Details for: RGN

Gene ID: 9104

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: RGN

Ensembl ID: ENSG00000130988

Description: regucalcin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Calcium ion binding
    (GO:0005509)
  • Cytoplasm
    (GO:0005737)
  • Enzyme regulator activity
    (GO:0030234)
  • Gluconolactonase activity
    (GO:0004341)
  • Intracellular calcium ion homeostasis
    (GO:0006874)
  • Kidney development
    (GO:0001822)
  • L-ascorbic acid biosynthetic process
    (GO:0019853)
  • Liver regeneration
    (GO:0097421)
  • Negative regulation of apoptotic process
    (GO:0043066)
  • Negative regulation of bone development
    (GO:1903011)
  • Negative regulation of dna biosynthetic process
    (GO:2000279)
  • Negative regulation of dna catabolic process
    (GO:1903625)
  • Negative regulation of epithelial cell proliferation
    (GO:0050680)
  • Negative regulation of flagellated sperm motility
    (GO:1901318)
  • Negative regulation of nitric oxide biosynthetic process
    (GO:0045019)
  • Negative regulation of rna biosynthetic process
    (GO:1902679)
  • Nucleus
    (GO:0005634)
  • Positive regulation of atp-dependent activity
    (GO:0032781)
  • Positive regulation of fatty acid biosynthetic process
    (GO:0045723)
  • Positive regulation of glucose metabolic process
    (GO:0010907)
  • Positive regulation of proteolysis involved in protein catabolic process
    (GO:1903052)
  • Positive regulation of triglyceride biosynthetic process
    (GO:0010867)
  • Regulation of calcium-mediated signaling
    (GO:0050848)
  • Spermatogenesis
    (GO:0007283)
  • Zinc ion binding
    (GO:0008270)

Significant Cells

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

  • centrilobular region hepatocyte CL0019029
    CSI 9.43
    rCSI 24.61%
    PRS 91.52
  • bronchus fibroblast of lung CL2000093
    CSI 8.69
    rCSI 7.06%
    PRS 95.25
  • lung pericyte CL0009089
    CSI 8.24
    rCSI 21.74%
    PRS 97.36
  • Kupffer cell CL0000091
    CSI 6.84
    rCSI 15.65%
    PRS 96.17
  • Bergmann glial cell CL0000644
    CSI 5.88
    rCSI 8.04%
    PRS 90.38
  • periportal region hepatocyte CL0019026
    CSI 5.5
    rCSI 21.38%
    PRS 92.02
  • midzonal region hepatocyte CL0019028
    CSI 4.18
    rCSI 9.82%
    PRS 92.29
  • hepatic stellate cell CL0000632
    CSI 3.84
    rCSI 14.38%
    PRS 93.21
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.37
    rCSI 8.54%
    PRS 92.04
  • cardiac muscle cell CL0000746
    CSI 3.34
    rCSI 4.79%
    PRS 89.78
  • cerebellar granule cell CL0001031
    CSI 3.24
    rCSI 4.77%
    PRS 92.14
  • hepatocyte CL0000182
    CSI 3.23
    rCSI 5.79%
    PRS 93.71
  • intestinal epithelial cell CL0002563
    CSI 3.08
    rCSI 3.22%
    PRS 93.6
  • pancreatic A cell CL0000171
    CSI 3.08
    rCSI 3.22%
    PRS 96.07
  • epithelial cell of proximal tubule CL0002306
    CSI 2.95
    rCSI 7.21%
    PRS 90.85
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.9
    rCSI 3.18%
    PRS 96.32
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.84
    rCSI 6.36%
    PRS 87.8
  • choroid plexus epithelial cell CL0000706
    CSI 2.81
    rCSI 4.6%
    PRS 91.05
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.79
    rCSI 6.79%
    PRS 85.69
  • endocardial cell CL0002350
    CSI 2.78
    rCSI 13.31%
    PRS 93.32
  • renal interstitial pericyte CL1001318
    CSI 2.74
    rCSI 7.54%
    PRS 94.23
  • tracheobronchial smooth muscle cell CL0019019
    CSI 2.34
    rCSI 4.13%
    PRS 96.89
  • colonocyte CL1000347
    CSI 2.21
    rCSI 3.17%
    PRS 93.67
  • basal cell CL0000646
    CSI 1.77
    rCSI 2.37%
    PRS 93.34
  • enterocyte CL0000584
    CSI 1.48
    rCSI 2.38%
    PRS 92.69
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.46
    rCSI 2.58%
    PRS 87.13
  • parietal epithelial cell CL1000452
    CSI 1.15
    rCSI 3.07%
    PRS 92.36
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.11
    rCSI 6.92%
    PRS 90.76
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.97
    rCSI 5.72%
    PRS 87.93
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.84
    rCSI 2.62%
    PRS 88.41
  • blood vessel smooth muscle cell CL0019018
    CSI 0.4
    rCSI 3.29%
    PRS 94.48

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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • 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 [RGN](/details-gene/9104), also known as regucalcin or Senescence Marker Protein-30 (SMP30), is a calcium-binding protein with gluconolactonase enzymatic activity. It plays a crucial role as a multi-functional regulator of intracellular calcium homeostasis and various cellular processes. [RGN](/details-gene/9104) is located on the X chromosome [Link](https://doi.org/10.1016/0167-4781(95)00120-6) and is associated with the OMIM entry for regucalcin deficiency ([300212](https://omim.org/entry/300212)). Functionally, it is involved in the biosynthesis of L-ascorbic acid [Link](https://doi.org/10.1371/journal.pone.0053706), and acts as a negative regulator of key signaling pathways, including cell proliferation and apoptosis. **Overall**, its expression is most significant in various types of [hepatocytes](/details-cell/CL0000182) within the liver, as well as in specific cell populations in the lung, kidney, and brain, highlighting its importance in metabolically active and specialized tissues. ## Cellular Roles and Expression Landscape The expression profile of [RGN](/details-gene/9104) demonstrates a strong and specific cellular signature, particularly within the liver. The gene shows its highest significance in [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 9.43), with prominent expression also noted in [periportal region hepatocytes](/details-cell/CL0019026) and [midzonal region hepatocytes](/details-cell/CL0019028). Beyond hepatocytes, other liver-resident cells such as [Kupffer cells](/details-cell/CL0000091) and [hepatic stellate cells](/details-cell/CL0000632) also exhibit significant [RGN](/details-gene/9104) expression, establishing its central role in hepatic biology. Outside of the liver, [RGN](/details-gene/9104) is a significant marker in several specialized cell types. It is highly expressed in structural cells of the lung, including [bronchus fibroblast of lung](/details-cell/CL2000093) and [lung pericytes](/details-cell/CL0009089). Its expression is also notable in the kidney, specifically in [kidney connecting tubule epithelial cells](/details-cell/CL1000768) and [epithelial cells of the proximal tubule](/details-cell/CL0002306), which is consistent with its annotated role in [kidney development](/details-cell/GO:0001822). Furthermore, its expression in central nervous system cells like [Bergmann glial cells](/details-cell/CL0000644) and [cerebellar granule cells](/details-cell/CL0001031) suggests a potential role in neural function or maintenance. This pattern indicates that while [RGN](/details-gene/9104) is a key feature of liver biology, it also contributes to specialized functions in other organ systems. ## Pathways and Molecular Function [RGN](/details-gene/9104) is a pleiotropic protein with both regulatory and enzymatic functions. Its primary role is in maintaining [intracellular calcium ion homeostasis](/details-cell/GO:0006874) through its [calcium ion binding](/details-cell/GO:0005509) capacity, which allows it to act as an [enzyme regulator](/details-cell/GO:0030234) for numerous calcium-dependent enzymes. This regulatory function extends to a broad range of cellular processes, where it predominantly acts as an inhibitor. It negatively regulates the [apoptotic process](/details-cell/GO:0043066), [DNA biosynthesis](/details-cell/GO:2000279), and [RNA biosynthesis](/details-cell/GO:1902679), thereby controlling cell survival and proliferation. In addition to its regulatory activities, [RGN](/details-gene/9104) possesses intrinsic enzymatic activity as a [gluconolactonase](/details-cell/GO:0004341), a key step in the [L-ascorbic acid (Vitamin C) biosynthetic process](/details-cell/GO:0019853) [Link](https://doi.org/10.1371/journal.pone.0053706). This dual functionality links calcium signaling with metabolic state. Its high expression in [hepatocytes](/details-cell/CL0000182) aligns with its involvement in hepatic functions such as [liver regeneration](/details-cell/GO:0097421), as well as the positive regulation of [glucose](/details-cell/GO:0010907), [fatty acid](/details-cell/GO:0045723), and [triglyceride](/details-cell/GO:0010867) biosynthesis. These functions underscore its role as a central hub integrating calcium signaling with core metabolic and homeostatic pathways, particularly in the liver. ## Research Directions The multifunctional nature of [RGN](/details-gene/9104) as both a calcium regulator and a negative modulator of cell growth and death presents intriguing avenues for research, particularly in the context of liver disease and cancer. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given its role in negatively regulating both cell proliferation ([GO:0050680](https://www.ebi.ac.uk/QuickGO/term/GO:0050680)) and apoptosis ([GO:0043066](https://www.ebi.ac.uk/QuickGO/term/GO:0043066)), the downregulation or loss of [RGN](/details-gene/9104) in [hepatocytes](/details-cell/CL0000182) could disrupt the delicate balance between cell survival and turnover. This dysregulation may lower the threshold for cellular transformation and contribute to the development or progression of hepatocellular carcinoma by uncoupling cell cycle control from apoptotic checkpoints. 2. **Hypothesis 2:** The significant expression of [RGN](/details-gene/9104) in [bronchus fibroblasts](/details-cell/CL2000093) and [lung pericytes](/details-cell/CL0009089) suggests it may modulate tissue remodeling and fibrosis. It is hypothesized that [RGN](/details-gene/9104) acts as a homeostatic brake on fibroblast activation and extracellular matrix deposition, and its altered expression during lung injury could be a key factor in the pathogenesis of idiopathic pulmonary fibrosis. ### Experimental Approach: To test the first hypothesis regarding the role of [RGN](/details-gene/9104) in liver cancer, a CRISPR-Cas9-mediated knockout of the gene could be performed in a non-transformed human hepatocyte cell line (e.g., THLE-2) and a hepatocellular carcinoma cell line (e.g., HepG2). The consequences of [RGN](/details-gene/9104) loss on cellular phenotype could be assessed by measuring proliferation rates (via IncuCyte live-cell imaging or Ki-67 staining), sensitivity to chemotherapy-induced apoptosis (via caspase-3/7 activity assays), and anchorage-independent growth (via soft agar colony formation assays). Furthermore, intracellular calcium dynamics in response to stimuli could be monitored using fluorescent calcium indicators to determine how its loss impacts calcium signaling fidelity. ### Therapeutic Potential: The role of [RGN](/details-gene/9104) as a negative regulator of cell proliferation suggests it may function as a tumor suppressor. If its expression is found to be diminished in certain cancers, particularly hepatocellular carcinoma, it could represent a novel therapeutic target. The therapeutic strategy would likely involve **activation** or restoration of its function. This could potentially be achieved through gene therapy approaches to re-introduce the gene or small molecule agonists designed to enhance its enzymatic or calcium-buffering activity. Such an approach could help re-establish homeostatic control over cell growth and survival pathways in malignant cells.

Genular Protein ID: 3651946858

Symbol: RGN_HUMAN

Name: Regucalcin

UniProtKB Accession Codes:

Q15493 A4FTW1 A8K271 Q53FC9 Q5JRR5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 11 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EC 2 EMBL 8 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 26 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 1 PRINTS 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 5 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7548213

Title: Isolation of cDNA clone encoding human homologue of senescence marker protein-30 (SMP30) and its location on the X chromosome.

PubMed ID: 7548213

DOI: 10.1016/0167-4781(95)00120-6

PubMed ID: 10677570

Title: Transcript heterogeneity of the human gene for Ca2+-binding protein regucalcin.

PubMed ID: 10677570

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 20329768

Title: Crystal structure of human senescence marker protein 30: insights linking structural, enzymatic, and physiological functions.

PubMed ID: 20329768

DOI: 10.1021/bi9022297

PubMed ID: 23349732

Title: Structural basis of the gamma-lactone-ring formation in ascorbic acid biosynthesis by the senescence marker protein-30/gluconolactonase.

PubMed ID: 23349732

DOI: 10.1371/journal.pone.0053706

Sequence Information:

  • Length: 299
  • Mass: 33253
  • Checksum: 95BA1C73B7B77635
  • Sequence:
    • MSSIKIECVL PENCRCGESP VWEEVSNSLL FVDIPAKKVC RWDSFTKQVQ RVTMDAPVSS 
VALRQSGGYV ATIGTKFCAL NWKEQSAVVL ATVDNDKKNN RFNDGKVDPA GRYFAGTMAE 
ETAPAVLERH QGALYSLFPD HHVKKYFDQV DISNGLDWSL DHKIFYYIDS LSYSVDAFDY 
DLQTGQISNR RSVYKLEKEE QIPDGMCIDA EGKLWVACYN GGRVIRLDPV TGKRLQTVKL 
PVDKTTSCCF GGKNYSEMYV TCARDGMDPE GLLRQPEAGG IFKITGLGVK GIAPYSYAG