ID:CHP1_HUMAN DESCRIPTION: RecName: Full=Calcineurin B homologous protein 1; AltName: Full=Calcineurin B-like protein; AltName: Full=Calcium-binding protein CHP; AltName: Full=Calcium-binding protein p22; AltName: Full=EF-hand calcium-binding domain-containing protein p22; 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. SUBUNIT: 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 C-terminus 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 (By similarity). Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the juxtamembrane region of the cytoplasmic C-terminus 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. SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By similarity). Cytoplasm, cytoskeleton (By similarity). Membrane (By similarity). Endoplasmic reticulum-Golgi intermediate compartment (By similarity). Endoplasmic reticulum (By similarity). Cell membrane. 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/NHE1 at the reticulum endoplasmic. Colocalizes with STK17B at the plasma membrane (By similarity). Colocalizes with SLC9A1/NHE1 at the cell membrane. TISSUE SPECIFICITY: Ubiquitously expressed. Has been found in fetal eye, lung, liver, muscle, heart, kidney, thymus and spleen. 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. PTM: 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. SIMILARITY: Belongs to the calcineurin regulatory subunit family. CHP subfamily. SIMILARITY: Contains 4 EF-hand domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99653
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001578 microtubule bundle formation GO:0001933 negative regulation of protein phosphorylation GO:0006469 negative regulation of protein kinase activity GO:0006611 protein export from nucleus GO:0006813 potassium ion transport GO:0007264 small GTPase mediated signal transduction GO:0010923 negative regulation of phosphatase activity GO:0015031 protein transport GO:0017156 calcium ion regulated exocytosis GO:0022406 membrane docking GO:0030214 hyaluronan catabolic process GO:0031122 cytoplasmic microtubule organization GO:0031397 negative regulation of protein ubiquitination GO:0031953 negative regulation of protein autophosphorylation GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032417 positive regulation of sodium:proton antiporter activity GO:0042308 negative regulation of protein import into nucleus GO:0050821 protein stabilization GO:0051222 positive regulation of protein transport GO:0051259 protein oligomerization GO:0051453 regulation of intracellular pH GO:0060050 positive regulation of protein glycosylation GO:0061024 membrane organization GO:0061025 membrane fusion GO:0070885 negative regulation of calcineurin-NFAT signaling cascade GO:0071468 cellular response to acidic pH GO:0090314 positive regulation of protein targeting to membrane GO:1901214 regulation of neuron death
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Common Gene Haplotype Alleles 
