ID G7P4P2_MACFA Unreviewed; 214 AA.
AC G7P4P2;
DT 25-JAN-2012, integrated into UniProtKB/TrEMBL.
DT 02-JUN-2021, sequence version 2.
DT 27-MAR-2024, entry version 73.
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|Ensembl:ENSMFAP00000002816.2};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541 {ECO:0000313|Ensembl:ENSMFAP00000002816.2, ECO:0000313|Proteomes:UP000233100};
RN [1] {ECO:0000313|Ensembl:ENSMFAP00000002816.2, ECO:0000313|Proteomes:UP000233100}
RP NUCLEOTIDE SEQUENCE.
RA Warren W., Wilson R.K.;
RL Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSMFAP00000002816.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
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}.
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DR AlphaFoldDB; G7P4P2; -.
DR Ensembl; ENSMFAT00000027966.2; ENSMFAP00000002816.2; ENSMFAG00000040286.2.
DR VEuPathDB; HostDB:ENSMFAG00000040286; -.
DR GeneTree; ENSGT01060000248544; -.
DR Proteomes; UP000233100; Chromosome 4.
DR Bgee; ENSMFAG00000040286; Expressed in spleen and 5 other cell types or tissues.
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: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:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:Ensembl.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:UniProtKB-UniRule.
DR GO; GO:0140374; P:antiviral innate immune response; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071316; P:cellular response to nicotine; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl.
DR GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl.
DR GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO: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:0050901; P:leukocyte tethering or rolling; IEA:Ensembl.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IEA:Ensembl.
DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl.
DR GO; GO:0097527; P:necroptotic signaling pathway; IEA:UniProtKB-UniRule.
DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; IEA:Ensembl.
DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; IEA:Ensembl.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0061048; P:negative regulation of branching involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; IEA:Ensembl.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0043242; P:negative regulation of protein-containing complex disassembly; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0061044; P:negative regulation of vascular wound healing; IEA:Ensembl.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IEA:Ensembl.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IEA:Ensembl.
DR GO; GO:2000334; P:positive regulation of blood microparticle formation; IEA:Ensembl.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:Ensembl.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl.
DR GO; GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0031622; P:positive regulation of fever generation; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0051798; P:positive regulation of hair follicle development; IEA:Ensembl.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IEA:Ensembl.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR GO; GO:0150129; P:positive regulation of interleukin-33 production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; IEA:Ensembl.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO: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:0071803; P:positive regulation of podosome assembly; IEA:Ensembl.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0051222; P:positive regulation of protein transport; IEA:Ensembl.
DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IEA:Ensembl.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IEA:Ensembl.
DR GO; GO:1901647; P:positive regulation of synoviocyte proliferation; 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:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0060693; P:regulation of branching involved in salivary gland morphogenesis; IEA:Ensembl.
DR GO; GO:2000351; P:regulation of endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IEA:Ensembl.
DR GO; GO:0002637; P:regulation of immunoglobulin production; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:1905038; P:regulation of membrane lipid metabolic process; IEA:Ensembl.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0050807; P:regulation of synapse organization; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0030730; P:sequestering of triglyceride; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0010573; P:vascular endothelial growth factor production; IEA:UniProtKB-UniRule.
DR CDD; cd00184; TNF; 1.
DR 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 3: Inferred from homology;
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 Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288, ECO:0000256|RuleBase:RU368112};
KW Membrane {ECO:0000256|ARBA:ARBA00023136};
KW Myristate {ECO:0000256|ARBA:ARBA00022707, ECO:0000256|RuleBase:RU368112};
KW Phosphoprotein {ECO:0000256|RuleBase:RU368112};
KW Reference proteome {ECO:0000313|Proteomes:UP000233100};
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 Transmembrane helix {ECO:0000256|ARBA:ARBA00022989}.
FT DOMAIN 70..214
FT /note="TNF family profile"
FT /evidence="ECO:0000259|PROSITE:PS50049"
SQ SEQUENCE 214 AA; 24113 MW; 9437391EA6A68521 CRC64;
MCADREGWRE KQRGGRRGCR KRCGKRWRTE RERWRGRMSG TWKFPKDPSL ISPLAQAVRS
SSRTPSDKPV AHVVANPQAE GQLQWLNRRA NALLANGVEL TDNQLVVPSE GLYLIYSQVL
FKGQGCPSNH VLLTHTISRI AVSYQTKVNL LSAIKSPCQR ETPEGAEAKP WYEPIYLGGV
FQLEKGDRLS AEINLPDYLD FAESGQVYFG IIAL
//
