T-complex protein 1 subunit delta (CCT4)

The protein contains 539 amino acids for an estimated molecular weight of 57924 Da.

 

Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable). (updated: Sept. 12, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs2272428

The reference OMIM entry for this protein is 605142

Chaperonin containing t-complex polypeptide 1, subunit 4; cct4
Chaperonin containing tcp1, subunit 4
Cct-delta; cctd
Stimulator of tar rna-binding proteins; srb

DESCRIPTION

The chaperonin containing TCP1 (186980) complex (CCT), also called the TCP1 ring complex, consists of 2 back-to-back rings, each containing 8 unique but homologous subunits, such as CCT4. CCT assists the folding of newly translated polypeptide substrates through multiple rounds of ATP-driven release and rebinding of partially folded intermediate forms. Substrates of CCT include the cytoskeletal proteins actin (see 102560) and tubulin (see 191130), as well as alpha-transducin (139330) (Won et al., 1998).

CLONING

Human immunodeficiency virus-1 (HIV-1) expression is dependent on a number of regulatory elements in the long terminal repeat. The binding of both RNA polymerase II and TAR-binding protein-1 (TARBP1; 605052) to the TAR regulatory element is enhanced by the presence of cofactors that are unable to bind TAR independently. By purifying cofactor proteins capable of enhancing the binding of TARBP1 to TAR, microsequence analysis, and PCR using degenerate primers on HeLa cell cDNA, Wu-Baer et al. (1996) isolated a cDNA encoding CCT4, which they called SRB (stimulator of TAR RNA-binding proteins). The deduced 539-amino acid CCT4 protein shares homology with a number of chaperonin family proteins. Northern blot analysis detected a 2.0-kb CCT4 transcript in all tissues tested. Western blot analysis showed that CCT4 is expressed as a 62-kD protein. Cyclin E (CCNE1; 123837), a partner of the cyclin-dependent kinase CDK2 (116953), is implicated in the positive control of the G1/S phase transition. CCNE1 degradation is regulated by ubiquitination and proteasomal action, which occur upon autophosphorylation and activation of the CCNE1-CDK2 complex. Using a yeast-based screen to identify proteins that interact with CCNE1, Won et al. (1998) obtained a cDNA encoding CCT4, which they called CCT-delta.

GENE FUNCTION

Binding analysis by Wu-Baer et al. (1996) confirmed that CCT4 enhances the binding of TARBP1 and RNA polymerase II to TAR. The binding was further enhanced by the presence of other recombinant cofactors, such as EEF1A1 (130590) and PTB (600693). By mutational analysis Won et al. (1998) found that CCT is essential for CCNE1 maturation and accumulation.

ANIMAL MODEL

Jacobs et al. (1981) described an autosomal recessive early-onset sensory neuropathy in a Sprague-Dawley rat strain, which they named 'mutilated foot' (mf). The main clinical features included ataxia, insensitivity to pain, and foot ulceration. The pathologic features included a severe reduction in the number of sensory ganglia and fibers. Lee et al. (2003) mapped the mf locus to the distal end of rat chromosome 14, a region syntenic to mouse proximal 11 and human 2p15. Sequence analysis of 4 candidate genes revealed a 1349G-A transition in CCT4, resulting in a cys450-to-tyr (C450Y) substitution at a highly conserved residue, segregating with the mf phenotype. No mutations were identified in the human CCT4 gene within a cohort of 39 patients with hereditary sensory neuropathy or axonal Charcot-Marie-Tooth disease type 2 (see 118210). As CCT4 is involved in folding tubulin (191130), actin (102560), and other cytosolic proteins, Lee et al. (2003) suggested that misfolding of proteins may be a cause of this group of neuropathies. ... More on the omim web site

Subscribe to this protein entry history

Oct. 2, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605142 was added.