CALCOCO2 — Calcium Binding and Coiled-Coil Domain 2

CALCOCO2 — Calcium Binding and Coiled-Coil Domain 2

Pathway Diagram

```mermaid
flowchart TD
CALCOCO2["CALCOCO2<br/>(NDP52)<br/>Autophagy Receptor"]

ULK1["ULK1<br/>Autophagy<br/>Initiation"]
BECN1["BECN1<br/>Autophagosome<br/>Formation"]
LC3["LC3<br/>Autophagosome<br/>Marker"]

OPTN["OPTN<br/>Optineurin<br/>Cargo Receptor"]
NBR1["NBR1<br/>Selective<br/>Autophagy"]

C9ORF72["C9ORF72<br/>ALS/FTD<br/>Risk Gene"]
G3BP1["G3BP1<br/>Stress Granule<br/>Component"]

ACTB["ACTB<br/>Actin<br/>Cytoskeleton"]

Autophagy["Selective<br/>Autophagy<br/>Process"]
StressGranules["Stress Granule<br/>Clearance"]

ALS["Amyotrophic<br/>Lateral Sclerosis"]
Alzheimer["Alzheimer's<br/>Disease"]
Parkinson["Parkinson's<br/>Disease"]

ProteinAgg["Protein<br/>Aggregation"]
Neurodegeneration["Neuronal<br/>Death"]

CALCOCO2 -->|"recruits"| ULK1
CALCOCO2 -->|"interacts"| BECN1
CALCOCO2 -->|"binds"| LC3

CALCOCO2 -->|"cooperates"| OPTN
CALCOCO2 -->|"partners"| NBR1

CALCOCO2 -->|"regulates"| Autophagy
CALCOCO2 -->|"facilitates"| StressGranules

CALCOCO2 -->|"interacts"| C9ORF72
CALCOCO2 -->|"targets"| G3BP1
CALCOCO2 -->|"associates"| ACTB

Autophagy -->|"clears"| ProteinAgg
StressGranules -->|"prevents"| ProteinAgg

ProteinAgg -->|"leads_to"| ALS
ProteinAgg -->|"causes"| Alzheimer
ProteinAgg -->|"triggers"| Parkinson

ALS -->|"results_in"| Neurodegeneration
Alzheimer -->|"results_in"| Neurodegeneration
Parkinson

CALCOCO2 — Calcium Binding and Coiled-Coil Domain 2

Pathway Diagram

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Calcium Binding and Coiled-Coil Domain 2</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>CALCOCO2</td></tr>
<tr><td><strong>Full Name</strong></td><td>Calcium Binding and Coiled-Coil Domain 2</td></tr>
<tr><td><strong>Chromosome</strong></td><td>17q25.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[10241](https://www.ncbi.nlm.nih.gov/gene/10241)</td></tr>
<tr><td><strong>OMIM</strong></td><td>604551</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000136436</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9BQB6](https://www.uniprot.org/uniprot/Q9BQB6)</td></tr>
<tr><td><strong>Aliases</strong></td><td>NDP52, TAX1BP1, CALCOCO2</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Inflammatory Disorders, Cancer</td></tr>
</table>
</div>

Introduction

CALCOCO2 (Calcium Binding and Coiled-Coil Domain 2), also known as NDP52 (Nuclear Dot Protein 52), is a selective [autophagy](/entities/autophagy) receptor that plays critical roles in xenophagy, mitophagy, and aggrephagy. This protein is essential for recognizing and targeting ubiquitinated cargo for autophagic degradation, making it a key player in neurodegenerative disease pathogenesis.

Gene Structure

The CALCOCO2 gene is located on chromosome 17q25.1 and encodes a 446-amino acid protein (52 kDa). The protein contains several functional domains:

• LC3-interacting region (LIR): Binds LC3/GABARAP family proteins
• Coiled-coil domain: Mediates homodimerization and interactions with autophagy proteins
• Skp2-binding domain: Regulates protein stability

Normal Function

Selective Autophagy Receptor

CALCOCO2 functions as a selective autophagy receptor through its ability to recognize ubiquitinated cargo[@thurston2009]:

Molecular Mechanisms

CALCOCO2 recruits autophagosomes to target cargo through[@wild2011]:

• Ubiquitin recognition: Binds K63-linked polyubiquitin chains on damaged organelles and aggregates
• LC3 interaction: LIR domain binds LC3/GABARAP on forming autophagosomes
• TBK1 phosphorylation: CALCOCO2 phosphorylation by TBK1 enhances its autophagy receptor function
• Cooperative binding: Works with other receptors like OPTN and SQSTM1

Key Interactions

• [LC3/GABARAP](/proteins/lc3): Autophagosome membrane protein
• [TBK1](/proteins/tbk1): Kinase that phosphorylates CALCOCO2
• [OPTN](/proteins/optn): Co-operating autophagy receptor
• [MyD88](/proteins/myd88): Innate immune signaling adaptor
• [TAX1BP1](/proteins/tax1bp1): Homologous protein with overlapping functions

Role in Neurodegeneration

Alzheimer's Disease

In Alzheimer's disease, CALCOCO2 dysfunction contributes to[@khaminets2015]:

• Mitophagy impairment: Reduced clearance of damaged mitochondria leads to oxidative stress
• Protein aggregate accumulation: Impaired aggrephagy contributes to amyloid and [tau](/proteins/tau) pathology
• Neuroinflammation: Dysregulated xenophagy affects microglial function

Parkinson's Disease

CALCOCO2 is particularly important in Parkinson's disease through[@sarraf2020]:

• PINK1/Parkin mitophagy: CALCOCO2 is recruited to damaged mitochondria in a Parkin-dependent manner
• Alpha-synuclein clearance: Required for selective autophagy of [alpha-synuclein](/proteins/alpha-synuclein) aggregates
• Dopaminergic neuron protection: Maintains mitochondrial quality in substantia nigra [neurons](/entities/neurons)

Neuroinflammation

• Regulates microglial autophagy in response to pathogens
• Controls inflammatory responses through NF-kappaB signaling
• Mutations affect immune cell function

Expression Pattern

CALCOCO2 is expressed in various tissues:

• High expression: Immune cells (macrophages, microglia, dendritic cells), epithelial cells
• Moderate expression: Brain, lung, liver
• Cellular localization: Cytoplasmic, associated with autophagosomes and endosomes

Therapeutic Implications

Target Strategies

Disease Context

• AD/PD: Boosting CALCOCO2 function may protect against neurodegeneration
• Cancer: CALCOCO2 can act as tumor suppressor; context determines therapeutic approach
• Inflammatory diseases: Modulating CALCOCO2 may regulate immune response

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Autophagy](/mechanisms/autophagy-lysosomal-pathway)
• [Mitophagy](/mechanisms/mitophagy)
• [Microglia](/cell-types/microglia-neuroinflammation)
• [OPTN](/proteins/optn)
• [SQSTM1](/proteins/sqstm1)
• [TBK1](/proteins/tbk1)

External Links

• [NCBI Gene: CALCOCO2](https://www.ncbi.nlm.nih.gov/gene/10241)
• [UniProt: CALCOCO2](https://www.uniprot.org/uniprot/Q9BQB6)
• [GeneCards: CALCOCO2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CALCOCO2)
• [Allen Brain Atlas: CALCOCO2](https://human.brain-map.org/microarray/search/show?search_term=CALCOCO2)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CALCOCO2 — Calcium Binding and Coiled-Coil Domain 2 discovered through SciDEX knowledge graph analysis: