ID   TNFA_PAPAN              Reviewed;         233 AA.
AC   P59695;
DT   23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-MAY-2003, sequence version 1.
DT   28-JUN-2023, entry version 108.
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   Papio anubis (Olive baboon).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Papio.
OX   NCBI_TaxID=9555;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11491535; DOI=10.1007/s002510100322;
RA   Villinger F.J., Bostik P., Mayne A.E., King C.L., Genain C.P., Weiss W.R.,
RA   Ansari A.A.;
RT   "Cloning, sequencing, and homology analysis of nonhuman primate Fas/Fas-
RT   ligand and co-stimulatory molecules.";
RL   Immunogenetics 53:315-328(2001).
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). Promotes osteoclastogenesis and therefore mediates
CC       bone resorption (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; AY234222; AAO85335.1; -; mRNA.
DR   RefSeq; NP_001106118.1; NM_001112648.1.
DR   AlphaFoldDB; P59695; -.
DR   SMR; P59695; -.
DR   STRING; 9555.ENSPANP00000011146; -.
DR   GlyCosmos; P59695; 1 site, No reported glycans.
DR   GeneID; 100126739; -.
DR   CTD; 7124; -.
DR   eggNOG; ENOG502S4K8; Eukaryota.
DR   Proteomes; UP000028761; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0097527; P:necroptotic signaling pathway; ISS:CAFA.
DR   GO; GO:0043242; P:negative regulation of protein-containing complex disassembly; ISS:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISS:UniProtKB.
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; ISS:UniProtKB.
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; Cytokine; Disulfide bond; Glycoprotein; Lipoprotein;
KW   Membrane; Myristate; Phosphoprotein; Reference proteome; Secreted;
KW   Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..233
FT                   /note="Tumor necrosis factor, membrane form"
FT                   /id="PRO_0000034439"
FT   CHAIN           1..39
FT                   /note="Intracellular domain 1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417263"
FT   CHAIN           1..35
FT                   /note="Intracellular domain 2"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417264"
FT   CHAIN           50..?
FT                   /note="C-domain 1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417265"
FT   CHAIN           52..?
FT                   /note="C-domain 2"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000417266"
FT   CHAIN           77..233
FT                   /note="Tumor necrosis factor, soluble form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000034440"
FT   TOPO_DOM        1..34
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        35..57
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        58..233
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
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            76..77
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        80
FT                   /note="O-linked (GalNAc...) serine; in soluble form"
FT                   /evidence="ECO:0000250"
FT   DISULFID        145..177
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   233 AA;  25736 MW;  0C477F9EB6CC9909 CRC64;
     MSTESMIRDV ELAEEALPRK TAGPQGSRRR WFLRLFSFLL VAGATTLFCL LHFGVIGPQR
     EEFPKDPSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVEPT
     DNQLVVPSEG LYLIYSQVLF KGQGCPSNHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE
     TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINLPDYLDF AESGQVYFGI IAL
//