CHP1

This gene encodes a phosphoprotein that binds to the Na+/H+ exchanger NHE1. This protein serves as an essential cofactor which supports the physiological activity of NHE family members and may play a role in the mitogenic regulation of NHE1. The protein shares similarity with calcineurin B and calmodulin and it is also known to be an endogenous inhibitor of calcineurin activity. [provided by RefSeq, Jul 2008]

Calcineurin Like EF-Hand Protein 1

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.

Cellular response to acidic pH Source: UniProtKB
Cytoplasmic microtubule organization Source: UniProtKB
Hyaluronan catabolic process Source: Reactome
Membrane docking Source: UniProtKB
Membrane fusion Source: UniProtKB
Membrane organization Source: UniProtKB
Microtubule bundle formation Source: UniProtKB
Negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
Negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
Negative regulation of phosphatase activity Source: UniProtKB
Negative regulation of protein autophosphorylation Source: UniProtKB
Negative regulation of protein import into nucleus Source: UniProtKB
Negative regulation of protein kinase activity Source: UniProtKB
Negative regulation of protein phosphorylation Source: UniProtKB
Negative regulation of protein ubiquitination Source: UniProtKB
Positive regulation of phospholipid biosynthetic process Source: FlyBase
Positive regulation of protein glycosylation Source: UniProtKB
Positive regulation of protein targeting to membrane Source: UniProtKB
Positive regulation of protein transport Source: UniProtKB
Positive regulation of sodium:proton antiporter activity Source: UniProtKB
Potassium ion transport Source: ProtInc
Protein complex oligomerization Source: Ensembl
Protein export from nucleus Source: UniProtKB
Protein stabilization Source: UniProtKB
Regulation of intracellular pH Source: UniProtKB
Regulation of neuron death Source: UniProtKB
Small GTPase mediated signal transduction Source: ProtInc
Vesicle fusion Source: Ensembl
Vesicle targeting Source: Ensembl

Cell membrane; Cytoplasm; Endoplasmic reticulum; Cytoskeleton; Nucleus; Endomembrane system; Endoplasmic reticulum-Golgi intermediate compartment; Membrane. 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.

Spastic ataxia 9, autosomal recessive (SPAX9): An autosomal recessive disorder characterized by onset of spastic ataxia in the first years of life. Clinical features include motor neuropathy, cerebellar atrophy, spastic paraparesis, intellectual disability, slow ocular saccades, axial hypotonia, distal muscle weakness and atrophy, and pyramidal symptoms, including hyperreflexia and extensor plantar responses.

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