Details for: CRISP2

Gene ID: 7180

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: CRISP2

Ensembl ID: ENSG00000124490

Description: cysteine rich secretory protein 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • multi-ciliated epithelial cell CL0005012
    CSI 4.28
    rCSI 4.27%
    PRS 95.47
  • mucus secreting cell CL0000319
    CSI 3.53
    rCSI 5.61%
    PRS 98.94
  • lung ciliated cell CL1000271
    CSI 2.26
    rCSI 2.62%
    PRS 95.63
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.34
    rCSI 3.05%
    PRS 94.09

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

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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 [CRISP2](/details-gene/7180) (Cysteine-Rich Secretory Protein 2) is a protein-coding gene that encodes a secreted, cysteine-rich protein. It is a member of the CRISP family, which is part of the broader CRISP, antigen 5, and PR-1 (CAP) superfamily of proteins. Historically, [CRISP2](/details-gene/7180) has been characterized as a testis-specific protein involved in sperm function and fertilization [Link](https://pubmed.ncbi.nlm.nih.gov/2613236/). However, integrated expression data also highlights its significant and specific expression in various epithelial cell types, particularly within the respiratory system. Its annotation as a component of the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) is consistent with a role as a secreted protein functioning outside the cell in diverse physiological contexts. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [CRISP2](/details-gene/7180) shows a strong and specific signature in epithelial cells responsible for barrier function and secretion, primarily within the respiratory tract. The gene demonstrates the highest significance in [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 4.28), [mucus secreting cell](/details-cell/CL0000319) (CSI: 3.53), and more specifically in [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.26) and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 1.34). This pattern suggests a functional role for [CRISP2](/details-gene/7180) in the processes of mucociliary clearance and maintenance of the airway surface liquid. This finding expands upon the classical understanding of [CRISP2](/details-gene/7180) as a protein primarily restricted to the male reproductive system. Seminal studies identified it as a testis-specific gene integral to sperm maturation and gamete fusion [Link](https://doi.org/10.1111/j.1432-1033.1996.t01-1-00827.x). The prominent expression in respiratory cells suggests that [CRISP2](/details-gene/7180) may have a broader, conserved function related to modifying extracellular environments, both in the reproductive tract and the airways. ## Pathways and Molecular Function The primary functional annotation for [CRISP2](/details-gene/7180) indicates its localization to the **extracellular space** ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)). As a secreted protein, its functions are mediated through interactions with other proteins or cellular surfaces in the extracellular milieu. In the context of the testis, it is known to be a component of the sperm acrosome and is implicated in sperm-egg fusion events. In the respiratory system, its secretion by [ciliated](/details-cell/CL0005012) and [mucus-secreting cells](/details-cell/CL0000319) suggests it may be a component of the mucus layer or the periciliary fluid, where it could influence mucus properties, ciliary function, or local innate immune responses. ## Research Directions The dual expression pattern of [CRISP2](/details-gene/7180) in both the male reproductive tract and the respiratory epithelium presents an intriguing area for further investigation. Its specific role in the airways, which is less characterized than its reproductive function, warrants significant exploration. **Proposed Testable Hypotheses:** 1. [CRISP2](/details-gene/7180) functions as a modulator of mucus rheology in the airways. By interacting with mucin polymers or other components of the airway surface liquid, it helps maintain optimal viscosity for effective mucociliary transport. 2. The expression of [CRISP2](/details-gene/7180) in respiratory epithelial cells is regulated by inflammatory or infectious stimuli, suggesting it acts as an antimicrobial peptide or a component of the innate immune defense at mucosal surfaces. **Suggested Experimental Approach:** To test the hypothesis that [CRISP2](/details-gene/7180) modulates mucociliary clearance (Hypothesis 1), a robust *in vitro* model could be employed. Primary human bronchial epithelial cells could be cultured at an air-liquid interface (ALI) to generate a differentiated, mucociliary epithelium. Using CRISPR-Cas9 to knock out [CRISP2](/details-gene/7180) in these cultures, one could then assess key functional outputs. Measurements would include ciliary beat frequency using high-speed video microscopy, mucus transport velocity by tracking fluorescent microbeads, and changes in mucus viscosity using particle-tracking microrheology. **Therapeutic Potential:** The therapeutic potential of [CRISP2](/details-gene/7180) is currently speculative but could be significant in the context of chronic respiratory diseases characterized by mucus hypersecretion and impaired clearance, such as cystic fibrosis, asthma, or chronic obstructive pulmonary disease (COPD). If [CRISP2](/details-gene/7180) is found to be a key factor in maintaining healthy mucus properties, recombinant [CRISP2](/details-gene/7180) protein could be explored as an inhaled biologic therapy to restore mucociliary function. Conversely, if its overexpression contributes to mucus pathology, it could be a target for inhibition via inhaled monoclonal antibodies or small molecule inhibitors. Its secreted nature makes it a highly accessible drug target.

Genular Protein ID: 2899652438

Symbol: CRIS2_HUMAN

Name: Cysteine-rich secretory protein 2

UniProtKB Accession Codes:

P16562 A8K8M0 Q53FF2 Q5U8Z9 Q7Z7B2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 1 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 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 14 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2613236

Title: Cloning and mapping of a testis-specific gene with sequence similarity to a sperm-coating glycoprotein gene.

PubMed ID: 2613236

DOI: 10.1016/0888-7543(89)90019-0

PubMed ID: 8665901

Title: The human cysteine-rich secretory protein (CRISP) family. Primary structure and tissue distribution of CRISP-1, CRISP-2 and CRISP-3.

PubMed ID: 8665901

DOI: 10.1111/j.1432-1033.1996.t01-1-00827.x

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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

Sequence Information:

  • Length: 243
  • Mass: 27259
  • Checksum: C5FE698C449CFAD9
  • Sequence:
    • MALLPVLFLV TVLLPSLPAE GKDPAFTALL TTQLQVQREI VNKHNELRKA VSPPASNMLK 
MEWSREVTTN AQRWANKCTL QHSDPEDRKT STRCGENLYM SSDPTSWSSA IQSWYDEILD 
FVYGVGPKSP NAVVGHYTQL VWYSTYQVGC GIAYCPNQDS LKYYYVCQYC PAGNNMNRKN 
TPYQQGTPCA GCPDDCDKGL CTNSCQYQDL LSNCDSLKNT AGCEHELLKE KCKATCLCEN 
KIY