TNFA_PIG
ID TNFA_PIG Reviewed; 232 AA.
AC P23563; A5D9N8;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 160.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2216741; DOI=10.1093/nar/18.18.5564;
RA Drews R.T., Coffee B.W., Prestwood A.K., McGraw R.A.;
RT "Gene sequence of porcine tumor necrosis factor alpha.";
RL Nucleic Acids Res. 18:5564-5564(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=1874444; DOI=10.1016/0378-1119(91)90075-m;
RA Kuhnert P., Wuethrich C., Peterhans E., Pauli U.;
RT "The porcine tumor necrosis factor-encoding genes: sequence and comparative
RT analysis.";
RL Gene 102:171-178(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RA Choi C.S., Molitor T.W., Lin G.F., Murtaugh M.P.;
RT "Complete nucleotide sequence of a cDNA encoding porcine tumor necrosis
RT factor-alpha.";
RL Anim. Biotechnol. 2:97-105(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Large white; TISSUE=Fibroblast;
RX PubMed=11169259; DOI=10.1034/j.1399-0039.2001.057001055.x;
RA Chardon P., Rogel-Gaillard C., Cattolico L., Duprat S., Vaiman M.,
RA Renard C.;
RT "Sequence of the swine major histocompatibility complex region containing
RT all non-classical class I genes.";
RL Tissue Antigens 57:55-65(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 44-232.
RX PubMed=2478420; DOI=10.1016/0378-1119(89)90350-8;
RA Pauli U., Beutler B., Peterhans E.;
RT "Porcine tumor necrosis factor alpha: cloning with the polymerase chain
RT reaction and determination of the nucleotide sequence.";
RL Gene 81:185-191(1989).
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). {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; X54001; CAA37949.1; -; Genomic_DNA.
DR EMBL; X54859; CAA38639.1; -; Genomic_DNA.
DR EMBL; X57321; CAA40591.1; -; mRNA.
DR EMBL; AJ251914; CAB63852.1; -; Genomic_DNA.
DR EMBL; BX548169; CAN59689.1; -; Genomic_DNA.
DR EMBL; M29079; AAA31128.1; -; mRNA.
DR PIR; S12606; S12606.
DR RefSeq; NP_999187.1; NM_214022.1.
DR AlphaFoldDB; P23563; -.
DR SMR; P23563; -.
DR STRING; 9823.ENSSSCP00000001491; -.
DR PaxDb; P23563; -.
DR PRIDE; P23563; -.
DR Ensembl; ENSSSCT00000001533; ENSSSCP00000001491; ENSSSCG00000001404.
DR Ensembl; ENSSSCT00005051419; ENSSSCP00005031803; ENSSSCG00005032154.
DR Ensembl; ENSSSCT00015077176; ENSSSCP00015031063; ENSSSCG00015057632.
DR Ensembl; ENSSSCT00025108213; ENSSSCP00025048968; ENSSSCG00025077751.
DR Ensembl; ENSSSCT00030091837; ENSSSCP00030042263; ENSSSCG00030065721.
DR Ensembl; ENSSSCT00035025057; ENSSSCP00035009452; ENSSSCG00035019345.
DR Ensembl; ENSSSCT00040097071; ENSSSCP00040043236; ENSSSCG00040070661.
DR Ensembl; ENSSSCT00045065761; ENSSSCP00045046558; ENSSSCG00045038014.
DR Ensembl; ENSSSCT00050008020; ENSSSCP00050003415; ENSSSCG00050005898.
DR Ensembl; ENSSSCT00055057060; ENSSSCP00055045643; ENSSSCG00055028741.
DR Ensembl; ENSSSCT00060058688; ENSSSCP00060025133; ENSSSCG00060043262.
DR Ensembl; ENSSSCT00065034958; ENSSSCP00065014573; ENSSSCG00065026040.
DR Ensembl; ENSSSCT00070048157; ENSSSCP00070040652; ENSSSCG00070024118.
DR GeneID; 397086; -.
DR KEGG; ssc:397086; -.
DR CTD; 7124; -.
DR VGNC; VGNC:94249; TNF.
DR eggNOG; ENOG502S4K8; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_070352_3_1_1; -.
DR InParanoid; P23563; -.
DR OMA; GATMLFC; -.
DR OrthoDB; 1124938at2759; -.
DR TreeFam; TF332169; -.
DR Reactome; R-SSC-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-SSC-5668541; TNFR2 non-canonical NF-kB pathway.
DR Proteomes; UP000008227; Chromosome 7.
DR Proteomes; UP000314985; Chromosome 7.
DR Bgee; ENSSSCG00000001404; Expressed in blood and 15 other tissues.
DR ExpressionAtlas; P23563; baseline and differential.
DR Genevisible; P23563; SS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IBA:GO_Central.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0097527; P:necroptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:AgBase.
DR GO; GO:2000866; P:positive regulation of estradiol secretion; IDA:CACAO.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IGI:ARUK-UCL.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central.
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; PTHR11471:SF23; 1.
DR Pfam; PF00229; TNF; 1.
DR PRINTS; PR01234; TNECROSISFCT.
DR PRINTS; PR01235; TNFALPHA.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 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..232
FT /note="Tumor necrosis factor, membrane form"
FT /id="PRO_0000034445"
FT CHAIN 1..39
FT /note="Intracellular domain 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417275"
FT CHAIN 1..35
FT /note="Intracellular domain 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417276"
FT CHAIN 50..?
FT /note="C-domain 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417277"
FT CHAIN 52..?
FT /note="C-domain 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000417278"
FT CHAIN 77..232
FT /note="Tumor necrosis factor, soluble form"
FT /id="PRO_0000034446"
FT TOPO_DOM 1..35
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..232
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT SITE 34..35
FT /note="Cleavage; by SPPL2A or SPPL2B"
FT /evidence="ECO:0000250"
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 19
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P01375"
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 144..176
FT /evidence="ECO:0000250"
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
