ID B8XJI5_ONYLE Unreviewed; 217 AA.
AC B8XJI5;
DT 03-MAR-2009, integrated into UniProtKB/TrEMBL.
DT 03-MAR-2009, sequence version 1.
DT 22-FEB-2023, entry version 47.
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};
DE Flags: Fragment;
GN Name=TNFA {ECO:0000313|EMBL:ACJ22886.1};
OS Onychomys leucogaster (Northern grasshopper mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Neotominae; Onychomys.
OX NCBI_TaxID=38668 {ECO:0000313|EMBL:ACJ22886.1};
RN [1] {ECO:0000313|EMBL:ACJ22886.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Spleen {ECO:0000313|EMBL:ACJ22886.1};
RA Woods M.E., Schountz T., Zeidner N.S., Gage K.L.;
RT "Cloning of grasshopper mouse cytokine and chemokine cDNAs.";
RL Submitted (OCT-2008) 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. 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 EMBL; FJ389356; ACJ22886.1; -; mRNA.
DR AlphaFoldDB; B8XJI5; -.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-UniRule.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0097527; P:necroptotic signaling pathway; IEA:UniProtKB-UniRule.
DR GO; GO:0065008; P:regulation of biological quality; IEA:UniProt.
DR GO; GO:0050793; P:regulation of developmental process; IEA:UniProt.
DR GO; GO:0051239; P:regulation of multicellular organismal process; IEA:UniProt.
DR GO; GO:0051046; P:regulation of secretion; IEA:UniProt.
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 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 27..48
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU368112"
FT DOMAIN 84..217
FT /note="TNF family profile"
FT /evidence="ECO:0000259|PROSITE:PS50049"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:ACJ22886.1"
FT NON_TER 217
FT /evidence="ECO:0000313|EMBL:ACJ22886.1"
SQ SEQUENCE 217 AA; 23964 MW; D6F90C74C0B3021F CRC64;
DVELAEEALP KKAWGPQNSS RCLCLSLFSF LLVAGATTLF CLLNFGVIGP QREEKFPNNL
PIIGSMAQTL TLRSSSQNSS DKPVAHVVAN HQVDEQLEWL SRRANALLAN GMDLKDNQLV
IPADGLYLVY SQVLFKGQGC SNYVLLTHTV SRFAVSYEDK VNLLSAIKSP CPKETPEGSE
LKPWYEPIYL GGVFQLEKGD RLSAEVNLPK YLDFAES
//
