UniProt functional annotation for P61023



	UniProt functional annotation for P61023

UniProt code: P61023.

Organism: Rattus norvegicus (Rat).

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

Function: Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane- type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium- dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner. {ECO:0000269|PubMed:12966074, ECO:0000269|PubMed:14657246, ECO:0000269|PubMed:15312048, ECO:0000269|PubMed:20720019, ECO:0000269|PubMed:21543739, ECO:0000269|PubMed:8626580}.

Subunit: Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the juxtamembrane region of the cytoplasmic C-terminal domain); the interaction occurs at the plasma membrane in a calcium-dependent manner and at a domain that is critical for growth factor stimulation of the exchanger (By similarity). Monomer. Interacts with STK17B; the interaction occurs in a calcium-independent manner and induces the translocation of CHP1 from the Golgi to the nucleus. Interacts with GAPDH; the interaction is direct, occurs in a N-myristoylation- dependent manner and facilitates the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the C-terminal end of the kinesin-motor domain); the interaction occurs in a calcium-dependent manner. Associates (via C-terminal domain) with microtubules; the association occurs with polymerized microtubules during the cell cycle in a myristoylation- and calcium-independent manner and is enhanced by GAPDH. {ECO:0000250|UniProtKB:Q99653, ECO:0000269|PubMed:11481038, ECO:0000269|PubMed:12204119, ECO:0000269|PubMed:12966074, ECO:0000269|PubMed:15312048, ECO:0000269|PubMed:15987692}.

Subcellular location: Nucleus {ECO:0000269|PubMed:20720019}. Cytoplasm {ECO:0000269|PubMed:12204119, ECO:0000269|PubMed:14769882}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10512881, ECO:0000269|PubMed:15312048}. Endomembrane system {ECO:0000269|PubMed:15312048}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305}. Endoplasmic reticulum {ECO:0000269|PubMed:14657246}. Cell membrane {ECO:0000269|PubMed:21543739}. Membrane {ECO:0000250|UniProtKB:Q99653}; Lipid-anchor {ECO:0000250|UniProtKB:Q99653}. Note=Localizes in cytoplasmic compartments in dividing cells. Localizes in the nucleus in quiescent cells. Exported from the nucleus to the cytoplasm through a nuclear export signal (NES) and CRM1-dependent pathway. May shuttle between nucleus and cytoplasm. Localizes with the microtubule- organizing center (MTOC) and extends toward the periphery along microtubules. Associates with membranes of the early secretory pathway in a GAPDH-independent, N-myristoylation- and calcium-dependent manner. Colocalizes with the mitotic spindle microtubules. Colocalizes with GAPDH along microtubules. Colocalizes with SLC9A1 at the reticulum endoplasmic and plasma membrane. Colocalizes with STK17B at the plasma membrane. {ECO:0000269|PubMed:14657246, ECO:0000269|PubMed:15312048, ECO:0000269|PubMed:20720019, ECO:0000269|PubMed:21543739}.

Tissue specificity: Expressed in liver and kidney (at protein level). Ubiquitously expressed. Expressed in the brain, lung, testes, kidney, spleen and heart. {ECO:0000269|PubMed:10512881, ECO:0000269|PubMed:15312048, ECO:0000269|PubMed:8626580}.

Ptm: Phosphorylated; decreased phosphorylation is associated with an increase in SLC9A1/NHE1 Na(+)/H(+) exchange activity. Phosphorylation occurs in serum-dependent manner. The phosphorylation state may regulate the binding to SLC9A1/NHE1 (By similarity). {ECO:0000250}.

Ptm: N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes. Both N-myristoylation and calcium-mediated conformational changes are essential in exocytic traffic.

Similarity: Belongs to the calcineurin regulatory subunit family. CHP 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-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane- type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium- dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner. {ECO:0000269\|PubMed:12966074, ECO:0000269\|PubMed:14657246, ECO:0000269\|PubMed:15312048, ECO:0000269\|PubMed:20720019, ECO:0000269\|PubMed:21543739, ECO:0000269\|PubMed:8626580}.


Subunit:		Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the juxtamembrane region of the cytoplasmic C-terminal domain); the interaction occurs at the plasma membrane in a calcium-dependent manner and at a domain that is critical for growth factor stimulation of the exchanger (By similarity). Monomer. Interacts with STK17B; the interaction occurs in a calcium-independent manner and induces the translocation of CHP1 from the Golgi to the nucleus. Interacts with GAPDH; the interaction is direct, occurs in a N-myristoylation- dependent manner and facilitates the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the C-terminal end of the kinesin-motor domain); the interaction occurs in a calcium-dependent manner. Associates (via C-terminal domain) with microtubules; the association occurs with polymerized microtubules during the cell cycle in a myristoylation- and calcium-independent manner and is enhanced by GAPDH. {ECO:0000250\|UniProtKB:Q99653, ECO:0000269\|PubMed:11481038, ECO:0000269\|PubMed:12204119, ECO:0000269\|PubMed:12966074, ECO:0000269\|PubMed:15312048, ECO:0000269\|PubMed:15987692}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:20720019}. Cytoplasm {ECO:0000269\|PubMed:12204119, ECO:0000269\|PubMed:14769882}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:10512881, ECO:0000269\|PubMed:15312048}. Endomembrane system {ECO:0000269\|PubMed:15312048}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305}. Endoplasmic reticulum {ECO:0000269\|PubMed:14657246}. Cell membrane {ECO:0000269\|PubMed:21543739}. Membrane {ECO:0000250\|UniProtKB:Q99653}; Lipid-anchor {ECO:0000250\|UniProtKB:Q99653}. Note=Localizes in cytoplasmic compartments in dividing cells. Localizes in the nucleus in quiescent cells. Exported from the nucleus to the cytoplasm through a nuclear export signal (NES) and CRM1-dependent pathway. May shuttle between nucleus and cytoplasm. Localizes with the microtubule- organizing center (MTOC) and extends toward the periphery along microtubules. Associates with membranes of the early secretory pathway in a GAPDH-independent, N-myristoylation- and calcium-dependent manner. Colocalizes with the mitotic spindle microtubules. Colocalizes with GAPDH along microtubules. Colocalizes with SLC9A1 at the reticulum endoplasmic and plasma membrane. Colocalizes with STK17B at the plasma membrane. {ECO:0000269\|PubMed:14657246, ECO:0000269\|PubMed:15312048, ECO:0000269\|PubMed:20720019, ECO:0000269\|PubMed:21543739}.
Tissue specificity:		Expressed in liver and kidney (at protein level). Ubiquitously expressed. Expressed in the brain, lung, testes, kidney, spleen and heart. {ECO:0000269\|PubMed:10512881, ECO:0000269\|PubMed:15312048, ECO:0000269\|PubMed:8626580}.
Ptm:		Phosphorylated; decreased phosphorylation is associated with an increase in SLC9A1/NHE1 Na(+)/H(+) exchange activity. Phosphorylation occurs in serum-dependent manner. The phosphorylation state may regulate the binding to SLC9A1/NHE1 (By similarity). {ECO:0000250}.
Ptm:		N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes. Both N-myristoylation and calcium-mediated conformational changes are essential in exocytic traffic.
Similarity:		Belongs to the calcineurin regulatory subunit family. CHP subfamily. {ECO:0000305}.