CALM1 — Calmodulin 1

CALM1 GeneCALM1 (

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CALM1 — Calmodulin 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CALM1</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Calmodulin 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>14q32.11</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>801</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62158</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000198668</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Calmodulin family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~16.7 kDa</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>149</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">CaMKII inhibitors</td>
<td>Memory enhancement</td>
</tr>
<tr>
<td class="label">Calcineurin modulators</td>
<td>Neuroprotection</td>
</tr>
<tr>
<td class="label">LRRK2-Calmodulin</td>
<td>Interaction blockers</td>
</tr>
<tr>
<td class="label">Calcium channel modulators</td>
<td>Restore Ca2+ homeostasis</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/cardiac" style=

...

CALM1 GeneCALM1 (

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CALM1 — Calmodulin 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CALM1</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Calmodulin 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>14q32.11</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>801</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P62158</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000198668</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Calmodulin family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~16.7 kDa</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>149</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">CaMKII inhibitors</td>
<td>Memory enhancement</td>
</tr>
<tr>
<td class="label">Calcineurin modulators</td>
<td>Neuroprotection</td>
</tr>
<tr>
<td class="label">LRRK2-Calmodulin</td>
<td>Interaction blockers</td>
</tr>
<tr>
<td class="label">Calcium channel modulators</td>
<td>Restore Ca2+ homeostasis</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">52 edges</a></td>
</tr>
</table>

Introduction

Calm1 — Calmodulin 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Calmodulin 1) encodes calmodulin, a ubiquitous calcium-binding messenger protein that transduces calcium signals by binding to and regulating target proteins. Calmodulin is one of the most conserved proteins in eukaryotes and plays critical roles in calcium signaling in all cell types, including [neurons](/entities/neurons). The CALM1 gene is located on chromosome 14q32.11 and produces a 149-amino acid protein. [@berridge2012]

Gene Information

Protein Structure

Calmodulin has a distinctive dumbbell-shaped structure:

• N-terminal domain: Two EF-hand calcium-binding motifs (EF1, EF2)
• Central linker: Flexible alpha-helical tether
• C-terminal domain: Two EF-hand calcium-binding motifs (EF3, EF4)

Each EF-hand motif binds one Ca2+ ion through a conserved aspartate-rich loop.

Normal Function

Calcium Signal Transduction

Calmodulin acts as a primary calcium sensor:

Binds 4 Ca2+ ions upon calcium elevation

Undergoes conformational change exposing hydrophobic patches

Binds to and modulates numerous target proteins

Regulates over 100 different proteins including:

• Calcium/calmodulin-dependent protein kinases (CaMK)
• Phosphatases (calcineurin)
• Ion channels
• Transcription factors
• Cytoskeletal proteins

Neuronal Functions

In neurons, calmodulin regulates:

• [Long-term potentiation](/mechanisms/long-term-potentiation) (LTP) and long-term depression (LTD)
• Synaptic vesicle release
• Neuronal excitability
• Gene transcription via CaM-dependent transcription factors
• Protein synthesis through [mTOR](/entities/mtor) pathway

Role in Neurodegeneration

Alzheimer's Disease

Calmodulin in AD:

• Dysregulated calcium homeostasis is an early feature
• Calmodulin levels altered in AD brains
• Regulates [APP](/entities/app-protein) processing through CaMK pathways
• Links [Aβ](/proteins/amyloid-beta) toxicity to intracellular signaling
• Therapeutic targeting of Ca2+ signaling under investigation

Parkinson's Disease

Calmodulin in PD:

• Regulates [LRRK2](/entities/lrrk2) kinase activity (mutations cause familial PD)
• Modulates [alpha-synuclein](/mechanisms/alpha-synuclein) aggregation
• Controls mitochondrial calcium handling
• Dopaminergic neuron survival pathways
• Calmodulin-LRRK2 interaction is therapeutic target

Huntington's Disease

In HD:

• Mutant [huntingtin](/proteins/huntingtin-protein) affects calcium signaling
• Calmodulin-dependent pathways dysregulated
• Calcineurin activity altered
• Contributes to transcriptional dysfunction
• Restoring calcium homeostasis is therapeutic approach

ALS

Calmodulin in ALS:

• Regulates [TDP-43](/proteins/tdp-43) aggregation
• RNA metabolism affected
• Axonal transport modulation
• Excitotoxicity pathways intersect
• Therapeutic potential of calmodulin modulators

Therapeutic Implications

Drug Targets

Calcium Stabilization Strategies

• L-type calcium channel blockers
• [NMDA](/entities/nmda-receptor) receptor antagonists
• Store-operated calcium entry modulators

Gene Expression

• Ubiquitous: Expressed in all cell types
• High in brain: Particularly in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum
• Isoforms: Multiple genes encode calmodulin (CALM1, CALM2, CALM3)

Animal Models

• CALM1 knockout: Embryonic lethal in mice
• Conditional knockouts: Reveal neuronal-specific functions
• Transgenic overexpression: Used to study Ca2+ dysregulation
• Knock-in mutations: Model of calcium signaling defects

Research Directions

• Developing brain-penetrant calmodulin modulators
• Understanding isoform-specific functions
• Biomarker potential of calmodulin-dependent pathways
• LRRK2-Calmodulin interaction inhibitors for PD

Background

The study of Calm1 — Calmodulin 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

• [NCBI Gene: CALM1](https://www.ncbi.nlm.nih.gov/gene/801)
• [UniProt: P62158](https://www.uniprot.org/uniprot/P62158)
• [GeneCards: CALM1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CALM1)
• [Human Protein Atlas: CALM1](https://www.proteinatlas.org/gene/CALM1)

References

Chin D, Means AR, (2000) (2000)

Berridge MJ, (2012) (2012)

Lee JH, et al, (2019) (2019)

Bezprozvanny I, (2009) (2009)

Popa-Wagner A, et al, (2013) (2013)

Snyder EM, et al, (2005) (2005)

See Also

• [ACTB Gene](/wiki/genes-actb) — associated_with
• [Gap Analysis & Research Strategy](/wiki/gaps-gap-analysis) — associated_with
• [ad-sphingolipid-ceramide-companies](/wiki/companies-ad-sphingolipid-ceramide-companies) — associated_with
• [ad-sphingolipid-ceramide-companies](/wiki/companies-ad-sphingolipid-ceramide-companies) — expressed_in

Pathway Diagram

The following diagram shows the key molecular relationships involving CALM1 — Calmodulin 1 discovered through SciDEX knowledge graph analysis: