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Gene Review

FLVCR2  -  feline leukemia virus subgroup C cellular...

Homo sapiens

Synonyms: C14orf58, CCT, Calcium-chelate transporter, EPV, FLJ20371, ...
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Disease relevance of FLVCR2

  • Disruption of the CCT complex by RNAi-mediated knockdown enhanced Htt-polyQ aggregate formation and cellular toxicity [1].
  • The cavity of ATP-charged group I chaperonins, typified by Escherichia coli GroEL [1], is sealed off by a co-chaperonin, whereas group II chaperonins--the archaeal thermosome and eukaryotic TRiC/CCT [2]--possess a built-in lid [3-5] [2].
  • Low attenuation values in CCT correlate better with changes in specific gravity, rather than water in infarcts, but they have a close relationship to water content in edema [3].
  • In 55 otherwise healthy, 6-mo-old Chilean infants (29 with iron deficiency anemia and 26 nonanemic control infants), the CCT was longer in those who had been anemic at 6 mo, with differences becoming more pronounced at 12- and 18-mo follow-ups despite effective iron therapy [4].
  • Patients with ABPA with GCT and AGG alleles showed significantly high levels of total IgE and percentage eosinophilia versus patients with ABPA with CCT and AGA alleles [5].

Psychiatry related information on FLVCR2

  • Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein epsilon4, did not discriminate between the two groups, and there were no differences on CCT scans [6].
  • Eating disorders as assessed by cranial computerized tomography (CCT, dSPECT, PET) [7].
  • The cognitive abilities of 69 children with traumatic head injury (THI) were evaluated with the California Verbal Learning Test-Children's Version (CVLT-C; Delis, Kramer, Kaplan, & Ober, 1994), the Children's Category Test (CCT; Boll, 1993), and the Wechsler Intelligence Scale for Children-Third Edition (WISC-III; Wechsler, 1991) [8].
  • Quantitative EEG analysis in early onset Alzheimer's disease: correlations with severity, clinical characteristics, visual EEG and CCT [9].

High impact information on FLVCR2

  • We examine the fate of newly synthesized substrate proteins bound to CCT in reticulocyte lysate or intact Xenopus oocytes [10].
  • Rather, a large hydrophobic surface patch is found in a novel helix-turn-helix motif, which is characteristic of all group II chaperonins including the eukaryotic TRiC/CCT complex [11].
  • However, the repeat expansion detection (RED) technique has identified additional large repeats of ATG, CCT, CTT, and TGG of potentially pathological significance in the human genome [12].
  • The eukaryotic chaperonin TCP-1 ring complex (TRiC, also called CCT) is indispensable for cell survival because the folding of an essential subset of cytosolic proteins requires TRiC, and this function cannot be substituted by other chaperones [13].
  • Here, we show that the hetero-oligomeric chaperonin TRiC (also known as CCT) physically interacts with polyglutamine-expanded variants of huntingtin (Htt) and effectively inhibits their aggregation [14].

Chemical compound and disease context of FLVCR2


Biological context of FLVCR2

  • Similarly, overexpression of all eight subunits of CCT suppressed Htt aggregation and neuronal cell death [1].
  • CCT stabilizes quasi-native structures in both proteins that are open through their domain-connecting hinge regions, suggesting a novel mechanism and function of CCT in assisted protein folding [19].
  • A large fraction of newly translated polypeptides associate transiently with Hsc70 and the chaperonin TRiC/CCT during their biogenesis [20].
  • PhLP phosphorylation permits the release of a PhLP x Gbeta intermediate from CCT, allowing Ggamma to associate with Gbeta in this intermediate complex [21].
  • Six haplotypes, CTG (49.7%), TCT (14.7%), CCT (20.3%), TTG (13.2%), CCG (1.4%), and TTT (0.7%), were found in the healthy controls [22].

Anatomical context of FLVCR2

  • Assembly of the native alpha/beta tubulin heterodimer, the subunit that polymerizes to form microtubules, requires the participation of several molecular chaperones, namely prefoldin, the cytosolic chaperonin CCT, and a series of five tubulin-specific chaperones termed cofactors A-E (TBCA-E) [23].
  • Furthermore, newly translated cyclin E, both in vitro in reticulocyte lysate and in vivo in human cells in culture, is efficiently bound and processed by the CCT [24].
  • Skeletal status was assessed by radiography of the hands with measurement of combined cortical thickness of the second metacarpal bones (CCT) or measurement of radial and lumbar bone density, or by both methods [25].
  • The central conduction time (CCT, or wave I-V interpeak latency) is considered an index of CNS development because myelination of nerve fibers and maturation of synaptic relays lead to an exponential reduction in the CCT from birth to 24 mo [4].
  • The band of increased attenuation seen on in vivo CCT images of adults, frequently designated as the cerebral cortex, has been proved clinically and experimentally to be an artifact in the reconstructed image [26].

Associations of FLVCR2 with chemical compounds

  • Inter alia, adw differs from ayw in that codon 15 is comprised of CCC instead of CCT [27].
  • Oligonucleotides containing 2-aminopurine (2-AP) in place of G or A in the recognition site of EcoRII (CCT/AGG) or SsoII (CCNGG) restriction endonucleases have been synthesized in order to investigate the specific interaction of DNA with these enzymes [28].
  • DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65 [29].
  • Comparison of different N-linked sphingosine derivatives suggests an inverse relationship between the length of the N-linked carbon chain and the derivatives ability to trigger apoptosis and inhibit CCT [30].
  • Apoptosis induced by antitumor phospholipid analogs takes place after the inhibition of the CTP:phosphocholine cytidylyltransferase (CCT; EC catalyzed step of phosphatidylcholine (PtdCho) biosynthesis [30].

Other interactions of FLVCR2

  • Mouse cells expressing a hybrid protein containing FLVCR2 backbone with the ECL6 sequence from FLVCR1 were highly susceptible to FeLV-C infection [31].

Analytical, diagnostic and therapeutic context of FLVCR2

  • RESULTS: Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively [32].
  • This case-control study was designed to analyze whether early cerebral CT (CCT) scanning provides reliable information for the prospective selection of stroke patients at risk of developing mMCAI [33].
  • Gel mobility shift assays revealed that the labeled putative rat ANG-IRE motif (N-878 to N-864, 5' CCT TCC CGC CCT TCA 3') was bound to the nuclear proteins of IRPTCS: This binding was displaced by unlabeled ANG-IRE and IRE of human glyceraldehyde phosphate dehydrogenase but not by mutants of ANG-IRE and IRE of the rat glucagon gene [34].
  • Cryoelectron microscopy and biochemical studies have revealed that both of these proteins interact with CCT in quasi-native, defined conformations [35].
  • Treatment regimens ranged from standard RT (SRT) to 60 Gy, hyperfractionated RT (HRT) to 69.6 Gy, induction chemotherapy (ICT) of cisplatin (CIS) and vinblastine (VBL) followed by SRT, ICT + concurrent CT (CCT) + SRT, and CCT + HRT; CCT consisted of etoposide or VBL + CIS [36].


  1. Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Kitamura, A., Kubota, H., Pack, C.G., Matsumoto, G., Hirayama, S., Takahashi, Y., Kimura, H., Kinjo, M., Morimoto, R.I., Nagata, K. Nat. Cell Biol. (2006) [Pubmed]
  2. Conformational rearrangements of an archaeal chaperonin upon ATPase cycling. Gutsche, I., Holzinger, J., Rössle, M., Heumann, H., Baumeister, W., May, R.P. Curr. Biol. (2000) [Pubmed]
  3. Correlative assay of computerized cranial tomography CCT, water content and specific gravity in normal and pathological postmortem brain. Torack, R.M., Alcala, H., Gado, M., Burton, R. J. Neuropathol. Exp. Neurol. (1976) [Pubmed]
  4. Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo: delayed maturation of auditory brainstem responses. Roncagliolo, M., Garrido, M., Walter, T., Peirano, P., Lozoff, B. Am. J. Clin. Nutr. (1998) [Pubmed]
  5. Association of polymorphisms in the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis. Saxena, S., Madan, T., Shah, A., Muralidhar, K., Sarma, P.U. J. Allergy Clin. Immunol. (2003) [Pubmed]
  6. The Alzheimer variant of lewy body disease: a pathologically confirmed case-control study. Perneczky, R., Mösch, D., Neumann, M., Kretzschmar, H., Müller, U., Busch, R., Förstl, H., Kurz, A. Dementia and geriatric cognitive disorders. (2005) [Pubmed]
  7. Eating disorders as assessed by cranial computerized tomography (CCT, dSPECT, PET). Krieg, J.C. Adv. Exp. Med. Biol. (1991) [Pubmed]
  8. Novel learning abilities after traumatic head injury in children. Hoffman, N., Donders, J., Thompson, E.H. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists. (2000) [Pubmed]
  9. Quantitative EEG analysis in early onset Alzheimer's disease: correlations with severity, clinical characteristics, visual EEG and CCT. Schreiter-Gasser, U., Gasser, T., Ziegler, P. Electroencephalography and clinical neurophysiology. (1994) [Pubmed]
  10. Chaperonin-mediated folding in the eukaryotic cytosol proceeds through rounds of release of native and nonnative forms. Farr, G.W., Scharl, E.C., Schumacher, R.J., Sondek, S., Horwich, A.L. Cell (1997) [Pubmed]
  11. Structure of the substrate binding domain of the thermosome, an archaeal group II chaperonin. Klumpp, M., Baumeister, W., Essen, L.O. Cell (1997) [Pubmed]
  12. Chromosomal localization of long trinucleotide repeats in the human genome by fluorescence in situ hybridization. Haaf, T., Sirugo, G., Kidd, K.K., Ward, D.C. Nat. Genet. (1996) [Pubmed]
  13. Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets. Spiess, C., Meyer, A.S., Reissmann, S., Frydman, J. Trends Cell Biol. (2004) [Pubmed]
  14. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Tam, S., Geller, R., Spiess, C., Frydman, J. Nat. Cell Biol. (2006) [Pubmed]
  15. Inhibition of thermolysin and neutral endopeptidase 24.11 by a novel glutaramide derivative: X-ray structure determination of the thermolysin-inhibitor complex. Holland, D.R., Barclay, P.L., Danilewicz, J.C., Matthews, B.W., James, K. Biochemistry (1994) [Pubmed]
  16. Molecular analysis of structural protein genes of the Yamagata-1 strain of defective subacute sclerosing panencephalitis virus. II. Nucleotide sequence of a cDNA corresponding to the P plus M dicistronic mRNA. Yoshikawa, Y., Tsuruoka, H., Matsumoto, M., Haga, T., Shioda, T., Shibuta, H., Sato, T.A., Yamanouchi, K. Virus Genes (1990) [Pubmed]
  17. Hormonal changes in cerebral infarction in the young and elderly. Elwan, O., Abdallah, M., Issa, I., Taher, Y., el-Tamawy, M. J. Neurol. Sci. (1990) [Pubmed]
  18. Effects of hypoxia, glucose deprivation and acidosis on phosphatidylcholine synthesis in HL-1 cardiomyocytes. CTP:phosphocholine cytidylyltransferase activity correlates with sarcolemmal disruption. Sarri, E., Garcia-Dorado, D., Abellan, A., Soler-Soler, J. Biochem. J. (2006) [Pubmed]
  19. Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations. Llorca, O., Martín-Benito, J., Ritco-Vonsovici, M., Grantham, J., Hynes, G.M., Willison, K.R., Carrascosa, J.L., Valpuesta, J.M. EMBO J. (2000) [Pubmed]
  20. In vivo newly translated polypeptides are sequestered in a protected folding environment. Thulasiraman, V., Yang, C.F., Frydman, J. EMBO J. (1999) [Pubmed]
  21. Mechanism of assembly of G protein betagamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the cytosolic chaperonin complex. Lukov, G.L., Baker, C.M., Ludtke, P.J., Hu, T., Carter, M.D., Hackett, R.A., Thulin, C.D., Willardson, B.M. J. Biol. Chem. (2006) [Pubmed]
  22. Association of IL1A gene polymorphisms with susceptibility to and severity of systemic sclerosis in the Japanese population. Kawaguchi, Y., Tochimoto, A., Ichikawa, N., Harigai, M., Hara, M., Kotake, S., Kitamura, Y., Kamatani, N. Arthritis Rheum. (2003) [Pubmed]
  23. Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD. Tian, G., Huang, M.C., Parvari, R., Diaz, G.A., Cowan, N.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  24. Maturation of human cyclin E requires the function of eukaryotic chaperonin CCT. Won, K.A., Schumacher, R.J., Farr, G.W., Horwich, A.L., Reed, S.I. Mol. Cell. Biol. (1998) [Pubmed]
  25. Reduced creatinine clearance in primary osteoporosis in women. Yendt, E.R., Cohanim, M., Jarzylo, S., Jones, G., Rosenberg, G. J. Bone Miner. Res. (1993) [Pubmed]
  26. The peripheral zone of increase density in cranial computed tomography. Gado, M., Phelps, M. Radiology. (1975) [Pubmed]
  27. Nucleic acid sequence analysis of the precore region of hepatitis B virus from sera of southern African black adult carriers of the virus. Kramvis, A., Bukofzer, S., Kew, M.C., Song, E. Hepatology (1997) [Pubmed]
  28. The interaction of DNA duplexes containing 2-aminopurine with restriction endonucleases EcoRII and SsoII. Petrauskene, O.V., Schmidt, S., Karyagina, A.S., Nikolskaya, I.I., Gromova, E.S., Cech, D. Nucleic Acids Res. (1995) [Pubmed]
  29. A novel point mutation in the insulin gene giving rise to hyperproinsulinemia. Warren-Perry, M.G., Manley, S.E., Ostrega, D., Polonsky, K., Mussett, S., Brown, P., Turner, R.C. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  30. Inhibition of CTP:phosphocholine cytidylyltransferase by C(2)-ceramide and its relationship to apoptosis. Ramos, B., El Mouedden, M., Claro, E., Jackowski, S. Mol. Pharmacol. (2002) [Pubmed]
  31. Comprehensive mapping of receptor-functioning domains in feline leukemia virus subgroup C receptor FLVCR1. Brown, J.K., Fung, C., Tailor, C.S. J. Virol. (2006) [Pubmed]
  32. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. Fermand, J.P., Katsahian, S., Divine, M., Leblond, V., Dreyfus, F., Macro, M., Arnulf, B., Royer, B., Mariette, X., Pertuiset, E., Belanger, C., Janvier, M., Chevret, S., Brouet, J.C., Ravaud, P. J. Clin. Oncol. (2005) [Pubmed]
  33. Attenuated corticomedullary contrast: An early cerebral computed tomography sign indicating malignant middle cerebral artery infarction. A case-control study. Haring, H.P., Dilitz, E., Pallua, A., Hessenberger, G., Kampfl, A., Pfausler, B., Schmutzhard, E. Stroke (1999) [Pubmed]
  34. Characterization of a putative insulin-responsive element and its binding protein(s) in rat angiotensinogen gene promoter: regulation by glucose and insulin. Chen, X., Zhang, S.L., Pang, L., Filep, J.G., Tang, S.S., Ingelfinger, J.R., Chan, J.S. Endocrinology (2001) [Pubmed]
  35. Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin. Llorca, O., Martín-Benito, J., Gómez-Puertas, P., Ritco-Vonsovici, M., Willison, K.R., Carrascosa, J.L., Valpuesta, J.M. J. Struct. Biol. (2001) [Pubmed]
  36. The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies. Movsas, B., Scott, C., Sause, W., Byhardt, R., Komaki, R., Cox, J., Johnson, D., Lawton, C., Dar, A.R., Wasserman, T., Roach, M., Lee, J.S., Andras, E. Int. J. Radiat. Oncol. Biol. Phys. (1999) [Pubmed]
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