Disease relevance of CTDSPL

• Methylation of WNT9A/CD558500 and CTDSPL/BC040563 promoters occurs frequently in primary colon cancers and acute lymphoid leukemias (ALL), respectively, and methylation was correlated with decreased gene expression in ALL patient samples [1].
• Azotobacter vinelandii NIFL is a flavoprotein that modulates transcriptional activation of nitrogen-fixation genes via a redox-sensitive switch [2].
• We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter [3].

High impact information on CTDSPL

• Sequence similarity with a known (NIFL) and a suspected (Aer) flavoprotein suggests that NPH1 LOV1 and LOV2 may be flavin-binding domains that regulate kinase activity in response to blue light-induced redox changes [4].
• We propose that the PII protein signals the nitrogen status by interaction with the NIFL-NIFA system under conditions of nitrogen excess, and that the inhibitory activity of NIFL is relieved by elevated levels of 2-oxoglutarate when PII is uridylylated under conditions of nitrogen limitation [5].
• RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies [6].
• By sequence analysis RBSP3/HYA22 belongs to a gene family of small C-terminal domain phosphatases that may control the RNA polymerase II transcription machinery [6].
• The NIFL regulatory protein controls transcriptional activation of nitrogen fixation (nif) genes in Azotobacter vinelandii by direct interaction with the enhancer binding protein NIFA [2].

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

• NIF-1 was cloned from rat pituitary and human cell lines and was found to interact in vivo and in vitro with NRC [12].

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

• The larger (NIF-1) and smaller (NIF-2) of the polypeptides were resolved by filtration on Bio-Gel P6 and purified to homogeneity by sequential reverse-phase high performance liquid chromatography and paper electrophoresis [15].
• Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis [14].
• Here we describe the cloning and characterization of a novel protein we refer to as NIF-1 (NRC-interacting factor 1) [12].

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].

References