Details for: FCN1

Gene ID: 2219

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: FCN1

Ensembl ID: ENSG00000085265

Description: ficolin 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 93.25
    rCSI 71.85%
    PRS 99.46
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 48.16
    rCSI 63.1%
    PRS 99.77
  • promonocyte CL0000559
    CSI 44.15
    rCSI 75.63%
    PRS 99.18
  • CD14-positive monocyte CL0001054
    CSI 43.03
    rCSI 53.59%
    PRS 99.78
  • classical monocyte CL0000860
    CSI 35.11
    rCSI 52.05%
    PRS 98.57
  • non-classical monocyte CL0000875
    CSI 29.62
    rCSI 47.47%
    PRS 98.79
  • conventional dendritic cell CL0000990
    CSI 25.39
    rCSI 21.19%
    PRS 94.08
  • mononuclear phagocyte CL0000113
    CSI 25.05
    rCSI 55.14%
    PRS 99.12
  • intermediate monocyte CL0002393
    CSI 23.19
    rCSI 34.99%
    PRS 99.51
  • erythrocyte CL0000232
    CSI 22.25
    rCSI 50.48%
    PRS 97.59
  • monocyte CL0000576
    CSI 22.08
    rCSI 39.91%
    PRS 98.81
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 21.7
    rCSI 26.22%
    PRS 99.52
  • elicited macrophage CL0000861
    CSI 18.96
    rCSI 17.41%
    PRS 99.46
  • dendritic cell CL0000451
    CSI 16.82
    rCSI 20.72%
    PRS 97.91
  • alveolar macrophage CL0000583
    CSI 14.08
    rCSI 23.2%
    PRS 98.8
  • professional antigen presenting cell CL0000145
    CSI 13.54
    rCSI 46.62%
    PRS 97.18
  • lung macrophage CL1001603
    CSI 11.2
    rCSI 25.02%
    PRS 99.57
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 10.68
    rCSI 64.63%
    PRS 99.65
  • promyelocyte CL0000836
    CSI 10.31
    rCSI 14.87%
    PRS 98.83
  • platelet CL0000233
    CSI 9.94
    rCSI 41.22%
    PRS 95.92
  • neutrophil CL0000775
    CSI 9.3
    rCSI 52.06%
    PRS 96.31
  • colon macrophage CL0009038
    CSI 8.94
    rCSI 41.31%
    PRS 99.69
  • myelocyte CL0002193
    CSI 7.92
    rCSI 52.01%
    PRS 99.19
  • dendritic cell, human CL0001056
    CSI 7.08
    rCSI 10.87%
    PRS 99.52
  • plasmablast CL0000980
    CSI 6.99
    rCSI 5.5%
    PRS 98.31
  • myeloid dendritic cell CL0000782
    CSI 4.6
    rCSI 6.67%
    PRS 99.83
  • granulocyte CL0000094
    CSI 3.56
    rCSI 5.44%
    PRS 99.03
  • mature NK T cell CL0000814
    CSI 3.45
    rCSI 4.42%
    PRS 98.84
  • megakaryocyte CL0000556
    CSI 3.45
    rCSI 14.97%
    PRS 97.51
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 3.13
    rCSI 34.02%
    PRS 99.65

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 [FCN1](/details-gene/2219) encodes Ficolin-1, a soluble pattern recognition receptor and a key component of the innate immune system. It functions primarily in the recognition of carbohydrate structures, such as sialic acid, on the surface of pathogens and apoptotic cells ([Link](https://doi.org/10.1074/jbc.m109.065854)). This binding initiates the lectin pathway of the complement system, leading to opsonization and clearance of targets. Expression data reveals that [FCN1](/details-gene/2219) is predominantly synthesized by cells of the myeloid lineage, with exceptionally high significance in monocyte subsets, highlighting its central role in frontline host defense mediated by the mononuclear phagocyte system. ## Cellular Roles and Expression Landscape The expression profile of [FCN1](/details-gene/2219) firmly establishes it as a specialized gene within the myeloid compartment of the immune system. **Overall**, the gene shows the highest significance in various monocyte populations, indicating it is a crucial functional protein for these cells. Its most pronounced role is in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 93.25), also known as non-classical monocytes, which are involved in patrolling the vasculature. High significance is also observed in [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) (intermediate monocytes) and [classical monocyte](/details-cell/CL0000860), suggesting a broad importance across the monocyte differentiation spectrum. The substantial CSI score in [promonocyte](/details-cell/CL0000559) (CSI: 44.15) suggests that [FCN1](/details-gene/2219) expression is initiated early during myelopoiesis. Beyond monocytes, [FCN1](/details-gene/2219) is also a significant marker for other professional phagocytes and antigen-presenting cells, including [conventional dendritic cell](/details-cell/CL0000990) and [alveolar macrophage](/details-cell/CL0000583). This expression pattern underscores its role as a secreted surveillance molecule deployed by cells that are primary sensors of infection and cellular debris. The finding that peripheral blood leucocytes are the major site of synthesis is well-supported by early research ([Link](https://pubmed.ncbi.nlm.nih.gov/8573080/)). ## Pathways and Molecular Function Functionally, [FCN1](/details-gene/2219) is integral to the '[Innate immune system](/details-pathway/R-HSA-168249)' and is a primary initiator of the '[Lectin pathway of complement activation](/details-pathway/R-HSA-166662)'. As a pattern recognition receptor ([GO:0038187](https://www.ebi.ac.uk/QuickGO/term/GO:0038187)), Ficolin-1 is secreted into the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) where its fibrinogen-like domain binds to specific carbohydrate structures on target surfaces ([Link](https://doi.org/10.1074/jbc.m608627200)). This includes binding to N-acetylglucosamine and sialic acid ([GO:0033691](https://www.ebi.ac.uk/QuickGO/term/GO:0033691)), which is critical for tethering to cell surfaces ([Link](https://doi.org/10.1189/jlb.1209802)). Upon binding its target, Ficolin-1 complexes with mannan-binding lectin-associated serine proteases (MASPs), triggering the '[Complement cascade](/details-pathway/R-HSA-166658)'. This process results in the opsonization of the target ([GO:1903028](https://www.ebi.ac.uk/QuickGO/term/GO:1903028)), facilitating its recognition and engulfment by phagocytes. This mechanism is crucial for the clearance of pathogens as well as apoptotic cells ([GO:0043654](https://www.ebi.ac.uk/QuickGO/term/GO:0043654)). Furthermore, Ficolin-1 signaling can lead to the '[Positive regulation of interleukin-8 production](/details-pathway/GO:0032757)', contributing to inflammatory responses and the recruitment of other immune cells, such as neutrophils. Its presence in secretory granule lumens ([GO:0034774](https://www.ebi.ac.uk/QuickGO/term/GO:0034774)) is consistent with its involvement in processes like '[Neutrophil degranulation](/details-pathway/R-HSA-6798695)'. ## Research Directions The highly specific expression and function of [FCN1](/details-gene/2219) within the innate immune system suggest several avenues for future investigation. Its distinct significance across different monocyte subsets points to specialized, rather than redundant, roles in host defense. ### Proposed Hypotheses: 1. The exceptionally high CSI value of [FCN1](/details-gene/2219) in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) suggests that Ficolin-1 is a primary effector molecule for this "patrolling" monocyte subset. It may be uniquely adapted to recognize and opsonize virally-infected endothelial cells or specific types of cellular debris encountered during surveillance of the vasculature, thereby mediating a distinct immunological response compared to classical monocytes. 2. Given that [FCN1](/details-gene/2219) binds sialic acid and recognizes apoptotic cells, it may function as a critical sensor for distinguishing between healthy and aberrant "self" cells. Dysregulation of [FCN1](/details-gene/2219) expression or function could contribute to autoimmune pathologies where the clearance of apoptotic material is impaired, leading to the presentation of self-antigens and a break in tolerance. ### Experimental Approach: To test the first hypothesis regarding the specialized role of [FCN1](/details-gene/2219) in patrolling monocytes, one could employ a functional genomics approach. Primary [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s could be isolated from human peripheral blood and treated with [FCN1](/details-gene/2219)-targeting siRNA or CRISPR-Cas9 ribonucleoproteins to achieve gene knockout. These modified cells, along with control cells, could then be co-cultured in a microfluidic system mimicking the vascular endothelium. The ability of the monocytes to adhere to, patrol, and phagocytose target cells (e.g., endothelial cells infected with a cytomegalovirus or apoptotic tumor cells) could be quantified via live-cell imaging and flow cytometry. A significant reduction in phagocytic efficiency or patrolling behavior in the [FCN1](/details-gene/2219)-deficient monocytes would confirm its specialized function in this cell type. ### Therapeutic Potential: As a soluble component of the innate immune system, [FCN1](/details-gene/2219) presents a unique therapeutic target. For conditions characterized by compromised immunity or susceptibility to encapsulated bacteria, administration of recombinant Ficolin-1 could serve as an opsonizing agent to augment the complement system, representing a potential activation strategy. Conversely, in autoimmune or inflammatory diseases driven by excessive lectin pathway activation (e.g., ischemia-reperfusion injury), a neutralizing monoclonal antibody targeting Ficolin-1 could be developed. Such an inhibition strategy would dampen complement-mediated tissue damage without broadly suppressing the entire immune system, offering a more targeted therapeutic intervention.

Genular Protein ID: 3505721304

Symbol: FCN1_HUMAN

Name: Ficolin-1

UniProtKB Accession Codes:

O00602 Q5VYV5 Q92596

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 5 ComplexPortal 2 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 26 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PIR 1 PRIDE 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 4 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniLectin 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8573080

Title: Human ficolin: cDNA cloning, demonstration of peripheral blood leucocytes as the major site of synthesis and assignment of the gene to chromosome 9.

PubMed ID: 8573080

DOI: 10.1042/bj3130473

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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: 8947836

Title: Characterization of ficolins as novel elastin-binding proteins and molecular cloning of human ficolin-1.

PubMed ID: 8947836

DOI: 10.1093/oxfordjournals.jbchem.a021474

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 21037097

Title: Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled receptor 43 and cross talks with plasma C-reactive protein to mediate immune signaling and regulate host defense.

PubMed ID: 21037097

DOI: 10.4049/jimmunol.1001225

PubMed ID: 20400674

Title: Tethering of Ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain.

PubMed ID: 20400674

DOI: 10.1189/jlb.1209802

PubMed ID: 17148457

Title: Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain.

PubMed ID: 17148457

DOI: 10.1074/jbc.m608627200

PubMed ID: 17897951

Title: Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch.

PubMed ID: 17897951

DOI: 10.1074/jbc.m705741200

PubMed ID: 20032467

Title: Carbohydrate recognition properties of human ficolins: glycan array screening reveals the sialic acid binding specificity of M-ficolin.

PubMed ID: 20032467

DOI: 10.1074/jbc.m109.065854

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 326
  • Mass: 35078
  • Checksum: 184D24B371B251AB
  • Sequence:
    • MELSGATMAR GLAVLLVLFL HIKNLPAQAA DTCPEVKVVG LEGSDKLTIL RGCPGLPGAP 
GPKGEAGVIG ERGERGLPGA PGKAGPVGPK GDRGEKGMRG EKGDAGQSQS CATGPRNCKD 
LLDRGYFLSG WHTIYLPDCR PLTVLCDMDT DGGGWTVFQR RMDGSVDFYR DWAAYKQGFG 
SQLGEFWLGN DNIHALTAQG SSELRVDLVD FEGNHQFAKY KSFKVADEAE KYKLVLGAFV 
GGSAGNSLTG HNNNFFSTKD QDNDVSSSNC AEKFQGAWWY ADCHASNLNG LYLMGPHESY 
ANGINWSAAK GYKYSYKVSE MKVRPA