Details for: PROCA1

Gene ID: 147011

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: PROCA1

Ensembl ID: ENSG00000167525

Description: protein interacting with cyclin A1

Cell Significance Landscape

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 3.89
    rCSI 3.42%
    PRS 99.69
  • glutamatergic neuron CL0000679
    CSI 2.23
    rCSI 4.59%
    PRS 99.05

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):
    • Very High
    • High
    • Medium
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    • 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 [PROCA1](/details-gene/147011) (Protein Interacting with Cyclin A1) is a protein-coding gene located on human chromosome 17q11.2. Functionally, it is annotated with roles in lipid metabolism, specifically demonstrating [phospholipase A2 activity](/details-cell/GO:0004623) and involvement in [arachidonate secretion](/details-cell/GO:0050482). It has also been identified as a binding partner for cyclin A1, consistent with its annotated [cyclin binding](/details-cell/GO:0030332) function [Link](https://doi.org/10.1074/jbc.m401708200). Expression data indicates that [PROCA1](/details-gene/147011) is most significantly expressed in [ciliated epithelial cells](/details-cell/CL0000067) and [glutamatergic neurons](/details-cell/CL0000679), suggesting specialized roles within these distinct cellular contexts. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [PROCA1](/details-gene/147011) points towards specialized functions in specific cell lineages rather than a ubiquitous housekeeping role. Its most significant expression is observed in [ciliated epithelial cells](/details-cell/CL0000067) (CSI: 3.89), which are critical for fluid and particle transport in tissues such as the respiratory tract and fallopian tubes. This suggests a potential role for [PROCA1](/details-gene/147011) in processes related to ciliary function or epithelial barrier integrity. A secondary but also significant expression is noted in [glutamatergic neurons](/details-cell/CL0000679) (CSI: 2.23). In this context, its function may relate to neuronal signaling, synaptic plasticity, or membrane dynamics, where lipid metabolism and cell cycle-related proteins are known to play important roles. The distinct expression in these two cell types suggests that the function of [PROCA1](/details-gene/147011) is highly context-dependent, potentially linking lipid signaling to either motility in epithelial cells or neurotransmission in neurons. ## Pathways and Molecular Function The molecular functions of [PROCA1](/details-gene/147011) are centered on two primary activities: enzyme catalysis and protein-protein interactions. Its annotation for [phospholipase A2 activity](/details-cell/GO:0004623) places it within a critical class of enzymes that hydrolyze phospholipids to produce fatty acids and lysophospholipids. This activity directly supports its involvement in the [phospholipid metabolic process](/details-cell/GO:0006644) and, more specifically, the biological process of [arachidonate secretion](/details-cell/GO:0050482). Arachidonic acid is a key precursor for a wide range of potent signaling molecules, including prostaglandins and leukotrienes, which are involved in inflammation and cellular signaling. Concurrently, [PROCA1](/details-gene/147011) is characterized by its ability to engage in [protein binding](/details-cell/GO:0005515), most notably with cyclin A1 [Link](https://doi.org/10.1074/jbc.m401708200). This [cyclin binding](/details-cell/GO:0030332) function suggests it may act as a linker between cell cycle regulation and cellular metabolism, potentially modulating kinase activity or localizing the cyclin A1-CDK2 complex to specific subcellular compartments. The intersection of these two distinct molecular functions suggests [PROCA1](/details-gene/147011) may coordinate metabolic changes with cell state transitions. ## Research Directions The dual functions of [PROCA1](/details-gene/147011) in both cyclin binding and phospholipase A2 activity, coupled with its specific expression pattern, open several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in [ciliated epithelial cells](/details-cell/CL0000067) and its role in [arachidonate secretion](/details-cell/GO:0050482), [PROCA1](/details-gene/147011) may be a key regulator of mucociliary clearance. It could generate lipid signaling molecules that modulate ciliary beat frequency or the hydration of the mucosal layer. 2. The interaction with cyclin A1 and its expression in post-mitotic [glutamatergic neurons](/details-cell/CL0000679) suggests a non-canonical role for [PROCA1](/details-gene/147011) in neuronal function. It may be involved in regulating synaptic plasticity or dendritic spine remodeling, processes where cell cycle proteins have been found to play unexpected roles independent of cell division. **Experimental Approach:** To test the first hypothesis regarding its role in ciliary function, an ideal model would be an air-liquid interface (ALI) culture of primary human bronchial epithelial cells, which differentiate to form a ciliated epithelium. One could perform a targeted knockdown of [PROCA1](/details-gene/147011) using siRNA or CRISPR interference. The functional consequences could be assayed by measuring ciliary beat frequency with high-speed video microscopy and assessing changes in the secretion of arachidonic acid and its downstream eicosanoid metabolites into the apical medium using mass spectrometry. **Therapeutic Potential:** As a member of the phospholipase A2 enzyme family, [PROCA1](/details-gene/147011) represents a potentially druggable target. This class of enzymes is central to inflammatory processes, and inhibitors have been widely explored. If the activity of [PROCA1](/details-gene/147011) is shown to contribute to inflammatory diseases of epithelial tissues, such as asthma or chronic obstructive pulmonary disease (COPD), by producing excess pro-inflammatory lipid mediators, then developing specific small molecule inhibitors could be a viable therapeutic strategy. Its restricted expression pattern may offer a favorable safety profile compared to inhibitors that target more ubiquitously expressed phospholipases.

Genular Protein ID: 2914056878

Symbol: PRCA1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8NCQ7 B4DX95 G5E9R8 Q6PKN3

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 6 Ensembl 1 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 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 6 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

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: 15159402

Title: Identification of interaction partners and substrates of the cyclin A1-CDK2 complex.

PubMed ID: 15159402

DOI: 10.1074/jbc.m401708200

Sequence Information:

  • Length: 364
  • Mass: 40506
  • Checksum: BAED65CDC427C7A3
  • Sequence:
    • MWVRTTLTIE RWTKEKTEPK ARSWDEALSD VNRLPSWERG HLLAGVASST DVSTFSEGGD 
CKEPDKCCWR HKQCTGHIIY PFASDCVRHS LHLHSVNHCN CNSRLKDSSE DSSSSRGAGP 
TCSHVIESPC FELTPEEEHV ERFRYGWCKS YRPVSVAVIH HPLYHECGAD DLNEEEEEEE 
EESKPPIPTQ VGPATASPDL GTSMATGTPD STAPITIWRS ESPTGKGQGS KVIKKVKKKK 
EKEKDKEEMD EKAKLKKKAK KGQLTKKKSP VKLEPSPPDV SRSLSARQLA RMSESSPESR 
EELESEDSYN GRGQGELSSE DIVESSSPRK RENTVQAKKT GAKPSQARKV NKRKSPPGSN 
PNLS