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HGNC Approved Gene Symbol: CMIP
Cytogenetic location: 16q23.2-q23.3 Genomic coordinates (GRCh38): 16:81,444,808-81,711,762 (from NCBI)
By screening for genes with the potential to encode large proteins expressed in brain, Nagase et al. (2000) cloned KIAA1694. The predicted protein contains 757 amino acids. RT-PCR ELISA detected ubiquitous expression of KIAA1694, with highest levels in brain, followed by ovary and kidney. Expression was high in all brain regions examined, with highest levels in subthalamic nucleus and amygdala.
Minimal change nephrotic syndrome (MCNS), also known as lipoid nephrosis, is the most frequent glomerular disease in children and likely results from abnormal T-cell activation. By subtractive cloning and differential screening using a cDNA library derived from MCNS patient T lymphocytes, Grimbert et al. (2003) isolated a splice variant of CMIP that encodes a truncated protein, which they called TCMIP. The predicted CMIP and TCMIP proteins contain 739 and 679 amino acids and have calculated molecular masses of 85 and 75 kD, respectively. Both have an N-terminal pleckstrin homology (PH) domain, numerous phosphorylation sites, and a C-terminal leucine-rich region. TCMIP, which uses an alternative exon 1, lacks 29 residues in the PH domain and 3 putative phosphorylation sites compared with CMIP. Northern blot analysis detected a 4.25-kb CMIP transcript that was highly expressed in peripheral blood mononuclear cells (PBMCs), kidney, and fetal liver, with lower levels in adult brain and liver. Northern blot analysis using a TCMIP-specific probe showed expression in thymus and fetal liver only. RT-PCR analysis of PBMC subsets revealed CMIP expression in resting monocytes, CD4 (186940)- and CD8 (see 186910)-positive T cells, and B cells, whereas TCMIP was expressed at low levels in T cells only. Confocal microscopy showed that CMIP was expressed in peripheral areas of transfected Jurkat T cells, whereas TCMIP was diffusely expressed, particularly in nuclear compartment.
Using RT-PCR analysis, Grimbert et al. (2003) showed that expression of CMIP and TCMIP was downregulated by activation in PBMCs from healthy subjects. However, TCMIP expression was not downregulated by activation in PBMCs from MCNS relapse patients. RT-PCR and Western blot analyses showed that TCMIP mRNA and protein expression was preferentially induced in Th2-polarized cells. Immunofluorescence microscopy demonstrated expression of TCMIP in nuclear and cytoplasmic compartments during MCNS relapse, whereas it was expressed in cytoplasm only during MCNS remission and not at all in normal patients. Transfection of TCMIP into Jurkat T cells induced nuclear expression of MAF (177075). Grimbert et al. (2003) concluded that truncation of the PH domain of CMIP allows for nuclear translocation of TCMIP, which is specifically recruited during MCNS.
Using a yeast 2-hybrid screen, Grimbert et al. (2004) identified filamin-A (FLNA; 300017) as a binding partner for both CMIP and TCMIP. Coimmunoprecipitation analysis confirmed the interactions. Immunofluorescence microscopy demonstrated homogeneous colocalization of CMIP and FLNA in the cytoplasm, but restriction of TCMIP/FLNA colocalization to points of intercellular contact. Western blot analysis showed increased FLNA expression in MCNS relapse patients. Grimbert et al. (2004) proposed that FLNA and CMIP/TCMIP interact in a T-cell signaling pathway.
Grimbert et al. (2003) determined that the CMIP gene contains 21 exons and spans 268 kb.
Using radiation hybrid analysis, Nagase et al. (2000) mapped the KIAA1694 gene to chromosome 16. By genomic sequence analysis, Grimbert et al. (2003) mapped the CMIP gene to chromosome 16q24.
For a discussion of a possible association between variation in the CMIP gene and nonword repetition ability in specific language impairment, see SLI1 (606711).
Grimbert, P., Valanciute, A., Audard, V., Lang, P., Guellaen, G., Sahali, D. The filamin-A is a partner of Tc-mip, a new adapter protein involved in c-maf-dependent Th2 signaling pathway. Molec. Immun. 40: 1257-1261, 2004. [PubMed: 15128042] [Full Text: https://doi.org/10.1016/j.molimm.2003.11.035]
Grimbert, P., Valanciute, A., Audard, V., Pawlak, A., Le gouvelo, S., Lang, P., Niaudet, P., Bensman, A., Guellaen, G., Sahali, D. Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization. J. Exp. Med. 198: 797-807, 2003. [PubMed: 12939343] [Full Text: https://doi.org/10.1084/jem.20030566]
Nagase, T., Kikuno, R., Hattori, A., Kondo, Y., Okumura, K., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 347-355, 2000. [PubMed: 11214970] [Full Text: https://doi.org/10.1093/dnares/7.6.347]