Details for: OIT3

Gene ID: 170392

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: OIT3

Ensembl ID: ENSG00000138315

Description: oncoprotein induced transcript 3

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ependymal cell CL0000065
    CSI 4.52
    rCSI 9.18%
    PRS 99.34
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 4.41
    rCSI 13.58%
    PRS 100
  • endothelial cell of vascular tree CL0002139
    CSI 1.57
    rCSI 8.6%
    PRS 99.79

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Oncoprotein induced transcript 3 ([OIT3](/details-gene/170392)) is a protein-coding gene located on chromosome 10q22.1. Despite its name suggesting a role in oncogenesis, its functional and expression data present a more complex picture. Current evidence points towards a highly specific expression pattern, with significant enrichment in specialized cell types such as [ependymal cells](/details-cell/CL0000065) of the brain and [endothelial cells of the pericentral hepatic sinusoid](/details-cell/CL0019022) in the liver. Functional annotations suggest involvement in calcium ion and protein binding, with conflicting reports on its subcellular localization, pointing to potential roles in both the nuclear envelope and the extracellular space. Research indicates it may be a liver-specific secreted protein that is paradoxically downregulated in hepatocellular carcinoma, suggesting a potential tumor-suppressive function ([Link](https://doi.org/10.1053/jhep.2003.50340)). ## Cellular Roles and Expression Landscape The expression profile of [OIT3](/details-gene/170392) indicates a highly specialized, rather than ubiquitous, role. **Overall**, the gene shows its highest significance in two distinct anatomical locations: the central nervous system and the liver. It is a top marker for [ependymal cells](/details-cell/CL0000065) (CSI: 4.52), which are the specialized epithelial cells lining the ventricular system of the brain and the central canal of the spinal cord. This localization suggests a potential function in maintaining the brain-cerebrospinal fluid barrier or regulating cerebrospinal fluid homeostasis. Concurrently, [OIT3](/details-gene/170392) is highly significant in [endothelial cells of the pericentral hepatic sinusoid](/details-cell/CL0019022) (CSI: 4.41), a specialized endothelial cell type found in the liver. Its expression is less pronounced in more generalized [endothelial cells of the vascular tree](/details-cell/CL0002139) (CSI: 1.57), reinforcing its role in a specific microenvironment. This is consistent with studies describing it as a liver-specific protein ([Link](https://doi.org/10.1053/jhep.2003.50340)). The dual enrichment in these lining/barrier cell types suggests a conserved function in regulating transport or signaling at critical tissue interfaces. ## Pathways and Molecular Function Functional annotations provide further insight into the molecular activities of [OIT3](/details-gene/170392), though some data present conflicting views on its cellular localization and function. * **Molecular Function**: The gene product is annotated with roles in [calcium ion binding](/term/GO:0005509) and general [protein binding](/term/GO:0005515). The ability to bind calcium suggests its activity could be regulated by intracellular calcium signaling pathways, which are critical in both endothelial and ependymal cell function. * **Biological Process**: It is associated with the [renal system process](/term/GO:0003014), although current expression data does not highlight a prominent role in kidney cell types. * **Cellular Component**: There is notable ambiguity regarding the subcellular localization of the OIT3 protein. Gene Ontology annotates it as a component of the [nuclear envelope](/term/GO:0005635). However, multiple studies suggest it is a secreted or transmembrane protein containing a Zona Pellucida (ZP) domain ([Link](https://doi.org/10.1101/gr.1293003)). Further evidence from glycoproteomic analysis of human liver tissue supports its presence outside the nucleus as a glycoprotein ([Link](https://doi.org/10.1021/pr8008012)). These discrepancies may be due to the existence of different protein isoforms generated by alternative splicing or post-translational cleavage, which could traffic to distinct cellular compartments. ## Research Directions The existing data for [OIT3](/details-gene/170392) raises several key questions, particularly regarding its paradoxical name and its role in liver pathology. ### Testable Hypotheses 1. **[OIT3](/details-gene/170392) functions as a tumor suppressor in the liver.** Despite its name, its reported downregulation in hepatocellular carcinoma (HCC) ([Link](https://doi.org/10.1053/jhep.2003.50340)) suggests that loss of [OIT3](/details-gene/170392) function contributes to liver tumorigenesis. Its expression in sinusoidal endothelial cells may be critical for maintaining liver homeostasis and preventing malignant transformation of nearby hepatocytes. 2. **[OIT3](/details-gene/170392) is a structural or signaling component of the brain-CSF barrier.** Given its high specificity in [ependymal cells](/details-cell/CL0000065) and its nature as a potential ZP-domain glycoprotein, it may play a role in the assembly of extracellular matrices at the ventricular surface or in cell-cell adhesion, thereby regulating the integrity of this critical barrier. 3. **The OIT3 protein is a dual-localization protein with distinct functions.** The conflict between nuclear envelope and secreted protein annotations could be resolved if [OIT3](/details-gene/170392) undergoes regulated processing, allowing it to function both intracellularly (e.g., regulating gene expression from the nuclear periphery) and extracellularly (e.g., mediating cell signaling or adhesion). ### Proposed Experiment To test the hypothesis that **[OIT3](/details-gene/170392) acts as a tumor suppressor in HCC**, one could perform a rescue experiment. This would involve re-expressing [OIT3](/details-gene/170392) via lentiviral transduction in HCC cell lines with low or absent endogenous expression. The functional consequences would be assessed by measuring key cancer hallmarks, including cell proliferation (via BrdU incorporation or cell counting assays), migration and invasion (via transwell assays), and anchorage-independent growth (via soft agar colony formation assays). A parallel *in vivo* experiment using a xenograft mouse model, where HCC cells with and without [OIT3](/details-gene/170392) re-expression are implanted, would be critical to determine its effect on tumor growth and metastasis in a physiological context. ### Therapeutic Potential The therapeutic potential of [OIT3](/details-gene/170392) appears to be linked to its potential tumor-suppressive role. If its loss promotes cancer, the therapeutic strategy would involve **activation or restoration** of its function rather than inhibition. This could be conceptually achieved through gene therapy to restore its expression in liver cells or with small molecules that stabilize the protein or enhance its expression. Furthermore, if the protein is secreted as suggested, its circulating levels could be explored as a non-invasive biomarker for liver health or early-stage HCC. However, a deeper understanding of its precise mechanism of action is required before it can be considered a viable therapeutic target.

Genular Protein ID: 554603325

Symbol: OIT3_HUMAN

Name: Oncoprotein-induced transcript 3 protein

UniProtKB Accession Codes:

Q8WWZ8 A0AVP3 Q8N1M8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 GO 3 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12939600

Title: A novel liver-specific zona pellucida domain containing protein that is expressed rarely in hepatocellular carcinoma.

PubMed ID: 12939600

DOI: 10.1053/jhep.2003.50340

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

Sequence Information:

  • Length: 545
  • Mass: 60022
  • Checksum: E4BDE126213484B0
  • Sequence:
    • MPPFLLLTCL FITGTSVSPV ALDPCSAYIS LNEPWRNTDH QLDESQGPPL CDNHVNGEWY 
HFTGMAGDAM PTFCIPENHC GTHAPVWLNG SHPLEGDGIV QRQACASFNG NCCLWNTTVE 
VKACPGGYYV YRLTKPSVCF HVYCGHFYDI CDEDCHGSCS DTSECTCAPG TVLGPDRQTC 
FDENECEQNN GGCSEICVNL KNSYRCECGV GRVLRSDGKT CEDVEGCHNN NGGCSHSCLG 
SEKGYQCECP RGLVLSEDNH TCQVPVLCKS NAIEVNIPRE LVGGLELFLT NTSCRGVSNG 
THVNILFSLK TCGTVVDVVN DKIVASNLVT GLPKQTPGSS GDFIIRTSKL LIPVTCEFPR 
LYTISEGYVP NLRNSPLEIM SRNHGIFPFT LEIFKDNEFE EPYREALPTL KLRDSLYFGI 
EPVVHVSGLE SLVESCFATP TSKIDEVLKY YLIRDGCVSD DSVKQYTSRD HLAKHFQVPV 
FKFVGKDHKE VFLHCRVLVC GVLDERSRCA QGCHRRMRRG AGGEDSAGLQ GQTLTGGPIR 
IDWED