LipidDB ID

LipidDB-9606-00998

Entry Name

UniProt Accession

P01375; O43647; Q9P1Q2; Q9UIV3;

Theoretical PI

6.44

Molecular Weight

25644.42

Genbank Protein ID

AAA61200.1; CAA26669.1; CAA25650.1; AAA61198.1; AAA36758.1; CAA78745.1; CAA75070.1; AAD18091.1; BAB63396.1; BAC54944.1; AAL47581.1; AAO21132.1; AAH28148.1; AAC03542.1; AAF71992.1;

Genbank Nucleotide ID

M16441; X02910; X01394; M10988; M26331; Z15026; Y14768; AF129756; BA000025; AB088112; AY066019; AY214167; BC028148; AF043342; AF098751;

Protein Name

Tumor necrosis factor, soluble form

Protein Synonyms/Alias

Cachectin; TNF-alpha; Tumor necrosis factor ligand superfamily member 2; TNF-a; N-terminal fragment; NTF; ICD1; ICD2;

Gene Name

TNF

Gene Synonyms/Alias

TNFA; TNFSF2;

Created Date

21-JUL-1986

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Utsumi T, Takeshige T, Tanaka K, Takami K, Kira Y, Klostergaard J, Ishisaka R.Transmembrane TNF (pro-TNF) is palmitoylated. FEBS Lett. 2001 Jun29;500(1-2):1-6.[PMID:11434916]
[2] Stevenson FT, Bursten SL, Locksley RM, Lovett DH. Myristyl acylation of thetumor necrosis factor alpha precursor on specific lysine residues. J Exp Med.1992 Oct 1;176(4):1053-62.[PMID:1402651]

Functional Description

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.

Sequence Annotation

Topological domain: 1 35 Cytoplasmic.
Transmembrane: 36 56 Helical; Signal-anchor for type IImembrane protein.
Topological domain: 57 233 Extracellular.
Functional site: 35 36 Cleavage; by SPPL2A or SPPL2B.
Functional site: 39 40 Cleavage; by SPPL2A or SPPL2B.
Functional site: 49 50 Cleavage; by SPPL2A or SPPL2B.
Functional site: 51 52 Cleavage; by SPPL2A or SPPL2B.
Functional site: 76 77 Cleavage; by ADAM17.
Modified residue: 2 2 Phosphoserine; by CK1.

Protein Length

233 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0009986; C:cell surface; IDA:BHF-UCL
GO:0009897; C:external side of plasma membrane; ISS:BHF-UCL
GO:0005576; C:extracellular region; TAS:Reactome
GO:0005615; C:extracellular space; IDA:BHF-UCL
GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL
GO:0045121; C:membrane raft; IDA:BHF-UCL
GO:0001891; C:phagocytic cup; ISS:BHF-UCL
GO:0005886; C:plasma membrane; TAS:Reactome
GO:0055037; C:recycling endosome; ISS:BHF-UCL
GO:0005125; F:cytokine activity; IDA:BHF-UCL
GO:0042802; F:identical protein binding; IDA:BHF-UCL
GO:0002020; F:protease binding; IPI:BHF-UCL
GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB
GO:0005164; F:tumor necrosis factor receptor binding; IDA:BHF-UCL
GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB
GO:0000187; P:activation of MAPK activity; IDA:BHF-UCL
GO:0000185; P:activation of MAPKKK activity; IDA:BHF-UCL
GO:0006915; P:apoptotic process; TAS:Reactome
GO:0097190; P:apoptotic signaling pathway; TAS:Reactome
GO:0019722; P:calcium-mediated signaling; IEA:Ensembl
GO:0001775; P:cell activation; IEA:Ensembl
GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl
GO:0071316; P:cellular response to nicotine; IDA:UniProtKB
GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB
GO:0002439; P:chronic inflammatory response to antigenic stimulus; IMP:BHF-UCL
GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl
GO:0048566; P:embryonic digestive tract development; IEP:DFLAT
GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IEA:Ensembl
GO:0030198; P:extracellular matrix organization; IEA:Ensembl
GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:UniProtKB
GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:UniProtKB
GO:0006006; P:glucose metabolic process; IEA:Ensembl
GO:0006959; P:humoral immune response; IEA:Ensembl
GO:0006954; P:inflammatory response; IDA:UniProtKB
GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl
GO:0007254; P:JNK cascade; IEA:Ensembl
GO:0050901; P:leukocyte tethering or rolling; IDA:BHF-UCL
GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB
GO:0000165; P:MAPK cascade; IMP:UniProtKB
GO:0097527; P:necroptotic signaling pathway; IDA:UniProtKB
GO:0010693; P:negative regulation of alkaline phosphatase activity; IEA:Ensembl
GO:0061048; P:negative regulation of branching involved in lung morphogenesis; IDA:UniProtKB
GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl
GO:0002740; P:negative regulation of cytokine secretion involved in immune response; IDA:BHF-UCL
GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:BHF-UCL
GO:0045599; P:negative regulation of fat cell differentiation; NAS:BHF-UCL
GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB
GO:0046325; P:negative regulation of glucose import; IEA:Ensembl
GO:0044130; P:negative regulation of growth of symbiont in host; IEA:Ensembl
GO:0032715; P:negative regulation of interleukin-6 production; IDA:BHF-UCL
GO:0002037; P:negative regulation of L-glutamate transport; IEA:Ensembl
GO:0050995; P:negative regulation of lipid catabolic process; IDA:BHF-UCL
GO:0010888; P:negative regulation of lipid storage; NAS:BHF-UCL
GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl
GO:0043242; P:negative regulation of protein complex disassembly; IDA:UniProtKB
GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB
GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB
GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL
GO:0009887; P:organ morphogenesis; IEA:Ensembl
GO:0030316; P:osteoclast differentiation; IEA:Ensembl
GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB
GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; IDA:BHF-UCL
GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IDA:BHF-UCL
GO:0045080; P:positive regulation of chemokine biosynthetic process; IDA:BHF-UCL
GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL
GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; IEA:Ensembl
GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB
GO:0001819; P:positive regulation of cytokine production; IDA:BHF-UCL
GO:0050715; P:positive regulation of cytokine secretion; IDA:BHF-UCL
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; NAS:BHF-UCL
GO:0031622; P:positive regulation of fever generation; ISS:BHF-UCL
GO:0010628; P:positive regulation of gene expression; IDA:AgBase
GO:0051798; P:positive regulation of hair follicle development; IEA:Ensembl
GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL
GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:BHF-UCL
GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl
GO:0032741; P:positive regulation of interleukin-18 production; IEA:Ensembl
GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl
GO:0045416; P:positive regulation of interleukin-8 biosynthetic process; IDA:BHF-UCL
GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl
GO:0043507; P:positive regulation of JUN kinase activity; IDA:UniProtKB
GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB
GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL
GO:0045840; P:positive regulation of mitosis; IEA:Ensembl
GO:0071677; P:positive regulation of mononuclear cell migration; NAS:BHF-UCL
GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl
GO:0042346; P:positive regulation of NF-kappaB import into nucleus; IDA:BHF-UCL
GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB
GO:0051533; P:positive regulation of NFAT protein import into nucleus; IDA:MGI
GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL
GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL
GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL
GO:0071803; P:positive regulation of podosome assembly; IDA:BHF-UCL
GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB
GO:0031334; P:positive regulation of protein complex assembly; IDA:BHF-UCL
GO:0043243; P:positive regulation of protein complex disassembly; IDA:UniProtKB
GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl
GO:2000010; P:positive regulation of protein localization to cell surface; IDA:BHF-UCL
GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB
GO:0051222; P:positive regulation of protein transport; IDA:BHF-UCL
GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL
GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL
GO:0050806; P:positive regulation of synaptic transmission; IEA:Ensembl
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB
GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB
GO:0045994; P:positive regulation of translational initiation by iron; IEA:Ensembl
GO:0060557; P:positive regulation of vitamin D biosynthetic process; IDA:BHF-UCL
GO:0000060; P:protein import into nucleus, translocation; IDA:UniProtKB
GO:0043491; P:protein kinase B signaling; IMP:UniProtKB
GO:0032800; P:receptor biosynthetic process; IDA:BHF-UCL
GO:0060693; P:regulation of branching involved in salivary gland morphogenesis; IEA:Ensembl
GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IDA:BHF-UCL
GO:0051023; P:regulation of immunoglobulin secretion; IEA:Ensembl
GO:0050796; P:regulation of insulin secretion; IDA:BHF-UCL
GO:2000377; P:regulation of reactive oxygen species metabolic process; IEA:Ensembl
GO:0014823; P:response to activity; IEA:Ensembl
GO:0042493; P:response to drug; IEA:Ensembl
GO:0051384; P:response to glucocorticoid; IDA:BHF-UCL
GO:0001666; P:response to hypoxia; IEA:Ensembl
GO:0009612; P:response to mechanical stimulus; IEA:Ensembl
GO:0009651; P:response to salt stress; TAS:BHF-UCL
GO:0009615; P:response to virus; IDA:BHF-UCL
GO:0030730; P:sequestering of triglyceride; IDA:BHF-UCL
GO:0003009; P:skeletal muscle contraction; IEA:Ensembl
GO:0006927; P:transformed cell apoptotic process; IDA:BHF-UCL
GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:BHF-UCL

Interpro

InterPro; IPR006053; TNF
InterPro; IPR002959; TNF_alpha
InterPro; IPR021184; TNF_CS
InterPro; IPR006052; TNF_dom
InterPro; IPR008983; Tumour_necrosis_fac-like_dom

Pfam

Pfam; PF00229; TNF;

SMART

SMART; SM00207; TNF;

PROSITE

PROSITE; PS00251; TNF_1;
PROSITE; PS50049; TNF_2;

PRINTS

PRINTS; PR01234; TNECROSISFCT;
PRINTS; PR01235; TNFALPHA;