ID Q5STB3_HUMAN Unreviewed; 233 AA. AC Q5STB3; E7DB75; DT 10-MAY-2005, integrated into UniProtKB/TrEMBL. DT 10-MAY-2005, sequence version 1. DT 27-MAR-2024, entry version 170. 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=TNF {ECO:0000313|EMBL:AHJ25918.1}; GN Synonyms=TNF-alpha {ECO:0000313|EMBL:QCI55733.1}, TNFA GN {ECO:0000313|EMBL:BAF31279.1}, TNLG1F {ECO:0000313|EMBL:CTQ86082.1}; GN ORFNames=hCG_43716 {ECO:0000313|EMBL:EAX03424.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:ADV31546.2}; RN [1] {ECO:0000313|EMBL:EAX03424.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=11181995; DOI=10.1126/science.1058040; RA Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G., RA Smith H.O., Yandell M., Evans C.A., Holt R.A., Gocayne J.D., Amanatides P., RA Ballew R.M., Huson D.H., Wortman J.R., Zhang Q., Kodira C.D., Zheng X.H., RA Chen L., Skupski M., Subramanian G., Thomas P.D., Zhang J., RA Gabor Miklos G.L., Nelson C., Broder S., Clark A.G., Nadeau J., RA McKusick V.A., Zinder N., Levine A.J., Roberts R.J., Simon M., Slayman C., RA Hunkapiller M., Bolanos R., Delcher A., Dew I., Fasulo D., Flanigan M., RA Florea L., Halpern A., Hannenhalli S., Kravitz S., Levy S., Mobarry C., RA Reinert K., Remington K., Abu-Threideh J., Beasley E., Biddick K., RA Bonazzi V., Brandon R., Cargill M., Chandramouliswaran I., Charlab R., RA Chaturvedi K., Deng Z., Di Francesco V., Dunn P., Eilbeck K., RA Evangelista C., Gabrielian A.E., Gan W., Ge W., Gong F., Gu Z., Guan P., RA Heiman T.J., Higgins M.E., Ji R.R., Ke Z., Ketchum K.A., Lai Z., Lei Y., RA Li Z., Li J., Liang Y., Lin X., Lu F., Merkulov G.V., Milshina N., RA Moore H.M., Naik A.K., Narayan V.A., Neelam B., Nusskern D., Rusch D.B., RA Salzberg S., Shao W., Shue B., Sun J., Wang Z., Wang A., Wang X., Wang J., RA Wei M., Wides R., Xiao C., Yan C., Yao A., Ye J., Zhan M., Zhang W., RA Zhang H., Zhao Q., Zheng L., Zhong F., Zhong W., Zhu S., Zhao S., RA Gilbert D., Baumhueter S., Spier G., Carter C., Cravchik A., Woodage T., RA Ali F., An H., Awe A., Baldwin D., Baden H., Barnstead M., Barrow I., RA Beeson K., Busam D., Carver A., Center A., Cheng M.L., Curry L., RA Danaher S., Davenport L., Desilets R., Dietz S., Dodson K., Doup L., RA Ferriera S., Garg N., Gluecksmann A., Hart B., Haynes J., Haynes C., RA Heiner C., Hladun S., Hostin D., Houck J., Howland T., Ibegwam C., RA Johnson J., Kalush F., Kline L., Koduru S., Love A., Mann F., May D., RA McCawley S., McIntosh T., McMullen I., Moy M., Moy L., Murphy B., RA Nelson K., Pfannkoch C., Pratts E., Puri V., Qureshi H., Reardon M., RA Rodriguez R., Rogers Y.H., Romblad D., Ruhfel B., Scott R., Sitter C., RA Smallwood M., Stewart E., Strong R., Suh E., Thomas R., Tint N.N., Tse S., RA Vech C., Wang G., Wetter J., Williams S., Williams M., Windsor S., RA Winn-Deen E., Wolfe K., Zaveri J., Zaveri K., Abril J.F., Guigo R., RA Campbell M.J., Sjolander K.V., Karlak B., Kejariwal A., Mi H., Lazareva B., RA Hatton T., Narechania A., Diemer K., Muruganujan A., Guo N., Sato S., RA Bafna V., Istrail S., Lippert R., Schwartz R., Walenz B., Yooseph S., RA Allen D., Basu A., Baxendale J., Blick L., Caminha M., Carnes-Stine J., RA Caulk P., Chiang Y.H., Coyne M., Dahlke C., Mays A., Dombroski M., RA Donnelly M., Ely D., Esparham S., Fosler C., Gire H., Glanowski S., RA Glasser K., Glodek A., Gorokhov M., Graham K., Gropman B., Harris M., RA Heil J., Henderson S., Hoover J., Jennings D., Jordan C., Jordan J., RA Kasha J., Kagan L., Kraft C., Levitsky A., Lewis M., Liu X., Lopez J., RA Ma D., Majoros W., McDaniel J., Murphy S., Newman M., Nguyen T., Nguyen N., RA Nodell M., Pan S., Peck J., Peterson M., Rowe W., Sanders R., Scott J., RA Simpson M., Smith T., Sprague A., Stockwell T., Turner R., Venter E., RA Wang M., Wen M., Wu D., Wu M., Xia A., Zandieh A., Zhu X.; RT "The sequence of the human genome."; RL Science 291:1304-1351(2001). RN [2] {ECO:0000313|EMBL:EAX03424.1} RP NUCLEOTIDE SEQUENCE. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000313|EMBL:BAE78639.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Peripheral blood leukocyte {ECO:0000313|EMBL:BAE78639.1}; RX PubMed=16702430; DOI=10.1534/genetics.106.057034; RA Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M., RA Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K., RA Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A., RA Wanner V., Sano K., Macquin C., Ikeo K., Tokunaga K., Gojobori T., RA Inoko H., Bahram S.; RT "Rapid evolution of major histocompatibility complex class I genes in RT primates generates new disease alleles in humans via hitchhiking RT diversity."; RL Genetics 173:1555-1570(2006). RN [4] {ECO:0000313|EMBL:BAG37464.1} RP NUCLEOTIDE SEQUENCE. RA Wakamatsu A., Yamamoto J., Kimura K., Kaida T., Tsuchiya K., Iida Y., RA Takayama Y., Murakawa K., Kanehori K., Andoh T., Kagawa N., Sato R., RA Kawamura Y., Tanaka S., Kisu Y., Sugano S., Goshima N., Nomura N., RA Isogai T.; RT "NEDO functional analysis of protein and research application project."; RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases. RN [5] {ECO:0000313|EMBL:ADV31546.2} RP NUCLEOTIDE SEQUENCE. RA Rajmani R.S., Tiwari A.K., Subudhi P., Ravi Kumar G., Sahoo A., Palia S.K., RA Uttara C., Lovleen S., Shika S., Sangeeta T., Doley J., Singh P.K.; RL Submitted (AUG-2010) to the EMBL/GenBank/DDBJ databases. RN [6] {ECO:0000313|EMBL:ADV31546.2} RP NUCLEOTIDE SEQUENCE. RA Rajmani R., Tiwari A., Ravi Kumar G., Sahoo A., Doley J., Singh P., RA Rajiv K., Lovleen S., Shikha S., Chaturvedi U., Palia S., Tiwari S.; RL Submitted (MAY-2011) to the EMBL/GenBank/DDBJ databases. RN [7] {ECO:0000313|EMBL:AHJ25918.1} RP NUCLEOTIDE SEQUENCE. RA Selby S.T., Hou L., Steiner N., Hurley C.K., Posch P.E.; RT "TNF and LTA diversity in Caucasians."; RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases. RN [8] {ECO:0000313|EMBL:CTQ86082.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=26646413; DOI=10.1007/s00251-015-0887-5; RA Premzl M.; RT "Comparative genomic analysis of eutherian tumor necrosis factor ligand RT genes."; RL Immunogenetics 68:125-132(2016). RN [9] {ECO:0000313|EMBL:AQY77148.1} RP NUCLEOTIDE SEQUENCE. RA Norman P.J., Norberg S.J., Nemat-Gorgani N., Ronaghi M., Parham P.; RT "CDS alleles of MHC region genes derived from homozygous individuals."; RL Submitted (APR-2017) to the EMBL/GenBank/DDBJ databases. RN [10] {ECO:0000313|EMBL:QCI55733.1} RP NUCLEOTIDE SEQUENCE. RA Mohanty S., Pande V., Das A.; RT "Possible association of TNF-alpha gene and promoter polymorphisms with RT different malaria outcomes in Odisha, India."; RL Submitted (APR-2018) to the EMBL/GenBank/DDBJ databases. RN [11] {ECO:0000313|EMBL:CTQ86082.1} RP NUCLEOTIDE SEQUENCE. RX DOI=10.1016/j.genrep.2019.100414; RA Premzl M.; RT "Eutherian third-party data gene collections."; RL Gene Rep 16:100414-100414(2019). CC -!- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It CC is mainly secreted by macrophages and can induce cell death of certain CC tumor cell lines. It is potent pyrogen causing fever by direct action CC or by stimulation of interleukin-1 secretion and is implicated in the CC induction of cachexia, Under certain conditions it can stimulate cell CC proliferation and induce cell differentiation. Induces insulin CC resistance in adipocytes via inhibition of insulin-induced IRS1 CC tyrosine phosphorylation and insulin-induced glucose uptake. Induces CC GKAP42 protein degradation in adipocytes which is partially responsible CC for TNF-induced insulin resistance. Plays a role in angiogenesis by CC inducing VEGF production synergistically with IL1B and IL6. CC {ECO:0000256|RuleBase:RU368112}. CC -!- FUNCTION: The TNF intracellular domain (ICD) form induces IL12 CC production in dendritic cells. {ECO:0000256|ARBA:ARBA00003559, CC ECO:0000256|RuleBase:RU368112}. CC -!- SUBUNIT: Homotrimer. Interacts with SPPL2B. CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004401, CC ECO:0000256|RuleBase:RU368112}; Single-pass type II membrane protein CC {ECO:0000256|ARBA:ARBA00004401, ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [C-domain 2]: Secreted CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, soluble form]: Secreted CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor, membrane form]: Membrane CC {ECO:0000256|RuleBase:RU368112}; Single-pass type II membrane protein CC {ECO:0000256|RuleBase:RU368112}. CC -!- SUBCELLULAR LOCATION: [C-domain 1]: Secreted CC {ECO:0000256|RuleBase:RU368112}. CC -!- PTM: O-glycosylated; glycans contain galactose, N-acetylgalactosamine CC and N-acetylneuraminic acid. {ECO:0000256|RuleBase:RU368112}. CC -!- PTM: The membrane form, but not the soluble form, is phosphorylated on CC serine residues. Dephosphorylation of the membrane form occurs by CC binding to soluble TNFRSF1A/TNFR1. {ECO:0000256|RuleBase:RU368112}. CC -!- PTM: The soluble form derives from the membrane form by proteolytic CC processing. The membrane-bound form is further proteolytically CC processed by SPPL2A or SPPL2B through regulated intramembrane CC proteolysis producing TNF intracellular domains (ICD1 and ICD2) CC released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into CC the extracellular space. {ECO:0000256|RuleBase:RU368112}. CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. CC {ECO:0000256|ARBA:ARBA00008670, ECO:0000256|RuleBase:RU368112}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; HQ201306; ADV31546.2; -; mRNA. DR EMBL; KF887965; AHJ25918.1; -; Genomic_DNA. DR EMBL; KF887966; AHJ25919.1; -; Genomic_DNA. DR EMBL; KF887967; AHJ25920.1; -; Genomic_DNA. DR EMBL; KF887968; AHJ25921.1; -; Genomic_DNA. DR EMBL; KF887969; AHJ25922.1; -; Genomic_DNA. DR EMBL; KF887970; AHJ25923.1; -; Genomic_DNA. DR EMBL; KF887971; AHJ25924.1; -; Genomic_DNA. DR EMBL; KF887972; AHJ25925.1; -; Genomic_DNA. DR EMBL; KY500676; AQY77148.1; -; Genomic_DNA. DR EMBL; KY500678; AQY77150.1; -; Genomic_DNA. DR EMBL; AB202113; BAE78639.1; -; Genomic_DNA. DR EMBL; AB103618; BAF31279.1; -; Genomic_DNA. DR EMBL; AK314960; BAG37464.1; -; mRNA. DR EMBL; LN874317; CTQ86082.1; -; mRNA. DR EMBL; CH471081; EAX03424.1; -; Genomic_DNA. DR EMBL; MH180323; QCI55733.1; -; Genomic_DNA. DR EMBL; MH180324; QCI55734.1; -; Genomic_DNA. DR EMBL; MH180325; QCI55735.1; -; Genomic_DNA. DR EMBL; MH180326; QCI55736.1; -; Genomic_DNA. DR EMBL; MH180327; QCI55737.1; -; Genomic_DNA. DR EMBL; MH180328; QCI55738.1; -; Genomic_DNA. DR EMBL; MH180329; QCI55739.1; -; Genomic_DNA. DR EMBL; MH180330; QCI55740.1; -; Genomic_DNA. DR EMBL; MH180331; QCI55741.1; -; Genomic_DNA. DR EMBL; MH180332; QCI55742.1; -; Genomic_DNA. DR EMBL; MH180333; QCI55743.1; -; Genomic_DNA. DR EMBL; MH180334; QCI55744.1; -; Genomic_DNA. DR EMBL; MH180335; QCI55745.1; -; Genomic_DNA. DR EMBL; MH180336; QCI55746.1; -; Genomic_DNA. DR EMBL; MH180337; QCI55747.1; -; Genomic_DNA. DR EMBL; MH180338; QCI55748.1; -; Genomic_DNA. DR EMBL; MH180339; QCI55749.1; -; Genomic_DNA. DR EMBL; MH180340; QCI55750.1; -; Genomic_DNA. DR EMBL; MH180341; QCI55751.1; -; Genomic_DNA. DR EMBL; MH180342; QCI55752.1; -; Genomic_DNA. DR EMBL; MH180343; QCI55753.1; -; Genomic_DNA. DR EMBL; MH180344; QCI55754.1; -; Genomic_DNA. DR EMBL; MH180345; QCI55755.1; -; Genomic_DNA. DR EMBL; MH180346; QCI55756.1; -; Genomic_DNA. DR EMBL; MH180347; QCI55757.1; -; Genomic_DNA. DR EMBL; MH180348; QCI55758.1; -; Genomic_DNA. DR EMBL; MH180349; QCI55759.1; -; Genomic_DNA. DR EMBL; MH180350; QCI55760.1; -; Genomic_DNA. DR EMBL; MH180351; QCI55761.1; -; Genomic_DNA. DR EMBL; MH180352; QCI55762.1; -; Genomic_DNA. DR EMBL; MH180353; QCI55763.1; -; Genomic_DNA. DR EMBL; MH180354; QCI55764.1; -; Genomic_DNA. DR EMBL; MH180355; QCI55765.1; -; Genomic_DNA. DR EMBL; MH180356; QCI55766.1; -; Genomic_DNA. DR EMBL; MH180357; QCI55767.1; -; Genomic_DNA. DR EMBL; MH180358; QCI55768.1; -; Genomic_DNA. DR EMBL; MH180359; QCI55769.1; -; Genomic_DNA. DR EMBL; MH180360; QCI55770.1; -; Genomic_DNA. DR EMBL; MH180361; QCI55771.1; -; Genomic_DNA. DR EMBL; MH180362; QCI55772.1; -; Genomic_DNA. DR EMBL; MH180363; QCI55773.1; -; Genomic_DNA. DR EMBL; MH180364; QCI55774.1; -; Genomic_DNA. DR EMBL; MH180365; QCI55775.1; -; Genomic_DNA. DR EMBL; MH180366; QCI55776.1; -; Genomic_DNA. DR EMBL; MH180367; QCI55777.1; -; Genomic_DNA. DR EMBL; MH180368; QCI55778.1; -; Genomic_DNA. DR EMBL; MH180369; QCI55779.1; -; Genomic_DNA. DR EMBL; MH180370; QCI55780.1; -; Genomic_DNA. DR EMBL; MH180371; QCI55781.1; -; Genomic_DNA. DR EMBL; MH180372; QCI55782.1; -; Genomic_DNA. DR EMBL; MH180373; QCI55783.1; -; Genomic_DNA. DR EMBL; MH180374; QCI55784.1; -; Genomic_DNA. DR EMBL; MH180375; QCI55785.1; -; Genomic_DNA. DR EMBL; MH180376; QCI55786.1; -; Genomic_DNA. DR EMBL; MH180377; QCI55787.1; -; Genomic_DNA. DR EMBL; MH180378; QCI55788.1; -; Genomic_DNA. DR EMBL; MH180379; QCI55789.1; -; Genomic_DNA. DR EMBL; MH180380; QCI55790.1; -; Genomic_DNA. DR EMBL; MH180381; QCI55791.1; -; Genomic_DNA. DR EMBL; MH180382; QCI55792.1; -; Genomic_DNA. DR EMBL; MH180383; QCI55793.1; -; Genomic_DNA. DR RefSeq; NP_000585.2; NM_000594.3. DR AlphaFoldDB; Q5STB3; -. DR SMR; Q5STB3; -. DR Antibodypedia; 27196; 5666 antibodies from 56 providers. DR DNASU; 7124; -. DR GeneID; 7124; -. DR KEGG; hsa:7124; -. DR UCSC; uc003nui.5; human. DR CTD; 7124; -. DR PharmGKB; PA435; -. DR VEuPathDB; HostDB:ENSG00000232810; -. DR HOGENOM; CLU_070352_3_1_1; -. DR OMA; GATMLFC; -. DR OrthoDB; 2909163at2759; -. DR BioGRID-ORCS; 7124; 11 hits in 1165 CRISPR screens. DR ChiTaRS; TNF; human. DR GenomeRNAi; 7124; -. DR ExpressionAtlas; Q5STB3; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-UniRule. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; 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:0038177; F:death receptor agonist activity; IEA:Ensembl. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:UniProtKB-UniRule. DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0045123; P:cellular extravasation; IEA:Ensembl. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. 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:0071346; P:cellular response to type II interferon; IEA:Ensembl. DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Ensembl. DR GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl. DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl. DR GO; GO:0006959; P:humoral immune response; IEA:Ensembl. DR GO; GO:0090594; P:inflammatory response to wounding; IEA:Ensembl. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl. DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl. DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IEA:Ensembl. DR GO; GO:0097421; P:liver regeneration; 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:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0120190; P:negative regulation of bile acid secretion; IEA:Ensembl. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl. DR GO; GO:0010459; P:negative regulation of heart rate; IEA:Ensembl. DR GO; GO:0002037; P:negative regulation of L-glutamate import across plasma membrane; IEA:Ensembl. DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0031642; P:negative regulation of myelination; IEA:Ensembl. DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0090324; P:negative regulation of oxidative phosphorylation; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0045760; P:positive regulation of action potential; IEA:Ensembl. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; IEA:Ensembl. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl. DR GO; GO:0031622; P:positive regulation of fever generation; IEA:Ensembl. DR GO; GO:0032724; P:positive regulation of fractalkine production; IEA:Ensembl. DR GO; GO:0051798; P:positive regulation of hair follicle development; IEA:Ensembl. DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IEA:Ensembl. DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IEA:Ensembl. DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl. DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0045834; P:positive regulation of lipid metabolic process; IEA:Ensembl. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:1902565; P:positive regulation of neutrophil activation; IEA:Ensembl. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; 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:0045994; P:positive regulation of translational initiation by iron; IEA:Ensembl. DR GO; GO:0032729; P:positive regulation of type II interferon production; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:0060693; P:regulation of branching involved in salivary gland morphogenesis; IEA:Ensembl. DR GO; GO:0002637; P:regulation of immunoglobulin production; IEA:Ensembl. DR GO; GO:1905038; P:regulation of membrane lipid metabolic process; IEA:Ensembl. DR GO; GO:0045670; P:regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0050708; P:regulation of protein 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: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:0009750; P:response to fructose; IEA:Ensembl. 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:0035900; P:response to isolation stress; IEA:Ensembl. DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl. DR GO; GO:0036005; P:response to macrophage colony-stimulating factor; IEA:Ensembl. DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:0010573; P:vascular endothelial growth factor production; IEA:UniProtKB-UniRule. 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; TUMOR NECROSIS FACTOR; 1. DR PANTHER; PTHR11471; TUMOR NECROSIS FACTOR FAMILY MEMBER; 1. DR Pfam; PF00229; TNF; 1. DR PRINTS; PR01234; TNECROSISFCT. DR PRINTS; PR01235; TNFALPHA. DR SMART; SM00207; TNF; 1. DR SUPFAM; SSF49842; TNF-like; 1. DR PROSITE; PS00251; TNF_1; 1. DR PROSITE; PS50049; TNF_2; 1. PE 2: Evidence at transcript level; KW Cell membrane {ECO:0000256|ARBA:ARBA00022475, KW ECO:0000256|RuleBase:RU368112}; KW Cytokine {ECO:0000256|ARBA:ARBA00022514, ECO:0000256|RuleBase:RU368112}; KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, KW ECO:0000256|RuleBase:RU368112}; KW 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..55 FT /note="Helical" FT /evidence="ECO:0000256|RuleBase:RU368112" FT DOMAIN 89..233 FT /note="TNF family profile" FT /evidence="ECO:0000259|PROSITE:PS50049" SQ SEQUENCE 233 AA; 25644 MW; 3DF90F96C9031FFE CRC64; MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL //