CHAPERONIN CONTAINING T-COMPLEX POLYPEPTIDE 1, SUBUNIT 8; CCT8

Alternative titles; symbols

• CHAPERONIN CONTAINING TCP1, SUBUNIT 8
• CCT-THETA; CCTQ
• KIAA0002

HGNC Approved Gene Symbol: CCT8

Cytogenetic location: 21q21.3 Genomic coordinates (GRCh38): 21:29,056,325-29,073,647 (from NCBI)

▼ Description
The cytosolic chaperonin containing T-complex protein-1 (TCP1; 186980) (CCT) complex consists of 2 stacked rings of 8 subunits, including CCT8. The CCT complex assists in the folding of newly synthesized multidomain proteins (summary by Ozdemir et al., 2016).

▼ Cloning and Expression
By sequencing clones obtained from a size-fractionated KG-1 human immature myeloid cell line cDNA library, Nomura et al. (1994) cloned CCT8, which they designated KIAA0002. The deduced 548-amino acid protein has an aspartyl protease active-site motif and shares significant similarity with human TCP1. Northern blot analysis detected variable KIAA0002 expression in all human tissues and cell lines examined, with highest expression in heart, brain, skeletal muscle, kidney, colon, leukocytes, and HeLa cells.

Kubota et al. (1995) cloned mouse Cct8, which they called Cct-theta. The deduced 548-amino acid protein has a calculated molecular mass of 59.6 kD. Cct-theta has 5 conserved Cct motifs and shares 23 to 29% amino acid identity with other Cct subunits and 29% identity with the archaebacterial chaperonin Tf55. Cct-theta had an apparent molecular mass of 62 kD by SDS-PAGE.

▼ Gene Function
Dyneins are multisubunit minus end-directed motor proteins that use ATP to transport cargo along microtubules. Using transfected A375 human melanoma cells, Ozdemir et al. (2016) found that epitope-tagged rat dynein intermediate chain-2 (IC2, or DYNC1I2; 603331) interacted with 5 subunits of the CCT complex, including CCT8. Immunoprecipitation analysis confirmed that CCT8 interacted with Ic2. Mutation analysis revealed that CCT8 interacted with the C-terminal half of Ic2, which forms a beta-propeller structure and binds dynein heavy chain (see 600112). The interaction was not detected following inhibition of protein synthesis, indicating that CCT8 interacted with newly synthesized Ic2.

▼ Gene Structure
Yamazaki et al. (1995) determined that the CCT8 gene has 15 exons and spans approximately 17 kb. It contains several Alu repetitive sequences throughout its length, and intron 14 has an AT cluster of over 200 nucleotides. The 5-prime end has 2 CpG islands, a long terminal repeat (LTR)-like sequence, and an SP1 (189906)-binding site.

▼ Mapping
By sequencing a cosmid clone, Yamazaki et al. (1995) mapped the CCT8 gene to chromosome 21q21.3-q22.1.

Hartz (2017) mapped the CCT8 gene to chromosome 21q21.3 based on an alignment of the CCT8 sequence (GenBank Z37163) with the genomic sequence (GRCh38).