Details for: CFP

Gene ID: 5199

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: CFP

Ensembl ID: ENSG00000126759

Description: complement factor properdin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 35.93
    rCSI 27.68%
    PRS 98.11
  • hematopoietic stem cell CL0000037
    CSI 19.02
    rCSI 12.64%
    PRS 97.32
  • promonocyte CL0000559
    CSI 17.2
    rCSI 29.47%
    PRS 97.15
  • myeloid leukocyte CL0000766
    CSI 16.96
    rCSI 15.64%
    PRS 97.34
  • non-classical monocyte CL0000875
    CSI 16.15
    rCSI 25.89%
    PRS 98.02
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 14.91
    rCSI 19.54%
    PRS 98.98
  • Kupffer cell CL0000091
    CSI 14.86
    rCSI 33.99%
    PRS 96.92
  • classical monocyte CL0000860
    CSI 12.59
    rCSI 18.67%
    PRS 97.34
  • conventional dendritic cell CL0000990
    CSI 11.84
    rCSI 9.89%
    PRS 90.84
  • CD14-positive monocyte CL0001054
    CSI 10.06
    rCSI 12.53%
    PRS 98.85
  • mononuclear phagocyte CL0000113
    CSI 9.24
    rCSI 20.35%
    PRS 97.75
  • dendritic cell, human CL0001056
    CSI 8.7
    rCSI 13.35%
    PRS 98.72
  • dendritic cell CL0000451
    CSI 8.15
    rCSI 10.04%
    PRS 95.6
  • monocyte CL0000576
    CSI 8
    rCSI 14.46%
    PRS 96.96
  • intermediate monocyte CL0002393
    CSI 7.05
    rCSI 10.63%
    PRS 98.34
  • lung macrophage CL1001603
    CSI 6.75
    rCSI 15.08%
    PRS 98.51
  • myeloid dendritic cell CL0000782
    CSI 6.65
    rCSI 9.63%
    PRS 99.29
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 5.96
    rCSI 36.04%
    PRS 98.62
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 5.79
    rCSI 6.99%
    PRS 98.44
  • elicited macrophage CL0000861
    CSI 5.62
    rCSI 5.16%
    PRS 98.4
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 4.75
    rCSI 14.62%
    PRS 96.65
  • professional antigen presenting cell CL0000145
    CSI 4.51
    rCSI 15.51%
    PRS 96.6
  • glial cell CL0000125
    CSI 3.56
    rCSI 13.55%
    PRS 92.34
  • colon macrophage CL0009038
    CSI 3.52
    rCSI 16.28%
    PRS 99.03
  • promyelocyte CL0000836
    CSI 3.51
    rCSI 5.06%
    PRS 96.99
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.1
    rCSI 2.69%
    PRS 97.32
  • common dendritic progenitor CL0001029
    CSI 3.04
    rCSI 3.82%
    PRS 98.34
  • common myeloid progenitor CL0000049
    CSI 2.74
    rCSI 2.22%
    PRS 97.34
  • Langerhans cell CL0000453
    CSI 2.56
    rCSI 3.9%
    PRS 98.72
  • myelocyte CL0002193
    CSI 0.73
    rCSI 4.8%
    PRS 98.38
  • pre-conventional dendritic cell CL0002010
    CSI 0.29
    rCSI 3.87%
    PRS 99.28

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 [CFP](/details-gene/5199), also known as complement factor properdin, encodes a key positive regulator of the alternative pathway of the complement system, a critical component of the innate immune response. This secreted glycoprotein functions by stabilizing the C3 and C5 convertase enzyme complexes, thereby amplifying complement activation on pathogen surfaces. Expression data indicates that [CFP](/details-gene/5199) is predominantly produced by cells of the myeloid lineage. It shows exceptionally high significance as a marker for [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s, [hematopoietic stem cell](/details-cell/CL0000037)s, and [promonocyte](/details-cell/CL0000559)s, highlighting its integral role within the mononuclear phagocyte system. Deficiencies in [CFP](/details-gene/5199) are associated with X-linked immunodeficiency, leading to increased susceptibility to bacterial infections ([OMIM: 300383](https://omim.org/entry/300383), [312060](https://omim.org/entry/312060)). ## Cellular Roles and Expression Landscape The expression profile of [CFP](/details-gene/5199) firmly establishes its function within the innate immune system, specifically within the myeloid compartment. **Overall**, the gene exhibits its highest significance in a range of monocyte subtypes and their precursors. It is the top marker for [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s (CSI: 35.93), also known as non-classical monocytes, which are involved in patrolling blood vessels and responding to inflammation. High significance is also observed in [hematopoietic stem cell](/details-cell/CL0000037)s (CSI: 19.02) and [promonocyte](/details-cell/CL0000559)s (CSI: 17.20), suggesting that its expression is initiated early in myeloid development. The consistent high ranking across the broader family of mononuclear phagocytes, including [non-classical monocyte](/details-cell/CL0000875)s, [classical monocyte](/details-cell/CL0000860)s, tissue-resident [Kupffer cell](/details-cell/CL0000091)s, and various [dendritic cell](/details-cell/CL0000451) populations, underscores its role as a fundamental effector molecule produced by these sentinel cells. The data strongly suggests that local production of properdin by these myeloid cells at sites of inflammation or infection is a key mechanism for rapidly amplifying the complement-mediated defense response. The confinement of its high expression to this lineage indicates a highly specialized immunological function. ## Pathways and Molecular Function The functional annotations for [CFP](/details-gene/5199) are highly consistent with its role as a key component of innate immunity. Its primary biological process is the `Complement activation, alternative pathway` ([GO:0006957](https://www.ebi.ac.uk/QuickGO/term/GO:0006957)), a critical arm of the immune system for opsonizing and eliminating pathogens. This is further supported by its annotation in `Defense response to bacterium` ([GO:0042742](https://www.ebi.ac.uk/QuickGO/term/GO:0042742)) and `Positive regulation of immune response` ([GO:0050778](https://www.ebi.ac.uk/QuickGO/term/GO:0050778)). As a secreted protein, its localization to the `Extracellular space` ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) is expected. Notably, its presence in the `Specific granule lumen` ([GO:0035580](https://www.ebi.ac.uk/QuickGO/term/GO:0035580)) and `Tertiary granule lumen` ([GO:1904724](https://www.ebi.ac.uk/QuickGO/term/1904724)) aligns with the Reactome pathway `Neutrophil degranulation` ([R-HSA-6798695](https://reactome.org/content/detail/R-HSA-6798695)), suggesting that myeloid cells can store properdin in granules for rapid release upon activation. Reactome analysis confirms its central role in the `Complement cascade` ([R-HSA-166658](https://reactome.org/content/detail/R-HSA-166658)) and `Alternative complement activation` ([R-HSA-173736](https://reactome.org/content/detail/R-HSA-173736)). Furthermore, pathways related to `O-linked glycosylation` ([R-HSA-5173105](https://reactome.org/content/detail/R-HSA-5173105)) are highlighted, which is consistent with literature demonstrating that post-translational modifications like C-mannosylation are crucial for properdin's structure and function [Link](https://doi.org/10.1074/jbc.m001732200). ## Research Directions The specific and high-level expression of [CFP](/details-gene/5199) within distinct myeloid populations, coupled with its critical function in amplifying the complement cascade, offers several avenues for future research. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s, we hypothesize that this "patrolling" monocyte subset acts as a primary source of localized properdin, creating a microenvironment of heightened complement readiness at the endothelial surface and in tissues during early-stage inflammation, independent of systemic liver-derived properdin. 2. Based on its known role in fighting bacterial infections, we hypothesize that inter-individual variation in the expression levels of [CFP](/details-gene/5199) within circulating monocytes correlates with susceptibility to diseases caused by encapsulated bacteria and may contribute to the severity of conditions characterized by complement dysregulation, such as sepsis. **Experimental Approach:** To test the first hypothesis regarding the role of monocyte-derived [CFP](/details-gene/5199), a conditional knockout mouse model could be generated. By crossing mice with floxed *Cfp* alleles to a strain expressing Cre recombinase under the control of a myeloid-specific promoter (e.g., *Lyz2*-Cre), one could specifically ablate properdin production in monocytes and neutrophils while preserving its systemic production by other sources like the liver. These mice, along with littermate controls, could be subjected to models of localized infection (e.g., intraperitoneal injection of *Neisseria meningitidis*) or sterile inflammation. Impaired bacterial clearance, reduced phagocytosis, and altered local inflammatory responses in the conditional knockout mice would provide strong evidence for the essential, non-redundant role of myeloid-derived properdin. **Therapeutic Potential:** As a positive regulator of the complement system, [CFP](/details-gene/5199) represents an attractive therapeutic target for diseases driven by excessive alternative pathway activation, such as C3 glomerulopathy, atypical hemolytic uremic syndrome, and paroxysmal nocturnal hemoglobinuria. The therapeutic strategy would be **inhibition**. Because properdin is a secreted protein that functions in the extracellular space, it is highly accessible to biologic drugs. The development of monoclonal antibodies or therapeutic aptamers that bind properdin and prevent it from stabilizing the C3 convertase could effectively dampen complement amplification at sites of disease, offering a targeted approach to treating complement-mediated pathologies.

Genular Protein ID: 864548476

Symbol: PROP_HUMAN

Name: Properdin

UniProtKB Accession Codes:

P27918 O15134 O15135 O15136 O75826

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 2 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 EMDB 2 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 12 PDBsum 12 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 6 RefSeq 2 SASBDB 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2009915

Title: Molecular cloning of the cDNA coding for properdin, a positive regulator of the alternative pathway of human complement.

PubMed ID: 2009915

DOI: 10.1002/eji.1830210333

PubMed ID: 1417780

Title: Characterization of the human properdin gene.

PubMed ID: 1417780

DOI: 10.1042/bj2870291

PubMed ID: 1431505

Title: Detection of properdin mRNA in human peripheral blood monocytes and spleen.

PubMed ID: 1431505

PubMed ID: 8530058

Title: Sequence-based analysis of properdin deficiency: identification of point mutations in two phenotypic forms of an X-linked immunodeficiency.

PubMed ID: 8530058

DOI: 10.1006/geno.1995.1208

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 10878002

Title: Properdin, the positive regulator of complement, is highly C-mannosylated.

PubMed ID: 10878002

DOI: 10.1074/jbc.m001732200

PubMed ID: 12096136

Title: C-mannosylation and O-fucosylation of thrombospondin type 1 repeats.

PubMed ID: 12096136

DOI: 10.1074/mcp.m100011-mcp200

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 19139490

Title: A strategy for precise and large scale identification of core fucosylated glycoproteins.

PubMed ID: 19139490

DOI: 10.1074/mcp.m800504-mcp200

PubMed ID: 20382442

Title: Native polymeric forms of properdin selectively bind to targets and promote activation of the alternative pathway of complement.

PubMed ID: 20382442

DOI: 10.1016/j.imbio.2010.02.002

PubMed ID: 15491616

Title: The dimeric and trimeric solution structures of the multidomain complement protein properdin by X-ray scattering, analytical ultracentrifugation and constrained modelling.

PubMed ID: 15491616

DOI: 10.1016/j.jmb.2004.09.001

PubMed ID: 28264884

Title: Functional and structural insight into properdin control of complement alternative pathway amplification.

PubMed ID: 28264884

DOI: 10.15252/embj.201696173

PubMed ID: 31507604

Title: Structural Basis for Properdin Oligomerization and Convertase Stimulation in the Human Complement System.

PubMed ID: 31507604

DOI: 10.3389/fimmu.2019.02007

PubMed ID: 8871668

Title: Molecular characterization of properdin deficiency type III: dysfunction produced by a single point mutation in exon 9 of the structural gene causing a tyrosine to aspartic acid interchange.

PubMed ID: 8871668

PubMed ID: 9710744

Title: Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations.

PubMed ID: 9710744

DOI: 10.1023/a:1027385806871

PubMed ID: 10909851

Title: Molecular characterisation of 10 Dutch properdin type I deficient families: mutation analysis and X-inactivation studies.

PubMed ID: 10909851

DOI: 10.1038/sj.ejhg.5200496

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: 469
  • Mass: 51276
  • Checksum: 5EB42B63F0283917
  • Sequence:
    • MITEGAQAPR LLLPPLLLLL TLPATGSDPV LCFTQYEESS GKCKGLLGGG VSVEDCCLNT 
AFAYQKRSGG LCQPCRSPRW SLWSTWAPCS VTCSEGSQLR YRRCVGWNGQ CSGKVAPGTL 
EWQLQACEDQ QCCPEMGGWS GWGPWEPCSV TCSKGTRTRR RACNHPAPKC GGHCPGQAQE 
SEACDTQQVC PTHGAWATWG PWTPCSASCH GGPHEPKETR SRKCSAPEPS QKPPGKPCPG 
LAYEQRRCTG LPPCPVAGGW GPWGPVSPCP VTCGLGQTME QRTCNHPVPQ HGGPFCAGDA 
TRTHICNTAV PCPVDGEWDS WGEWSPCIRR NMKSISCQEI PGQQSRGRTC RGRKFDGHRC 
AGQQQDIRHC YSIQHCPLKG SWSEWSTWGL CMPPCGPNPT RARQRLCTPL LPKYPPTVSM 
VEGQGEKNVT FWGRPLPRCE ELQGQKLVVE EKRPCLHVPA CKDPEEEEL