Alternative titles; symbols
HGNC Approved Gene Symbol: IK
Cytogenetic location: 5q31.3 Genomic coordinates (GRCh38): 5:140,647,829-140,662,480 (from NCBI)
Major histocompatibility class II antigens participate in the antigen presentation process and modulate the immune response (Radka et al., 1986). Loss of HLA class II expression by certain cancers is responsible for the mechanism of escape from immunorecognition. Antigen presentation can be induced by interferon-gamma (147570) and certain cell types, such as K562 cells, secrete factors which inhibit this process. Krief et al. (1994) purified a 19-kD cytokine, designated IK factor, with such inhibitory activity. Antibodies to the IK factor were produced and used to screen an expression cDNA library of K562 cell mRNA. A cDNA was isolated that recognized a 2.1-kb mRNA in a variety of cell types, and transient transfection of COS cells produced the expected 19-kD protein.
Assier et al. (1999) determined that IK is part of a larger gene, which they termed RED, encoding a 557-amino acid protein that is 98% identical to the mouse sequence and contains an extensive stretch of arg-glu-asp (RED) repeats. Notably, the codon usage in the RED repeat is varied, suggesting the sequence is not a result of repetitive duplication. RE repeats are found in atrophin-1 (607462), and RD repeats are found in RD (154040). Northern and dot blot analyses revealed ubiquitous expression of a 2.0-kb RED transcript in human and mouse tissue. Western blot analysis showed that RED is expressed in both bacterial and mammalian cells as an 80-kD protein. Sequence analysis predicted and immunofluorescence analysis demonstrated that RED is localized to nuclear dots similar to the expression pattern of PML bodies (see SP100; 604585); however, RED does not colocalize with PML (102578) or coilin (COIL; 600272) and appears to be sequestered from the nucleoplasm.
Cao et al. (1997) used semiquantitative RT-PCR to detect IK mRNA in CD34 (142230)-positive stem cells purified from cord blood. IK expression increased with growth factor-induced cell differentiation, decreased with IK antisense treatment, and was inversely correlated with expression of HLA-DR as well as CD34. Colony-forming assays showed that IK antisense treatment reduced the size and number of colonies differentiating from CD34-positive stem cells, particularly by multilineage early erythroid and granulomonocytic progenitor cells.
By a yeast 2-hybrid screen of human spleen and fetal brain cDNA libraries using 2 influenza virus polymerase subunits as bait, Fournier et al. (2014) identified RED as the predominant interactor. RED interacted with the virus and with SMU1 (617811) in infected cells. The N-terminal domain of RED interacts with both viral polymerase subunits and with SMU1, whereas SMU1 interacts directly only with RED. Western blot and immunofluorescence microscopy demonstrated nuclear expression of both proteins. Knockdown of either RED or SMU1 indicated that the proteins stabilize each other within cells, and that lack of either RED or SMU1 impairs expression of viral NS2 mRNA, reduces the NS2/NS1 protein ratio, and reduces production of infectious influenza virions. Fournier et al. (2014) concluded that the RED and SMU1 splicing factors act jointly as key regulators of influenza virus gene expression.
By in situ hybridization, Krief et al. (1994) mapped the IK gene to chromosome 2p15-p14. However, using radiation hybrid analysis, Assier et al. (1999) determined that this localization is incorrect and mapped the RED gene to chromosome 5q22-q23. Gross (2011) mapped the IK gene to chromosome 5q31.3 based on an alignment of the IK sequence (GenBank BC013005) with the genomic sequence (GRCh37).
Assier, E., Bouzinba-Segard, H., Stolzenberg, M.-C., Stephens, R., Bardos, J., Freemont, P., Charron, D., Trowsdale, J., Rich, T. Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat. Gene 230: 145-154, 1999. [PubMed: 10216252] [Full Text: https://doi.org/10.1016/s0378-1119(99)00066-9]
Cao, L.-X., Le Bousse-Kerdiles, M.-C., Clay, D., Oshevski, S., Jasmin, C., Krief, P. Implication of a new molecule IK in CD34+ hematopoietic progenitor cell proliferation and differentiation. Blood 89: 3615-3623, 1997. [PubMed: 9160666]
Fournier, G., Chiang, C., Munier, S., Tomoiu, A., Demeret, C., Vidalain, P.-O., Jacob, Y., Naffakh, N. Recruitment of RED-SMU1 complex by influenza A virus RNA polymerase to control viral mRNA splicing. PLoS Pathog. 10: e1004164, 2014. Note: Electronic Article. Erratum: PLoS Pathog. 10: e1004317, 2014. [PubMed: 24945353] [Full Text: https://doi.org/10.1371/journal.ppat.1004164]
Gross, M. B. Personal Communication. Baltimore, Md. 4/20/2011.
Krief, P., Augery-Bourget, Y., Plaisance, S., Merck, M.-F., Assier, E., Tanchou, V., Billard, M., Boucheix, C., Jasmin, C., Azzarone, B. A new cytokine (IK) down-regulating HLA class II: monoclonal antibodies, cloning and chromosome localization. Oncogene 9: 3449-3456, 1994. [PubMed: 7970704]
Radka, S. F., Charron, D. J., Brodsky, F. M. Class II molecules of the major histocompatibility complex considered as differentiation markers. Hum. Immun. 16: 390-400, 1986. [PubMed: 2428784] [Full Text: https://doi.org/10.1016/0198-8859(86)90065-0]