Calcium binding protein 1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the CABP1

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Calcium-binding protein 1 is a

calcium-binding protein Calcium-binding proteins are proteins that participate in calcium cell signalling pathways by binding to Ca2+, the calcium ion that plays an important role in many cellular processes. Calcium-binding proteins have specific domains that bind to calc ...

discovered in 1999. It has two

EF hand The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins. The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...

motifs and is expressed in neuronal cells in such areas as

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, habenular nucleus of the

epithalamus The epithalamus is a posterior (dorsal) segment of the diencephalon. The epithalamus includes the habenular nuclei and their interconnecting fibers, the habenular commissure, the stria medullaris and the pineal gland. Functions The function of ...

Purkinje cell Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech people, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839. Stru ...

layer of the cerebellum, and the

amacrine cell Amacrine cells are interneurons in the retina. They are named from the Greek roots ''a–'' ("non"), ''makr–'' ("long") and ''in–'' ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they proje ...

s and cone bipolar cells of the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

. Calcium-binding protein 1 which is a neuron -specific member of the calmodulin (CaM) superfamily which modulates Ca²⁺-dependent activity of

inositol trisphosphate receptor Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physio ...

s (InsP3RS). 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. Calcium-binding protein 1 (CaBP1) is placed in the lumen of the endoplasmic reticulum.it is relocated outside cells during

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

and involved in the

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

of apoptotic cells. CaBP1 and CaM. 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

Protein that attributes for CABP1 Gene is

homodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...

. It interacts with

ITPR1 Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ''ITPR1'' gene. Interactions ITPR1 has been shown to interact with: * AHCYL1, * CA8, * EPB41L1 * FKBP1A, * MRVI1, * PRKG1, * RHOA, and * TRPC4 ...

ITPR2 Inositol 1,4,5-trisphosphate receptor, type 2, also known as ITPR2, is a protein which in humans is encoded by the ''ITPR2'' gene. The protein encoded by this gene is both a receptor for inositol triphosphate and a calcium channel. See also * I ...

and

ITPR3 Inositol 1,4,5-trisphosphate receptor, type 3, also known as ITPR3, is a protein which in humans is encoded by the ''ITPR3'' gene. The protein encoded by this gene is both a receptor for inositol triphosphate and a calcium channel. Function IT ...

via C-terminus. The binding is calcium dependent and the interaction correlates with calcium concentration. CABP1 also interacts with

CACNA1A Cav2.1, also called the P/ Q voltage-dependent calcium channel, is a calcium channel found mainly in the brain. Specifically, it is found on the presynaptic terminals of neurons in the brain and cerebellum. Cav2.1 plays an important role in con ...

in the pre and post synaptic membranes via

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

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 The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...

stimulation and thus this prevents nuclear import of NSMF.

Function

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. CAbp1 suppresses the inactivated calcium dependent CACNA1D. it also inhibits

TRPC5 Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the ''TRPC5'' gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion ...

. 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. CaBP1 And CaM both bind to IQ-domain in the cytoplasmic

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 is deleted it abolishes the effect of CaBP1 prolonging Ca_v1.2 Ca²⁺ currents, but spared Ca²⁺-dependent is inactivated due to CaM overexpressed L-CaBP1 suppresses the rise in a²⁺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 a²⁺responses to agonist stimulation. Measurement of a²⁺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 a²⁺oscillations in

HeLa cells HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta La ...

. L-CaBP1 is able to specifically regulate InsP3 receptor-mediated alterations in a²⁺during agonist stimulation. Cellular expression of caldendrin is restricted to the

somatodendritic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

compartment, with the exception of

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

, where

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

al labeling was detected. CAbP1 and CAbP2 contain a consensus sequence for N-terminal myristoylation. Transcription factor binding sites identified by

Qiagen QIAGEN N.V., the global corporate headquarter of the QIAGEN group, is located in Venlo, The Netherlands. Furthermore, European, American, and Asia regional headquarters are located in respectively Hilden, Germany, Maryland United States, and Sh ...

in the CABP1 gene promoter include

Nkx2-5 Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the ''NKX2-5'' gene. Function Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as deter ...

, RSRFC4,

TAL1 __NOTOC__ T-cell acute lymphocytic leukemia protein 1 (i.e. TAL1 but also termed stem cell leukemia/T-cell acute leukemia 1 .e. SCL/TAL1 is a protein that in humans is encoded by the ''TAL1'' gene. The protein encoded by TAL1 is a basic helix-lo ...

, and

HSF1 Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the ''HSF1'' gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regul ...

. CaBP1 interacts with inositol 1,4,5-triphosphate (InsP3) receptors to elicit channel activation when InsP3 is absent.

Clinical significance

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

, one study demonstrated a decrease in the number of CABP1-expressing cells, specifically in the left

dorsolateral prefrontal cortex The dorsolateral prefrontal cortex (DLPFC or DL-PFC) is an area in the prefrontal cortex of the primate brain. It is one of the most recently derived parts of the human brain. It undergoes a prolonged period of maturation which lasts until adultho ...

. This change, however, was compensated on a whole-brain scale by an increase in the protein levels.

References

{{NLM content EF-hand-containing proteins