Calmodulin-1

Function

Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2. Component of the silencing factor of the integrated stress response (SIFI) complex, a multiprotein complex required to turn off the mitochondrial stress response after a specific stress event has been resolved.

Classification

Family (Pfam)

PF13499 EF-hand_7

InterPro

CALM/Myosin/TropC-like, EF-hand-dom_pair, EF_Hand_1_Ca_BS, EF_hand_dom

Functional cluster

Ribosomal Protein L12 & Acyl Carriers

Experimental structures · PDB · 286

• 1CDL X-ray 2.00A
• 1CLL X-ray 1.70A
• 1CTR X-ray 2.45A
• 1IWQ X-ray 2.00A
• 1J7O NMR
• 1J7P NMR
• 1K90 X-ray 2.75A
• 1K93 X-ray 2.95A
• 1L7Z X-ray 2.30A
• 1LVC X-ray 3.60A
• 1NKF NMR
• 1PK0 X-ray 3.30A
• … and 274 more

A predicted model is available from AlphaFold.

Gene Ontology · 53

• GO:0034704 calcium channel complex
• GO:0044305 calyx of Held
• GO:1902494 catalytic complex
• GO:0005813 centrosome
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005576 extracellular region
• GO:0043209 myelin sheath
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0099523 presynaptic cytosol
• GO:0032991 protein-containing complex
• GO:0030017 sarcomere
• GO:0097225 sperm midpiece
• GO:0005876 spindle microtubule
• GO:0000922 spindle pole
• GO:0031982 vesicle
• GO:0008076 voltage-gated potassium channel complex
• GO:0010856 adenylate cyclase activator activity
• GO:0019855 calcium channel inhibitor activity
• GO:0005246 calcium channel regulator activity
• GO:0005509 calcium ion binding
• GO:0048306 calcium-dependent protein binding
• GO:0019901 protein kinase binding
• GO:0072542 protein phosphatase activator activity
• GO:0043539 protein serine/threonine kinase activator activity
• GO:0031432 titin binding
• GO:0044325 transmembrane transporter binding
• GO:0016240 autophagosome membrane docking
• GO:0097720 calcineurin-mediated signaling
• GO:0035458 cellular response to interferon-beta
• GO:0071346 cellular response to type II interferon
• GO:0005513 detection of calcium ion
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0060291 long-term synaptic potentiation
• GO:1990456 mitochondrion-endoplasmic reticulum membrane tethering
• GO:1905913 negative regulation of calcium ion export across plasma membrane
• GO:1901842 negative regulation of high voltage-gated calcium channel activity
• GO:0060315 negative regulation of ryanodine-sensitive calcium-release channel activity
• GO:0140056 organelle localization by membrane tethering
• GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
• GO:0140238 presynaptic endocytosis
• GO:0098901 regulation of cardiac muscle cell action potential
• GO:0055117 regulation of cardiac muscle contraction
• GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
• GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction
• GO:0032465 regulation of cytokinesis
• GO:0002027 regulation of heart rate
• GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
• GO:0060314 regulation of ryanodine-sensitive calcium-release channel activity
• GO:0051592 response to calcium ion
• GO:0021762 substantia nigra development

Disease associations

• catecholaminergic polymorphic ventricular tachycardia 4 MONDO:0013966
• long QT syndrome 14 MONDO:0014548

Drugs targeting this protein · 2

• BENZIODARONE inhibitor
• PRENYLAMINE inhibitor

Related proteins · sequence + function similarity

• Calmodulin 1.00
• Calmodulin 1.00
• Calmodulin 1.00
• Calmodulin-2 B 1.00
• Calmodulin-2 A 1.00
• Calmodulin 1.00
• Calmodulin-1 1.00
• Calmodulin-2 1.00
• Calmodulin-2 1.00
• Calmodulin 1.00
• Calmodulin 1.00
• Calmodulin-3 1.00

Co-cited proteins · studied together in the literature

• Calmodulin-2 26 shared papers
• Calmodulin-3 23 shared papers
• Calmodulin-sensitive adenylate cyclase 2 shared papers
• Myristoylated alanine-rich C-kinase substrate 1 shared papers
• Small conductance calcium-activated potassium channel protein 3 1 shared papers
• Lens fiber major intrinsic protein 1 shared papers
• Non-structural polyprotein p200 1 shared papers
• Intermediate conductance calcium-activated potassium channel protein 4 1 shared papers
• Calmodulin 1 shared papers
• Potassium voltage-gated channel subfamily KQT member 1 2 shared papers
• E3 ubiquitin-protein ligase KCMF1 4 shared papers
• Calmodulin-dependent glutamylase SidJ 1 shared papers

Literature · 75 cited papers

• Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control. Science · 2025
• Molecular basis of SIFI activity in the integrated stress response. Nature · 2025
• Stress response silencing by an E3 ligase mutated in neurodegeneration. Nature · 2024
• Structural mechanisms of calmodulin activation of Shigella effector OspC3 to ADP-riboxanate caspase-4/11 and block pyroptosis. Nat. Struct. Mol. Biol. · 2023
• Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin. Mol. Cell · 2022
• A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. Cell · 2022
• Calmodulin binding activates chromobacterium CopC effector to ADP-riboxanate host apoptotic caspases. MBio · 2022
• Architecture of the human NALCN channelosome. Cell Discov. · 2022
• Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases. Mol. Cell · 2022
• Structural architecture of the human NALCN channelosome. Nature · 2022
• Calmodulin binds to the STAS domain of SLC26A5 prestin with a calcium-dependent, one-lobe, binding mode. J. Struct. Biol. · 2021
• Genetic mosaicism in calmodulinopathy. Circ. Genom. Precis. Med. · 2019
• … and 63 more in the literature graph