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Tbio T-complex protein 1 subunit epsilon

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Known to play a role, in vitro, in the folding of actin and tubulin.

The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Mutations in this gene cause hereditary sensory and autonomic neuropathy with spastic paraplegia (HSNSP). Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 13. [provided by RefSeq, Apr 2015]

 Comments

Property Summary

NCBI Gene PubMed Count 52
PubMed Score 24.54
PubTator Score 12.94

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Disease Target Count Z-score Confidence
Neuropathy 210 0.0 4.0

Expression

  Differential Expression (9)

Disease log2 FC p
psoriasis -1.400 2.4e-04
medulloblastoma, large-cell 1.100 4.3e-04
non-small cell lung cancer 1.352 6.0e-21
intraductal papillary-mucinous neoplasm ... 1.300 1.5e-02
lung cancer 1.900 1.5e-05
Breast cancer 3.200 3.2e-02
group 3 medulloblastoma 1.100 4.6e-04
invasive ductal carcinoma 1.100 1.6e-03
ovarian cancer 1.100 1.5e-02

Synonym

Accession P48643 A8JZY8 A8K2X8 B4DYD8 TCP-1-epsilon
Symbols CCTE
HEL-S-69
PNAS-102
CCT-epsilon
TCP-1-epsilon

Gene

CCT5

PANTHER Protein Class (2)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (14)

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 GO Function (3)

 GO Component (10)

 GO Process (9)

 Compartment GO Term (43)

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 HCA RNA Cell Line (56)

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Pathway (14)

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Protein-protein Interaction (54)

TUBAL3   GNB5   HDAC3   TP53   CCNE1   CCT6A   STAT3   CCT3   CCT8   GNG2   TUBA1B   TUBA4A   TUBB4B   CSNK2A1   TUBA3C   TUBB2A   TBCE   TUBA3E   BBS12   TUBA1A   BBS10   CCT7   TBCD   TUBB6   WRAP53   TUBB2B   TUBB1   TUBA4B   CCT4   WDR70   KATNA1   CCT6B   UTP18   PDCL3   METAP2   TXNDC9   DDB2   TUBD1   KLHL8   CDC20   CCT2   PDCL   DCAF13   DTL   JMJD4   DCAF12   KATNB1   NLE1   RFWD3   FBXW8   FBXW9   MIOS   DCAF4   KLHDC8B  

Gene RIF (9)

PMID Text
25995452 CCT5 complex caps mutant mHTT fibrils at their tips and encapsulates mHTT oligomers, providing a structural description of the inhibition of mHTTQ46-Ex1 by CCT5 complex and a shared mechanism of mHTT inhibition between TRiC chaperonin and the CCT5 complex
25124038 H147R CCT5 was not as efficient in chaperoning these substrates as wild type CCT5.
23612981 Both CCT4 and CCT5 homo-oligomers have the property of forming 8-fold double rings absent the other subunits, and these complexes carry out chaperonin reactions without other partner subunits.
22232265 introduction of the truncated human CCT epsilon subunit into yeast cells
20468064 Observational study of gene-disease association. (HuGE Navigator)
19651702 Observational study of gene-disease association. (HuGE Navigator)
18421076 Observational study of gene-disease association. (HuGE Navigator)
16821082 mRNA expression of CCT5, RGS3, and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel.
16399879 A missense mutation within the CCT5 gene is associated with autosomal recessive mutilating sensory neuropathy with spastic paraplegia.

AA Sequence 

MASMGTLAFDEYGRPFLIIKDQDRKSRLMGLEALKSHIMAAKAVANTMRTSLGPNGLDKMMVDKDGDVTV      1 - 70
TNDGATILSMMDVDHQIAKLMVELSKSQDDEIGDGTTGVVVLAGALLEEAEQLLDRGIHPIRIADGYEQA     71 - 140
ARVAIEHLDKISDSVLVDIKDTEPLIQTAKTTLGSKVVNSCHRQMAEIAVNAVLTVADMERRDVDFELIK    141 - 210
VEGKVGGRLEDTKLIKGVIVDKDFSHPQMPKKVEDAKIAILTCPFEPPKPKTKHKLDVTSVEDYKALQKY    211 - 280
EKEKFEEMIQQIKETGANLAICQWGFDDEANHLLLQNNLPAVRWVGGPEIELIAIATGGRIVPRFSELTA    281 - 350
EKLGFAGLVQEISFGTTKDKMLVIEQCKNSRAVTIFIRGGNKMIIEEAKRSLHDALCVIRNLIRDNRVVY    351 - 420
GGGAAEISCALAVSQEADKCPTLEQYAMRAFADALEVIPMALSENSGMNPIQTMTEVRARQVKEMNPALG    421 - 490
IDCLHKGTNDMKQQHVIETLIGKKQQISLATQMVRMILKIDDIRKPGESEE                       491 - 541
//

Text Mined References (61)

PMID Year Title
25995452 2015 Structural Mechanisms of Mutant Huntingtin Aggregation Suppression by the Synthetic Chaperonin-like CCT5 Complex Explained by Cryoelectron Tomography.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25852190 2015 Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
25467444 2014 Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1.
25345891 2014 A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model.
25329145 2014 Antibody-validated proteins in inflamed islets of fulminant type 1 diabetes profiled by laser-capture microdissection followed by mass spectrometry.
25124038 2014 Biochemical characterization of mutants in chaperonin proteins CCT4 and CCT5 associated with hereditary sensory neuropathy.
24375412 2014 Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate ?-tubulin folding.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23897027 2013 Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
23612981 2013 Human CCT4 and CCT5 chaperonin subunits expressed in Escherichia coli form biologically active homo-oligomers.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23011926 2013 Human TRiC complex purified from HeLa cells contains all eight CCT subunits and is active in vitro.
22956598 2013 Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22232265 2012 A novel function of the human chaperonin CCT epsilon subunit in yeast.
22223895 2012 Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-?-acetylation features.
21701561 2011 The crystal structure of yeast CCT reveals intrinsic asymmetry of eukaryotic cytosolic chaperonins.
21525035 2011 PEX14 is required for microtubule-based peroxisome motility in human cells.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
21093005 2011 Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein.
20468064 2010 Association study of 182 candidate genes in anorexia nervosa.
20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
20193073 2010 Chaperonin genes on the rise: new divergent classes and intense duplication in human and other vertebrate genomes.
20080638 2010 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly.
19651702 2009 Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19376773 2009 Role of molecular chaperones in G protein beta5/regulator of G protein signaling dimer assembly and G protein betagamma dimer specificity.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18775504 2009 The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1.
18421076 2008 A genome-wide scan maps a novel high myopia locus to 5p15.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
16821082 2007 Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers.
16548883 2006 Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection.
16399879 2006 Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia.
16236267 2005 Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
16169070 2005 A human protein-protein interaction network: a resource for annotating the proteome.
15889144 2005 Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15372022 2004 The DNA sequence and comparative analysis of human chromosome 5.
15231747 2004 A protein interaction framework for human mRNA degradation.
14743216 2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14532270 2003 A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death.
12530067 Identification of differentially expressed genes in classical and atypical multidrug-resistant gastric carcinoma cells.
12502735 2002 Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11580270 2001 Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin.
11580269 2001 Point mutations in a hinge linking the small and large domains of beta-actin result in trapped folding intermediates bound to cytosolic chaperonin CCT.
11532003 2001 Cytosolic chaperonin-containing t-complex polypeptide 1 changes the content of a particular subunit species concomitant with substrate binding and folding activities during the cell cycle.
11358150 2001 Differential expression of molecular chaperones in brain of patients with Down syndrome.
11162507 2001 Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease.
10747865 2000 Insertional mutation of the murine kisimo locus caused a defect in spermatogenesis.
10393949 1999 SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: identification of common effectors with p53 and p21(Waf1).
9250675 1997 Elucidation of the subunit orientation in CCT (chaperonin containing TCP1) from the subunit composition of CCT micro-complexes.
7953530 1994 Identification of six Tcp-1-related genes encoding divergent subunits of the TCP-1-containing chaperonin.
7788527 1995 Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1.
7615668 1995 Cytoplasmic chaperonin complexes enter neurites developing in vitro and differ in subunit composition within single cells.