FCN3
Ficolin-3
Also known as: FCN3_HUMAN, FCNH, HAKA1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O75636
- Gene
- FCN3
- Ensembl
- ENSG00000142748
- Chromosome
- 1
- Canonical length
- 299 aa
- Protein class
- Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins
- Secretome location
- Secreted to blood
- Quaternary structure
- Homotrimer
OverviewNCBI Gene
Ficolins are a group of proteins which consist of a collagen-like domain and a fibrinogen-like domain. In human serum, there are two types of ficolins, both of which have lectin activity. The protein encoded by this gene is a thermolabile beta-2-macroglycoprotein found in all human serum and is a member of the ficolin/opsonin p35 lectin family. The protein, which was initially identified based on its reactivity with sera from patients with systemic lupus erythematosus, has been shown to have a calcium-independent lectin activity. The protein can activate the complement pathway in association with MASPs and sMAP, thereby aiding in host defense through the activation of the lectin pathway. Alternative splicing occurs at this locus and two variants, each encoding a distinct isoform, have been identified. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
299 residues, UniProt reviewed canonical sequence.
>O75636|FCN3
1 MDLLWILPSL WLLLLGGPAC LKTQEHPSCP GPRELEASKV VLLPSCPGAP GSPGEKGAPG
61 PQGPPGPPGK MGPKGEPGDP VNLLRCQEGP RNCRELLSQG ATLSGWYHLC LPEGRALPVF
121 CDMDTEGGGW LVFQRRQDGS VDFFRSWSSY RAGFGNQESE FWLGNENLHQ LTLQGNWELR
181 VELEDFNGNR TFAHYATFRL LGEVDHYQLA LGKFSEGTAG DSLSLHSGRP FTTYDADHDS
241 SNSNCAVIVH GAWWYASCYR SNLNGRYAVS EAAAHKYGID WASGRGVGHP YRRVRMMLRLocalizationUniProt · AlphaFold · HPA
Whether an antibody against FCN3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 688 nTPM
Expression across tissuesHPA
Tissue
- lung: 688 nTPM
- liver: 261 nTPM
- heart muscle: 59 nTPM
- adipose tissue: 58 nTPM
- kidney: 52 nTPM
- choroid plexus: 48 nTPM
Single-cell type
- vascular endothelial cells: 389 nCPM
- kupffer cells: 95 nCPM
- cholangiocytes: 27 nCPM
- submucosal glandular cells: 20 nCPM
- hepatic stellate cells: 19 nCPM
- respiratory ciliated cells: 13 nCPM
Immune cell
- basophil: 0.2 nTPM
- naive B-cell: 0.1 nTPM
- naive CD8 T-cell: 0.1 nTPM
- neutrophil: 0.1 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
Brain region
- choroid plexus: 20 nTPM
- hippocampal formation: 2.6 nTPM
- cerebral cortex: 1.9 nTPM
- medulla oblongata: 1.9 nTPM
- pons: 1.9 nTPM
- midbrain: 1.8 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about FCN3.
Disease | AllUniProt
Conditions FCN3 is implicated in, by any mechanism.
- Ficolin 3 deficiency (FCN3D) MIM:613860
Disease | GeneticClinVar
5 pathogenic / likely-pathogenic of 80 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Immunodeficiency due to ficolin3 deficiency
ReferencesPubMed · IEDB
Publications for FCN3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
3 publications
- Ficolin-3 Deficiency Is Associated with Disease and an Increased Risk of Systemic Lupus Erythematosus.
2019 · J Clin Immunol · RCR 1.3 · 25 citations - Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus.
2016 · PLoS One · RCR 1.2 · 28 citations - Anti-Ficolin-2 and Anti-Ficolin-3 Autoantibody Detection by ELISA.
2021 · Methods Mol Biol · RCR 0.1 · 2 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.9
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.42
- DepMap mean gene effect
- -0.02
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell surface pattern recognition receptor signaling pathway
- complement activation
- complement activation, lectin pathway
- defense response to virus
- host-mediated suppression of symbiont invasion
- positive regulation of opsonization
- proteolysis
- recognition of apoptotic cell
- negative regulation of RNA biosynthetic process
Molecular functions
- antigen binding
- carbohydrate binding
- carbohydrate derivative binding
- metal ion binding
- pattern recognition receptor activity
- signaling receptor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of FCN3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads FCN3 as an antibody target. Whether an autoantibody or antibody against FCN3 could matter depends on whether native FCN3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FCN3 is annotated at the cell surface, where native FCN3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label FCN3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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