Details for: PRAP1

Gene ID: 118471

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: PRAP1

Ensembl ID: ENSG00000165828

Description: proline rich acidic protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Cellular response to x-ray
    (GO:0071481)
  • Deactivation of mitotic spindle assembly checkpoint
    (GO:1902426)
  • Dna damage response
    (GO:0006974)
  • Dna damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
    (GO:0006977)
  • Endoplasmic reticulum
    (GO:0005783)
  • Extracellular region
    (GO:0005576)
  • Negative regulation of apoptotic process
    (GO:0043066)
  • Positive regulation of intestinal lipid absorption
    (GO:1904731)
  • Positive regulation of phospholipid transport
    (GO:2001140)
  • Positive regulation of triglyceride transport
    (GO:1905885)
  • Protein binding
    (GO:0005515)
  • Triglyceride binding
    (GO:0017129)

Significant Cells

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

  • intestinal epithelial cell CL0002563
    CSI 15.95
    rCSI 16.68%
    PRS 90.6
  • myofibroblast cell CL0000186
    CSI 12.94
    rCSI 17.92%
    PRS 89.85
  • colonocyte CL1000347
    CSI 12.37
    rCSI 17.73%
    PRS 90.81
  • colon epithelial cell CL0011108
    CSI 10.5
    rCSI 11%
    PRS 90.58
  • midzonal region hepatocyte CL0019028
    CSI 9.5
    rCSI 22.3%
    PRS 90
  • enterocyte CL0000584
    CSI 9.42
    rCSI 15.18%
    PRS 89.97
  • centrilobular region hepatocyte CL0019029
    CSI 6.39
    rCSI 16.66%
    PRS 88.91
  • type L enteroendocrine cell CL0002279
    CSI 6.01
    rCSI 11.27%
    PRS 93.76
  • epithelial cell of proximal tubule CL0002306
    CSI 4.51
    rCSI 11.03%
    PRS 87.37
  • periportal region hepatocyte CL0019026
    CSI 4.51
    rCSI 17.53%
    PRS 89.66
  • goblet cell CL0000160
    CSI 4.13
    rCSI 3.91%
    PRS 90.62
  • BEST4+ enteroycte CL4030026
    CSI 4.05
    rCSI 5.03%
    PRS 92.11
  • paneth cell of epithelium of small intestine CL1000343
    CSI 3.18
    rCSI 8.9%
    PRS 94.69
  • small intestine goblet cell CL1000495
    CSI 3.07
    rCSI 6.73%
    PRS 94.21
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.88
    rCSI 6.33%
    PRS 94.51
  • intestine goblet cell CL0019031
    CSI 2.67
    rCSI 2.37%
    PRS 90.57
  • M cell of gut CL0000682
    CSI 2.62
    rCSI 2.79%
    PRS 94.32
  • IgA plasma cell CL0000987
    CSI 2.6
    rCSI 2.66%
    PRS 93.51
  • stem cell CL0000034
    CSI 2.53
    rCSI 2.44%
    PRS 89.31
  • enteroendocrine cell CL0000164
    CSI 2.48
    rCSI 3.39%
    PRS 90.78
  • brush cell CL0002204
    CSI 2.42
    rCSI 4.79%
    PRS 94.47
  • hepatocyte CL0000182
    CSI 2.19
    rCSI 3.92%
    PRS 91.04
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.18
    rCSI 5.87%
    PRS 94.2
  • paneth cell CL0000510
    CSI 1.84
    rCSI 2.72%
    PRS 96.39
  • intestinal tuft cell CL0019032
    CSI 1.82
    rCSI 2.79%
    PRS 93.8
  • transit amplifying cell of colon CL0009011
    CSI 1.73
    rCSI 2.03%
    PRS 92.67
  • transit amplifying cell of small intestine CL0009012
    CSI 1.17
    rCSI 5.13%
    PRS 95.05
  • enterocyte of epithelium of large intestine CL0002071
    CSI 1.02
    rCSI 5.33%
    PRS 94.02
  • type EC enteroendocrine cell CL0000577
    CSI 0.95
    rCSI 3.36%
    PRS 93.44
  • paneth cell of colon CL0009009
    CSI 0.36
    rCSI 3.52%
    PRS 94.89

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 Proline rich acidic protein 1, encoded by the [PRAP1](/details-gene/118471) gene, is a secreted protein implicated in fundamental cellular processes including DNA damage response, apoptosis, and cell cycle regulation. **Overall**, expression data reveals that [PRAP1](/details-gene/118471) is highly and specifically expressed in epithelial and secretory cells of the gastrointestinal tract and liver, particularly in [intestinal epithelial cells](/details-cell/CL0002563), [colonocytes](/details-cell/CL1000347), and [hepatocytes](/details-cell/CL0019028). Research indicates that [PRAP1](/details-gene/118471) acts as an executor of p53-dependent survival pathways following DNA damage ([Link](https://doi.org/10.1038/cddis.2012.180)) and plays a protective role in the gastrointestinal epithelium against radiation-induced apoptosis ([Link](https://doi.org/10.1016/j.jcmgh.2020.06.011)). It has also been identified as a tumor suppressor whose expression is epigenetically silenced in some cancers ([Link](https://pubmed.ncbi.nlm.nih.gov/14583459/)). ## Cellular Roles and Expression Landscape The expression profile of [PRAP1](/details-gene/118471) strongly indicates a specialized function in absorptive and metabolic tissues. **Overall**, the gene shows its highest significance in the gastrointestinal system, with the most prominent expression observed in [intestinal epithelial cells](/details-cell/CL0002563) (CSI: 15.95), [colonocytes](/details-cell/CL1000347) (CSI: 12.37), and [enterocytes](/details-cell/CL0000584) (CSI: 9.42). This suggests a primary role in maintaining the function and integrity of the intestinal lining. High significance is also noted in [myofibroblast cells](/details-cell/CL0000186) (CSI: 12.94), suggesting a potential role in tissue structure and repair within the gut. Furthermore, [PRAP1](/details-gene/118471) is a key marker in various hepatocyte populations, including [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 9.50), [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 6.39), and [periportal region hepatocytes](/details-cell/CL0019026) (CSI: 4.51), pointing to its involvement in liver biology. Its expression in secretory cell types such as [goblet cells](/details-cell/CL0000160) and [Paneth cells](/details-cell/CL1000343) is consistent with its classification as a secreted protein ([Link](https://doi.org/10.1101/gr.1293003)). ## Pathways and Molecular Function Functional annotation aligns closely with the observed expression pattern and published research. [PRAP1](/details-gene/118471) is centrally involved in the cellular response to genotoxic stress, as evidenced by its roles in the [DNA damage response](/details-cell/GO:0006974), specifically through [p53 class mediator signaling resulting in cell cycle arrest](/details-cell/GO:0006977), and the [cellular response to x-ray](/details-cell/GO:0071481). Consistent with a pro-survival function, it is also annotated for the [negative regulation of apoptotic process](/details-cell/GO:0043066). This anti-apoptotic role has been experimentally validated in the context of gastrointestinal protection from radiation ([Link](https://doi.org/10.1016/j.jcmgh.2020.06.011)). In addition to its role in stress response, [PRAP1](/details-gene/118471) appears to participate in metabolic processes, particularly in the gut. Gene Ontology terms link it to the [positive regulation of intestinal lipid absorption](/details-cell/GO:1904731) and [positive regulation of triglyceride transport](/details-cell/GO:1905885), which is consistent with its high expression in [enterocytes](/details-cell/CL0000584). At a molecular level, its functions include [protein binding](/details-cell/GO:0005515) and localization to the [extracellular region](/details-cell/GO:0005576), befitting a secreted protein that may interact with other molecules in the cellular microenvironment. ## Research Directions The available data points to [PRAP1](/details-gene/118471) as a critical cytoprotective and tumor-suppressive protein, particularly in the gastrointestinal tract and liver. Its epigenetic silencing in cancer and its protective role against DNA damage suggest it is a key node in cellular homeostasis and disease. **Testable Hypotheses:** 1. Given its role as an executor of p53-dependent survival mechanisms, the forced re-expression of [PRAP1](/details-gene/118471) in epigenetically silenced colon cancer cell lines will re-sensitize them to DNA-damaging chemotherapies by restoring proper cell cycle checkpoints, rather than promoting survival. 2. Based on its interaction with MAD1 and its suppressive role in the mitotic checkpoint in hepatocellular carcinoma ([Link](https://doi.org/10.1002/path.4319)), the knockout of [PRAP1](/details-gene/118471) in non-transformed hepatocytes will lead to an increased rate of mitotic errors and aneuploidy, a key step in hepatocarcinogenesis. **Proposed Experiment:** To test the second hypothesis, a CRISPR-Cas9-mediated knockout of [PRAP1](/details-gene/118471) could be performed in a human immortalized, non-cancerous hepatocyte cell line (e.g., THLE-2). [PRAP1](/details-gene/118471)-deficient and isogenic control cells would be synchronized and treated with a spindle poison like nocodazole to induce mitotic arrest. The strength of the spindle assembly checkpoint would be assessed by measuring the mitotic index over time using live-cell imaging and flow cytometry for phospho-histone H3. Additionally, chromosome spreads from resulting daughter cells could be analyzed to quantify the rates of aneuploidy and chromosomal mis-segregation. **Therapeutic Potential:** The function of [PRAP1](/details-gene/118471) suggests two main therapeutic avenues. First, as a cytoprotective agent, administration of recombinant [PRAP1](/details-gene/118471) protein or a small-molecule agonist could serve as an adjuvant therapy to protect the gastrointestinal epithelium from damage caused by radiation or chemotherapy, potentially reducing debilitating side effects. This would be an **activation** or supplementation strategy. Second, in cancers where [PRAP1](/details-gene/118471) acts as a tumor suppressor and is silenced, therapies aimed at restoring its expression, such as epigenetic modifiers (e.g., DNA methyltransferase or histone deacetylase inhibitors), could represent a viable strategy to inhibit tumor growth.

Genular Protein ID: 1183383816

Symbol: PRAP1_HUMAN

Name: Proline-rich acidic protein 1

UniProtKB Accession Codes:

Q96NZ9 B7ZL57 B7ZL58 E9KL31 Q5VWY4 Q7Z4X5 Q8IWR3 Q8NCS2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 15 Ensembl 2 ExpressionAtlas 1 GO 11 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 2 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14583459

Title: The proline-rich acidic protein is epigenetically regulated and inhibits growth of cancer cell lines.

PubMed ID: 14583459

PubMed ID: 20736409

Title: Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins.

PubMed ID: 20736409

DOI: 10.1074/mcp.m110.001719

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: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 23235459

Title: PRAP1 is a novel executor of p53-dependent mechanisms in cell survival after DNA damage.

PubMed ID: 23235459

DOI: 10.1038/cddis.2012.180

PubMed ID: 24374861

Title: Proline-rich acidic protein 1 (PRAP1) is a novel interacting partner of MAD1 and has a suppressive role in mitotic checkpoint signalling in hepatocellular carcinoma.

PubMed ID: 24374861

DOI: 10.1002/path.4319

PubMed ID: 32629119

Title: Proline-Rich Acidic Protein 1 (PRAP1) Protects the Gastrointestinal Epithelium From Irradiation-Induced Apoptosis.

PubMed ID: 32629119

DOI: 10.1016/j.jcmgh.2020.06.011

Sequence Information:

  • Length: 151
  • Mass: 17208
  • Checksum: B751EDBFD24D08CA
  • Sequence:
    • MRRLLLVTSL VVVLLWEAGA VPAPKVPIKM QVKHWPSEQD PEKAWGARVV EPPEKDDQLV 
VLFPVQKPKL LTTEEKPRGQ GRGPILPGTK AWMETEDTLG HVLSPEPDHD SLYHPPPEED 
QGEERPRLWV MPNHQVLLGP EEDQDHIYHP Q

Genular Protein ID: 341314013

Symbol: A6XND8_HUMAN

Name: N/A

UniProtKB Accession Codes:

A6XND8

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 HOGENOM 1 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 1 PharmGKB 1 RefSeq 1 SAM 2 UCSC 1 VEuPathDB 1

Sequence Information:

  • Length: 142
  • Mass: 16332
  • Checksum: 149282D65B6346E6
  • Sequence:
    • MRRLLLVTSL VVVLLWEAGA VPAPKVPIKM QVKHWPSEQD PEKAWGARVV EPPEKDDQLV 
VLFPVQKPKL LTTEEKPRGT KAWMETEDTL GHVLSPEPDH DSLYHPPPEE DQGEERPRLW 
VMPNHQVLLG PEEDQDHIYH PQ