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Tumor necrosis factor (Cachectin) (TNF-alpha) (Tumor necrosis factor ligand superfamily member 2) (TNF-a) [Cleaved into: Tumor necrosis factor, membrane form (N-terminal fragment) (NTF); Intracellular domain 1 (ICD1); Intracellular domain 2 (ICD2); C-domain 1; C-domain 2; Tumor necrosis factor, soluble form]

 TNFA_HORSE              Reviewed;         234 AA.
P29553; Q9TTJ3;
01-APR-1993, integrated into UniProtKB/Swiss-Prot.
01-APR-1993, sequence version 1.
25-OCT-2017, entry version 133.
RecName: Full=Tumor necrosis factor;
AltName: Full=Cachectin;
AltName: Full=TNF-alpha;
AltName: Full=Tumor necrosis factor ligand superfamily member 2;
Short=TNF-a;
Contains:
RecName: Full=Tumor necrosis factor, membrane form;
AltName: Full=N-terminal fragment;
Short=NTF;
Contains:
RecName: Full=Intracellular domain 1;
Short=ICD1;
Contains:
RecName: Full=Intracellular domain 2;
Short=ICD2;
Contains:
RecName: Full=C-domain 1;
Contains:
RecName: Full=C-domain 2;
Contains:
RecName: Full=Tumor necrosis factor, soluble form;
Flags: Precursor;
Name=TNF; Synonyms=TNFA, TNFSF2;
Equus caballus (Horse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
NCBI_TaxID=9796;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=1748301; DOI=10.1016/0378-1119(91)90333-7;
Su X., Morris D.D., McGraw R.A.;
"Cloning and characterization of gene TNF alpha encoding equine tumor
necrosis factor alpha.";
Gene 107:319-321(1991).
[2]
NUCLEOTIDE SEQUENCE.
STRAIN=Thoroughbred; TISSUE=Artery;
Ishida N., Sato F., Hasegawa T.;
"Molecular cloning of equine tumor necrosis factor-alpha mRNA.";
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: Cytokine that binds to TNFRSF1A/TNFR1 and
TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can
induce cell death of certain tumor cell lines. It is potent
pyrogen causing fever by direct action or by stimulation of
interleukin-1 secretion and is implicated in the induction of
cachexia, Under certain conditions it can stimulate cell
proliferation and induce cell differentiation.
-!- FUNCTION: The TNF intracellular domain (ICD) form induces IL12
production in dendritic cells. {ECO:0000250}.
-!- SUBUNIT: Homotrimer. Interacts with SPPL2B (By similarity).
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass
type II membrane protein {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Tumor necrosis factor, membrane form:
Membrane {ECO:0000250}; Single-pass type II membrane protein
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Tumor necrosis factor, soluble form:
Secreted {ECO:0000250}.
-!- SUBCELLULAR LOCATION: C-domain 1: Secreted {ECO:0000250}.
-!- SUBCELLULAR LOCATION: C-domain 2: Secreted {ECO:0000250}.
-!- PTM: The soluble form derives from the membrane form by
proteolytic processing. The membrane-bound form is further
proteolytically processed by SPPL2A or SPPL2B through regulated
intramembrane proteolysis producing TNF intracellular domains
(ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-
domain 2 secreted into the extracellular space (By similarity).
{ECO:0000250}.
-!- PTM: The membrane form, but not the soluble form, is
phosphorylated on serine residues. Dephosphorylation of the
membrane form occurs by binding to soluble TNFRSF1A/TNFR1 (By
similarity). {ECO:0000250}.
-!- PTM: O-glycosylated; glycans contain galactose, N-
acetylgalactosamine and N-acetylneuraminic acid. {ECO:0000250}.
-!- SIMILARITY: Belongs to the tumor necrosis factor family.
{ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; M64087; AAA30959.1; -; Genomic_DNA.
EMBL; AB035735; BAA88349.1; -; mRNA.
PIR; JQ1344; JQ1344.
RefSeq; NP_001075288.2; NM_001081819.2.
UniGene; Eca.13019; -.
ProteinModelPortal; P29553; -.
SMR; P29553; -.
STRING; 9796.ENSECAP00000001460; -.
PaxDb; P29553; -.
PRIDE; P29553; -.
Ensembl; ENSECAT00000002048; ENSECAP00000001460; ENSECAG00000001174.
GeneID; 100033834; -.
KEGG; ecb:100033834; -.
CTD; 7124; -.
eggNOG; ENOG410ISAN; Eukaryota.
eggNOG; ENOG410YQC4; LUCA.
GeneTree; ENSGT00530000062992; -.
HOGENOM; HOG000048729; -.
HOVERGEN; HBG012516; -.
InParanoid; P29553; -.
KO; K03156; -.
OMA; PWYEPIY; -.
OrthoDB; EOG091G0HIG; -.
TreeFam; TF332169; -.
Proteomes; UP000002281; Chromosome 20.
Bgee; ENSECAG00000001174; -.
ExpressionAtlas; P29553; baseline.
GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
GO; GO:0045121; C:membrane raft; IEA:Ensembl.
GO; GO:0001891; C:phagocytic cup; IEA:Ensembl.
GO; GO:0055037; C:recycling endosome; IEA:Ensembl.
GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
GO; GO:0002020; F:protease binding; IEA:Ensembl.
GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:Ensembl.
GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:Ensembl.
GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
GO; GO:0000187; P:activation of MAPK activity; IEA:Ensembl.
GO; GO:0000185; P:activation of MAPKKK activity; IEA:Ensembl.
GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
GO; GO:0071316; P:cellular response to nicotine; IEA:Ensembl.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl.
GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl.
GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IEA:Ensembl.
GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
GO; GO:0006959; P:humoral immune response; IEA:Ensembl.
GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
GO; GO:0050901; P:leukocyte tethering or rolling; IEA:Ensembl.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
GO; GO:0097527; P:necroptotic signaling pathway; ISS:UniProtKB.
GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IEA:Ensembl.
GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; IEA:Ensembl.
GO; GO:0061048; P:negative regulation of branching involved in lung morphogenesis; IEA:Ensembl.
GO; GO:0002740; P:negative regulation of cytokine secretion involved in immune response; IEA:Ensembl.
GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl.
GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
GO; GO:0044130; P:negative regulation of growth of symbiont in host; IEA:Ensembl.
GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl.
GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl.
GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; IEA:Ensembl.
GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
GO; GO:0043242; P:negative regulation of protein complex disassembly; ISS:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0045071; P:negative regulation of viral genome replication; IEA:Ensembl.
GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
GO; GO:2000334; P:positive regulation of blood microparticle formation; IEA:Ensembl.
GO; GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; IEA:Ensembl.
GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl.
GO; GO:0045080; P:positive regulation of chemokine biosynthetic process; IEA:Ensembl.
GO; GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
GO; GO:0050715; P:positive regulation of cytokine secretion; IEA:Ensembl.
GO; GO:0031622; P:positive regulation of fever generation; IEA:Ensembl.
GO; GO:0051798; P:positive regulation of hair follicle development; IEA:Ensembl.
GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IEA:Ensembl.
GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl.
GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
GO; GO:0045416; P:positive regulation of interleukin-8 biosynthetic process; IEA:Ensembl.
GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; IEA:Ensembl.
GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
GO; GO:0042346; P:positive regulation of NF-kappaB import into nucleus; IEA:Ensembl.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
GO; GO:0051533; P:positive regulation of NFAT protein import into nucleus; IEA:Ensembl.
GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl.
GO; GO:0071803; P:positive regulation of podosome assembly; IEA:Ensembl.
GO; GO:0043243; P:positive regulation of protein complex disassembly; ISS:UniProtKB.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
GO; GO:1901671; P:positive regulation of superoxide dismutase activity; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0045994; P:positive regulation of translational initiation by iron; IEA:Ensembl.
GO; GO:1904707; P:positive regulation of vascular smooth muscle cell proliferation; IEA:Ensembl.
GO; GO:0000060; P:protein import into nucleus, translocation; IEA:Ensembl.
GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
GO; GO:0032800; P:receptor biosynthetic process; IEA:Ensembl.
GO; GO:0060693; P:regulation of branching involved in salivary gland morphogenesis; IEA:Ensembl.
GO; GO:1903140; P:regulation of establishment of endothelial barrier; IEA:Ensembl.
GO; GO:0051023; P:regulation of immunoglobulin secretion; IEA:Ensembl.
GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
GO; GO:0009615; P:response to virus; IEA:Ensembl.
GO; GO:0030730; P:sequestering of triglyceride; IEA:Ensembl.
GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
Gene3D; 2.60.120.40; -; 1.
InterPro; IPR006053; TNF.
InterPro; IPR002959; TNF_alpha.
InterPro; IPR021184; TNF_CS.
InterPro; IPR006052; TNF_dom.
InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
PANTHER; PTHR11471:SF23; PTHR11471:SF23; 1.
Pfam; PF00229; TNF; 1.
PRINTS; PR01234; TNECROSISFCT.
PRINTS; PR01235; TNFALPHA.
SMART; SM00207; TNF; 1.
SUPFAM; SSF49842; SSF49842; 1.
PROSITE; PS00251; TNF_1; 1.
PROSITE; PS50049; TNF_2; 1.
2: Evidence at transcript level;
Cell membrane; Complete proteome; Cytokine; Disulfide bond;
Glycoprotein; Lipoprotein; Membrane; Myristate; Phosphoprotein;
Reference proteome; Secreted; Signal-anchor; Transmembrane;
Transmembrane helix.
CHAIN 1 234 Tumor necrosis factor, membrane form.
/FTId=PRO_0000034421.
CHAIN 1 39 Intracellular domain 1. {ECO:0000250}.
/FTId=PRO_0000417227.
CHAIN 1 35 Intracellular domain 2. {ECO:0000250}.
/FTId=PRO_0000417228.
CHAIN 50 ? C-domain 1. {ECO:0000250}.
/FTId=PRO_0000417229.
CHAIN 52 ? C-domain 2. {ECO:0000250}.
/FTId=PRO_0000417230.
CHAIN 78 234 Tumor necrosis factor, soluble form.
/FTId=PRO_0000034422.
TOPO_DOM 1 35 Cytoplasmic. {ECO:0000255}.
TRANSMEM 36 56 Helical; Signal-anchor for type II
membrane protein. {ECO:0000255}.
TOPO_DOM 57 234 Extracellular. {ECO:0000255}.
SITE 34 35 Cleavage; by SPPL2A or SPPL2B.
{ECO:0000250}.
SITE 39 40 Cleavage; by SPPL2A or SPPL2B.
{ECO:0000250}.
SITE 49 50 Cleavage; by SPPL2A or SPPL2B.
{ECO:0000250}.
SITE 51 52 Cleavage; by SPPL2A or SPPL2B.
{ECO:0000250}.
SITE 77 78 Cleavage; by ADAM17. {ECO:0000250}.
MOD_RES 2 2 Phosphoserine; by CK1. {ECO:0000250}.
LIPID 19 19 N6-myristoyl lysine. {ECO:0000250}.
LIPID 20 20 N6-myristoyl lysine. {ECO:0000250}.
CARBOHYD 81 81 O-linked (GalNAc...) serine; in soluble
form. {ECO:0000250}.
DISULFID 146 178 {ECO:0000250}.
CONFLICT 177 179 PCH -> LAN (in Ref. 2; BAA88349).
{ECO:0000305}.
SEQUENCE 234 AA; 25469 MW; E79ACE91143DF373 CRC64;
MSTESMIRDV ELAEEELAKK AGGPQGSRRC LCLSLFSFLL VAGATTLFCL LHFGVIGPQR
EEQLPNAFQS INPLAQTLRS SSRTPSDKPV AHVVANPQAE GQLQWLSGRA NALLANGVKL
TDNQLVVPLD GLYLIYSQVL FKGQGCPSTH VLLTHTISRL AVSYPSKVNL LSAIKSPCHT
ESPEQAEAKP WYEPIYLGGV FQLEKGDQLS AEINQPNYLD FAESGQVYFG IIAL


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