UniProt functional annotation for P29994



	UniProt functional annotation for P29994

UniProt code: P29994.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways. {ECO:0000250|UniProtKB:P11881}.

Subunit: Homotetramer. Interacts with TRPC4 (PubMed:11163362). The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1 (By similarity). Interacts with CABP1 (via N-terminus) (PubMed:12032348). Interacts with TESPA1. Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated); the interaction suppresses inositol 1,4,5- trisphosphate binding to ITPR1 and is increased in the presence of BCL2L10. Interacts with AHCYL2 (with lower affinity than with AHCYL1) (By similarity). Interacts with BCL2L10; the interaction is increased in the presence of AHCLY1 (By similarity). Interacts with BOK (via BH4. domain); protects ITPR1 from proteolysis by CASP3 during apoptosis (By similarity). {ECO:0000250|UniProtKB:P11881, ECO:0000250|UniProtKB:Q14643, ECO:0000250|UniProtKB:Q9TU34, ECO:0000269|PubMed:11163362, ECO:0000269|PubMed:12032348}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9TU34}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:Q9TU34}; Multi-pass membrane protein {ECO:0000255}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q14643}. Note=Endoplasmic reticulum and secretory granules (By similarity). {ECO:0000250|UniProtKB:Q9TU34}.

Tissue specificity: [Isoform 3]: Expressed in the brain. {ECO:0000269|PubMed:2165071}.

Tissue specificity: [Isoform 7]: Expressed in the fetal brain and peripheral tissues. {ECO:0000269|PubMed:1849282}.

Domain: The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand- binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.

Ptm: Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the ligand-induced opening of the calcium channels. Phosphorylation by PKA increases the interaction with inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1. {ECO:0000250|UniProtKB:P11881}.

Ptm: Phosphorylated on tyrosine residues. {ECO:0000250|UniProtKB:Q14643}.

Ptm: Ubiquitination at multiple lysines targets ITPR1 for proteasomal degradation. Approximately 40% of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'- linked. {ECO:0000269|PubMed:18955483}.

Ptm: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function. {ECO:0000250|UniProtKB:P11881}.

Miscellaneous: Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor.

Similarity: Belongs to the InsP3 receptor family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways. {ECO:0000250\|UniProtKB:P11881}.


Subunit:		Homotetramer. Interacts with TRPC4 (PubMed:11163362). The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1 (By similarity). Interacts with CABP1 (via N-terminus) (PubMed:12032348). Interacts with TESPA1. Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated); the interaction suppresses inositol 1,4,5- trisphosphate binding to ITPR1 and is increased in the presence of BCL2L10. Interacts with AHCYL2 (with lower affinity than with AHCYL1) (By similarity). Interacts with BCL2L10; the interaction is increased in the presence of AHCLY1 (By similarity). Interacts with BOK (via BH4. domain); protects ITPR1 from proteolysis by CASP3 during apoptosis (By similarity). {ECO:0000250\|UniProtKB:P11881, ECO:0000250\|UniProtKB:Q14643, ECO:0000250\|UniProtKB:Q9TU34, ECO:0000269\|PubMed:11163362, ECO:0000269\|PubMed:12032348}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q9TU34}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250\|UniProtKB:Q9TU34}; Multi-pass membrane protein {ECO:0000255}. Cytoplasm, perinuclear region {ECO:0000250\|UniProtKB:Q14643}. Note=Endoplasmic reticulum and secretory granules (By similarity). {ECO:0000250\|UniProtKB:Q9TU34}.
Tissue specificity:		[Isoform 3]: Expressed in the brain. {ECO:0000269\|PubMed:2165071}.
Tissue specificity:		[Isoform 7]: Expressed in the fetal brain and peripheral tissues. {ECO:0000269\|PubMed:1849282}.
Domain:		The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand- binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.
Ptm:		Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the ligand-induced opening of the calcium channels. Phosphorylation by PKA increases the interaction with inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1. {ECO:0000250\|UniProtKB:P11881}.
Ptm:		Phosphorylated on tyrosine residues. {ECO:0000250\|UniProtKB:Q14643}.
Ptm:		Ubiquitination at multiple lysines targets ITPR1 for proteasomal degradation. Approximately 40% of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'- linked. {ECO:0000269\|PubMed:18955483}.
Ptm:		Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function. {ECO:0000250\|UniProtKB:P11881}.
Miscellaneous:		Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor.
Similarity:		Belongs to the InsP3 receptor family. {ECO:0000305}.