OSGIN1 (oxidative stress induced growth inhibitor 1)

Note	Human OSGIN1 is located on chromosome 16 in the region of q23.3.
	OSGIN1 genomic organization and transcript. The schematic representation of human OSGIN1 gene and its transcript. ATG: translation start codon; TAA: translation stop codon; UTR: untranslated region; ORF: open reading frame (according to Ref-seq).
Description	Human OSGIN1 gene is 13111 bp in length, composed of 6 exons and 5 introns, and located at chromosome 16q23.3.
Transcription	OSGIN1 transcript contains 6 exons. ORF is 1434 bp, which expands from exon 2 to exon 6. And exon 6 also contributes to 371 bp 3'UTR.

Note	Human OSGIN1/BDGI has a dominant isoform containing 477 amino acids with calculated 52 kDa molecular weight (derived from transcript variants HuOKL38-1a/2a). Besides, there are a 61 kDa longer isoform of OSGIN1 with 560 amino acids (transcribed from variant HuOKL38-2b), a 59 kDa longer isoform of OSGIN1 with 560 amino acids (transcribed from variant HuOKL38-2c), and a 34 kDa shorter isoform with 317 amino acids, which was the first one to identify in 2001 and might be generated by internal transcription start codon within ORF or cleaved from longer isoforms.
	The predicted OSGIN1 structure contains a potential flavoprotein involved in K+ transport domain (TrkA) (201 aa), a potential NAD(P)-binding Rossmann-like domain (NAD_binding_8) (134 aa), a potential pyridine nucleotide-disulphide oxidoreductase domain (Pyr_redox_2) (201 aa) and a potential putative bacillithiol system oxidoreductase, YpdA family domain (Bthiol_YpdA) (295 aa).
Description	OSGIN1, described as a pregnancy-induced growth inhibitor, belongs to OKL38 protein family.
Expression	OSGIN1 gene was identified in rat mammary secretory epithelial cells, which was up-regulated significantly in mammary gland during pregnancy and lactation. In various human normal tissues, OSGIN1 transcripts are observed with basal levels, but increase remarkably in liver, followed by kidney, ovary, testis, and spleen especially. On the contrary, OSGIN1 show low or undetectable mRNA expression in liver, kidney, ovary tumor tissues compared to their paired normal counterparts. Similarly, it is rarely expressed in many cancer cell lines, including HepG2, SL, NIH, U2OS, MCF-7.
Localisation	Nucleus and mitochondria.
Function	OSGIN1 was first discovered in 2001 as a pregnancy-induced growth inhibitor. It is highly expressed in ovary, kidney and liver. Stable expression of OSGIN1 is characterized by relatively low proliferative rate and extensive differentiation. Conversely, loss of OKL38 activity leads to a disruption in the balance between cell growth, cell proliferation and cell death, and is associated with rapid tumor growth. OSGIN1 is inducible by distinct stress signals in multiple cell types. Oxidative stress induced by oxidized phospholipids (OxPAPC and its component lipid PEIPC) mediates expression of OSGIN1 regulated via Nox/Nrf2 pathway. After DNA damage treatment in cancer cells such as MCF-7 and U2OS, OSGIN1 is also up-regulated by p53, and then triggers apoptosis by changing mitochondrial morphology, elevating ROS levels and inducing cytochrome c release. Thus, OKL38 likely plays a critical role in multiple tissues to guard against tumorigenesis.
Homology	An alignment of the amino acid sequences in ClustalW showed that OSGIN1 and OSGIN2, another member of OKL38 family, share 49% sequence identity, especially in C-terminal region of the two proteins. However, the biological function of OSGIN2 remains unclear so far, which may be implicated in Nijmegen breakage syndrome and gastric cancer.

Somatic	Based on analysis of tumor and adjacent noncancerous tissues from total 400 patients of hepatocellular carcinoma (HCC), a single-nucleotide variation from G to A at nt 1494 of OSGIN1 was identified, resulting in an amino acid substitution R438H at codon region. Although OSGIN1 1494A variant appears in both tumor and noncancerous tissues, it shows higher occurrence in the tumor tissues than the common variant 1494G. And the allele-specific imbalance of OSGIN1 at nt1494 is highly possible due to its localization at chromosome 16q23.3, which is prone to loss of heterozygosity in a variety of cancers. Functional studies revealed that OSGIN1 1494A variant may have defects in translocation to mitochondria and apoptosis.

Search in all EBI   NCBI

For comments and suggestions or contributions, please contact us