UniProt functional annotation for P14598



	UniProt functional annotation for P14598

UniProt code: P14598.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). {ECO:0000269|PubMed:19801500, ECO:0000269|PubMed:2547247, ECO:0000269|PubMed:2550933}.

Subunit: Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts (via C-terminus) with NCF2 (via the C-terminal SH3 domain). Interacts with NCF4. Interacts with CYBB. Interacts (via the second SH3 domain) with CYBA. Interacts with NOXA1. Interacts with ADAM15. Interacts with TRAF4. Interacts with FASLG. Interacts with PARK7 (via C-terminus); the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (By similarity). {ECO:0000250|UniProtKB:Q09014, ECO:0000269|PubMed:12023963, ECO:0000269|PubMed:12169629, ECO:0000269|PubMed:12716910, ECO:0000269|PubMed:12732142, ECO:0000269|PubMed:15657040, ECO:0000269|PubMed:16052631, ECO:0000269|PubMed:16326715, ECO:0000269|PubMed:19718658, ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:2550933, ECO:0000269|PubMed:9224653}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:2550933}. Membrane {ECO:0000269|PubMed:12356722}; Peripheral membrane protein {ECO:0000269|PubMed:12356722}; Cytoplasmic side {ECO:0000269|PubMed:12356722}.

Tissue specificity: Detected in peripheral blood monocytes and neutrophils (at protein level). {ECO:0000269|PubMed:2547247, ECO:0000269|PubMed:2550933}.

Domain: The PX domain mediates interaction with phosphatidylinositol 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, unphosphorylated state an intramolecular interaction with the C- terminal SH3 domain precludes phospholipid binding and interaction with CYBA. Phosphorylation disrupts the autoinhibited state. {ECO:0000269|PubMed:12356722, ECO:0000269|PubMed:12732142}.

Ptm: Phosphorylated by PRKCD; phosphorylation induces activation of NCF1 and NADPH oxidase activity. {ECO:0000269|PubMed:19801500, ECO:0000269|PubMed:8089108}.

Disease: Granulomatous disease, chronic, cytochrome-b-positive 1, autosomal recessive (CGD1) [MIM:233700]: A form of chronic granulomatous disease, a primary immunodeficiency characterized by severe recurrent bacterial and fungal infections, along with manifestations of chronic granulomatous inflammation. It results from an impaired ability of phagocytes to mount a burst of reactive oxygen species in response to pathogens. {ECO:0000269|PubMed:11133775, ECO:0000269|PubMed:23910690}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 2]: Due to intron retention. {ECO:0000305}.

Sequence caution: Sequence=BAF84783.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG54596.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). {ECO:0000269\|PubMed:19801500, ECO:0000269\|PubMed:2547247, ECO:0000269\|PubMed:2550933}.


Subunit:		Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts (via C-terminus) with NCF2 (via the C-terminal SH3 domain). Interacts with NCF4. Interacts with CYBB. Interacts (via the second SH3 domain) with CYBA. Interacts with NOXA1. Interacts with ADAM15. Interacts with TRAF4. Interacts with FASLG. Interacts with PARK7 (via C-terminus); the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (By similarity). {ECO:0000250\|UniProtKB:Q09014, ECO:0000269\|PubMed:12023963, ECO:0000269\|PubMed:12169629, ECO:0000269\|PubMed:12716910, ECO:0000269\|PubMed:12732142, ECO:0000269\|PubMed:15657040, ECO:0000269\|PubMed:16052631, ECO:0000269\|PubMed:16326715, ECO:0000269\|PubMed:19718658, ECO:0000269\|PubMed:19807924, ECO:0000269\|PubMed:2550933, ECO:0000269\|PubMed:9224653}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:2550933}. Membrane {ECO:0000269\|PubMed:12356722}; Peripheral membrane protein {ECO:0000269\|PubMed:12356722}; Cytoplasmic side {ECO:0000269\|PubMed:12356722}.
Tissue specificity:		Detected in peripheral blood monocytes and neutrophils (at protein level). {ECO:0000269\|PubMed:2547247, ECO:0000269\|PubMed:2550933}.
Domain:		The PX domain mediates interaction with phosphatidylinositol 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, unphosphorylated state an intramolecular interaction with the C- terminal SH3 domain precludes phospholipid binding and interaction with CYBA. Phosphorylation disrupts the autoinhibited state. {ECO:0000269\|PubMed:12356722, ECO:0000269\|PubMed:12732142}.
Ptm:		Phosphorylated by PRKCD; phosphorylation induces activation of NCF1 and NADPH oxidase activity. {ECO:0000269\|PubMed:19801500, ECO:0000269\|PubMed:8089108}.
Disease:		Granulomatous disease, chronic, cytochrome-b-positive 1, autosomal recessive (CGD1) [MIM:233700]: A form of chronic granulomatous disease, a primary immunodeficiency characterized by severe recurrent bacterial and fungal infections, along with manifestations of chronic granulomatous inflammation. It results from an impaired ability of phagocytes to mount a burst of reactive oxygen species in response to pathogens. {ECO:0000269\|PubMed:11133775, ECO:0000269\|PubMed:23910690}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 2]: Due to intron retention. {ECO:0000305}.
Sequence caution:		Sequence=BAF84783.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG54596.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};