ZNF184 explained

Zinc finger protein 184, also known as ZNF184, is a protein that in humans is encoded by the ZNF184 gene^[1] on chromosome 6. It was first identified by Goldwurm et al. in 1996.^[2]

The National Center for Biotechnology Information (NCBI) Gene database entry for ZNF184 identifies conserved domains KRAB_A (Krüppel associated box) near the N-terminus and Zn-finger (Zinc finger) at the C-terminus of the translated protein. The former is associated with transcription repression^[3] and the latter with DNA binding (see Zinc finger).

Domains and Structure

The figure below is a reformatted and annotated conceptual translation display of ZNF184s Consensus CDS.^[4] CCDS displays exons in alternating black and blue font, with red indicating a residue coded across a splice boundary.

ZNF184 has 19 zinc finger motifs at the end of its final and longest exon. The figure shows regularity among the fingers in this protein, including the 2 columns of green-highlighted Cysteine residues and the 2 columns of blue-highlighted His residues which are the reason this type of zinc finger is called C2H2. Light grey highlighted columns (one with all F; one with mostly L, and F substitutions) are highly conserved hydrophobic residues within the zinc finger motif. The other light grey highlighted column (mostly K, with a similar R substitution) is an example of fairly strong conservation in the coil sections connecting adjacent fingers.

Near the N-terminus is a KRAB_A domain followed by a KRAB_B domain. KRAB_A has a shorter α-Helix followed by a longer α-Helix. The KRAB_A motif in a zinc finger protein is known to bind with a KAP-1 protein (aka TRIM28) to accomplish a transcription repressor function, however a gene so regulated by ZNF184 has yet to be identified. The length-11 finger helices are indicated, as well as the overlapping 7-residue section in each finger which binds targeted DNA (if the finger is functioning).

Further reading

• Book: Zinc Finger Proteins: From Atomic Contact to Cellular Function . Molecular Biology Intelligence Unit . Shiro . Iuchi . Natalie . Kuldell . Landes Bioscience/Eurekah.com and Kluwer Academic/Plenum Publishers . 2005 . 978-0-306-48229-8 .
• Shi J, Levinson DF, Duan J, etal . Common variants on chromosome 6p22.1 are associated with schizophrenia. . Nature . 460 . 7256 . 753–7 . 2009 . 19571809 . 10.1038/nature08192 . 2775422. 2009Natur.460..753S .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1996 . 8889548 . 10.1101/gr.6.9.791. free .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129.
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Ravasi T, Suzuki H, Cannistraci CV, etal . An atlas of combinatorial transcriptional regulation in mouse and man. . Cell . 140 . 5 . 744–52 . 2010 . 20211142 . 10.1016/j.cell.2010.01.044 . 2836267.
• Barbe L, Lundberg E, Oksvold P, etal . Toward a confocal subcellular atlas of the human proteome. . Mol. Cell. Proteomics . 7 . 3 . 499–508 . 2008 . 18029348 . 10.1074/mcp.M700325-MCP200 . free .

Notes and References

1. Web site: Entrez Gene: zinc finger protein 184 .
2. Goldwurm S, Menzies ML, Banyer JL, Powell LW, Jazwinska EC . Identification of a novel Krueppel-related zinc finger gene (ZNF184) mapping to 6p21.3. . Genomics . 40 . 3 . 486–9 . 1997-03-15 . 9073517 . 10.1006/geno.1996.4583 .
3. Peng H, Begg GE, Harper SL, Friedman JR, Speicher DW, Rauscher III FJ . Biochemical Analysis of the Kruppel-associated Box (KRAB) Transcriptional Repression Domain . Journal of Biological Chemistry . 275 . 24 . 18000–10 . 2000-03-30 . 10748030 . 10.1074/jbc.M001499200 . free .
4. Web site: Consensus CDS: zinc finger protein 184 .