O77774
SS
Gene name |
NCF1 |
Protein name |
Neutrophil cytosol factor 1 |
Names |
NCF-1, 47 kDa neutrophil oxidase factor, NCF-47K, Neutrophil NADPH oxidase factor 1, p47-phox |
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:281345 |
EC number |
|
Protein Class |
|
Descriptions
Phagocyte NADPH oxidase is a multisubunit enzyme responsible for the production of reactive oxygen species. NCF1 (p47phox) is a cytosolic component of the NADPH oxidase and plays an important role in the assembly of the activated complex. NCF1 is composed of several domains including a PX domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region(PBR/AIR), and a proline-rich region (PRR). In a structural study with a human homolog NCF1 (P14598), in an inactive state, the binding surface of the tandem SH3 domains for the binding to the PRR region of p22phox (CYBA) is masked through the intramolecular interaction with PBR/AIR. Phosphorylations of the Ser residues in PBR/AIR by PKC or Akt cause a conformational change in NCF1 and activation of the NADPH oxidase.
Autoinhibitory domains (AIDs)
Target domain |
156-215 (N-SH3); 226-285 (C-SH3) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Yuzawa S et al. (2004) "A molecular mechanism for autoinhibition of the tandem SH3 domains of p47phox, the regulatory subunit of the phagocyte NADPH oxidase", Genes to cells : devoted to molecular & cellular mechanisms, 9, 443-56
- Yuzawa S et al. (2003) "Crystallization and preliminary crystallographic analysis of the autoinhibited form of the tandem SH3 domain of p47(phox)", Acta crystallographica. Section D, Biological crystallography, 59, 1479-80
Autoinhibited structure
Activated structure
1 structures for O77774
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O77774-F1 | Predicted | AlphaFoldDB |
No variants for O77774
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for O77774 | |||||
No associated diseases with O77774
6 regional properties for O77774
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | SH3 domain | 156 - 215 | IPR001452-1 |
| domain | SH3 domain | 226 - 285 | IPR001452-2 |
| domain | Phox homology | 3 - 125 | IPR001683 |
| domain | Neutrophil cytosol factor 1, C-terminal | 360 - 392 | IPR015039 |
| domain | Neutrophil cytosol factor 1, PX domain | 6 - 123 | IPR034909 |
| domain | Neutrophil cytosol factor 1, first SH3 domain | 160 - 212 | IPR035756 |
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| extrinsic component of membrane | The component of a membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it. |
| NADPH oxidase complex | A enzyme complex of which the core is a heterodimer composed of a light (alpha) and heavy (beta) chain, and requires several other water-soluble proteins of cytosolic origin for activity. Functions in superoxide generation by the NADPH-dependent reduction of O2. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| phosphatidylinositol binding | Binding to an inositol-containing glycerophospholipid, i.e. phosphatidylinositol (PtdIns) and its phosphorylated derivatives. |
| phosphatidylinositol-3,4-bisphosphate binding | Binding to phosphatidylinositol-3,4-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3' and 4' positions. |
| superoxide-generating NADPH oxidase activator activity | Increases the activity of the enzyme superoxide-generating NADPH oxidase. |
3 GO annotations of biological process
| Name | Definition |
|---|---|
| protein targeting to membrane | The process of directing proteins towards a membrane, usually using signals contained within the protein. |
| respiratory burst | A phase of elevated metabolic activity, during which oxygen consumption increases; this leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals. |
| superoxide anion generation | The enzymatic generation of superoxide, the superoxide anion O2- (superoxide free radical), or any compound containing this species, by a cell in response to environmental stress, thereby mediating the activation of various stress-inducible signaling pathways. |
6 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P14598 | NCF1 | Neutrophil cytosol factor 1 | Homo sapiens (Human) | EV |
| A6NI72 | NCF1B | Putative neutrophil cytosol factor 1B | Homo sapiens (Human) | SS |
| A8MVU1 | NCF1C | Putative neutrophil cytosol factor 1C | Homo sapiens (Human) | SS |
| P97369 | Ncf4 | Neutrophil cytosol factor 4 | Mus musculus (Mouse) | PR |
| Q09014 | Ncf1 | Neutrophil cytosol factor 1 | Mus musculus (Mouse) | SS |
| F1M707 | Ncf1 | Neutrophil cytosolic factor 1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MGDHFIRHIA | LLGFEKRFVP | SQHYVYMFLV | KWQDLSEKVV | YRRFTEIYEF | HKILKEMFPI |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EAGDINPENR | IIPHLPAPRW | YDGQRVAESR | QGTLTEYCST | LMSLPVKISR | CPHLLNFFKV |
| 130 | 140 | 150 | 160 | 170 | 180 |
| RPDDLKLPTD | SQVKKPETYL | MPKDGKNNAA | DITGPIILQT | YRAIADYEKG | SSSQMALATG |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DVVDVVEKNE | SGWWFCQMKT | KRGWVPASYL | EPLDSPDEAE | DPEPNYAGEP | YITIKAYTAV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LEDEISLEEG | EAIEVIHKLL | DGWWVIRKED | VTGYFPSMYL | QKAGQDVAQA | KSQIKSRGAP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| PRRSSIRNAH | SIHQRSRKRL | SQDTYRRNSV | RFMQQRRHQR | PEPQRSRSAL | REQQQPKTER |
| 370 | 380 | 390 | |||
| PKPQPAVPPR | PSADLILHRC | SESTKRKLAS | AV |