CAMK2D (Calcium/Calmodulin Dependent Protein Kinase II Delta)
A multifunctional serine/threonine kinase implicated in cardiac, neuronal, and cancer biology.
Gene Information Card
| Symbol | CAMK2D |
|---|---|
| Full Name | Calcium/calmodulin dependent protein kinase II delta |
| Gene Type | protein coding |
| Chromosomal Location | 4q26 |
| NCBI Gene ID | 817 ncbi.nlm.nih.gov/gene/817 |
| Ensembl ID | ENSG00000145349 |
| UniProt ID | Q13557 |
| OMIM ID | 607708 |
| HGNC ID | 1462 |
| Aliases | CAMKD, CAMK2D, CaMKIID, CAMK2D1, CAMK2D2, CAMK2D3, CAMK2D4 |
Description
CAMK2D encodes the delta subunit of calcium/calmodulin-dependent protein kinase II (CaMKII), a multifunctional serine/threonine kinase that is activated by calcium-calmodulin complexes. It plays critical roles in various cellular processes including synaptic plasticity, cardiac excitation-contraction coupling, and cell cycle regulation. Alternative splicing generates multiple isoforms with distinct tissue-specific functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac hypertrophy | CAMK2D activation promotes hypertrophic signaling via HDAC4 phosphorylation and MEF2 activation. | PMID: 19047562; OMIM 607708 |
| Heart failure | Chronic CAMK2D activation leads to maladaptive remodeling and apoptosis in cardiomyocytes. | PMID: 20018947; OMIM 607708 |
| Arrhythmia | CAMK2D phosphorylates ion channels (e.g., RyR2, Nav1.5) altering cardiac excitability. | PMID: 21106934; ClinVar |
| Cancer (e.g., breast, lung) | CAMK2D overexpression/activation promotes proliferation, migration, and invasion in various cancers. | COSMIC; PMID: 28778955 |
| Neurodevelopmental disorders | CAMK2D variants are associated with intellectual disability and autism spectrum disorder. | ClinVar; PMID: 28135719 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High | Cardiac muscle predominant |
| Brain | High | Neuronal tissues, especially cortex and hippocampus |
| Skeletal Muscle | Medium | Skeletal muscle |
| Liver | Low | Low expression |
| Kidney | Medium | Renal tissues |
| Lung | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | High | Embryonic kidney cells; commonly used for overexpression studies |
| HeLa | Medium | Cervical cancer cell line |
| MCF7 | Medium | Breast cancer cell line |
| A549 | Low | Lung carcinoma cell line |
| H9c2 | High | Rat cardiomyoblast cell line; used for cardiac studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg436Cys | Missense | Rare | Impaired kinase activity; associated with neurodevelopmental delay |
| p.Thr287Ala | Missense | Somatic | Constitutive activation; found in cancer (COSMIC) |
| p.Leu299Phe | Missense | Somatic | Altered substrate specificity; reported in lung cancer |
| p.Gly303Asp | Missense | Somatic | Potential gain-of-function; observed in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce kinase activity or protein stability, leading to impaired calcium signaling (e.g., p.Arg436Cys).
Gain of Function (GOF)
Mutations that increase kinase activity or autophosphorylation, promoting oncogenic signaling (e.g., p.Thr287Ala).
Dominant Negative (DN)
Mutations that produce a truncated or inactive protein that interferes with wild-type CAMK2D function, though not well documented.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • calmodulin binding |
| • protein serine/threonine kinase activity | • ATP binding |
| • calcium/calmodulin-dependent protein kinase activity | • signal transduction |
| • regulation of cardiac muscle contraction | • synaptic plasticity |
| • cell proliferation | • apoptotic process |
Pathways
• Calcium signaling pathway
• Cardiac muscle contraction
• Neurotrophin signaling pathway
• Wnt signaling pathway
• ErbB signaling pathway
• Regulation of autophagy
Protein Summary
The CAMK2D protein is a 499-amino acid serine/threonine kinase with a catalytic domain, an autoregulatory domain, and a C-terminal association domain. It forms homo- or hetero-oligomeric holoenzymes. Upon calcium/calmodulin binding, it undergoes autophosphorylation at Thr287, leading to calcium-independent activity. It phosphorylates numerous substrates including ion channels, transcription factors, and signaling proteins, thereby modulating diverse cellular functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CAMK2D Knockout HEK293 Cell Line | EDJ-KQ111 | Human | 817 | Details Get a Quote |
| CAMK2D Knockout A-549 Cell Line | EDJ-KQ18388 | Human | 817 | Details Get a Quote |
| CAMK2D Knockout HCT 116 Cell Line | EDJ-KQ18390 | Human | 817 | Details Get a Quote |
| CAMK2D Knockout HeLa Cell Line | EDJ-KQ18391 | Human | 817 | Details Get a Quote |
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