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Gene Review

CTDSPL  -  CTD (carboxy-terminal domain, RNA...

Homo sapiens

Synonyms: C3orf8, CTD small phosphatase-like protein, CTDSP-like, Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 3, HYA22, ...
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Disease relevance of CTDSPL


High impact information on CTDSPL


Chemical compound and disease context of CTDSPL

  • The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains [7].
  • Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions [3].

Biological context of CTDSPL

  • Interestingly, the HYA22 gene (human ortholog of the yeast YA22 gene) was located at the borders of both breakpoints, evolutionarily conserved gene cluster and homozygous deletions detected in lung, kidney and other cancers [8].
  • The predicted amino acid sequences of one of the two novel genes showed high homology to villin, a human cytoskeleton protein; those of the other gene, termed HYA22, revealed significant homology to YA22, a hypothetical protein predicted from DNA sequences of Schizosaccharomyces pombe [9].
  • The NLI-IF amino acid sequence has homology to proteins that have a high degree of homology with the NLI-interacting factor from Gallus gallus and are found in divergent species ranging from yeast to plants [10].
  • The human NLI-IF gene begins 4721 bp downstream of the NRAMP1 stop codon and is composed of seven exons varying in size from 57 bp to 1644 bp [10].
  • Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility [11].

Anatomical context of CTDSPL


Associations of CTDSPL with chemical compounds

  • In addition to its ability to act as a redox sensor, the activity of NIFL is also responsive to adenosine nucleotides, particularly ADP [2].
  • Spectral features of purified NIFL and chromatographic analysis indicate that it is a flavoprotein with FAD as the prosthetic group, which undergoes reduction in the presence of sodium dithionite [2].
  • Removal of the first 146 residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in a large family of sensory proteins from eubacteria, archea and eukarya eliminates the redox response [7].
  • The inhibitory activity of NIFL towards NIFA is stimulated by ADP binding to the C-terminal domain of NIFL, which bears significant homology to the histidine protein kinase transmitter domains [13].
  • In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed phosphatidylserine [14].

Other interactions of CTDSPL


Analytical, diagnostic and therapeutic context of CTDSPL

  • Northern blot analysis of 15 different human tissues revealed a 2.6-kb NLI-IF mRNA that was ubiquitously expressed, but at varying levels [10].
  • In a case-control study with a Caucasian population, three cosmopolitan SNPs (204C > A, 402T > C and 472 - 42G > A) in NLI-IF showed no significant association with human susceptibility to tuberculosis [11].


  1. Silencing of bidirectional promoters by DNA methylation in tumorigenesis. Shu, J., Jelinek, J., Chang, H., Shen, L., Qin, T., Chung, W., Oki, Y., Issa, J.P. Cancer Res. (2006) [Pubmed]
  2. Azotobacter vinelandii NIFL is a flavoprotein that modulates transcriptional activation of nitrogen-fixation genes via a redox-sensitive switch. Hill, S., Austin, S., Eydmann, T., Jones, T., Dixon, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL. Eydmann, T., Söderbäck, E., Jones, T., Hill, S., Austin, S., Dixon, R. J. Bacteriol. (1995) [Pubmed]
  4. Arabidopsis NPH1: a protein kinase with a putative redox-sensing domain. Huala, E., Oeller, P.W., Liscum, E., Han, I.S., Larsen, E., Briggs, W.R. Science (1997) [Pubmed]
  5. Signal transduction to the Azotobacter vinelandii NIFL-NIFA regulatory system is influenced directly by interaction with 2-oxoglutarate and the PII regulatory protein. Little, R., Reyes-Ramirez, F., Zhang, Y., van Heeswijk, W.C., Dixon, R. EMBO J. (2000) [Pubmed]
  6. RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies. Kashuba, V.I., Li, J., Wang, F., Senchenko, V.N., Protopopov, A., Malyukova, A., Kutsenko, A.S., Kadyrova, E., Zabarovska, V.I., Muravenko, O.V., Zelenin, A.V., Kisselev, L.L., Kuzmin, I., Minna, J.D., Winberg, G., Ernberg, I., Braga, E., Lerman, M.I., Klein, G., Zabarovsky, E.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains. Söderbäck, E., Reyes-Ramirez, F., Eydmann, T., Austin, S., Hill, S., Dixon, R. Mol. Microbiol. (1998) [Pubmed]
  8. An integrated physical and gene map of the 3.5-Mb chromosome 3p21.3 (AP20) region implicated in major human epithelial malignancies. Protopopov, A., Kashuba, V., Zabarovska, V.I., Muravenko, O.V., Lerman, M.I., Klein, G., Zabarovsky, E.R. Cancer Res. (2003) [Pubmed]
  9. Sequence analysis of a 685-kb genomic region on chromosome 3p22-p21.3 that is homozygously deleted in a lung carcinoma cell line. Ishikawa, S., Kai, M., Tamari, M., Takei, Y., Takeuchi, K., Bandou, H., Yamane, Y., Ogawa, M., Nakamura, Y. DNA Res. (1997) [Pubmed]
  10. Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on chromosome region 2q35. Marquet, S., Lepage, P., Hudson, T.J., Musser, J.M., Schurr, E. Mamm. Genome (2000) [Pubmed]
  11. Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility. Ma, X., Wright, J., Dou, S., Olsen, P., Teeter, L., Adams, G., Graviss, E. J. Hum. Genet. (2002) [Pubmed]
  12. NRC-interacting factor 1 is a novel cotransducer that interacts with and regulates the activity of the nuclear hormone receptor coactivator NRC. Mahajan, M.A., Murray, A., Samuels, H.H. Mol. Cell. Biol. (2002) [Pubmed]
  13. Protein-protein interactions in the complex between the enhancer binding protein NIFA and the sensor NIFL from Azotobacter vinelandii. Money, T., Barrett, J., Dixon, R., Austin, S. J. Bacteriol. (2001) [Pubmed]
  14. Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Wang, X., Wu, Y.C., Fadok, V.A., Lee, M.C., Gengyo-Ando, K., Cheng, L.C., Ledwich, D., Hsu, P.K., Chen, J.Y., Chou, B.K., Henson, P., Mitani, S., Xue, D. Science (2003) [Pubmed]
  15. Isolation of two polypeptides comprising the neutrophil-immobilizing factor of human leucocytes. Watt, K.W., Brightman, I.L., Goetzl, E.J. Immunology (1983) [Pubmed]
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