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Gene Review

CYS1  -  cystin 1

Homo sapiens

Synonyms: Cilia-associated protein, Cystin-1
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Disease relevance of CYS1

  • We studied affected individuals of eight families with nephronophthisis and liver fibrosis for evidence of CYS1 mutations [1].
  • Despite the failure to detect a mutation, the human cystin gene remains an interesting candidate for recessive cystic kidney disease [1].
  • Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease [2].

High impact information on CYS1

  • When expressed exogenously in polarized renal epithelial cells, cystin is detected in cilia, and its expression overlaps with polaris, another PKD-related protein [2].
  • The folding intermediate possessing these two disulfide bridges already binds to lysine-Sepharose, indicating that the third native bridge, which in native kringle 4 connects residues Cys1 and Cys79, is not essential for the maintenance of the biologically active conformation of kringle 4 [3].
  • Structural and functional analyses of the modified TIMP-2 showed that carbamylation of the alpha-amino group of the NH2-terminal Cys1 of TIMP-2 led to complete loss of the inhibitory activity [4].
  • The large interaction interface in the TIMP-1.MMP-3 complex includes a contiguous region of TIMP-1 around the disulfide bond between Cys1 and Cys70 that inserts into the active site of MMP-3 [5].
  • The results indicate that the side chain of Asn101 and the backbone nitrogen of Gly102 function to stabilize a tetrahedral oxyanion resulting from attack of Cys1 on the glutamine carboxamide [6].

Biological context of CYS1

  • CYS1 is located on Chromosome 2p25 [1].
  • The CYS1 genomic region comprises three coding exons, which span 22 kb [1].
  • The transcript harbors an open reading frame of 477 nucleotides encoding a protein with 158 amino acid residues, which is called cystin [1].
  • Chain reversals in model peptides: studies of cystine-containing cyclic peptides. II. Effects of valyl residues and possible i-to-(i + 3) attractive ionic interactions on cyclization of [Cys1], [Cys6] hexapeptides [7].

Associations of CYS1 with chemical compounds

  • Cys1, Arg73, Asn101, Gly102, and Asp127 are conserved in the NH2-terminal domain of a subfamily of amidotransferases that includes asparagine synthetase, glucosamine 6-phosphate synthase, and glutamate synthase, implying a common function in the four enzymes [6].
  • The cyclic nature due to a disulfide bridge between Cys1 and Cys6 of vasopressin provides structural rigidity to the peptide hormone [8].
  • This is believed to be regulated not by varying the disulfide bond itself, but by modulating the stability of the dithiol form of the protein through interactions with the ionized form of the Cys1 thiol group [9].
  • The IGF-I and IGF-II binding activities were dramatically reduced by the single mutation, Cys9/Arg (>25-fold), and to a lesser degree, by the single mutation, Cys12/Arg (the first N-terminal Cys residue was designated Cys1) [10].

Other interactions of CYS1

  • All individuals were examined for homozygous deletions in NPHP1 and directly sequenced for BCL2 and CYS1 [11].
  • The calculated structure of Ptu1 belongs to the inhibitory cystin knot structural family (ICK) that consists of a compact disulfide-bonded core from which four loops emerge [12].


  1. Identification of the human CYS1 gene and candidate gene analysis in Boichis disease. Fliegauf, M., Fröhlich, C., Horvath, J., Olbrich, H., Hildebrandt, F., Omran, H. Pediatr. Nephrol. (2003) [Pubmed]
  2. Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease. Hou, X., Mrug, M., Yoder, B.K., Lefkowitz, E.J., Kremmidiotis, G., D'Eustachio, P., Beier, D.R., Guay-Woodford, L.M. J. Clin. Invest. (2002) [Pubmed]
  3. Folding autonomy of the kringle 4 fragment of human plasminogen. Trexler, M., Patthy, L. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  4. Reactive site-modified tissue inhibitor of metalloproteinases-2 inhibits the cell-mediated activation of progelatinase A. Higashi, S., Miyazaki, K. J. Biol. Chem. (1999) [Pubmed]
  5. Residue 2 of TIMP-1 is a major determinant of affinity and specificity for matrix metalloproteinases but effects of substitutions do not correlate with those of the corresponding P1' residue of substrate. Meng, Q., Malinovskii, V., Huang, W., Hu, Y., Chung, L., Nagase, H., Bode, W., Maskos, K., Brew, K. J. Biol. Chem. (1999) [Pubmed]
  6. Structure and function of the glutamine phosphoribosylpyrophosphate amidotransferase glutamine site and communication with the phosphoribosylpyrophosphate site. Kim, J.H., Krahn, J.M., Tomchick, D.R., Smith, J.L., Zalkin, H. J. Biol. Chem. (1996) [Pubmed]
  7. Chain reversals in model peptides: studies of cystine-containing cyclic peptides. II. Effects of valyl residues and possible i-to-(i + 3) attractive ionic interactions on cyclization of [Cys1], [Cys6] hexapeptides. Milburn, P.J., Meinwald, Y.C., Takahashi, S., Ooi, T., Scheraga, H.A. Int. J. Pept. Protein Res. (1988) [Pubmed]
  8. Trypsin inhibition by a peptide hormone: crystal structure of trypsin-vasopressin complex. Syed Ibrahim, B., Pattabhi, V. J. Mol. Biol. (2005) [Pubmed]
  9. Electrostatic interactions in the active site of the N-terminal thioredoxin-like domain of protein disulfide isomerase. Kortemme, T., Darby, N.J., Creighton, T.E. Biochemistry (1996) [Pubmed]
  10. Localization of the IGF binding domain and evaluation of the role of cysteine residues in IGF binding in IGF binding protein-4. Byun, D., Mohan, S., Baylink, D.J., Qin, X. J. Endocrinol. (2001) [Pubmed]
  11. Mutational analysis in 119 families with nephronophthisis. O'toole, J.F., Otto, E.A., Hoefele, J., Helou, J., Hildebrandt, F. Pediatr. Nephrol. (2007) [Pubmed]
  12. Solution structure of Ptu1, a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type. Bernard, C., Corzo, G., Mosbah, A., Nakajima, T., Darbon, H. Biochemistry (2001) [Pubmed]
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