; ISO:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
DR GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; ISO:MGI.
DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:ARUK-UCL.
DR GO; GO:1902565; P:positive regulation of neutrophil activation; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:BHF-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:0051173; P:positive regulation of nitrogen compound metabolic process; IGI:ARUK-UCL.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI.
DR GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0071803; P:positive regulation of podosome assembly; ISO:MGI.
DR GO; GO:0043068; P:positive regulation of programmed cell death; ISO:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:MGI.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0051222; P:positive regulation of protein transport; ISO:MGI.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISS:UniProtKB.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:1901671; P:positive regulation of superoxide dismutase activity; ISO:MGI.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IMP:ARUK-UCL.
DR GO; GO:1901647; P:positive regulation of synoviocyte proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0045994; P:positive regulation of translational initiation by iron; IDA:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; ISO:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0060693; P:regulation of branching involved in salivary gland morphogenesis; IDA:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR GO; GO:2000351; P:regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:MGI.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0002637; P:regulation of immunoglobulin production; IDA:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IDA:MGI.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IDA:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0050708; P:regulation of protein secretion; IDA:MGI.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IDA:MGI.
DR GO; GO:0050807; P:regulation of synapse organization; IMP:ARUK-UCL.
DR GO; GO:1905242; P:response to 3,3',5-triiodo-L-thyronine; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:1990268; P:response to gold nanoparticle; IEA:Ensembl.
DR GO; GO:0140460; P:response to Gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; IDA:MGI.
DR GO; GO:1901554; P:response to paracetamol; IEA:Ensembl.
DR GO; GO:0009314; P:response to radiation; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0030730; P:sequestering of triglyceride; ISO:MGI.
DR GO; GO:0003009; P:skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:MGI.
DR GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytokine; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Lipoprotein; Membrane; Myristate;
KW Phosphoprotein; Reference proteome; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..235
FT /note="Tumor necrosis factor, membrane form"
FT /id="PRO_0000034435"
FT CHAIN 1..39
FT /note="Intracellular domain 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417255"
FT CHAIN 1..35
FT /note="Intracellular domain 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417256"
FT CHAIN 50..?
FT /note="C-domain 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417257"
FT CHAIN 52..?
FT /note="C-domain 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417258"
FT CHAIN 80..235
FT /note="Tumor necrosis factor, soluble form"
FT /id="PRO_0000034436"
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 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 DISULFID 148..179
FT VARIANT 7
FT /note="I -> T (in strain: BALB/c and C57BL/6)"
FT /evidence="ECO:0000269|PubMed:9089109"
FT VARIANT 77
FT /note="T -> A (in strain: BALB/c and C57BL/6)"
FT /evidence="ECO:0000269|PubMed:9089109"
FT CONFLICT 79..81
FT /note="Missing (in Ref. 8; AAB65593)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="G -> R (in Ref. 3 and 4)"
FT /evidence="ECO:0000305"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 130..147
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:2TNF"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 168..176
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 191..204
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:2TNF"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:2TNF"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:2TNF"
SQ SEQUENCE 235 AA; 25896 MW; 16DD2A9676D68C5D CRC64;
MSTESMIRDV ELAEEALPQK MGGFQNSRRC LCLSLFSFLL VAGATTLFCL LNFGVIGPQR
DEKFPNGLPL ISSMAQTLTL RSSSQNSSDK PVAHVVANHQ VEEQLEWLSQ RANALLANGM
DLKDNQLVVP ADGLYLVYSQ VLFKGQGCPD YVLLTHTVSR FAISYQEKVN LLSAVKSPCP
KDTPEGAELK PWYEPIYLGG VFQLEKGDQL SAEVNLPKYL DFAESGQVYF GVIAL
