Zinc finger protein 804A

Last updated
ZNF804A
Identifiers
Aliases ZNF804A , C2orf10, zinc finger protein 804A
External IDs OMIM: 612282 MGI: 2442949 HomoloGene: 18461 GeneCards: ZNF804A
Orthologs
SpeciesHumanMouse
Entrez

91752

241514

Ensembl

ENSG00000170396

ENSMUSG00000070866

UniProt

Q7Z570

A2AKY4

RefSeq (mRNA)

NM_194250

NM_175513

RefSeq (protein)

NP_919226

NP_780722

Location (UCSC) Chr 2: 184.6 – 184.94 Mb Chr 2: 81.88 – 82.09 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Zinc finger protein 804A is a protein that in humans is encoded by the ZNF804A gene. [5] The human gene maps to chromosome 2 q32.1 and consists of 4 exons that code for a protein of 1210 amino acids (137 kDa). [6]

Contents

Little is known about the characteristics and function of the encoded protein. However, the protein sequence codes for a domain characteristic of a classical C2H2-type zinc finger near the N-terminal end. [6] [7]

Interactions

ZNF804A binds to the N-terminus of ATXN1. [8]

Binding of DNA

The tertiary structure of the C2H2 finger consists of a beta hairpin folded against an alpha helix. The folding occurs via a zinc(II) ion that coordinates to two cysteine residues (one on each beta sheet) and two histidine residues (both on the α-helix). [9] ZNF804A might use its zinc finger to bind DNA in a sequence-specific manner. For example, Carl Pabo and his colleagues in 1991 discovered that mouse transcription factor Zif268 binds DNA using three linked C2H2 zinc fingers. Amino acid residues sticking out from the α-helices of the zinc fingers interact with the guanine-rich region of the DNA double helix through hydrogen bonds and electrostatic and hydrophobic interactions. The spacing of the residues matches the spacing of the base pairs. Zinc fingers fit into the major groove and wrap around the DNA helix for almost one turn. [9]

Association with schizophrenia

In humans, ZNF804A is expressed broadly throughout the brain, especially in the developing hippocampus and the cortex, as well as in the adult cerebellum. [10] ZNF804A is expected to bind DNA and thus regulate gene expression like other zinc finger proteins. [6] The mouse homologue of ZNF804A, zfp804a, has recently been reported as a target for HOXC8, suggesting that ZNF804A may be involved in the regulation of early neurodevelopment. [7]

A Genome-wide association study (GWAS) has identified ZNF804A as a susceptibility gene for schizophrenia. [11] From family, twin, and adoption studies, schizophrenia is found to have heritability of ~80% [7] and it is suspected that risk results from multiple genetic variants of small effect. The single-nucleotide polymorphism (SNP) rs1344706 in intron 2 of ZNF804A has been identified as a variant that is most strongly associated with schizophrenia. [11]

The same SNP has been reported to correlate with slightly disturbed functional coupling of several brain regions in healthy persons, resembling the changes described in schizophrenia. [12] [13] [14] A further study revealed that the SNP rs1344706 was consistent with schizophrenia association in European patients, but not in Han Chinese patients. Moreover, the study showed that SNPs rs1021042 and rs359895 are associated with schizophrenia in Han Chinese patients, and that the rs359895 allele increases the promoter activity of ZNF804A. [7] The results of another study suggest that there is no relationship between variant rs1344706 and impaired cognitive function in schizophrenia patients [6] and the results of yet another study indicate that ZNF804A also plays a role in how schizophrenia symptoms respond to antipsychotics. [15]

Related Research Articles

<span class="mw-page-title-main">Zinc finger</span> Small structural protein motif found mostly in transcriptional proteins

A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. It was originally coined to describe the finger-like appearance of a hypothesized structure from the African clawed frog (Xenopus laevis) transcription factor IIIA. However, it has been found to encompass a wide variety of differing protein structures in eukaryotic cells. Xenopus laevis TFIIIA was originally demonstrated to contain zinc and require the metal for function in 1983, the first such reported zinc requirement for a gene regulatory protein followed soon thereafter by the Krüppel factor in Drosophila. It often appears as a metal-binding domain in multi-domain proteins.

<span class="mw-page-title-main">EGR1</span> Protein-coding gene in the species Homo sapiens

EGR-1 also known as ZNF268 or NGFI-A is a protein that in humans is encoded by the EGR1 gene.

<span class="mw-page-title-main">Chromosome 8</span> Human chromosome

Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 146 million base pairs and represents between 4.5 and 5.0% of the total DNA in cells.

<span class="mw-page-title-main">ZNF638</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ZNF74</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 74 is a protein that in humans is encoded by the ZNF74 gene. Schizophrenia susceptibility has been associated with a mutation in this protein.

<span class="mw-page-title-main">ZNF202</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 202 is a transcription factor first associated with breast cancer. It is a protein that, in humans, is encoded by the ZNF202 gene.

<span class="mw-page-title-main">ZNF655</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 655 is a protein that in humans is encoded by the ZNF655 gene.

<span class="mw-page-title-main">ZNF238</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 238 is a zinc finger containing transcription factor that in humans is encoded by the ZNF238 gene.

<span class="mw-page-title-main">ZNF384</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 384 is a protein that in humans is encoded by the ZNF384 gene.

<span class="mw-page-title-main">ZNF423</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 423 is a protein that in humans is encoded by the ZNF423 gene.

<span class="mw-page-title-main">SUHW4</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 280D, also known as Suppressor Of Hairy Wing Homolog 4, SUWH4, Zinc Finger Protein 634, ZNF634, or KIAA1584, is a protein that in humans is encoded by the ZNF280D gene located on chromosome 15q21.3.

<span class="mw-page-title-main">Neuregulin 3</span> Protein-coding gene in Homo sapiens

Neuregulin 3, also known as NRG3, is a neural-enriched member of the neuregulin protein family which in humans is encoded by the NRG3 gene. The NRGs are a group of signaling proteins part of the superfamily of epidermal growth factor, EGF like polypeptide growth factor. These groups of proteins possess an 'EGF-like domain' that consists of six cysteine residues and three disulfide bridges predicted by the consensus sequence of the cysteine residues.

<span class="mw-page-title-main">ZFP57</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein 57 homolog (ZFP57), also known as zinc finger protein 698 (ZNF698), is a protein that in humans is encoded by the ZFP57 gene.

<span class="mw-page-title-main">ZNF184</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">GATA zinc finger</span>

In molecular biology, GATA zinc fingers are zinc-containing domains found in a number of transcription factors. Some members of this class of zinc fingers specifically bind the DNA sequence (A/T)GATA(A/G) in the regulatory regions of genes., giving rise to the name of the domain. In these domains, a single zinc ion is coordinated by 4 cysteine residues. NMR studies have shown the core of the Znf to comprise 2 irregular anti-parallel beta-sheets and an alpha-helix, followed by a long loop to the C-terminal end of the finger. The N-terminal part, which includes the helix, is similar in structure, but not sequence, to the N-terminal zinc module of the glucocorticoid receptor DNA-binding domain. The helix and the loop connecting the 2 beta-sheets interact with the major groove of the DNA, while the C-terminal tail wraps around into the minor groove. Interactions between the Znf and DNA are mainly hydrophobic, explaining the preponderance of thymines in the binding site; a large number of interactions with the phosphate backbone have also been observed. Two GATA zinc fingers are found in GATA-family transcription factors. However, there are several proteins that only contain a single copy of the domain. It is also worth noting that many GATA-type Znfs have not been experimentally demonstrated to be DNA-binding domains. Furthermore, several GATA-type Znfs have been demonstrated to act as protein-recognition domains. For example, the N-terminal Znf of GATA1 binds specifically to a zinc finger from the transcriptional coregulator FOG1 (ZFPM1).

<span class="mw-page-title-main">FEZF1</span> Protein-coding gene in the species Homo sapiens

FEZ family zinc finger 1 is a protein that in humans is encoded by the FEZF1 gene.

<span class="mw-page-title-main">Zinc finger protein 226</span> Protein found in humans

Zinc finger protein 226 is a protein that in humans is encoded by the ZNF226 gene.

<span class="mw-page-title-main">ZNF821</span> Zinc Finger 821

Zinc Finger Protein 821, also known as ZNF821, is a protein encoded by the ZNF821 gene. This gene is located on the 16th chromosome and is expressed highly in the testes, moderately expressed in the brain and low expression in 23 other tissues. The protein encoded is 412 amino acids long with 2 Zinc Finger motifs and a 23 amino acid long STPR domain.

<span class="mw-page-title-main">C2orf80</span> Gene

C2orf80 is a protein that in humans is encoded by the c2orf80 gene. The gene c2orf80 also goes by the alias GONDA1. In humans, c2orf80 is exclusively expressed in the brain. While relatively little is known about the function of c2orf80, medical studies have shown a strong association between variations in c2orf80 and IDH-mutant gliomas, 46,XY gonadal dysgenesis, and a possible association with blood pressure.

<span class="mw-page-title-main">ZNF548</span> Protein-coding gene in the species Homo sapiens

Zinc Finger Protein 548 (ZNF548) is a human protein encoded by the ZNF548 gene which is located on chromosome 19. It is found in the nucleus and is hypothesized to play a role in the regulation of transcription by RNA Polymerase II. It belongs to the Krüppel C2H2-type zinc-finger protein family as it contains many zinc-finger repeats.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170396 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070866 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: Zinc finger protein 804A".
  6. 1 2 3 4 Walters JT, Corvin A, Owen MJ, Williams H, Dragovic M, Quinn EM, Judge R, Smith DJ, Norton N, Giegling I, et al. (July 2010). "Psychosis susceptibility gene ZNF804A and cognitive performance in schizophrenia". Arch. Gen. Psychiatry. 67 (7): 692–700. doi: 10.1001/archgenpsychiatry.2010.81 . PMID   20603450.
  7. 1 2 3 4 Li M, Luo XJ, Xiao X, Shi L, Liu XY, Yin LD, Diao HB, Su B (December 2011). "Allelic differences between Han Chinese and Europeans for functional variants in ZNF804A and their association with schizophrenia". Am J Psychiatry. 168 (12): 1318–25. doi:10.1176/appi.ajp.2011.11030381. PMID   21890790.
  8. ↑ Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi: 10.1016/j.cell.2006.03.032 . PMID   16713569. S2CID   13709685.
  9. 1 2 Isalan M (2004). "Zinc fingers". In Lennarz WJ, Lane MD, Modrich P, Dixon J, Carafoli E, Exton J, Cleveland D (eds.). Encyclopedia of Biological Chemistry. Amsterdam: Elsevier. pp. 435–439. doi:10.1016/B0-12-443710-9/00713-4. ISBN   0-12-443710-9.
  10. ↑ Lencz T, Szeszko PR, DeRosse P, Burdick KE, Bromet EJ, Bilder RM, Malhotra AK (July 2010). "A Schizophrenia Risk Gene, ZNF804A, Influences Neuroanatomical and Neurocognitive Phenotypes". Neuropsychopharmacology. 35 (11): 2284–2291. doi:10.1038/npp.2010.102. PMC   2939918 . PMID   20664580.
  11. 1 2 O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, et al. (September 2008). "Identification of loci associated with schizophrenia by genome-wide association and follow-up". Nat. Genet. 40 (9): 1053–5. doi:10.1038/ng.201. PMID   18677311. S2CID   205345009.
  12. ↑ Esslinger C, Walter H, Kirsch P, Erk S, Schnell K, Arnold C, Haddad L, Mier D, Opitz von Boberfeld C, Raab K, Witt SH, Rietschel M, Cichon S, Meyer-Lindenberg A (May 2009). "Neural mechanisms of a genome-wide supported psychosis variant". Science. 324 (5927): 605. Bibcode:2009Sci...324..605E. doi:10.1126/science.1167768. PMID   19407193. S2CID   206517207.
  13. ↑ "Schizophrenia-associated Variant in ZNF804A Gene Affects Brain Connectivity". Schizophrenia Research Forum. Archived from the original on 2012-02-15. Retrieved 2009-05-06.
  14. ↑ Hill MJ, Jeffries AR, Dobson RJ, Price J, Bray NJ (March 2012). "Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion". Hum. Mol. Genet. 21 (5): 1018–24. doi: 10.1093/hmg/ddr532 . PMID   22080834.
  15. ↑ Mössner R, Schuhmacher A, Wagner M, Lennertz L, Steinbrecher A, Quednow BB, Rujescu D, Rietschel M, Maier W (April 2012). "The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms" (PDF). Eur Arch Psychiatry Clin Neurosci. 262 (3): 193–7. doi:10.1007/s00406-011-0235-1. PMID   21892778. S2CID   5635120.
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