Details for: CHP2

Gene ID: 63928

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: CHP2

Ensembl ID: ENSG00000166869

Description: calcineurin like EF-hand protein 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intestinal epithelial cell CL0002563
    CSI 21.75
    rCSI 22.73%
    PRS 91
  • colonocyte CL1000347
    CSI 14.59
    rCSI 20.91%
    PRS 91.25
  • goblet cell CL0000160
    CSI 14.17
    rCSI 13.39%
    PRS 91.01
  • colon epithelial cell CL0011108
    CSI 13.64
    rCSI 14.28%
    PRS 91.05
  • respiratory suprabasal cell CL4033048
    CSI 10.24
    rCSI 13.13%
    PRS 94.26
  • transit amplifying cell of colon CL0009011
    CSI 9.13
    rCSI 10.72%
    PRS 93.1
  • respiratory basal cell CL0002633
    CSI 8.89
    rCSI 9.2%
    PRS 94.3
  • secretory cell CL0000151
    CSI 8.12
    rCSI 8.48%
    PRS 92.25
  • enterocyte CL0000584
    CSI 7.33
    rCSI 11.82%
    PRS 90.35
  • club cell CL0000158
    CSI 7.24
    rCSI 10.6%
    PRS 89.54
  • keratinocyte CL0000312
    CSI 7.17
    rCSI 6.01%
    PRS 92.75
  • BEST4+ enteroycte CL4030026
    CSI 5.59
    rCSI 6.95%
    PRS 92.62
  • intestine goblet cell CL0019031
    CSI 4.63
    rCSI 4.11%
    PRS 91.05
  • enterocyte of epithelium of large intestine CL0002071
    CSI 4.46
    rCSI 23.43%
    PRS 94.23
  • transit amplifying cell CL0009010
    CSI 4.25
    rCSI 6.5%
    PRS 95.55
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 3.67
    rCSI 9.9%
    PRS 94.56
  • progenitor cell CL0011026
    CSI 3.11
    rCSI 6.62%
    PRS 87.45
  • paneth cell of colon CL0009009
    CSI 2.84
    rCSI 27.89%
    PRS 95.05
  • transit amplifying cell of small intestine CL0009012
    CSI 2.82
    rCSI 12.39%
    PRS 95.24
  • bronchial goblet cell CL1000312
    CSI 2.58
    rCSI 10.29%
    PRS 95.38
  • enterocyte of epithelium of small intestine CL1000334
    CSI 1.54
    rCSI 23.88%
    PRS 94.56
  • basal cell of epithelium of trachea CL1000348
    CSI 1.41
    rCSI 9.92%
    PRS 93.36
  • type L enteroendocrine cell CL0002279
    CSI 1.34
    rCSI 2.52%
    PRS 93.96
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.21
    rCSI 3.4%
    PRS 94.93
  • colon goblet cell CL0009039
    CSI 1.14
    rCSI 2.7%
    PRS 93.99
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.93
    rCSI 7.01%
    PRS 96.19
  • respiratory goblet cell CL0002370
    CSI 0.43
    rCSI 4.69%
    PRS 95.18

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)

Loading network (please wait)...

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 [CHP2](/details-gene/63928) (Calcineurin B Homologous Protein 2) is a protein-coding gene that functions as a calcium-binding protein involved in the regulation of the calcineurin-NFAT signaling pathway. Its expression is highly significant in various epithelial tissues, particularly within the intestinal and respiratory tracts. It plays a key role in cellular processes such as proliferation and protein transport. Research suggests [CHP2](/details-gene/63928) can enhance the oncogenic potential of cells, and its nuclear accumulation is associated with increased tumor cell proliferation ([Link](https://doi.org/10.1111/j.1365-2443.2011.01497.x), [Link](https://doi.org/10.1074/jbc.m806684200)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [CHP2](/details-gene/63928) indicates a highly specific role in epithelial cell function. The gene shows its most significant expression in cells lining the gastrointestinal tract, including [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 21.75), [colonocyte](/details-cell/CL1000347) (CSI: 14.59), [goblet cell](/details-cell/CL0000160) (CSI: 14.17), and [enterocyte](/details-cell/CL0000584) (CSI: 7.33). Its high significance in proliferative populations like the [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 9.13) is consistent with its documented role in promoting cell growth. Beyond the gut, [CHP2](/details-gene/63928) is also a significant marker in respiratory epithelia, including [respiratory suprabasal cell](/details-cell/CL4033048) (CSI: 10.24), [respiratory basal cell](/details-cell/CL0002633) (CSI: 8.89), and [club cell](/details-cell/CL0000158) (CSI: 7.24). Its notable expression in [keratinocyte](/details-cell/CL0000312) (CSI: 7.17) further reinforces its identity as a key gene in diverse epithelial tissues. The collective data suggests that [CHP2](/details-gene/63928) is a fundamental component of epithelial cell biology across multiple organ systems. ## Pathways and Molecular Function Functionally, [CHP2](/details-gene/63928) is an integral part of calcium-dependent signaling. Its primary molecular function is [calcium ion binding](/details-go/GO:0005509), which enables its involvement in the [cellular response to calcium ion](/details-go/GO:0071277). This activity is central to its role in the [positive regulation of calcineurin-nfat signaling cascade](/details-go/GO:0070886), a critical pathway for cell proliferation and gene transcription ([Link](https://doi.org/10.1074/jbc.m806684200)). The activation of this pathway likely underlies its contribution to the [positive regulation of cell population proliferation](/details-go/GO:0008284) and [positive regulation of transcription by rna polymerase ii](/details-go/GO:0045944). Furthermore, [CHP2](/details-gene/63928) interacts with the Na+/H+ exchanger NHE1, regulating intracellular pH and protecting cells from apoptosis under stress conditions like serum deprivation ([Link](https://doi.org/10.1074/jbc.m208313200), [Link](https://doi.org/10.1038/sj.emboj.7601145)). Cellular localization studies show its presence in the [cytoplasm](/details-go/GO:0005737), [nucleus](/details-go/GO:0005634), and [plasma membrane](/details-go/GO:0005886), consistent with its diverse regulatory roles. ## Research Directions The established role of [CHP2](/details-gene/63928) in promoting proliferation, coupled with its high expression in rapidly renewing tissues like the colonic epithelium, strongly suggests its involvement in the pathogenesis of epithelial malignancies. It has been identified as a hepatocellular carcinoma-associated antigen ([Link](https://doi.org/10.4049/jimmunol.169.2.1102)) and its overexpression has been shown to enhance oncogenic potential ([Link](https://doi.org/10.1074/jbc.m806684200)). This provides a strong basis for investigating its role as a driver of cancer. Based on the available data, several testable hypotheses can be proposed: 1. Mis-regulation or overexpression of [CHP2](/details-gene/63928) in intestinal [transit amplifying cell](/details-cell/CL0009010) populations disrupts normal cell cycle control, leading to hyperproliferation and acting as an initiating event in colorectal cancer development. 2. In established tumors, elevated [CHP2](/details-gene/63928) levels confer a survival advantage by enhancing Na+/H+ exchanger activity, allowing cancer cells to resist the acidic tumor microenvironment and evade apoptosis. To test the first hypothesis, a specific experimental approach could be employed: * **Experiment:** Utilize a CRISPR activation (CRISPRa) lentiviral system to specifically overexpress [CHP2](/details-gene/63928) in primary human colon organoids. The impact on organoid morphology, crypt budding frequency, and cell proliferation could be monitored over time. Changes in the expression of proliferation markers (e.g., Ki-67) and downstream NFAT target genes (e.g., *MYC*, *CCND1*) would be quantified by immunofluorescence and RNA-sequencing to determine if [CHP2](/details-gene/63928) overexpression is sufficient to induce a pre-malignant phenotype. Given its function as an intracellular signaling protein that promotes proliferation and cell survival, [CHP2](/details-gene/63928) represents a potential therapeutic target. A strategy of **inhibition**, rather than activation, would be pursued. Since it is not a cell-surface protein, the development of specific small-molecule inhibitors that disrupt its binding to calcineurin or other key partners could be a viable approach for treating epithelial cancers, particularly colorectal carcinomas, where its expression is most pronounced.

Genular Protein ID: 1218170557

Symbol: CHP2_HUMAN

Name: Calcineurin B homologous protein 2

UniProtKB Accession Codes:

O43745 A8K2I8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTC 1 CTD 1 ChEBI 9 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 EvolutionaryTrace 1 GO 14 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12097419

Title: Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.

PubMed ID: 12097419

DOI: 10.4049/jimmunol.169.2.1102

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 12226101

Title: Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger.

PubMed ID: 12226101

DOI: 10.1074/jbc.m208313200

PubMed ID: 18815128

Title: CHP2 activates the calcineurin/nuclear factor of activated T cells signaling pathway and enhances the oncogenic potential of HEK293 cells.

PubMed ID: 18815128

DOI: 10.1074/jbc.m806684200

PubMed ID: 21392185

Title: Nuclear accumulation of calcineurin B homologous protein 2 (CHP2) results in enhanced proliferation of tumor cells.

PubMed ID: 21392185

DOI: 10.1111/j.1365-2443.2011.01497.x

PubMed ID: 16511206

Title: Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1.

PubMed ID: 16511206

DOI: 10.1107/s1744309105030836

PubMed ID: 16710297

Title: Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation.

PubMed ID: 16710297

DOI: 10.1038/sj.emboj.7601145

Sequence Information:

  • Length: 196
  • Mass: 22452
  • Checksum: F5113D558AFA27DE
  • Sequence:
    • MGSRSSHAAV IPDGDSIRRE TGFSQASLLR LHHRFRALDR NKKGYLSRMD LQQIGALAVN 
PLGDRIIESF FPDGSQRVDF PGFVRVLAHF RPVEDEDTET QDPKKPEPLN SRRNKLHYAF 
QLYDLDRDGK ISRHEMLQVL RLMVGVQVTE EQLENIADRT VQEADEDGDG AVSFVEFTKS 
LEKMDVEQKM SIRILK