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OSGIN1 (oxidative stress induced growth inhibitor 1)

Written2014-05Jing Hu, Yanming Wang
University of California, San Diego, USA (JH); Pennsylvania State University, USA (YW)

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)BDGI
OKL38
Other alias
HGNC (Hugo) OSGIN1
LocusID (NCBI) 29948
Atlas_Id 45760
Location 16q23.3  [Link to chromosome band 16q23]
Location_base_pair Starts at 83953222 and ends at 83966332 bp from pter ( according to hg19-Feb_2009)  [Mapping OSGIN1.png]
Fusion genes
(updated 2016)
JPH3 (16q24.2) / OSGIN1 (16q23.3)MLYCD (16q23.3) / OSGIN1 (16q23.3)OSGIN1 (16q23.3) / CDH13 (16q23.3)

DNA/RNA

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.

Protein

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.

Mutations

 
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.

Implicated in

Note
  
Entity Hepatocellular carcinoma (HCC)
Disease HCC is the most common type of liver cancer and one of the top human malignances worldwide. Generally, chronic liver injury by cirrhosis and infection of hepatitis viruses are two major causes of HCC. HCC also show higher incidence in population of Asia/Africa than North America/Western Europe, suggesting a variety of underlying genetic and environmental factors.
Prognosis OSGIN1 expression analysis between tumor and paired noncancerous tissues from 89 HCC patients with clinicopathological data indicated the patients with less OSGIN1 transcripts and higher occupancy of OSGIN1 1494A variant have more sever symptoms and shorter survival time. Thus, quantitation of OSGIN1 expression and presence of OSGIN1 1494A variant may help diagnose HCC patients at early clinical trail and their responses after chemotherapy.
Oncogenesis OSGIN1 expression is higher in immortal liver cell lines (LO2 and Miha) that that in HCC cell lines (PLC8024 and Hep3B). Loss of wild-type OSGIN1 in HCC tumors at higher stages and HCC cell lines may be due to its 5' untranslated region (5'UTR)-regulated mRNA translation suppression. And OSGIN1 1494A variant coded protein is less capable to translocate from nucleus to mitochondria and induce apoptosis compared to its wide-type protein, suggesting its impaired role as tumor suppressor.
  
  
Entity Renal cell carcinoma (RCC)
Disease Renal cell carcinoma (RCC) is the primary type of the adult kidney cancer. In contrast to HCC, RCC incidence rates are higher in North America/Western Europe region but lower in Asia/Africa region. The causes of RCC are complicated, probably due to lifestyle-related and/or hereditary factors.
Prognosis Both OKL38 transcripts and protein levels are low or undetected in majority of the kidney tumors examined compared to patient's corresponding normal adjacent tissues using cancer profiling assay, western blot assay and immunohistological analysis.
Oncogenesis Forced overexpression of OSGIN1 in human kidney cancer cell A498 inhibits cell growth and stimulates cell death.
  
  
Entity Breast cancer
Disease Breast cancer is the most common cancer and the second top cause of cancer death among women. The American Cancer Society's estimates about 232670 new cases of invasive breast cancer will be diagnosed in women in the US for 2014. Risk factors associated with breast cancer include age, geography, family history and so on. Especially, genetic risk factors with mutations in some signature genes (e.g. BRCA1 and BRCA2) have been studied well for prognosis and treatment of breast cancer. Interestingly, some particular reproductive factors like earlier age at first full-term pregnancy and higher number of pregnancies can reduce breast cancer significantly.
Oncogenesis Overexpression of OSGIN1 in MCF-7 human breast adenocarcinoma cells decreases their in vitro metastatic activity and in vivo tumor formation. The mechanistic study found that high expression of OSGIN1 may direct cell cycle arrested in S phase, and induce apoptosis further. These data suggest a potential correlation between OSGIN1 and the reduction in breast cancer risk observed in pregnancy-associated cases.
  

Bibliography

Interaction of OKL38 and p53 in regulating mitochondrial structure and function.
Hu J, Yao H, Gan F, Tokarski A, Wang Y.
PLoS One. 2012;7(8):e43362. doi: 10.1371/journal.pone.0043362. Epub 2012 Aug 17.
PMID 22912861
 
Cloning and characterization of a novel pregnancy-induced growth inhibitor in mammary gland.
Huynh H, Ng CY, Ong CK, Lim KB, Chan TW.
Endocrinology. 2001 Aug;142(8):3607-15.
PMID 11459809
 
OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids.
Li R, Chen W, Yanes R, Lee S, Berliner JA.
J Lipid Res. 2007 Mar;48(3):709-15. Epub 2006 Dec 27.
PMID 17192422
 
Allele-specific imbalance of oxidative stress-induced growth inhibitor 1 associates with progression of hepatocellular carcinoma.
Liu M, Li Y, Chen L, Chan TH, Song Y, Fu L, Zeng TT, Dai YD, Zhu YH, Li Y, Chen J, Yuan YF, Guan XY.
Gastroenterology. 2014 Apr;146(4):1084-96. doi: 10.1053/j.gastro.2013.12.041. Epub 2014 Jan 11.
PMID 24417816
 
The role of 5' untranslated region in translational suppression of OKL38 mRNA in hepatocellular carcinoma.
Ong CK, Leong C, Tan PH, Van T, Huynh H.
Oncogene. 2007 Feb 22;26(8):1155-65. Epub 2006 Aug 21.
PMID 16924236
 
Genomic structure of human OKL38 gene and its differential expression in kidney carcinogenesis.
Ong CK, Ng CY, Leong C, Ng CP, Foo KT, Tan PH, Huynh H.
J Biol Chem. 2004 Jan 2;279(1):743-54. Epub 2003 Oct 21.
PMID 14570898
 
Bone marrow stromal cell-derived growth inhibitor inhibits growth and migration of breast cancer cells via induction of cell cycle arrest and apoptosis.
Wang T, Xia D, Li N, Wang C, Chen T, Wan T, Chen G, Cao X.
J Biol Chem. 2005 Feb 11;280(6):4374-82. Epub 2004 Nov 29.
PMID 15569677
 
Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis.
Yao H, Li P, Venters BJ, Zheng S, Thompson PR, Pugh BF, Wang Y.
J Biol Chem. 2008 Jul 18;283(29):20060-8. doi: 10.1074/jbc.M802940200. Epub 2008 May 22.
PMID 18499678
 

Citation

This paper should be referenced as such :
J Hu, Y Wang
OSGIN1 (oxidative stress induced growth inhibitor 1)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(2):117-120.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/OSGIN1ID45760ch16q23.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)OSGIN1   30093
Cards
AtlasOSGIN1ID45760ch16q23
Entrez_Gene (NCBI)OSGIN1  29948  oxidative stress induced growth inhibitor 1
AliasesBDGI; OKL38
GeneCards (Weizmann)OSGIN1
Ensembl hg19 (Hinxton)ENSG00000140961 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000140961 [Gene_View]  chr16:83953222-83966332 [Contig_View]  OSGIN1 [Vega]
ICGC DataPortalENSG00000140961
TCGA cBioPortalOSGIN1
AceView (NCBI)OSGIN1
Genatlas (Paris)OSGIN1
WikiGenes29948
SOURCE (Princeton)OSGIN1
Genetics Home Reference (NIH)OSGIN1
Genomic and cartography
GoldenPath hg38 (UCSC)OSGIN1  -     chr16:83953222-83966332 +  16q23.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)OSGIN1  -     16q23.3   [Description]    (hg19-Feb_2009)
EnsemblOSGIN1 - 16q23.3 [CytoView hg19]  OSGIN1 - 16q23.3 [CytoView hg38]
Mapping of homologs : NCBIOSGIN1 [Mapview hg19]  OSGIN1 [Mapview hg38]
OMIM607975   
Gene and transcription
Genbank (Entrez)AF191740 AK290383 AY037158 AY258066 AY258067
RefSeq transcript (Entrez)NM_013370 NM_182980 NM_182981
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)OSGIN1
Cluster EST : UnigeneHs.128055 [ NCBI ]
CGAP (NCI)Hs.128055
Alternative Splicing GalleryENSG00000140961
Gene ExpressionOSGIN1 [ NCBI-GEO ]   OSGIN1 [ EBI - ARRAY_EXPRESS ]   OSGIN1 [ SEEK ]   OSGIN1 [ MEM ]
Gene Expression Viewer (FireBrowse)OSGIN1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29948
GTEX Portal (Tissue expression)OSGIN1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UJX0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UJX0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UJX0
Splice isoforms : SwissVarQ9UJX0
PhosPhoSitePlusQ9UJX0
Domains : Interpro (EBI)FAD/NAD-binding_dom    OKL38_fam    OSGIN1   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)OSGIN1
DMDM Disease mutations29948
Blocks (Seattle)OSGIN1
SuperfamilyQ9UJX0
Human Protein AtlasENSG00000140961
Peptide AtlasQ9UJX0
HPRD06412
IPIIPI00337549   IPI00413139   
Protein Interaction databases
DIP (DOE-UCLA)Q9UJX0
IntAct (EBI)Q9UJX0
FunCoupENSG00000140961
BioGRIDOSGIN1
STRING (EMBL)OSGIN1
ZODIACOSGIN1
Ontologies - Pathways
QuickGOQ9UJX0
Ontology : AmiGOprotein binding  cellular_component  multicellular organism development  growth factor activity  oxidoreductase activity  cell differentiation  negative regulation of cell growth  positive regulation of apoptotic process  oxidation-reduction process  
Ontology : EGO-EBIprotein binding  cellular_component  multicellular organism development  growth factor activity  oxidoreductase activity  cell differentiation  negative regulation of cell growth  positive regulation of apoptotic process  oxidation-reduction process  
NDEx NetworkOSGIN1
Atlas of Cancer Signalling NetworkOSGIN1
Wikipedia pathwaysOSGIN1
Orthology - Evolution
OrthoDB29948
GeneTree (enSembl)ENSG00000140961
Phylogenetic Trees/Animal Genes : TreeFamOSGIN1
HOVERGENQ9UJX0
HOGENOMQ9UJX0
Homologs : HomoloGeneOSGIN1
Homology/Alignments : Family Browser (UCSC)OSGIN1
Gene fusions - Rearrangements
Fusion : MitelmanJPH3/OSGIN1 [16q24.2/16q23.3]  [t(16;16)(q23;q24)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerOSGIN1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)OSGIN1
dbVarOSGIN1
ClinVarOSGIN1
1000_GenomesOSGIN1 
Exome Variant ServerOSGIN1
ExAC (Exome Aggregation Consortium)OSGIN1 (select the gene name)
Genetic variants : HAPMAP29948
Genomic Variants (DGV)OSGIN1 [DGVbeta]
DECIPHEROSGIN1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisOSGIN1 
Mutations
ICGC Data PortalOSGIN1 
TCGA Data PortalOSGIN1 
Broad Tumor PortalOSGIN1
OASIS PortalOSGIN1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICOSGIN1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDOSGIN1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch OSGIN1
DgiDB (Drug Gene Interaction Database)OSGIN1
DoCM (Curated mutations)OSGIN1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)OSGIN1 (select a term)
intoGenOSGIN1
NCG5 (London)OSGIN1
Cancer3DOSGIN1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607975   
Orphanet
MedgenOSGIN1
Genetic Testing Registry OSGIN1
NextProtQ9UJX0 [Medical]
TSGene29948
GENETestsOSGIN1
Target ValidationOSGIN1
Huge Navigator OSGIN1 [HugePedia]
snp3D : Map Gene to Disease29948
BioCentury BCIQOSGIN1
ClinGenOSGIN1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD29948
Chemical/Pharm GKB GenePA162398489
Clinical trialOSGIN1
Miscellaneous
canSAR (ICR)OSGIN1 (select the gene name)
Probes
Litterature
PubMed23 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineOSGIN1
EVEXOSGIN1
GoPubMedOSGIN1
iHOPOSGIN1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:33:09 CEST 2017

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