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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCT2
chaperonin containing TCP1 subunit 2
Chromosome 12 · 12q15
NCBI Gene: 10576Ensembl: ENSG00000166226.14HGNC: HGNC:1615UniProt: P78371
366PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of telomere maintenance via telomerasechaperone-mediated protein complex assemblyscaRNA localization to Cajal bodyprotein bindingLeber congenital amaurosisatrial fibrillationclavicle fractureshoulder fracture
✦AI Summary

CCT2 (chaperonin containing TCP1 subunit 2) is a multifunctional protein that serves dual roles as both a molecular chaperone and an autophagy receptor. As a component of the TRiC chaperonin complex, CCT2 assists in the ATP-dependent folding of actin, tubulin, and other proteins, with assembly occurring through a hierarchical pathway where CCT2 forms part of the negatively charged hemisphere 1. Beyond its traditional chaperone function, CCT2 uniquely functions as an aggrephagy receptor for the selective clearance of solid protein aggregates 2. This dual functionality is achieved through a functional switch where aggregation-prone proteins induce CCT2 monomer formation, exposing a VLIR motif that enables interaction with ATG8 proteins, thereby promoting autophagic degradation independent of ubiquitination 2. The aggrephagy function is regulated by ATG1-mediated phosphorylation at Ser412 and Ser470, and interaction with ATG11 adaptor protein 3. Clinically, CCT2 has significant disease relevance, being overexpressed in multiple cancers including breast cancer, glioblastoma, and papillary thyroid carcinoma, where it promotes tumor progression through various mechanisms including KRAS stabilization and EMT regulation 456. The protein's role in clearing solid aggregates makes it a potential therapeutic target for neurodegenerative diseases and cancer treatment 7.

Sources cited
1
CCT2 forms part of the negatively charged hemisphere in TRiC complex assembly through a hierarchical pathway
PMID: 37625406
2
CCT2 functions as an aggrephagy receptor for solid protein aggregates through a functional switch involving monomer formation and VLIR motif exposure
PMID: 35366418
3
CCT2-ATG8 binding is regulated by ATG1-mediated phosphorylation at Ser412/Ser470 and interaction with ATG11
PMID: 39322741
4
CCT2 is overexpressed in breast cancer and promotes progression through JAK2/STAT3 signaling
PMID: 39079960
5
CCT2 promotes glioblastoma progression by binding to and stabilizing KRAS protein
PMID: 38582394
6
CCT2 promotes papillary thyroid carcinoma metastasis through ZEB1 and EMT regulation
PMID: 39327245
7
CCT2-mediated aggrephagy represents a potential therapeutic target for neurodegenerative diseases
PMID: 39478698
Disease Associationsⓘ20
Leber congenital amaurosisOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.42Moderate
clavicle fractureOpen Targets
0.27Weak
shoulder fractureOpen Targets
0.27Weak
albuminuriaOpen Targets
0.23Weak
Retinal dystrophyOpen Targets
0.15Weak
Moderate albuminuriaOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
neuroblastomaOpen Targets
0.07Suggestive
age-related macular degenerationOpen Targets
0.07Suggestive
HepatoblastomaOpen Targets
0.07Suggestive
choroidal dystrophy, central areolar, 1Open Targets
0.05Suggestive
X-linked retinal dysplasiaOpen Targets
0.05Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
small cell lung carcinomaOpen Targets
0.05Suggestive
gastric cancerOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCNE1Protein interaction100%CDC20Protein interaction100%PDCLProtein interaction100%PFDN1Protein interaction100%PFDN2Protein interaction100%PFDN4Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
58%
Heart
39%
Ovary
34%
Lung
33%
Liver
28%
Gene Interaction Network
Click a node to explore
CCT2CCNE1CDC20PDCLPFDN1PFDN2PFDN4
PROTEIN STRUCTURE
Preparing viewer…
PDB7NVL · 2.50 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.45Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.26 [0.16–0.45]
RankingsWhere CCT2 stands among ~20K protein-coding genes
  • #842of 20,598
    Most Researched366 · top 5%
  • #2,454of 17,882
    Most Constrained (LOEUF)0.45 · top quartile
Genes detectedCCT2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
CCT2 is an aggrephagy receptor for clearance of solid protein aggregates.
PMID: 35366418
Cell · 2022
1.00
2
Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4
PMID: 39079960
Cell Death Dis · 2024
0.90
3
Targeting the molecular chaperone CCT2 inhibits GBM progression by influencing KRAS stability.
PMID: 38582394
Cancer Lett · 2024
0.80
4
PRRSV degrades MDA5 via dual autophagy receptors P62 and CCT2 to evade antiviral innate immunity.
PMID: 38272236
Virol Sin · 2024
0.80
5
Two distinct regulatory pathways govern Cct2-Atg8 binding in the process of solid aggrephagy.
PMID: 39322741
EMBO Rep · 2024
0.70