Calcium-binding protein 1

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Available structures
PDB Human UniProt search: PDBe RCSB
Aliases CABP1, CALBRAIN, HCALB_BR, calcium binding protein 1
External IDs HomoloGene: 128292 GeneCards: CABP1
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 12: 120.64 – 120.67 Mb n/a
PubMed search [1] n/a
View/Edit Human

Calcium binding protein 1 is a protein that in humans is encoded by the CABP1 gene.[2] Calcium-binding protein 1 is a calcium-binding protein[3] discovered in 1999.[4] It has two EF hand motifs and is expressed in neuronal cells in such areas as hippocampus, habenular nucleus of the epithalamus, Purkinje cell layer of the cerebellum, and the amacrine cells and cone bipolar cells of the retina.

Calcium-binding protein 1 which is a neuron -specific member of the calmodulin (CaM) superfamily which modulates Ca2+-dependent activity of inositol trisphosphate receptors (InsP3RS).[5] L-CaBP1 is also associated with the cytoskeleton structures. But the S-CaBP1 is situated in or near the plasma membrane.In brain, CaBp1 is found in the cerebral cortex and hippocampus and in the protein, Cabp1 is found in cone bipolar and amacrine cells. We can also express that CaBP1 may regulate Ca2+ dependent activity of InSP3Rs by promoting structural contacts between suppressor and core domains but has no effect on INsP3 binding to the receptor. CaBP1 contains four EF-hands in two separate domains namely, EF1 and Ef2 is contained in N-domain whereas Ef3 and EF4 is contained in c domain to which Ca2+ binds.[6] Calcium-binding protein 1 (CaBP1) is placed in the lumen of the endoplasmic is relocated outside cells during apoptosis and involved in the phagocytosis of apoptotic cells.[7] CaBP1[6] and CaM.[8][9] lobes fold independently. CaBP1-CaM chimeras based on exchange of three elements these are N-lobe, C-lobe and inter lobe linker. Expression of CaBP1 helps to block Ca2+-dependent facilitation of P/Q-type Ca2+ current which is markedly reduced facilitation of synaptic transmission.

Protein structure[edit]

Protein that attributes for CABP1 Gene is homodimer. It interacts with ITPR1, ITPR2 and ITPR3 via C-terminus. The binding is calcium dependent and the interaction correlates with calcium concentration. CABP1 also interacts with CACNA1A in the pre and post synaptic membranes via C-terminal calcium binding motif. It also interacts with CACNA1C via C-terminal C and IQ motifs. It interacts with TRPC5 and also interacts with MAP1LC3B via C-terminus and EF-hands 1 and 2 respectively. It interacts with C9orf9. It also interacts NSMF via the central NLF- containing motif region. This interaction occurs in calcium dependent manner after the Synaptic NMDA receptor stimulation and thus this prevents nuclear import of NSMF.[10]


Calcium binding proteins are an important component of calcium mediated cellular signal transduction. This gene encodes a protein that belongs to a subfamily of calcium binding proteins which share similarity to calmodulin. The protein encoded by this gene regulates the gating of voltage-gated calcium ion channels. This protein causes rapid inactivation that is independent of calcium, and does not support Calcium-dependent facilitation.[11] CAbp1 supressess the inactivated calcium dependent CACNA1D. it also inhibits TRPC5. CABP1 prevents NMDA receptor- induced cellular degeneration.This protein also regulates calcium-dependent activity of inositol 1,4,5-triphosphate receptors, P/Q-type voltage-gated calcium channels, and transient receptor potential channel TRPC5. This gene is predominantly expressed in retina and brain.[2]

CaBP1 And CaM both bind to IQ-domain in the cytoplasmic C-terminal domain. Mutations of the IQ-Domain that weakens this two protein binding, stops the functional effect of CaM but not CaBP1. If the N-terminal domain(NT) is deleted it abolishes the effect of CaBP1 prolonging Cav1.2 Ca2+ currents, but spared Ca2+-dependent is inactivated due to CaM[12] overexpressed L-CaBP1 suppresses the rise in [Ca2+] in response to physiological agonists acting on purinergic receptors and thus this inhibition occurs in large part to blockade of release from intracellular Ca2+ stores. The related protein neuronal calcium sensor-1did not get affected on the [Ca2+] responses to agonist stimulation. Measurement of [Ca2+] within the ER of permeabilized PC12 cells demonstrated that LCaBP1 directly inhibited InsP3-mediated Ca2+ release. Expression of L-CaBP1 also help in the inhibition of histamine-induced [Ca2+] oscillations in HeLa cells. L-CaBP1 is able to specifically regulate InsP3 receptor-mediated alterations in [Ca2+] during agonist stimulation.

Cellular expression of caldendrin is restricted to the somatodendritic compartment, with the exception of hypothalamus, where axonal labeling was detected.[13] CAbP1 and CAbP2 contain a consensus sequence for N-terminal myristoylation. Transcription factor binding sites identified by Qiagen in the CABP1 gene promoter include Nkx2-5, RSRFC4, TAL1, and HSF1. CaBP1 interacts with inositol 1,4,5-triphosphate (InsP3) receptors to elicit channel activation when InsP3 is absent.

Clinical significance[edit]

In schizophrenia, one study demonstrated a decrease in the number of CABP1-expressing cells, specifically in the left dorsolateral prefrontal cortex. This change, however, was compensated on a whole-brain scale by an increase in the protein levels.[14]


  1. ^ "Human PubMed Reference:". 
  2. ^ a b "Entrez Gene: Calcium binding protein 1". 
  3. ^ McCue HV, Haynes LP, Burgoyne RD (August 2010). "The diversity of calcium sensor proteins in the regulation of neuronal function". Cold Spring Harbor Perspectives in Biology. 2 (8): a004085. doi:10.1101/cshperspect.a004085. PMC 2908765Freely accessible. PMID 20668007. 
  4. ^ Yamaguchi K, Yamaguchi F, Miyamoto O, Sugimoto K, Konishi R, Hatase O, Tokuda M (February 1999). "Calbrain, a novel two EF-hand calcium-binding protein that suppresses Ca2+/calmodulin-dependent protein kinase II activity in the brain". The Journal of Biological Chemistry. 274 (6): 3610–6. doi:10.1074/jbc.274.6.3610. PMID 9920909. 
  5. ^ Haeseleer F, Sokal I, Verlinde CL, Erdjument-Bromage H, Tempst P, Pronin AN, Benovic JL, Fariss RN, Palczewski K (2000). "Five members of a novel Ca2+-binding protein (CABP) subfamily with similarity to calmodulin". The Journal of Biological Chemistry. 275 (2): 1247–60. PMC 1364469Freely accessible. PMID 10625670. 
  6. ^ a b Li C, Chan J, Haeseleer F, Mikoshiba K, Palczewski K, Ikura M, Ames JB (January 2009). "Structural insights into Ca2+-dependent regulation of inositol 1,4,5-trisphosphate receptors by CaBP1". The Journal of Biological Chemistry. 284 (4): 2472–81. doi:10.1074/jbc.M806513200. PMC 2629100Freely accessible. PMID 19008222. 
  7. ^ "Gene Dmel\CaBP1". FlyBase. 
  8. ^ Masino L, Martin SR, Bayley PM (2000). "Ligand binding and thermodynamic stability of a multidomain protein, calmodulin". Protein Science : a Publication of the Protein Society. 9 (8): 1519–29. doi:10.1110/ps.9.8.1519. PMC 2144730Freely accessible. PMID 10975573. 
  9. ^ Tsalkova TN, Privalov PL (1985). "Thermodynamic study of domain organization in troponin C and calmodulin". Journal of Molecular Biology. 181 (4): 533–44. doi:10.1016/0022-2836(85)90425-5. PMID 3999139. 
  10. ^ "CABP1 Gene". GeneCards. 
  11. ^ Lee A, Westenbroek RE, Haeseleer F, Palczewski K, Scheuer T, Catterall WA (2002). "Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1". Nature Neuroscience. 5 (3): 210–7. doi:10.1038/nn805. PMC 1435861Freely accessible. PMID 11865310. 
  12. ^ Zhou H, Yu K, McCoy KL, Lee A (August 2005). "Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by calmodulin and Ca2+-binding protein-1". The Journal of Biological Chemistry. 280 (33): 29612–9. doi:10.1074/jbc.M504167200. PMID 15980432. 
  13. ^ Bernstein HG, Seidenbecher CI, Smalla KH, Gundelfinger ED, Bogerts B, Kreutz MR (August 2003). "Distribution and cellular localization of caldendrin immunoreactivity in adult human forebrain". The Journal of Histochemistry and Cytochemistry. 51 (8): 1109–12. doi:10.1177/002215540305100816. PMID 12871994. 
  14. ^ Bernstein HG, Sahin J, Smalla KH, Gundelfinger ED, Bogerts B, Kreutz MR (November 2007). "A reduced number of cortical neurons show increased Caldendrin protein levels in chronic schizophrenia". Schizophrenia Research. 96 (1-3): 246–56. doi:10.1016/j.schres.2007.05.038. PMID 17719205. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.