Details for: PFN4

Gene ID: 375189

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: PFN4

Ensembl ID: ENSG00000176732

Description: profilin family member 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • conventional dendritic cell CL0000990
    CSI 40.45
    rCSI 33.76%
    PRS 99.62
  • mast cell CL0000097
    CSI 39.95
    rCSI 86.27%
    PRS 99.63
  • innate lymphoid cell CL0001065
    CSI 23.09
    rCSI 47.67%
    PRS 99.64
  • basal cell of epidermis CL0002187
    CSI 13.6
    rCSI 24.1%
    PRS 98.24
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 12.75
    rCSI 15.45%
    PRS 98.77
  • helper T cell CL0000912
    CSI 9.08
    rCSI 12.83%
    PRS 99.72
  • melanocyte of skin CL1000458
    CSI 6.33
    rCSI 8.62%
    PRS 98.7
  • suprabasal keratinocyte CL4033013
    CSI 3.04
    rCSI 4.97%
    PRS 99.2

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.

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  • 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 [PFN4](/details-gene/375189) (Profilin 4) is a protein-coding gene located on chromosome 2p23.3. As a member of the profilin family, its primary molecular function is binding to actin monomers ([GO:0003785](https://www.ebi.ac.uk/QuickGO/term/GO:0003785)), a critical process for regulating actin cytoskeleton dynamics. While extensively studied for its specialized role in male fertility, specifically in spermatogenesis, acrosome assembly, and sperm motility ([Link](https://doi.org/10.1093/molehr/gah132), [Link](https://doi.org/10.1186/1471-2121-10-34)), expression data reveals its significant presence in various immune and epithelial cell types. **Overall**, [PFN4](/details-gene/375189) shows high expression significance in [conventional dendritic cell](/details-cell/CL0000990) and [mast cell](/details-cell/CL0000097), suggesting a potentially broader, though less characterized, role in immune surveillance and inflammatory responses. ## Cellular Roles and Expression Landscape The expression profile of [PFN4](/details-gene/375189) highlights a dual identity in both reproductive and immune contexts. Its functional annotation is strongly tied to its role in male germ cells, yet its highest expression significance is observed in hematopoietic lineages. **Overall**, the most significant expression is found in key cells of the innate and adaptive immune systems. [PFN4](/details-gene/375189) is a particularly strong marker for [conventional dendritic cell](/details-cell/CL0000990) (CSI: 40.45) and [mast cell](/details-cell/CL0000097) (CSI: 39.95), suggesting its actin-modulating function is crucial for processes such as antigen presentation, cell migration, and degranulation in these cells. Significant expression is also noted in [innate lymphoid cell](/details-cell/CL0001065), [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), and [helper T cell](/details-cell/CL0000912). In addition to immune cells, [PFN4](/details-gene/375189) demonstrates notable significance in epithelial and pigment-producing cells of the skin, including [basal cell of epidermis](/details-cell/CL0002187) and [melanocyte of skin](/details-cell/CL1000458). This pattern suggests that its role in regulating the actin cytoskeleton may also be important for maintaining tissue structure and cellular function in the epidermis. ## Pathways and Molecular Function The established molecular function of [PFN4](/details-gene/375189) is [actin monomer binding](/details-cell/GO:0003785), which allows it to sequester actin monomers ([GO:0042989](https://www.ebi.ac.uk/QuickGO/term/GO:0042989)) and regulate their availability for polymerization into cytoskeletal filaments. This core function is leveraged in several highly specialized biological processes related to male reproduction. Functional annotation strongly implicates [PFN4](/details-gene/375189) in multiple stages of [spermatogenesis](/details-cell/GO:0007283). It is involved in [acrosome assembly](/details-cell/GO:0001675) and localizes to the acroplaxome-manchette complex, a unique cytoskeletal structure in developing spermatids, as described in published research ([Link](https://doi.org/10.1186/1471-2121-10-34)). This role is critical for both [manchette assembly](/details-cell/GO:1905198) and the subsequent elongation of the sperm head. Furthermore, it plays a role in [sperm flagellum assembly](/details-cell/GO:0120316), which is essential for achieving [flagellated sperm motility](/details-cell/GO:0030317). While not explicitly annotated in the provided data, its high expression in immune cells suggests this fundamental actin-binding function is likely repurposed for processes like cell migration, phagocytosis, and immunological synapse formation. ## Research Directions The discrepancy between the well-documented role of [PFN4](/details-gene/375189) in spermatogenesis and its high expression significance in immune cells presents a compelling area for future investigation. Its function outside of the testis remains poorly understood. **Proposed Hypotheses:** 1. Given its high CSI in [conventional dendritic cell](/details-cell/CL0000990), [PFN4](/details-gene/375189) is likely a key regulator of dendritic cell motility and antigen uptake. Its disruption may impair the ability of these cells to migrate to lymph nodes and initiate adaptive immune responses. 2. The high significance of [PFN4](/details-gene/375189) in [mast cell](/details-cell/CL0000097) suggests a critical role in the actin-dependent process of degranulation. It may modulate the release of histamine and other inflammatory mediators, thereby influencing the severity of allergic and inflammatory reactions. **Experimental Approach:** To test the hypothesis regarding the role of [PFN4](/details-gene/375189) in dendritic cell function, a targeted knockdown or knockout approach could be employed. Specifically, CRISPR-Cas9 could be used to disrupt [PFN4](/details-gene/375189) in primary human monocytes, which would then be differentiated into dendritic cells. The functional consequences could be assessed by comparing wild-type and knockout cells in key assays, including transwell migration assays to measure chemotaxis and flow cytometry-based phagocytosis assays to quantify antigen uptake. Subsequent T-cell co-culture experiments would reveal any impact on antigen presentation and T-cell activation. **Therapeutic Potential:** The potential of [PFN4](/details-gene/375189) as a therapeutic target is complex. As an intracellular protein involved in the fundamental process of actin dynamics, targeting it with high specificity is challenging. However, if its function in [mast cell](/details-cell/CL0000097) or [dendritic cell](/details-cell/CL0000990) is confirmed to be a driver of inflammatory or autoimmune diseases, development of small molecule inhibitors could be considered. The primary challenge would be achieving cell-type specificity to avoid adverse effects, most notably on male fertility, where its function is critical. Therefore, any therapeutic strategy would require a deep understanding of its context-specific protein interactions and regulatory mechanisms.

Genular Protein ID: 1210519111

Symbol: PROF4_HUMAN

Name: Profilin-4

UniProtKB Accession Codes:

Q8NHR9 Q53TL9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 4 SMART 1 SMR 1 STRING 1 SUPFAM 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: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 15591451

Title: Novel testis-expressed profilin IV associated with acrosome biogenesis and spermatid elongation.

PubMed ID: 15591451

DOI: 10.1093/molehr/gah132

PubMed ID: 19419568

Title: Testis-expressed profilins 3 and 4 show distinct functional characteristics and localize in the acroplaxome-manchette complex in spermatids.

PubMed ID: 19419568

DOI: 10.1186/1471-2121-10-34

PubMed ID: 33438010

Title: Single-cell ATAC-Seq reveals cell type-specific transcriptional regulation and unique chromatin accessibility in human spermatogenesis.

PubMed ID: 33438010

DOI: 10.1093/hmg/ddab006

Sequence Information:

  • Length: 129
  • Mass: 14319
  • Checksum: 2BB7C78E66C0EAEF
  • Sequence:
    • MSHLQSLLLD TLLGTKHVDS AALIKIQERS LCVASPGFNV TPSDVRTLVN GFAKNPLQAR 
REGLYFKGKD YRCVRADEYS LYAKNENTGV VVVKTHLYLL VATYTEGMYP SICVEATESL 
GDYLRKKGS