ID   B3GDZ6_PIG              Unreviewed;       232 AA.
AC   B3GDZ6;
DT   22-JUL-2008, integrated into UniProtKB/TrEMBL.
DT   22-JUL-2008, sequence version 1.
DT   13-SEP-2023, entry version 100.
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=TNFa {ECO:0000313|EMBL:ACD81655.1};
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823 {ECO:0000313|EMBL:ACD81655.1};
RN   [1] {ECO:0000313|EMBL:ACD81655.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=PBMC {ECO:0000313|EMBL:ACD81655.1};
RA   Boyd P., Tompkins D., Hudgens T., Baldwin C., Lunney J.;
RT   "U.S. Veterinary Immune Reagent Network: Expressed Swine Gene Sequences.";
RL   Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|EMBL:AEP25618.1}
RP   NUCLEOTIDE SEQUENCE.
RA   Huo J.L., Zhao Y., Zeng Y.Z.;
RT   "cDNA Cloning, Sequence Analysis and Tissue Expression Profile of TNF-alpha
RT   in Banna Mini-pig Inbred Line (BMI).";
RL   Submitted (APR-2011) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000313|EMBL:HCZ82439.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=30723633; DOI=.7717/peerj.6374;
RA   Gilbert D.G.;
RT   "Genes of the pig, Sus scrofa, reconstructed with EvidentialGene.";
RL   PeerJ 7:E6374-E6374(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|ARBA:ARBA00025967, 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; EU682384; ACD81655.1; -; mRNA.
DR   EMBL; JF831365; AEP25618.1; -; mRNA.
DR   EMBL; DQIR01026964; HCZ82439.1; -; Transcribed_RNA.
DR   EMBL; DQIR01102174; HDA57650.1; -; Transcribed_RNA.
DR   RefSeq; NP_999187.1; NM_214022.1.
DR   AlphaFoldDB; B3GDZ6; -.
DR   SMR; B3GDZ6; -.
DR   GeneID; 397086; -.
DR   KEGG; ssc:397086; -.
DR   CTD; 7124; -.
DR   HOGENOM; CLU_070352_3_1_1; -.
DR   OMA; GATMLFC; -.
DR   OrthoDB; 2909163at2759; -.
DR   ExpressionAtlas; B3GDZ6; baseline and differential.
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:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:AgBase.
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        30..53
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU368112"
FT   DOMAIN          88..232
FT                   /note="TNF family profile"
FT                   /evidence="ECO:0000259|PROSITE:PS50049"
SQ   SEQUENCE   232 AA;  25254 MW;  65B28F702D99C8BE CRC64;
     MSTESMIRDV ELAEEALAKK AGGPQGSRRC LCLSLFSFLL VAGATTLFCL LHFEVIGPQK
     EEFPAGPLSI NPLAQGLRSS SQTSDKPVAH VVANVKAEGQ LQWQSGYANA LLANGVKLKD
     NQLVVPTDGL YLIYSQVLFR GQGCPSTNVF LTHTISRIAV SYQTKVNLLS AIKSPCQRET
     PEGAEAKPWY EPIYLGGVFQ LEKDDRLSAE INLPDYLDFA ESGQVYFGII AL
//