ZC3H11B

ZC3H11B also known as zinc finger CCCH-type containing protein 11B is a protein in humans that is encoded by the ZC3H11B gene.[3] The zc3h11b gene is located on chromosome 1, on the long arm, in band 4 section 1. This protein is also known as ZC3HDC11B. The zc3h11b gene is a total of 5,134 base pairs long, and the protein is 805 amino acids in length. The zc3h11b gene has 2 exons in total.

ZC3H11B
Identifiers
Aliases	ZC3H11B, ZC3HDC11B, zinc finger CCCH-type containing 11B pseudogene, zinc finger CCCH-type containing 11B
External IDs	GeneCards: ZC3H11B
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q41 Start 219,608,010 bp[1] End 219,613,145 bp[1]
Orthologs
Species	Human	Mouse
Entrez	643136	n/a
Ensembl	ENSG00000215817	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	NM_001085394 NM_001355457	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	Chr 1: 219.61 – 219.61 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

Function

The ZC3H11B protein is expressed in various tissues including those of the testis, heart, leg, and adrenal.[4] ZC3H11B is predicted to be involved in metal ion binding, a mechanism that involves combination of a metal ion or chelation, as inferred from Electronic Association.[3]

Structure

Domains

The ZC3H11B protein has three conserved domains. These include zinc finger domains, which are one of the most common or abundant protein groups often involved in regulation of cellular processes,[5] and coiled coil domains, which are a structurally conserved protein group present in all domains of life often involved in molecular spacing, vesicle tethering, and DNA recognition and cleavage.[6] Both the zinc finger and coiled coil domains are conserved in eukaryotes.

Zinc finger C3H1-type 1 is located from amino acids 2-29, and zinc finger C3H1-type 2 is located from amino acids 31–57.[7] Zinc finger C3H1-type proteins have been identified to interact with 3' region of untranslated mRNAs.[8] Coiled coil is located from positions 403-423 amino acids of the protein.[7]

Secondary

Currently the secondary structure of ZC3H11B is unknown.

The predicted secondary structure of ZC3H11B is a loop secondary structure composition,[9] which are irregular secondary structures that connect two secondary structural elements and are able to change the direction of polypeptide chain propagation.[10] The loop is predicted to be exposed for binding.[9]

Post-translational modifications

ZC3H11B is likely found in the nucleus.[11] ZC3H11B is predicted to undergo various phosphorylations, O-GlcNAcylations, glycations, and O-glycosylations.[12]

Example of sites predicted for phosphorylation, a mechanism in which a phosphoryl group is added and important in biological regulation and other cellular processes,[13] occur on 108, 149, 196,229, 290, and 330.[12] Example of sites predicted for O-GlcNAcylations, a mechanism in which an O-linked N-acetylglucosamine (O-GlcNAc) is added and important for regulation of cellular processes,[14] are 488, 744, and 732.[12] Examples of sites predicted for glycations, a mechanism in which glucose binds with proteins and lipids, are 140, 359, 669, and 776.[12] Example of sites predicted for O-glycosylation, a mechanism in which sugars ormonosaccharides add to hydroxyl groups of proteins, occur on 179 and 386.[12]

Homology

There are several identified homologs of the zc3h11b protein in a variety of species including various mammals, insects, and amphibians.

Paralogs

Currently, there is one paralog of ZC3H11B in the same CCCH-type zinc finger family based on BLAST analysis (NCBI).

Name	Species	NCBI accession number	Length (AA)	Protein identity
ZC3H11A	H. sapiens	NP_001306167.1	810	93.29%

C12orf50 (H. sapiens) has also been predicted as a paralog of ZC3H11B.[7][4]

Orthologs

There are several species that have been found as having orthologs to the zc3h11b protein in their genome based on BLAST analysis (NCBI).

Name	Species	NCBI accession number	Length (AA)	Protein identity
ZC3H11A	P. troglodytes	XP_016791924.1	810	93.29%
ZC3H11A	M. mulatta	NP_001247891.1	810	92.67%
ZC3H11A	C. lupus	XP_022271137.1	815	84.34%
ZC3H11A	F. catus	XP_006942949.1	816	83.60%
ZC3H11A	E. caballus	NP_001295209.1	815	83.70%

ZC3H11A (B. Taurus), Zc3h11a (M. musculus), Zc3h11a (R. norvegicus), ZC3H11A (G. gallus), zc3h11a, (X. tropicalis), zc3h11a (D. rerio), AT2G02160 (A. thaliana), ZC3H11A (M. domesticia), zc3h11a (A. carolinensis), and ZC3H11A (S. scrofa) have also been predicted as orthologs of ZC3H11B.[7][4]

Clinical significance

Current research has identified ZC3H11B as single-nucleotide polymorphisms (SNPs) that are the most common genetic variation among groups with high myopia and corneal astigmatism.[15][16] As of April 2020, there have been no other published association studies linking ZC3H11B with other conditions.

Myopia

Myopia, also known as shortsightedness or nearsightedness, is a condition caused by a refractive error in which the shape of the eye is either elongated or the cornea is too curved.[17] In developed countries, this condition occurs in over 50% of the population with a high rate of occurrence among adults (80-90%) in East Asia and occurs approximately in 30% of the population in the United States.[17][18]

Myopia is categorized in two groups. The first of which comprises people with low to medium amount of myopia, or simple myopia, and is diagnosed at 0 to -6 diopters and is treated with corrective lenses. The second is classified as high myopia and is diagnosed at greater than -6 diopters and typically are found in cases of retinal detachment, macular degeneration, and glaucoma.[19]  Myopia is considered as one of the leading causes of blindness and visual impairment in the world by the World Health Organization.[20]

An elongated ocular axial length (AL), or distance from the anterior corneal surface to the retinal pigment epithelium,[21] is a determinant of the development of myopia. A genome-wide association study conducted in a population of Chinese adults and children as well as Malay adults identified that ZC3H11B is associated with AL and high myopia.[15] There were ZC3H11B mRNA expression levels in the brain, placenta, neural retina, retina pigment epithelium, and sclera with a greater decrease in quantity or down-regulated expression levels in myopic eyes than non-myopic eyes. This identification was confirmed in another genome-wide association study along with the identification of additional significant loci for AL of RSPO1 (involved in Wnt signaling or regulation of eyeball size), C3orf26, ZNRF3 (involved in Wnt signaling), and ALPPL2.[22] Thus, this identification of shared association AL genes indicates that AL and refraction may be caused by different optic pathways. Additionally, a genome-wide association study in Chinese populations confirmed that ZC3H11B is a susceptibility gene for the development of high and extreme myopia.[23]

Astigmatism

An astigmatism is a condition in which the curvature of the cornea or lens is abnormal.[24] Astigmatisms can be classified as corneal astigmatism in which the corneal shape is irregular, lenticular astigmatism in which the lens shape is irregular, or refractive astigmatism. Astigmatism is typically treated with corrective lenses or surgery (such as LASIK).[25]

Refractive and corneal astigmatism may lead to the development of amblyopia, or lazy eye, if left untreated. A genome-wide association study of individuals of European ancestry identified the ZC3H11B gene as significant for corneal astigmatism.[16] Additionally, there were two other loci were identified to demonstrate genome-wide significant association for corneal astigmatism, HERC2 and TSPAN10/NPLOC4.

References

1. GRCh38: Ensembl release 89: ENSG00000215817 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "National Center for Biotechnology Information, U.S. National Library of Medicine zinc finger CCCH-type containing 11B [ Homo sapiens (human) ]". www.ncbi.nlm.nih.gov. Retrieved 2020-04-15.
4. "Monarch Initiative Explorer". monarchinitiative.org. Retrieved 2020-04-15.
5. Cassandri M, Smirnov A, Novelli F, Pitolli C, Agostini M, Malewicz M, et al. (2017-11-13). "Zinc-finger proteins in health and disease". Cell Death Discovery. 3 (1): 17071. doi:10.1038/cddiscovery.2017.71. PMC 5683310. PMID 29152378.
6. Truebestein L, Leonard TA (September 2016). "Coiled-coils: The long and short of it". BioEssays. 38 (9): 903–16. doi:10.1002/bies.201600062. PMC 5082667. PMID 27492088.
7. "UniProtKB - A0A1B0GTU1 (ZC11B_HUMAN) =". UniProt.
8. Hall TM (June 2005). "Multiple modes of RNA recognition by zinc finger proteins". Current Opinion in Structural Biology. Sequences and topology/Nucleic acids. 15 (3): 367–73. doi:10.1016/j.sbi.2005.04.004. PMID 15963892.
9. "PredictProtein". PredictProtein.
10. Dhar J, Chakrabarti P (June 2015). "Defining the loop structures in proteins based on composite β-turn mimics". Protein Engineering, Design & Selection. 28 (6): 153–61. doi:10.1093/protein/gzv017. PMID 25870305.
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13. Nestler EJ, Greengard P (1999). "Protein Phosphorylation is of Fundamental Importance in Biological Regulation". Basic Neurochemistry: Molecular, Cellular and Medical Aspects. (6th ed.).
14. Yang X, Qian K (July 2017). "Protein O-GlcNAcylation: emerging mechanisms and functions". Nature Reviews. Molecular Cell Biology. 18 (7): 452–465. doi:10.1038/nrm.2017.22. PMC 5667541. PMID 28488703.
15. Fan Q, Barathi VA, Cheng CY, Zhou X, Meguro A, Nakata I, et al. (2012). "Genetic variants on chromosome 1q41 influence ocular axial length and high myopia". PLOS Genetics. 8 (6): e1002753. doi:10.1371/journal.pgen.1002753. PMC 3369958. PMID 22685421.
16. Shah RL, Guggenheim JA (December 2018). "Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci". Human Genetics. 137 (11–12): 881–896. doi:10.1007/s00439-018-1942-8. PMC 6267700. PMID 30306274.
17. "Myopia (Nearsightedness)". www.aoa.org. Retrieved 2020-04-15.
18. Wu PC, Huang HM, Yu HJ, Fang PC, Chen CT (2016). "Epidemiology of Myopia". Asia-Pacific Journal of Ophthalmology. 5 (6): 386–393. doi:10.1097/APO.0000000000000236. PMID 27898441.
19. Fredrick DR (May 2002). "Myopia". BMJ. 324 (7347): 1195–9. doi:10.1136/bmj.324.7347.1195. PMC 1123161. PMID 12016188.
20. Pararajasegaram R (September 1999). "VISION 2020-the right to sight: from strategies to action". American Journal of Ophthalmology. 128 (3): 359–60. doi:10.1016/s0002-9394(99)00251-2. PMID 10511033.
21. Bhardwaj V, Rajeshbhai GP (October 2013). "Axial length, anterior chamber depth-a study in different age groups and refractive errors". Journal of Clinical and Diagnostic Research. 7 (10): 2211–2. doi:10.7860/JCDR/2013/7015.3473. PMC 3843406. PMID 24298478.
22. Cheng CY, Schache M, Ikram MK, Young TL, Guggenheim JA, Vitart V, et al. (August 2013). "Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error". American Journal of Human Genetics. 93 (2): 264–77. doi:10.1016/j.ajhg.2013.06.016. PMC 3772747. PMID 24144296.
23. Tang SM, Li FF, Lu SY, Kam KW, Tam PO, Tham CC, et al. (July 2019). "SNTB1 genes with myopia of different severities". The British Journal of Ophthalmology. doi:10.1136/bjophthalmol-2019-314203. PMID 31300455.
24. "What Is Astigmatism?". American Academy of Ophthalmology. 2018-08-31. Retrieved 2020-04-15.
25. Publishing, Harvard Health. "Astigmatism". Harvard Health. Retrieved 2020-04-15.