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Gene Review

RCAN2  -  regulator of calcineurin 2

Homo sapiens

Synonyms: CSP2, Calcipressin-2, DSCR1L1, Down syndrome candidate region 1-like 1, MCIP2, ...
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Disease relevance of DSCR1L1

  • Though not influenced by hypothyroidism, there were several regions of the brain in which ZAKI-4 mRNA was strongly expressed [1].

High impact information on DSCR1L1

  • We further demonstrate that overexpression of DSCR1 and ZAKI-4 inhibits calcineurin-dependent gene transcription through the inhibition of NF-AT translocation to the nucleus [2].
  • Northern blot analysis revealed that there were two ZAKI-4 mRNA species (3.4 and 1.4 kilobases (kb)), and they were up-regulated by a physiological concentration of triiodothyronine (T3) [3].
  • Molecular cloning of a novel thyroid hormone-responsive gene, ZAKI-4, in human skin fibroblasts [3].
  • This T3 effect was abolished by the treatment with cycloheximide, indicating the possibility that gene ZAKI-4 is regulated by T3 in an indirect fashion, through an intermediate product of T3, rather directly by T3 itself [3].
  • Utilizing a method called "differential display of mRNAs by means of polymerase chain reaction", the cDNA fragment of a thyroid hormone-responsive gene ZAKI-4 was cloned from cultured human skin fibroblasts [3].

Biological context of DSCR1L1

  • DSCR1L1 and DSCR1L2 murine genes are also located in chromosomal segments of chromosome 17 and 4, respectively, exactly corresponding to those containing the respective human homologs on chromosomes 6 and 1 [4].
  • Systematic expressed-sequence-tags (EST) database search and reverse-transcription polymerase chain rection (RT-PCR) product sequencing allowed identification of the murine DSCR1, DSCR1L1 and DSCR1L2 [4].
  • No effect of T3 on ZAKI-4 mRNA stability suggested that T3 induces the mRNA at the transcriptional level [3].
  • However, these mutations altered the effect of Csp on exocytosis only after additional truncation of the extreme C terminus as found in the Csp splice variant Csp2 [5].
  • A number of short CH/Csp2 contacts have been unveiled in these complexes at the boundary of TBP and the TATA box minor groove [6].

Anatomical context of DSCR1L1


Associations of DSCR1L1 with chemical compounds

  • In contrast, expression of MCIP2 in the heart is not altered by activated calcineurin but responds to thyroid hormone, which has no effect on MCIP1 [8].
  • S4 of Csp2, -3, and -7 represents an opposite group with a conformation that is highly specific in binding an Asp [9].
  • Thus, 17 pairs of NBD-amino acid enantiomers and NBD-glycine were separated on CSP 2 except for six NBD-amino acids (D-Asn, D-Ser, D-Gln, L-Pro, L-Ser and Gly) [10].
  • Se-Met expression has been performed with a view to solving the CSP2 structure with MAD data collection using the Se absorption edge [11].

Other interactions of DSCR1L1

  • In the present study, we have demonstrated three different ZAKI-4 transcripts, alpha, beta1 and beta2, in human brain by 5'- and 3'-RACE (rapid amplification of cDNA ends) [12].
  • Recently it has been reported that ZAKI-4 belongs to an evolutionary conserved family of proteins that function as calcineurin inhibitor [1].

Analytical, diagnostic and therapeutic context of DSCR1L1

  • The columns with CSP-1 and CSP-2 were tested for the separation of 22 racemates by HPLC with two different mobile phase systems and the results are compared with those obtained by using a structurally related commercial column [13].
  • In situ hybridization revealed that ZAKI-4 mRNA is widely expressed in neurons throughout the brain [1].
  • Recombinant chemosensory protein (CSP2) from the moth Mamestra brassicae: crystallization and preliminary crystallographic study [11].


  1. Expression of ZAKI-4 messenger ribonucleic acid in the brain during rat development and the effect of hypothyroidism. Siddiq, A., Miyazaki, T., Takagishi, Y., Kanou, Y., Hayasaka, S., Inouye, M., Seo, H., Murata, Y. Endocrinology (2001) [Pubmed]
  2. DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Fuentes, J.J., Genescà, L., Kingsbury, T.J., Cunningham, K.W., Pérez-Riba, M., Estivill, X., de la Luna, S. Hum. Mol. Genet. (2000) [Pubmed]
  3. Molecular cloning of a novel thyroid hormone-responsive gene, ZAKI-4, in human skin fibroblasts. Miyazaki, T., Kanou, Y., Murata, Y., Ohmori, S., Niwa, T., Maeda, K., Yamamura, H., Seo, H. J. Biol. Chem. (1996) [Pubmed]
  4. The murine DSCR1-like (Down syndrome candidate region 1) gene family: conserved synteny with the human orthologous genes. Strippoli, P., Petrini, M., Lenzi, L., Carinci, P., Zannotti, M. Gene (2000) [Pubmed]
  5. Mutational analysis of cysteine-string protein function in insulin exocytosis. Zhang, H., Kelley, W.L., Chamberlain, L.H., Burgoyne, R.D., Lang, J. J. Cell. Sci. (1999) [Pubmed]
  6. CH/pi interactions in the crystal structure of TATA-box binding protein/DNA complexes. Umezawa, Y., Nishio, M. Bioorg. Med. Chem. (2000) [Pubmed]
  7. A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2). Strippoli, P., Lenzi, L., Petrini, M., Carinci, P., Zannotti, M. Genomics (2000) [Pubmed]
  8. Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Yang, J., Rothermel, B., Vega, R.B., Frey, N., McKinsey, T.A., Olson, E.N., Bassel-Duby, R., Williams, R.S. Circ. Res. (2000) [Pubmed]
  9. Structural and functional analysis of caspase active sites. Chéreau, D., Kodandapani, L., Tomaselli, K.J., Spada, A.P., Wu, J.C. Biochemistry (2003) [Pubmed]
  10. Preparation and evaluation of new Pirkle type chiral stationary phases with long alkyl chains for the separation of amino acid enantiomers derivatized with NBD-F. Kato, M., Fukushima, T., Santa, T., Nakashima, K., Nishioka, R., Imai, K. The Analyst. (1998) [Pubmed]
  11. Recombinant chemosensory protein (CSP2) from the moth Mamestra brassicae: crystallization and preliminary crystallographic study. Campanacci, V., Spinelli, S., Lartigue, A., Lewandowski, C., Brown, K., Tegoni, M., Cambillau, C. Acta Crystallogr. D Biol. Crystallogr. (2001) [Pubmed]
  12. Novel human ZAKI-4 isoforms: hormonal and tissue-specific regulation and function as calcineurin inhibitors. Cao, X., Kambe, F., Miyazaki, T., Sarkar, D., Ohmori, S., Seo, H. Biochem. J. (2002) [Pubmed]
  13. Solid-phase synthesis of chiral stationary phases based on 2,4,5,6-tetrachloro-1,3-dicyanobenzene derivatives spaced from N-3,5-dinitrobenzoyl alpha-amino acids: comparative study of their resolution efficacy. Kontrec, D., Abatangelo, A., Vinkovic, V., Sunjic, V. Chirality. (2001) [Pubmed]
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