UniProt functional annotation for Q8NEB9



	UniProt functional annotation for Q8NEB9

UniProt code: Q8NEB9.

Organism: Homo sapiens (Human).

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

Function: Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. As part of PI3KC3-C1, promotes endoplasmic reticulum membrane curvature formation prior to vesicle budding (PubMed:32690950). Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity). {ECO:0000250|UniProtKB:O88763, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:7628435, ECO:0000305}.

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.137; Evidence={ECO:0000269|PubMed:7628435}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; Evidence={ECO:0000305|PubMed:7628435};

Cofactor: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:7628435};

Subunit: Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are: the PI3K complex I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2) containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:7628435, PubMed:19050071, PubMed:20643123, PubMed:19270696, PubMed:23878393, PubMed:25490155). PI3KC3-C1 probably associates with PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3R4 (PubMed:14617358). Interacts with AMBRA1 (By similarity). Interacts with BECN1P1/BECN2 (PubMed:23954414). Interacts with SLAMF1(PubMed:22493499). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts with NCKAP1L (PubMed:16417406). Interacts with ATG14; this interaction is increased in the absence of TMEM39A (PubMed:31806350). Interacts with STEEP1; the interaction is STING1-dependent and required for trafficking of STING1 from the endoplasmic reticulum (PubMed:32690950). {ECO:0000250|UniProtKB:Q6PF93, ECO:0000250|UniProtKB:Q9TXI7, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:16417406, ECO:0000269|PubMed:19050071, ECO:0000269|PubMed:19270696, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:22493499, ECO:0000269|PubMed:23878393, ECO:0000269|PubMed:23954414, ECO:0000269|PubMed:25490155, ECO:0000269|PubMed:31806350, ECO:0000269|PubMed:32690950, ECO:0000269|PubMed:7628435, ECO:0000305}.

Subcellular location: Midbody {ECO:0000269|PubMed:20208530}. Late endosome {ECO:0000269|PubMed:14617358}. Cytoplasmic vesicle, autophagosome {ECO:0000305|PubMed:14617358}. Note=As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes (Probable). Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme (By similarity). {ECO:0000250|UniProtKB:Q6PF93, ECO:0000305|PubMed:14617358}.

Tissue specificity: Ubiquitously expressed, with a highest expression in skeletal muscle. {ECO:0000269|PubMed:7628435}.

Similarity: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE- ProRule:PRU00880}.

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:		Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. As part of PI3KC3-C1, promotes endoplasmic reticulum membrane curvature formation prior to vesicle budding (PubMed:32690950). Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity). {ECO:0000250\|UniProtKB:O88763, ECO:0000269\|PubMed:14617358, ECO:0000269\|PubMed:20208530, ECO:0000269\|PubMed:20643123, ECO:0000269\|PubMed:32690950, ECO:0000269\|PubMed:7628435, ECO:0000305}.


Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216; EC=2.7.1.137; Evidence={ECO:0000269\|PubMed:7628435}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710; Evidence={ECO:0000305\|PubMed:7628435};
Cofactor:		Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:7628435};
Subunit:		Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are: the PI3K complex I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2) containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:7628435, PubMed:19050071, PubMed:20643123, PubMed:19270696, PubMed:23878393, PubMed:25490155). PI3KC3-C1 probably associates with PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3R4 (PubMed:14617358). Interacts with AMBRA1 (By similarity). Interacts with BECN1P1/BECN2 (PubMed:23954414). Interacts with SLAMF1(PubMed:22493499). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts with NCKAP1L (PubMed:16417406). Interacts with ATG14; this interaction is increased in the absence of TMEM39A (PubMed:31806350). Interacts with STEEP1; the interaction is STING1-dependent and required for trafficking of STING1 from the endoplasmic reticulum (PubMed:32690950). {ECO:0000250\|UniProtKB:Q6PF93, ECO:0000250\|UniProtKB:Q9TXI7, ECO:0000269\|PubMed:14617358, ECO:0000269\|PubMed:16417406, ECO:0000269\|PubMed:19050071, ECO:0000269\|PubMed:19270696, ECO:0000269\|PubMed:20643123, ECO:0000269\|PubMed:22493499, ECO:0000269\|PubMed:23878393, ECO:0000269\|PubMed:23954414, ECO:0000269\|PubMed:25490155, ECO:0000269\|PubMed:31806350, ECO:0000269\|PubMed:32690950, ECO:0000269\|PubMed:7628435, ECO:0000305}.
Subcellular location:		Midbody {ECO:0000269\|PubMed:20208530}. Late endosome {ECO:0000269\|PubMed:14617358}. Cytoplasmic vesicle, autophagosome {ECO:0000305\|PubMed:14617358}. Note=As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes (Probable). Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme (By similarity). {ECO:0000250\|UniProtKB:Q6PF93, ECO:0000305\|PubMed:14617358}.
Tissue specificity:		Ubiquitously expressed, with a highest expression in skeletal muscle. {ECO:0000269\|PubMed:7628435}.
Similarity:		Belongs to the PI3/PI4-kinase family. {ECO:0000255\|PROSITE- ProRule:PRU00880}.