UniProtKB - P01375 (TNFA_HUMAN)
Tumor necrosis factor
TNF
Functioni
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. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918, PubMed:16829952, PubMed:23396208).
Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity).
Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819).
By similarity4 PublicationsThe TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
1 PublicationGO - Molecular functioni
- cytokine activity Source: BHF-UCL
- identical protein binding Source: BHF-UCL
- protease binding Source: BHF-UCL
- transcription cis-regulatory region binding Source: UniProtKB
- tumor necrosis factor receptor binding Source: BHF-UCL
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- acute inflammatory response Source: Ensembl
- astrocyte activation Source: ARUK-UCL
- calcium-mediated signaling Source: Ensembl
- cellular response to amino acid stimulus Source: Ensembl
- cellular response to amyloid-beta Source: Ensembl
- cellular response to interferon-gamma Source: Ensembl
- cellular response to nicotine Source: UniProtKB
- cellular response to organic cyclic compound Source: UniProtKB
- cellular response to retinoic acid Source: Ensembl
- cellular response to toxic substance Source: Ensembl
- chronic inflammatory response to antigenic stimulus Source: BHF-UCL
- circadian rhythm Source: Ensembl
- cognition Source: ARUK-UCL
- cortical actin cytoskeleton organization Source: UniProtKB
- defense response to Gram-positive bacterium Source: Ensembl
- detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
- embryonic digestive tract development Source: DFLAT
- endothelial cell apoptotic process Source: Ensembl
- epithelial cell proliferation involved in salivary gland morphogenesis Source: Ensembl
- extracellular matrix organization Source: Ensembl
- extrinsic apoptotic signaling pathway Source: UniProtKB
- extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
- glucose metabolic process Source: Ensembl
- humoral immune response Source: Ensembl
- inflammatory response Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
- JNK cascade Source: Ensembl
- leukocyte migration involved in inflammatory response Source: Ensembl
- leukocyte tethering or rolling Source: BHF-UCL
- lipopolysaccharide-mediated signaling pathway Source: UniProtKB
- liver regeneration Source: Ensembl
- MAPK cascade Source: UniProtKB
- microglial cell activation Source: ARUK-UCL
- necroptotic signaling pathway Source: UniProtKB
- negative regulation of alkaline phosphatase activity Source: Ensembl
- negative regulation of amyloid-beta clearance Source: ARUK-UCL
- negative regulation of apoptotic signaling pathway Source: ARUK-UCL
- negative regulation of bicellular tight junction assembly Source: UniProtKB
- negative regulation of bile acid secretion Source: Ensembl
- negative regulation of blood vessel endothelial cell migration Source: BHF-UCL
- negative regulation of branching involved in lung morphogenesis Source: UniProtKB
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
- negative regulation of cytokine production involved in immune response Source: BHF-UCL
- negative regulation of endothelial cell proliferation Source: Ensembl
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
- negative regulation of fat cell differentiation Source: BHF-UCL
- negative regulation of gene expression Source: UniProtKB
- negative regulation of glucose import Source: Ensembl
- negative regulation of heart rate Source: Ensembl
- negative regulation of interleukin-6 production Source: BHF-UCL
- negative regulation of L-glutamate import across plasma membrane Source: Ensembl
- negative regulation of lipid catabolic process Source: BHF-UCL
- negative regulation of lipid storage Source: BHF-UCL
- negative regulation of mitotic cell cycle Source: Ensembl
- negative regulation of myelination Source: Ensembl
- negative regulation of myoblast differentiation Source: Ensembl
- negative regulation of myosin-light-chain-phosphatase activity Source: UniProtKB
- negative regulation of neurogenesis Source: ARUK-UCL
- negative regulation of osteoblast differentiation Source: Ensembl
- negative regulation of oxidative phosphorylation Source: Ensembl
- negative regulation of production of miRNAs involved in gene silencing by miRNA Source: ARUK-UCL
- negative regulation of protein-containing complex disassembly Source: UniProtKB
- negative regulation of signaling receptor activity Source: BHF-UCL
- negative regulation of systemic arterial blood pressure Source: Ensembl
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- negative regulation of vascular wound healing Source: BHF-UCL
- negative regulation of viral genome replication Source: BHF-UCL
- osteoclast differentiation Source: Ensembl
- positive regulation of action potential Source: Ensembl
- positive regulation of amyloid-beta formation Source: ARUK-UCL
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of blood microparticle formation Source: BHF-UCL
- positive regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
- positive regulation of calcineurin-NFAT signaling cascade Source: MGI
- positive regulation of cell adhesion Source: UniProtKB
- positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
- positive regulation of chemokine production Source: BHF-UCL
- positive regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: Ensembl
- positive regulation of cytokine production Source: BHF-UCL
- positive regulation of cytokine production involved in inflammatory response Source: ARUK-UCL
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of DNA biosynthetic process Source: Ensembl
- positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
- positive regulation of extrinsic apoptotic signaling pathway Source: GO_Central
- positive regulation of fever generation Source: BHF-UCL
- positive regulation of fractalkine production Source: ARUK-UCL
- positive regulation of gene expression Source: UniProtKB
- positive regulation of glial cell proliferation Source: ARUK-UCL
- positive regulation of hair follicle development Source: Ensembl
- positive regulation of hepatocyte proliferation Source: Ensembl
- positive regulation of heterotypic cell-cell adhesion Source: BHF-UCL
- positive regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
- positive regulation of I-kappaB phosphorylation Source: ARUK-UCL
- positive regulation of inflammatory response Source: ARUK-UCL
- positive regulation of interferon-gamma production Source: Ensembl
- positive regulation of interleukin-18 production Source: Ensembl
- positive regulation of interleukin-1 beta production Source: ARUK-UCL
- positive regulation of interleukin-33 production Source: ARUK-UCL
- positive regulation of interleukin-6 production Source: ARUK-UCL
- positive regulation of interleukin-8 production Source: BHF-UCL
- positive regulation of JNK cascade Source: Ensembl
- positive regulation of JUN kinase activity Source: UniProtKB
- positive regulation of leukocyte adhesion to arterial endothelial cell Source: BHF-UCL
- positive regulation of leukocyte adhesion to vascular endothelial cell Source: BHF-UCL
- positive regulation of MAPK cascade Source: BHF-UCL
- positive regulation of MAP kinase activity Source: UniProtKB
- positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
- positive regulation of mitotic nuclear division Source: Ensembl
- positive regulation of mononuclear cell migration Source: BHF-UCL
- positive regulation of neuroinflammatory response Source: ARUK-UCL
- positive regulation of neuron apoptotic process Source: ARUK-UCL
- positive regulation of neutrophil activation Source: Ensembl
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
- positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
- positive regulation of nitric-oxide synthase activity Source: ARUK-UCL
- positive regulation of nitrogen compound metabolic process Source: ARUK-UCL
- positive regulation of osteoclast differentiation Source: BHF-UCL
- positive regulation of oxidative stress-induced neuron death Source: Ensembl
- positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
- positive regulation of phagocytosis Source: AgBase
- positive regulation of phosphatidylinositol 3-kinase signaling Source: ARUK-UCL
- positive regulation of podosome assembly Source: BHF-UCL
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of programmed cell death Source: UniProtKB
- positive regulation of protein catabolic process Source: AgBase
- positive regulation of protein-containing complex assembly Source: BHF-UCL
- positive regulation of protein-containing complex disassembly Source: UniProtKB
- positive regulation of protein kinase activity Source: AgBase
- positive regulation of protein kinase B signaling Source: ARUK-UCL
- positive regulation of protein localization to cell surface Source: BHF-UCL
- positive regulation of protein localization to plasma membrane Source: ARUK-UCL
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of protein transport Source: BHF-UCL
- positive regulation of receptor signaling pathway via JAK-STAT Source: ARUK-UCL
- positive regulation of smooth muscle cell proliferation Source: BHF-UCL
- positive regulation of superoxide dismutase activity Source: BHF-UCL
- positive regulation of synaptic transmission Source: ARUK-UCL
- positive regulation of synoviocyte proliferation Source: ARUK-UCL
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of translational initiation by iron Source: Ensembl
- positive regulation of tyrosine phosphorylation of STAT protein Source: ARUK-UCL
- positive regulation of vascular associated smooth muscle cell proliferation Source: Ensembl
- positive regulation of vitamin D biosynthetic process Source: BHF-UCL
- protein kinase B signaling Source: UniProtKB
- protein localization to plasma membrane Source: UniProtKB
- regulation of branching involved in salivary gland morphogenesis Source: Ensembl
- regulation of endothelial cell apoptotic process Source: ARUK-UCL
- regulation of establishment of endothelial barrier Source: UniProtKB
- regulation of fat cell differentiation Source: ARUK-UCL
- regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
- regulation of immunoglobulin production Source: Ensembl
- regulation of insulin secretion Source: BHF-UCL
- regulation of reactive oxygen species metabolic process Source: Ensembl
- regulation of synapse organization Source: ARUK-UCL
- regulation of synaptic transmission, glutamatergic Source: ARUK-UCL
- regulation of transcription by RNA polymerase II Source: ARUK-UCL
- response to 3,3',5-triiodo-L-thyronine Source: Ensembl
- response to activity Source: Ensembl
- response to ethanol Source: Ensembl
- response to glucocorticoid Source: BHF-UCL
- response to gold nanoparticle Source: Ensembl
- response to Gram-negative bacterium Source: Ensembl
- response to hypoxia Source: Ensembl
- response to nutrient levels Source: Ensembl
- response to paracetamol Source: Ensembl
- response to radiation Source: Ensembl
- response to salt stress Source: BHF-UCL
- response to virus Source: BHF-UCL
- response to xenobiotic stimulus Source: Ensembl
- sequestering of triglyceride Source: BHF-UCL
- skeletal muscle contraction Source: Ensembl
- toll-like receptor 3 signaling pathway Source: Ensembl
- tumor necrosis factor-mediated signaling pathway Source: ARUK-UCL
- vascular endothelial growth factor production Source: UniProtKB
- vasodilation Source: Ensembl
Keywordsi
Molecular function | Cytokine |
Enzyme and pathway databases
PathwayCommonsi | P01375 |
Reactomei | R-HSA-381340, Transcriptional regulation of white adipocyte differentiation R-HSA-5357786, TNFR1-induced proapoptotic signaling R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5626978, TNFR1-mediated ceramide production R-HSA-5668541, TNFR2 non-canonical NF-kB pathway R-HSA-6783783, Interleukin-10 signaling R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-75893, TNF signaling |
SignaLinki | P01375 |
SIGNORi | P01375 |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor necrosis factorAlternative name(s): Cachectin TNF-alpha Tumor necrosis factor ligand superfamily member 2 Short name: TNF-a Cleaved into the following 6 chains: Alternative name(s): N-terminal fragment Short name: NTF |
Gene namesi | Name:TNF Synonyms:TNFA, TNFSF2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11892, TNF |
MIMi | 191160, gene |
neXtProti | NX_P01375 |
VEuPathDBi | HostDB:ENSG00000232810 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Extracellular region or secreted
Extracellular region or secreted
Extracellular region or secreted
Endosome
- recycling endosome Source: BHF-UCL
Extracellular region or secreted
- extracellular region Source: ARUK-UCL
- extracellular space Source: BHF-UCL
Plasma Membrane
- external side of plasma membrane Source: BHF-UCL
- integral component of plasma membrane Source: BHF-UCL
- phagocytic cup Source: BHF-UCL
- plasma membrane Source: Reactome
Other locations
- cell surface Source: BHF-UCL
- membrane Source: ARUK-UCL
- membrane raft Source: BHF-UCL
- neuronal cell body Source: Ensembl
- protein-containing complex Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 35 | CytoplasmicSequence analysisAdd BLAST | 35 | |
Transmembranei | 36 – 56 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 57 – 233 | ExtracellularSequence analysisAdd BLAST | 177 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Psoriatic arthritis (PSORAS)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 105 | L → S: Low activity. 1 Publication | 1 | |
Mutagenesisi | 108 | R → W: Biologically inactive. 1 Publication | 1 | |
Mutagenesisi | 112 | L → F: Biologically inactive. 1 Publication | 1 | |
Mutagenesisi | 160 | A → V: Biologically inactive. 1 Publication | 1 | |
Mutagenesisi | 162 | S → F: Biologically inactive. 1 Publication | 1 | |
Mutagenesisi | 167 | V → A or D: Biologically inactive. 1 Publication | 1 | |
Mutagenesisi | 222 | E → K: Biologically inactive. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 7124 |
MalaCardsi | TNF |
MIMi | 607507, phenotype 610424, phenotype 611162, phenotype |
OpenTargetsi | ENSG00000232810 |
Orphaneti | 40050, NON RARE IN EUROPE: Psoriatic arthritis |
PharmGKBi | PA435 |
Miscellaneous databases
Pharosi | P01375, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1825 |
DrugBanki | DB00051, Adalimumab DB04956, Afelimomab DB05879, AME-527 DB01427, Amrinone DB05767, Andrographolide DB05513, Atiprimod DB11967, Binimetinib DB11752, Bryostatin 1 DB08904, Certolizumab pegol DB00608, Chloroquine DB01407, Clenbuterol DB05744, CRx-139 DB05758, CYT007-TNFQb DB06444, Dexanabinol DB12140, Dilmapimod DB00668, Epinephrine DB00005, Etanercept DB05869, Ethyl pyruvate DB10770, Foreskin fibroblast (neonatal) DB10772, Foreskin keratinocyte (neonatal) DB01296, Glucosamine DB13751, Glycyrrhizic acid DB06674, Golimumab DB00065, Infliximab DB05303, OMS-103HP DB06495, Onercept DB05992, Plinabulin DB05218, PN0621 DB09221, Polaprezinc DB08910, Pomalidomide DB05968, PR-104 DB01411, Pranlukast DB00852, Pseudoephedrine DB05207, SD118 DB05412, Talmapimod DB01041, Thalidomide DB05470, VX-702 DB05017, YSIL6 |
DrugCentrali | P01375 |
Genetic variation databases
BioMutai | TNF |
DMDMi | 135934 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000034423 | 1 – 233 | Tumor necrosis factor, membrane formAdd BLAST | 233 | |
ChainiPRO_0000417231 | 1 – 39 | Intracellular domain 1Add BLAST | 39 | |
ChainiPRO_0000417232 | 1 – 35 | Intracellular domain 2Add BLAST | 35 | |
ChainiPRO_0000417233 | 50 – ? | C-domain 1 | ||
ChainiPRO_0000417234 | 52 – ? | C-domain 2 | ||
ChainiPRO_0000034424 | 77 – 233 | Tumor necrosis factor, soluble form1 PublicationAdd BLAST | 157 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | Phosphoserine; by CK1Curated | 1 | |
Lipidationi | 19 | N6-myristoyl lysine1 Publication | 1 | |
Lipidationi | 20 | N6-myristoyl lysine1 Publication | 1 | |
Glycosylationi | 80 | O-linked (GalNAc...) serine; in soluble form1 Publication | 1 | |
Disulfide bondi | 145 ↔ 177 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 35 – 36 | Cleavage; by SPPL2A or SPPL2B | 2 | |
Sitei | 39 – 40 | Cleavage; by SPPL2A or SPPL2B | 2 | |
Sitei | 49 – 50 | Cleavage; by SPPL2A or SPPL2B | 2 | |
Sitei | 51 – 52 | Cleavage; by SPPL2A or SPPL2B | 2 | |
Sitei | 76 – 77 | Cleavage; by ADAM17 | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, Myristate, PhosphoproteinProteomic databases
MassIVEi | P01375 |
PaxDbi | P01375 |
PeptideAtlasi | P01375 |
PRIDEi | P01375 |
ProteomicsDBi | 51379 |
PTM databases
GlyConnecti | 609, 3 O-Linked glycans (1 site) |
GlyGeni | P01375, 1 site, 5 O-linked glycans (1 site) |
iPTMneti | P01375 |
PhosphoSitePlusi | P01375 |
SwissPalmi | P01375 |
Expressioni
Gene expression databases
Bgeei | ENSG00000232810, Expressed in granulocyte and 112 other tissues |
ExpressionAtlasi | P01375, baseline and differential |
Genevisiblei | P01375, HS |
Organism-specific databases
HPAi | ENSG00000232810, Tissue enhanced (bone marrow, lymphoid tissue) |
Interactioni
Subunit structurei
Homotrimer.
Interacts with SPPL2B.
1 PublicationBinary interactionsi
P01375
GO - Molecular functioni
- cytokine activity Source: BHF-UCL
- identical protein binding Source: BHF-UCL
- protease binding Source: BHF-UCL
- tumor necrosis factor receptor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 112979, 308 interactors |
CORUMi | P01375 |
DIPi | DIP-2895N |
IntActi | P01375, 113 interactors |
MINTi | P01375 |
STRINGi | 9606.ENSP00000398698 |
Chemistry databases
BindingDBi | P01375 |
Miscellaneous databases
RNActi | P01375, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P01375 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P01375 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502S4K8, Eukaryota |
GeneTreei | ENSGT01040000240509 |
HOGENOMi | CLU_070352_3_1_1 |
InParanoidi | P01375 |
OMAi | GATMLFC |
OrthoDBi | 1124938at2759 |
PhylomeDBi | P01375 |
TreeFami | TF332169 |
Family and domain databases
CDDi | cd00184, TNF, 1 hit |
Gene3Di | 2.60.120.40, 1 hit |
InterProi | View protein in InterPro IPR006053, TNF IPR002959, TNF_alpha IPR021184, TNF_CS IPR006052, TNF_dom IPR008983, Tumour_necrosis_fac-like_dom |
PANTHERi | PTHR11471:SF23, PTHR11471:SF23, 1 hit |
Pfami | View protein in Pfam PF00229, TNF, 1 hit |
PRINTSi | PR01234, TNECROSISFCT PR01235, TNFALPHA |
SMARTi | View protein in SMART SM00207, TNF, 1 hit |
SUPFAMi | SSF49842, SSF49842, 1 hit |
PROSITEi | View protein in PROSITE PS00251, TNF_1, 1 hit PS50049, TNF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG
110 120 130 140 150
QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV
160 170 180 190 200
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF
210 220 230
QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A140T922 | A0A140T922_HUMAN | Cachectin | TNF | 171 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 63 | F → S in AAA61198 (PubMed:3856324).Curated | 1 | |
Sequence conflicti | 84 – 86 | PSD → VNR in AAF71992 (Ref. 17) Curated | 3 | |
Sequence conflicti | 183 | E → R in AAC03542 (Ref. 16) Curated | 1 |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019378 | 84 | P → L1 PublicationCorresponds to variant dbSNP:rs4645843EnsemblClinVar. | 1 | |
Natural variantiVAR_011927 | 94 | A → T. Corresponds to variant dbSNP:rs1800620Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M16441 Genomic DNA Translation: AAA61200.1 X02910 Genomic DNA Translation: CAA26669.1 X01394 mRNA Translation: CAA25650.1 M10988 mRNA Translation: AAA61198.1 M26331 Genomic DNA Translation: AAA36758.1 Z15026 Genomic DNA Translation: CAA78745.1 Y14768 Genomic DNA Translation: CAA75070.1 Sequence problems. AF129756 Genomic DNA Translation: AAD18091.1 BA000025 Genomic DNA Translation: BAB63396.1 AB088112 Genomic DNA Translation: BAC54944.1 AY066019 Genomic DNA Translation: AAL47581.1 AY214167 Genomic DNA Translation: AAO21132.1 BC028148 mRNA Translation: AAH28148.1 AF043342 mRNA Translation: AAC03542.1 AF098751 mRNA Translation: AAF71992.1 Frameshift. |
CCDSi | CCDS4702.1 |
PIRi | A93585, QWHUN |
RefSeqi | NP_000585.2, NM_000594.3 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Tumor necrosis factor alpha entry |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
NIEHS-SNPs |
SeattleSNPs |
SHMPD The Singapore human mutation and polymorphism database |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M16441 Genomic DNA Translation: AAA61200.1 X02910 Genomic DNA Translation: CAA26669.1 X01394 mRNA Translation: CAA25650.1 M10988 mRNA Translation: AAA61198.1 M26331 Genomic DNA Translation: AAA36758.1 Z15026 Genomic DNA Translation: CAA78745.1 Y14768 Genomic DNA Translation: CAA75070.1 Sequence problems. AF129756 Genomic DNA Translation: AAD18091.1 BA000025 Genomic DNA Translation: BAB63396.1 AB088112 Genomic DNA Translation: BAC54944.1 AY066019 Genomic DNA Translation: AAL47581.1 AY214167 Genomic DNA Translation: AAO21132.1 BC028148 mRNA Translation: AAH28148.1 AF043342 mRNA Translation: AAC03542.1 AF098751 mRNA Translation: AAF71992.1 Frameshift. |
CCDSi | CCDS4702.1 |
PIRi | A93585, QWHUN |
RefSeqi | NP_000585.2, NM_000594.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1A8M | X-ray | 2.30 | A/B/C | 77-233 | [»] | |
1TNF | X-ray | 2.60 | A/B/C | 77-233 | [»] | |
2AZ5 | X-ray | 2.10 | A/B/C/D | 86-233 | [»] | |
2E7A | X-ray | 1.80 | A/B/C | 77-233 | [»] | |
2TUN | X-ray | 3.10 | A/B/C/D/E/F | 77-233 | [»] | |
2ZJC | X-ray | 2.50 | A/B/C | 77-233 | [»] | |
2ZPX | X-ray | 2.83 | A/B/C | 77-233 | [»] | |
3ALQ | X-ray | 3.00 | A/B/C/D/E/F | 77-233 | [»] | |
3IT8 | X-ray | 2.80 | A/B/C/G/H/I | 82-233 | [»] | |
3L9J | X-ray | 2.10 | T | 85-233 | [»] | |
3WD5 | X-ray | 3.10 | A | 77-233 | [»] | |
4G3Y | X-ray | 2.60 | C | 77-233 | [»] | |
4TSV | X-ray | 1.80 | A | 84-233 | [»] | |
4TWT | X-ray | 2.85 | A/B/C/D | 77-233 | [»] | |
4Y6O | X-ray | 1.60 | C/D | 17-23 | [»] | |
5M2I | X-ray | 2.15 | A/B/C/D/E/F | 77-233 | [»] | |
5M2J | X-ray | 1.90 | A | 77-233 | [»] | |
5M2M | X-ray | 2.30 | A/B/C/G/I/M | 77-233 | [»] | |
5MU8 | X-ray | 3.00 | A/B/C/D/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d/e | 77-233 | [»] | |
5TSW | X-ray | 2.50 | A/B/C/D/E/F | 84-233 | [»] | |
5UUI | X-ray | 1.40 | A | 77-233 | [»] | |
5WUX | X-ray | 2.90 | E/F/G | 77-233 | [»] | |
5YOY | X-ray | 2.73 | A/B/C/J/K/L | 76-233 | [»] | |
6OOY | X-ray | 2.50 | A/B/C | 77-233 | [»] | |
6OOZ | X-ray | 2.80 | A/B/C | 77-233 | [»] | |
6OP0 | X-ray | 2.55 | A/B/C | 77-233 | [»] | |
6RMJ | X-ray | 2.65 | A/B/C | 77-233 | [»] | |
6X81 | X-ray | 2.81 | A/B/C/D/E/F | 77-233 | [»] | |
6X82 | X-ray | 2.75 | A/B/C/D/E/F | 77-233 | [»] | |
6X83 | X-ray | 2.83 | A/B/C/D/E/F | 77-233 | [»] | |
6X85 | X-ray | 2.85 | A/B/C/D/E/F | 77-233 | [»] | |
6X86 | X-ray | 2.93 | A/B/C/D/E/F | 77-233 | [»] | |
7ASY | NMR | - | A | 28-60 | [»] | |
7AT7 | NMR | - | A | 28-60 | [»] | |
7ATB | NMR | - | A | 28-60 | [»] | |
7JRA | X-ray | 2.10 | A/B/C | 77-233 | [»] | |
7KP9 | X-ray | 2.15 | A/B/C | 77-233 | [»] | |
7KPA | X-ray | 2.30 | A/B/C | 77-233 | [»] | |
7KPB | X-ray | 3.00 | A/B/C | 77-233 | [»] | |
SMRi | P01375 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112979, 308 interactors |
CORUMi | P01375 |
DIPi | DIP-2895N |
IntActi | P01375, 113 interactors |
MINTi | P01375 |
STRINGi | 9606.ENSP00000398698 |
Chemistry databases
BindingDBi | P01375 |
ChEMBLi | CHEMBL1825 |
DrugBanki | DB00051, Adalimumab DB04956, Afelimomab DB05879, AME-527 DB01427, Amrinone DB05767, Andrographolide DB05513, Atiprimod DB11967, Binimetinib DB11752, Bryostatin 1 DB08904, Certolizumab pegol DB00608, Chloroquine DB01407, Clenbuterol DB05744, CRx-139 DB05758, CYT007-TNFQb DB06444, Dexanabinol DB12140, Dilmapimod DB00668, Epinephrine DB00005, Etanercept DB05869, Ethyl pyruvate DB10770, Foreskin fibroblast (neonatal) DB10772, Foreskin keratinocyte (neonatal) DB01296, Glucosamine DB13751, Glycyrrhizic acid DB06674, Golimumab DB00065, Infliximab DB05303, OMS-103HP DB06495, Onercept DB05992, Plinabulin DB05218, PN0621 DB09221, Polaprezinc DB08910, Pomalidomide DB05968, PR-104 DB01411, Pranlukast DB00852, Pseudoephedrine DB05207, SD118 DB05412, Talmapimod DB01041, Thalidomide DB05470, VX-702 DB05017, YSIL6 |
DrugCentrali | P01375 |
PTM databases
GlyConnecti | 609, 3 O-Linked glycans (1 site) |
GlyGeni | P01375, 1 site, 5 O-linked glycans (1 site) |
iPTMneti | P01375 |
PhosphoSitePlusi | P01375 |
SwissPalmi | P01375 |
Genetic variation databases
BioMutai | TNF |
DMDMi | 135934 |
Proteomic databases
MassIVEi | P01375 |
PaxDbi | P01375 |
PeptideAtlasi | P01375 |
PRIDEi | P01375 |
ProteomicsDBi | 51379 |
Protocols and materials databases
ABCDi | P01375, 41 sequenced antibodies |
Antibodypediai | 27196, 5151 antibodies from 55 providers |
DNASUi | 7124 |
Genome annotation databases
Organism-specific databases
CTDi | 7124 |
DisGeNETi | 7124 |
GeneCardsi | TNF |
HGNCi | HGNC:11892, TNF |
HPAi | ENSG00000232810, Tissue enhanced (bone marrow, lymphoid tissue) |
MalaCardsi | TNF |
MIMi | 191160, gene 607507, phenotype 610424, phenotype 611162, phenotype |
neXtProti | NX_P01375 |
OpenTargetsi | ENSG00000232810 |
Orphaneti | 40050, NON RARE IN EUROPE: Psoriatic arthritis |
PharmGKBi | PA435 |
VEuPathDBi | HostDB:ENSG00000232810 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S4K8, Eukaryota |
GeneTreei | ENSGT01040000240509 |
HOGENOMi | CLU_070352_3_1_1 |
InParanoidi | P01375 |
OMAi | GATMLFC |
OrthoDBi | 1124938at2759 |
PhylomeDBi | P01375 |
TreeFami | TF332169 |
Enzyme and pathway databases
PathwayCommonsi | P01375 |
Reactomei | R-HSA-381340, Transcriptional regulation of white adipocyte differentiation R-HSA-5357786, TNFR1-induced proapoptotic signaling R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5626978, TNFR1-mediated ceramide production R-HSA-5668541, TNFR2 non-canonical NF-kB pathway R-HSA-6783783, Interleukin-10 signaling R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-75893, TNF signaling |
SignaLinki | P01375 |
SIGNORi | P01375 |
Miscellaneous databases
BioGRID-ORCSi | 7124, 3 hits in 1041 CRISPR screens |
ChiTaRSi | TNF, human |
EvolutionaryTracei | P01375 |
GeneWikii | Tumor_necrosis_factor-alpha |
GenomeRNAii | 7124 |
Pharosi | P01375, Tclin |
PROi | PR:P01375 |
RNActi | P01375, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000232810, Expressed in granulocyte and 112 other tissues |
ExpressionAtlasi | P01375, baseline and differential |
Genevisiblei | P01375, HS |
Family and domain databases
CDDi | cd00184, TNF, 1 hit |
Gene3Di | 2.60.120.40, 1 hit |
InterProi | View protein in InterPro IPR006053, TNF IPR002959, TNF_alpha IPR021184, TNF_CS IPR006052, TNF_dom IPR008983, Tumour_necrosis_fac-like_dom |
PANTHERi | PTHR11471:SF23, PTHR11471:SF23, 1 hit |
Pfami | View protein in Pfam PF00229, TNF, 1 hit |
PRINTSi | PR01234, TNECROSISFCT PR01235, TNFALPHA |
SMARTi | View protein in SMART SM00207, TNF, 1 hit |
SUPFAMi | SSF49842, SSF49842, 1 hit |
PROSITEi | View protein in PROSITE PS00251, TNF_1, 1 hit PS50049, TNF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TNFA_HUMAN | |
Accessioni | P01375Primary (citable) accession number: P01375 Secondary accession number(s): O43647, Q9P1Q2, Q9UIV3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | February 23, 2022 | |
This is version 262 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families