NNAT

Official Full Name

neuronatin

Organism

Homo sapiens

Gene ID

4826

Background

The protein encoded by this gene is a proteolipid that may be involved in the regulation of ion channels during brain development. The encoded protein may also play a role in forming and maintaining the structure of the nervous system. This gene is found within an intron of another gene, bladder cancer associated protein, but on the opposite strand. This gene is imprinted and is expressed only from the paternal allele. [provided by RefSeq, Apr 2016]

Synonyms

Peg5

Cat.No.	Product Name	Price
CSC-DC010473	Panoply™ Human NNAT Knockdown Stable Cell Line	Inquiry
CSC-SC010473	Panoply™ Human NNAT Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD10869Z	Human NNAT adenoviral particles	Inquiry
LV19676L	human NNAT (NM_005386) lentivirus particles	Inquiry
LV19677L	human NNAT (NM_181689) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH353344	shRNA set against Human NNAT (NM_181689.1)	Inquiry
SHH353348	shRNA set against Mouse NNAT (NM_180960.2)	Inquiry
SHH353352	shRNA set against Rat NNAT (NM_053601.2)	Inquiry
SHR014528	shRNA set against Mouse Nnat(NM_010923.2)	Inquiry
SHR014546	shRNA set against Human NNAT(NM_181689.1)	Inquiry
SHR014718	shRNA set against Mouse Nnat(NM_180960.2)	Inquiry
SHR014772	shRNA set against Human NNAT(NM_005386.2)	Inquiry

Cat.No.	Product Name	Price
CDFG011940	Human NNAT cDNA Clone(NM_181689.1)	Inquiry
CDFH012628	Human NNAT cDNA Clone(NM_005386.2)	Inquiry
MiUTR1H-06824	NNAT miRNA 3'UTR clone	Inquiry
MiUTR1H-06825	NNAT miRNA 3'UTR clone	Inquiry
MiUTR1M-07718	NNAT miRNA 3'UTR clone	Inquiry
MiUTR1M-07719	NNAT miRNA 3'UTR clone	Inquiry
CDCB156230	Cynomolgus NNAT ORF clone (XM_005568966.1)	Inquiry
CDCB193084	Rabbit NNAT ORF clone (XM_008256010.1)	Inquiry
CDCR249853	Mouse Nnat ORF Clone(NM_010923.2)	Inquiry
CDCR275427	Mouse Nnat ORF Clone(NM_180960.2)	Inquiry
CDCR290377	Human NNAT ORF Clone(NM_005386.2)	Inquiry
CDCR324024	Human NNAT ORF Clone(NM_181689.1)	Inquiry
CDCR380410	Rat Nnat ORF Clone(NM_053601.2)	Inquiry
CDCR382045	Rat Nnat ORF Clone(NM_181687.2)	Inquiry
CDCS412231	Human NNAT ORF Clone (BC001768)	Inquiry

Detailed Information

Nnat is a brain-specific, highly conserved new gene related to mammalian development. Neuronation (Nnat) is a brain-specific imprinted gene originally cloned from brain in 1996. The human Nnat gene is 3973 bp in length and contains 3 exons and 2 introns. Nnat mRNA has two splicing forms: α and β, both of which have open reading frames in uniform phase, encoding 81 and 54 amino acids, respectively. The difference is that the second exon of β form is cut off.

NNAT Figure 1. Schematic representation of the relationship between neuronatin (Nnat) and glucose-induced endoplasmic reticulum (ER) stress in pancreatic b-cells. (Asahara, S. I, et al. 2018)

Nnat Expression

Using Northern blot analysis, it was found that Nnat was selectively expressed in the brain of newborn rats, but not expressed in three tissues such as heart, kidney, and liver. It first appeared in the middle stage of the embryo, at which time the neural tube was closed and neuroepithelial cells began to proliferate. At the peak of neural development at 16 to 19 days, Nnat mRNA expression was significantly enhanced. As the development of the nervous system is completed, its expression declines to the expression level of the adult brain. The transmembrane protein encoded by Nnat may act as a protein ligand, helper, smaller cell adhesion molecule, etc., and participate in the signal of the maturation of the nervous system, development or differentiation of the hindbrain and anterior pituitary.

Subtractive hybridization also confirmed that mouse Nnat expression was down-regulated in P19 embryonic cancer cells, and transiently expressed in rhizomes 3 and 5 of the early hindbrain development and the bottom of the foregut pocket. In the later stage of embryogenesis, the Nnat gene is strongly expressed in the central and peripheral nervous systems. These results indicate that Nnat is involved in the maturation or maintenance of segment identity and nervous system structure during the development of the hindbrain and pituitary. Studies have found that nerve growth factor (NGF) can cause PC12 cell proliferation to stop and transform into a neuronal phenotype, while Nnat mRNA expression is down-regulated. After NGF was removed, Nnat mRNA expression returned to background levels. The role of NGF does not depend on protein and RNA synthesis. Of the two splice forms, only the alpha form is expressed in PC12 cells. In addition, in thyrotropic tumor treated with thyroid hormone, up-regulation of Nnat mRNA expression was also observed.

NNAT and Disease

The expression of two splicing forms of Nnat α and β was detected in three of the four lipoma samples. The gene expression was also detected in tumor cell lines, but not in cultured fibroblasts and adipose tissue. The presence of transcription of Nnat in tumor studies suggests the neural origin of these tumor cells. Similarly, strong expression of Nnat was observed in several patients with pituitary adenomas. However, Nnat mRNA expression was up-regulated in thyroid-stimulating tumors treated with thyroid hormones. Subtractive hybridization analysis demonstrated that Nnat mRNA was present in cell lines expressing thyroid-stimulating hormone, but not in progenitor cell lines expressing alpha subunits. The result may be a calcium-dependent thyroid-stimulating signal transduction pathway.

Studies have shown that the unmethylated Nnat allele is completely missing in the region where the human Nnat gene is located, in leukemia cell lines, and in 20 samples (29 total) of acute myeloid lymphoid leukemia. Through methylation analysis, it was found that Nnat mRNA showed normal methylation in normal hematopoietic progenitor cells and leukemia cells, but gene expression could not be detected in hypermethylated leukemia cells. After demethylation of hypermethylated leukemia cells by treatment with 5'-aza-2'-edoxy cytidine, with the recovery of the normal methylation pattern of the gene, the expression of Nnat was again activated. These results indicate that hypermethylation of the Nnat locus is a common event in children with acute myeloid and lymphoid leukemia. The abnormal methylation of the Nnat locus is the result of 20q11.2 to q12 gene regulation disorders in leukemias.

References:

Asahara, S. I. . (2018). Neuronatin and glucose-induced stress in pancreatic β cells. Journal of Diabetes Investigation.
Shi, Y. , Stornetta, R. L. , Stornetta, D. S. , Onengut-Gumuscu, S. , Farber, E. A. , & Turner, S. D. , et al. (2017). Neuromedin b expression defines the mouse retrotrapezoid nucleus. The Journal of Neuroscience, 2055-17.
Pitale, P. M. , Howse, W. , & Gorbatyuk, M. . (2016). Neuronatin protein in health and disease. Journal of Cellular Physiology.

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