| UniProt ID | TNFA_HUMAN | |
|---|---|---|
| UniProt AC | P01375 | |
| Protein Name | Tumor necrosis factor | |
| Gene Name | TNF | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 233 | |
| Subcellular Localization |
Cell membrane Single-pass type II membrane protein . Tumor necrosis factor, membrane form: Membrane Single-pass type II membrane protein. Tumor necrosis factor, soluble form: Secreted. C-domain 1: Secreted. C-domain 2: Secreted. |
|
| Protein 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. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates 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] | |
| Protein Sequence | MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQREEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 2 | Phosphorylation | ------MSTESMIRD ------CCHHHHHHH | 40.66 | 30631047 | |
| 19 | N6-myristoyl lysine | LAEEALPKKTGGPQG HHHHHCCCCCCCCCC | 64.91 | - | |
| 19 | Myristoylation | LAEEALPKKTGGPQG HHHHHCCCCCCCCCC | 64.91 | 1402651 | |
| 20 | N6-myristoyl lysine | AEEALPKKTGGPQGS HHHHCCCCCCCCCCH | 50.92 | - | |
| 20 | Myristoylation | AEEALPKKTGGPQGS HHHHCCCCCCCCCCH | 50.92 | 1402651 | |
| 30 | S-palmitoylation | GPQGSRRCLFLSLFS CCCCHHHHHHHHHHH | 2.83 | 23159491 | |
| 37 | Phosphorylation | CLFLSLFSFLIVAGA HHHHHHHHHHHHHHH | 25.16 | 24719451 | |
| 46 | Phosphorylation | LIVAGATTLFCLLHF HHHHHHHHHHHHHHH | 19.80 | 24719451 | |
| 49 | S-palmitoylation | AGATTLFCLLHFGVI HHHHHHHHHHHHCCC | 4.43 | 11434916 | |
| 80 | O-linked_Glycosylation | LAQAVRSSSRTPSDK HHHHHHHCCCCCCCC | 17.18 | 8631363 | |
| 162 | Phosphorylation | TISRIAVSYQTKVNL EHHHHHCCHHHHHHH | 11.51 | 27174698 | |
| 163 | Phosphorylation | ISRIAVSYQTKVNLL HHHHHCCHHHHHHHH | 17.38 | 27174698 | |
| 165 | Phosphorylation | RIAVSYQTKVNLLSA HHHCCHHHHHHHHHH | 28.82 | 27174698 | |
| 171 | Phosphorylation | QTKVNLLSAIKSPCQ HHHHHHHHHCCCCCC | 30.98 | 27174698 | |
| 175 | Phosphorylation | NLLSAIKSPCQRETP HHHHHCCCCCCCCCC | 25.46 | 27174698 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 2 | S | Phosphorylation | Kinase | CK2-FAMILY | - | GPS |
| 2 | S | Phosphorylation | Kinase | CK1 | - | Uniprot |
| 2 | S | Phosphorylation | Kinase | CK2_GROUP | - | PhosphoELM |
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of TNFA_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of TNFA_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| H00079 | Asthma | |||||
| H00080 | Systemic lupus erythematosus | |||||
| H00083 | Allograft rejection | |||||
| H00084 | Graft-versus-host disease | |||||
| OMIM Disease | ||||||
| 607507 | Psoriatic arthritis (PSORAS) | |||||
| Kegg Drug | ||||||
| D00742 | Etanercept (genetical recombination) (JAN); Etanercept (USAN/INN); Enbrel (TN) | |||||
| D02597 | Adalimumab (genetical recombination) (JAN); Adalimumab (USAN/INN); Humira (TN) | |||||
| D02598 | Infliximab (genetical recombination) (JAN); Infliximab (USAN/INN); Remicade (TN) | |||||
| D03441 | Certolizumab pegol (genetical recombination) (JAN); Certolizumab pegol (USAN/INN); Cimzia (TN) | |||||
| D04358 | Golimumab (genetical recombination) (JAN); Golimumab (USAN/INN); Simponi (TN) | |||||
| D04687 | Lenalidomide (USAN/INN); Revlimid (TN) | |||||
| D04690 | Lenercept (USAN/INN) | |||||
| D05146 | Nerelimomab (USAN/INN) | |||||
| D05263 | Onercept (USAN/INN) | |||||
| D05393 | Pegsunercept (USAN) | |||||
| D07436 | Afelimomab (INN) | |||||
| D08562 | Tasonermin (INN); Beromun (TN) | |||||
| D09624 | Golnerminogene pradenovec (USAN/INN) | |||||
| D09813 | Lenalidomide hydrate (JAN); Revlimid (TN) | |||||
| D09944 | Ozoralizumab (USAN) | |||||
| D10320 | Placulumab (USAN/INN) | |||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Myristoylation | |
| Reference | PubMed |
| "Myristyl acylation of the tumor necrosis factor alpha precursor onspecific lysine residues."; Stevenson F.T., Bursten S.L., Locksley R.M., Lovett D.H.; J. Exp. Med. 176:1053-1062(1992). Cited for: MYRISTOYLATION AT LYS-19 AND LYS-20. | |
| O-linked Glycosylation | |
| Reference | PubMed |
| "O-glycosylated species of natural human tumor-necrosis factor-alpha."; Takakura-Yamamoto R., Yamamoto S., Fukuda S., Kurimoto M.; Eur. J. Biochem. 235:431-437(1996). Cited for: PROTEIN SEQUENCE OF 77-99, AND GLYCOSYLATION AT SER-80. | |
