CIR (also known as CIR1; officially designated CIRSR by HGNC) is a protein-coding gene located on human chromosome 2q31.1. It encodes the corepressor interacting with RBPJ 1 protein, also referred to as the corepressor of RBPJ and splicing regulator.
Official Nomenclature
The gene's official symbol is now CIRSR (corepressor of RBPJ and splicing regulator), as assigned by the HUGO Gene Nomenclature Committee (HGNC:24217). It was previously known as CIR and CIR1. The NCBI Gene ID is 9541.
Function
The CIR/CIR1/CIRSR gene encodes a protein that functions as a transcriptional corepressor. It links the DNA-binding factor CBF1 (also known as RBPJ) to the histone deacetylase (HDAC) complex, thereby mediating transcriptional repression. Key molecular functions include:
- Histone deacetylase binding activity
- Protein kinase binding activity
- Transcription corepressor activity
The protein acts upstream of or within the negative regulation of transcription by RNA polymerase II.
Cellular Localization
The CIR protein is located in the centrosome and nuclear speckles, and is part of a protein-containing complex.
Expression
CIR is ubiquitously expressed across human tissues, with notable expression in bone marrow (RPKM 20.7), testis (RPKM 18.7), and 25 other tissues.
Interactions
CIR has been shown to interact with SNW1 (SKI-interacting protein), as well as with PAP-1, and it has been implicated in alternative splicing regulation. It also interacts with the Epstein-Barr virus RPMS protein, which negatively regulates the activity of EBNA2 and NotchIC.
Model Organism Studies
A conditional knockout mouse line (Cir1tm3a(KOMP)Wtsi) has been generated. Phenotypic screening of these mice showed abnormal homozygous viability at P14 (postnatal day 14) and an abnormal recessive lethal phenotype, indicating that the gene is essential for normal development. Other assessed parameters (body weight, neurological function, grip strength, immune function, etc.) were normal.
References
- Hsieh JJ, Zhou S, Chen L, Young DB, Hayward SD (Jan 1999). "CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex". Proceedings of the National Academy of Sciences. 96 (1): 23–28. doi:10.1073/pnas.96.1.23
- Maita H, Kitaura H, Ariga H, Iguchi-Ariga SM (Feb 2005). "CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing". Experimental Cell Research. 303 (2): 375–387. doi:10.1016/j.yexcr.2004.10.012
- NCBI Gene entry for CIRSR (Gene ID: 9541)
- Wikipedia: CIR1
