UniProt functional annotation for P16885



	UniProt functional annotation for P16885

UniProt code: P16885.

Organism: Homo sapiens (Human).

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

Function: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. {ECO:0000269|PubMed:23000145}.

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2- diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456, ChEBI:CHEBI:203600; EC=3.1.4.11; Evidence={ECO:0000269|PubMed:23000145}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; Evidence={ECO:0000305|PubMed:23000145};

Cofactor: Name=Ca(2+); Xref=ChEBI:CHEBI:29108;

Subunit: Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts constitutively with THEMIS2. {ECO:0000250|UniProtKB:Q8CIH5}.

Ptm: Phosphorylated on tyrosine residues by CSF1R (By similarity). Phosphorylated on tyrosine residues by BTK and SYK; upon ligand-induced activation of a variety of growth factor receptors and immune system receptors. Phosphorylation leads to increased phospholipase activity. {ECO:0000250|UniProtKB:Q8CIH5, ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:12181444}.

Disease: Familial cold autoinflammatory syndrome 3 (FCAS3) [MIM:614468]: An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B-cells, defective B-cells, increased susceptibility to infection, and increased risk of autoimmune disorders. {ECO:0000269|PubMed:22236196}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) [MIM:614878]: An autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies. {ECO:0000269|PubMed:23000145}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAA60112.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAQ76815.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAD92151.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA32194.1; Type=Frameshift; 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:		The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. {ECO:0000269\|PubMed:23000145}.


Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2- diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456, ChEBI:CHEBI:203600; EC=3.1.4.11; Evidence={ECO:0000269\|PubMed:23000145}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; Evidence={ECO:0000305\|PubMed:23000145};
Cofactor:		Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
Subunit:		Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts constitutively with THEMIS2. {ECO:0000250\|UniProtKB:Q8CIH5}.
Ptm:		Phosphorylated on tyrosine residues by CSF1R (By similarity). Phosphorylated on tyrosine residues by BTK and SYK; upon ligand-induced activation of a variety of growth factor receptors and immune system receptors. Phosphorylation leads to increased phospholipase activity. {ECO:0000250\|UniProtKB:Q8CIH5, ECO:0000269\|PubMed:11606584, ECO:0000269\|PubMed:12181444}.
Disease:		Familial cold autoinflammatory syndrome 3 (FCAS3) [MIM:614468]: An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B-cells, defective B-cells, increased susceptibility to infection, and increased risk of autoimmune disorders. {ECO:0000269\|PubMed:22236196}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) [MIM:614878]: An autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies. {ECO:0000269\|PubMed:23000145}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAA60112.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAQ76815.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAD92151.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA32194.1; Type=Frameshift; Evidence={ECO:0000305};