Alternative titles; symbols
HGNC Approved Gene Symbol: ZNF384
Cytogenetic location: 12p13.31 Genomic coordinates (GRCh38) : 12:6,666,477-6,689,572 (from NCBI)
ZNF384 is a nucleocytoplasmic shuttling protein that localizes at fibroblast focal adhesions, contains multiple zinc fingers, and regulates expression of matrix metalloproteinases (e.g., MMP3; 185250) (Thunyakitpisal et al., 2001).
By screening adult and fetal human brain cDNA libraries for clones containing CAG repeats, Margolis et al. (1997) isolated a partial cDNA encoding ZNF384, which they called CAGH1.
By Far Western screening of a rat embryonic fibroblast cDNA library with the SH3 domain of Cas (BCAR1; 602941) as probe, Nakamoto et al. (2000) isolated several splice variants of Znf384, which they called Ciz. The longest variant encodes a predicted 579-residue protein with an N-terminal leucine zipper, multiple serine and proline residues, a nuclear localization signal, 8 centrally located Kruppel-type C2H2 zinc fingers, and C-terminal glutamine-alanine and glutamine repeat regions, suggesting that Ciz may be a transcription factor. The shorter variants encode proteins with only 5 or 6 zinc fingers. Northern blot analysis of rat tissues revealed ubiquitous expression of a 3.0-kb transcript, with highest levels in testis, heart, kidney, and brain. A 4.0-kb transcript was also detected in brain, liver, and kidney. Immunofluorescence microscopy showed that Ciz shuttled in and out of the nucleus and localized at stably formed focal adhesions and in the nucleus.
Thunyakitpisal et al. (2001) independently cloned and characterized rat Znf384, which they termed Nmp4, based on its interaction with type I collagen alpha-1 (COL1A1; 120150). They identified several novel variants, including one that lacks the C-terminal glutamine-alanine repeat region.
Using precipitation analysis, Nakamoto et al. (2000) showed that rat Ciz bound specifically and constitutively to the SH3 domain of Cas. Immunoprecipitation and EMSA analysis demonstrated that Ciz bound to the promoter of human MMP1 (120353) and upregulated transcription of human MMP1 and MMP7 (178990) and rat Mmp3.
Thunyakitpisal et al. (2001) showed that rat Nmp4 interacted with Col1a1 and regulated its expression in osteoblasts. They concluded that NMP4 contributes to extracellular matrix turnover in bone and other tissues.
Shen et al. (2002) overexpressed Ciz in a mouse osteoblast cell line and found that it inhibited Bmp2 (112261)-induced expression of alkaline phosphatase (see ALPL; 171760), osteocalcin (BGLAP; 112260), type I collagen, and Cbfa1 (RUNX2; 600211). They concluded that CIZ is an inhibitory protein that modulates BMP2-induced differentiation of osteoblastic cells.
Margolis et al. (1997) stated that the ZNF384 gene maps to chromosome 12p12. Alvarez et al. (2001) mapped the mouse Znf384 gene to chromosome 6F1, a region that shows homology of synteny to human chromosome 12p12.
Alexander et al. (2018) found that rearrangement of ZNF384 occurred in 48% of 35 cases of the B-cell/myeloid form of mixed phenotype acute leukemia.
Morinobu et al. (2005) found that Ciz -/- mice had increased bone volume and rates of bone formation, but no alteration in bone resorption. Ciz -/- mice expressed higher levels of mRNA for proteins involved in osteoblastic phenotypes, such as alkaline phosphatase and osterix (SP7; 606633). Ciz deficiency increased newly formed bone mass after femoral bone marrow ablation, and it increased Bmp2-induced bone formation in adult mouse calvaria. Morinobu et al. (2005) concluded that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.
Alexander, T. B., Gu, Z., Iacobucci, I., Dickerson, K., Choi, J. K., Xu, B., Payne-Turner, D., Yoshihara, H., Loh, M. L., Horan, J., Buldini, B., Basso, G., and 50 others. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature 562: 373-379, 2018. [PubMed: 30209392] [Full Text: https://doi.org/10.1038/s41586-018-0436-0]
Alvarez, M. B., Thunyakitpisal, P., Rhodes, S. J., Everett, E. T., Bidwell, J. P. Assignment of Nmp4 to mouse chromosome 6 band F1 flanked by D6Mit134 and D6Mit255 using radiation hybrid mapping and fluorescence in situ hybridization. Cytogenet. Cell Genet. 94: 244-245, 2001. [PubMed: 11856889] [Full Text: https://doi.org/10.1159/000048824]
Margolis, R. L., Abraham, M. R., Gatchell, S. B., Li, S.-H., Kidwai, A. S., Breschel, T. S., Stine, O. C., Callahan, C., McInnis, M. G., Ross, C. A. cDNAs with long CAG trinucleotide repeats from human brain. Hum. Genet. 100: 114-122, 1997. [PubMed: 9225980] [Full Text: https://doi.org/10.1007/s004390050476]
Morinobu, M., Nakamoto, T., Hino, K., Tsuji, K., Shen, Z.-J., Nakashima, K., Nifuji, A., Yamamoto, H., Hirai, H., Noda, M. The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation. J. Exp. Med. 201: 961-970, 2005. [PubMed: 15781586] [Full Text: https://doi.org/10.1084/jem.20041097]
Nakamoto, T., Yamagata, T., Sakai, R., Ogawa, S., Honda, H., Ueno, H., Hirano, N., Yazaki, Y., Hirai, H. CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases. Molec. Cell. Biol. 20: 1649-1658, 2000. [PubMed: 10669742] [Full Text: https://doi.org/10.1128/MCB.20.5.1649-1658.2000]
Shen, Z.-J., Nakamoto, T., Tsuji, K., Nifuji, A., Miyazono, K., Komori, T., Hirai, H., Noda, M. Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts. J. Biol. Chem. 277: 29840-29846, 2002. [PubMed: 12023967] [Full Text: https://doi.org/10.1074/jbc.M203157200]
Thunyakitpisal, P., Alvarez, M., Tokunaga, K., Onyia, J. E., Hock, J., Ohashi, N., Feister, H., Rhodes, S. J., Bidwell, J. P. Cloning and functional analysis of a family of nuclear matrix transcription factors (NP/NMP4) that regulate type I collagen expression in osteoblasts. J. Bone Miner. Res. 16: 10-23, 2001. [PubMed: 11149472] [Full Text: https://doi.org/10.1359/jbmr.2001.16.1.10]