UniProt functional annotation for B0LPN4



	UniProt functional annotation for B0LPN4

UniProt code: B0LPN4.

Organism: Rattus norvegicus (Rat).

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

Function: Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development (By similarity). {ECO:0000250|UniProtKB:Q92736, ECO:0000269|PubMed:20431056, ECO:0000269|PubMed:20471962}.

Activity regulation: Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites (By similarity). {ECO:0000250|UniProtKB:P11716}.

Subunit: Homotetramer. Can also form heterotetramers with RYR3. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A (By similarity). Interacts with FKBP1A and FKBP1B; these interactions may stabilize the channel in its closed state and prevent Ca(2+) leaks. Interacts with CALM and S100A1; these interactions regulate channel activity. Interacts with SELENON (By similarity). In cardiac muscles, identified in a complex composed of FSD2, CMYA5 and RYR2 (By similarity). {ECO:0000250|UniProtKB:E9Q401, ECO:0000250|UniProtKB:P30957, ECO:0000250|UniProtKB:Q92736, ECO:0000269|PubMed:18650434, ECO:0000269|PubMed:20431056}.

Subcellular location: Sarcoplasmic reticulum membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Sarcoplasmic reticulum {ECO:0000250|UniProtKB:P30957}. Note=The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C-terminus seem to be cytoplasmic. {ECO:0000250}.

Tissue specificity: Detected in heart muscle myocytes (at protein level). Widely expressed. Detected in heart muscle and cerebral artery smooth muscle. Detected in pancreatic islet cells. {ECO:0000269|PubMed:18755143, ECO:0000269|PubMed:20431056, ECO:0000269|PubMed:20445169, ECO:0000269|PubMed:20471962}.

Domain: The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm. {ECO:0000305}.

Ptm: Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2798 and Ser-2804 increases the open probability of the calcium channel. Phosphorylation is increased in failing heart, leading to calcium leaks and increased cytoplasmic Ca(2+) levels (By similarity). {ECO:0000250}.

Ptm: Phosphorylation at Ser-2021 by PKA enhances the response to lumenal calcium. {ECO:0000250}.

Similarity: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily. {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:		Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development (By similarity). {ECO:0000250\|UniProtKB:Q92736, ECO:0000269\|PubMed:20431056, ECO:0000269\|PubMed:20471962}.


Activity regulation:		Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites (By similarity). {ECO:0000250\|UniProtKB:P11716}.
Subunit:		Homotetramer. Can also form heterotetramers with RYR3. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A (By similarity). Interacts with FKBP1A and FKBP1B; these interactions may stabilize the channel in its closed state and prevent Ca(2+) leaks. Interacts with CALM and S100A1; these interactions regulate channel activity. Interacts with SELENON (By similarity). In cardiac muscles, identified in a complex composed of FSD2, CMYA5 and RYR2 (By similarity). {ECO:0000250\|UniProtKB:E9Q401, ECO:0000250\|UniProtKB:P30957, ECO:0000250\|UniProtKB:Q92736, ECO:0000269\|PubMed:18650434, ECO:0000269\|PubMed:20431056}.
Subcellular location:		Sarcoplasmic reticulum membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. Sarcoplasmic reticulum {ECO:0000250\|UniProtKB:P30957}. Note=The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C-terminus seem to be cytoplasmic. {ECO:0000250}.
Tissue specificity:		Detected in heart muscle myocytes (at protein level). Widely expressed. Detected in heart muscle and cerebral artery smooth muscle. Detected in pancreatic islet cells. {ECO:0000269\|PubMed:18755143, ECO:0000269\|PubMed:20431056, ECO:0000269\|PubMed:20445169, ECO:0000269\|PubMed:20471962}.
Domain:		The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm. {ECO:0000305}.
Ptm:		Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2798 and Ser-2804 increases the open probability of the calcium channel. Phosphorylation is increased in failing heart, leading to calcium leaks and increased cytoplasmic Ca(2+) levels (By similarity). {ECO:0000250}.
Ptm:		Phosphorylation at Ser-2021 by PKA enhances the response to lumenal calcium. {ECO:0000250}.
Similarity:		Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily. {ECO:0000305}.