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FLASH GENE
Symbol CRP contributors: mct/npt/pgu - updated : 11-02-2019
HGNC name C-reactive protein, pentraxin-related
HGNC id 2367
DNA
TYPE functioning gene
STRUCTURE 2.30 kb     2 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • a negative regulatory element located within the proximal promoter region
  • MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2024 25 224 - 1992 1477104
    4 - 691 - 91 - 1992 1477104
    3 - 1316 - 224 - 1992 1477104
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Urinarybladder   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion plasma
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a pentraxin domain
  • a single sequence motif, i.e. cholesterol binding sequence (CBS, AA. 35-47), wich is responsible for mediating the interactions of mCRP with diverse ligands, and is the major recognition site of mCRP, suggesting that this motif may be exploited to tune the proinflammatory actions of mCRP
  • mono polymer homomer , pentamer
    HOMOLOGY
    interspecies homolog to rattus Crp (67.1 pc)
    homolog to murine Crp (70.4 pc)
    Homologene
    FAMILY
  • pentraxin family of proteins
  • CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • acting as a bacterial catabolite activator protein, acute phase reactant, activating the classical complement pathway
  • having both a recognition and an effector function
  • displaying several functions associated with host defense
  • promoting agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine
  • may scavenge nuclear material released from damaged circulating cells
  • induces expression of adhesion molecules in endothelial cells and plays an important role in promoting the inflammatory component of atherosclerosis
  • may promote coagulation by enhancing the expression and activity of tissue factor and reducing that of tissue factor pathway inhibitor by activating NF-kappaB and extracellular signal-regulated kinase via FCGR2B
  • up-regulates CSF1 release from monocyte-derived macrophages and aortic endothelial cells and increased macrophage proliferation)
  • induces cell cycle arrest in G0/G1 phase and significant reduction in the levels of CDK4, CDK6 and cyclin D1 in cardiac myocytes
  • may play an important role in the cardiac remodeling process, in particular, given that cardiac myocytes are continually exposed to stresses from many exogenous sources responsible for the decrease in cardiac myocytes number
  • may affect events leading to cell death in cardiac myocytes, mediated by action mechanism such as cell cycle arrest
  • in women CRP may contribute to cardiovascular disease by increasing oxidative stress
  • emerges as an important mediator of cardiovascular lesions
  • enhances IgG-mediated phagocyte responses and thrombocytopenia
  • CRP may play a role in the pathological and physiological states of pregnancy
  • effect of CRP on the cardiac differentiation of embryonic stem (ES) cells
  • CRP may have a direct role on osteoclast and osteoblast differentiation via TLR signaling pathways
  • accumulation of CRP may regulate the skin inflammation and keratinocyte proliferation by modulating keratinocyte cytokine expression and adhesion to substrate
  • CRP may be a potent inducer of the anti-inflammatory cytokine IL10
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    a component
  • pentaxin (or pentraxin) have a discoid arrangement of five non-covalently bound subunits
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Ca2+ (2 ions per subunit)
  • protein
  • USF1-binding sites
  • binding to leptin and attenuating its physiological functions (contributing to leptin resistance and to increased adiposity)
  • lectin-like oxidized LDL receptor (OLR1), is a receptor for CRP
  • binding to histones
  • CRP binding is enhanced by conformational bending at the neck region of FCN1, to avoid steric hindrance by the COL domain
  • interacting with CFH (Factor H is one essential complement inhibitor that binds to the acute phase reactant C-reactive protein)
  • CRP induced FCAR surface expression, phagocytosis, and TNF secretion
  • significantly increased TP53 accumulation and phosphorylation at Ser15 in a concentration-dependent manner
  • POU2F1 acts as a transcriptional repressor of CRP expression
  • CRP-induced decline of protein S-nitrosylation by activating NFKB1 via reduction of S-nitrosylation of RELA, which may contribute to the endothelial dysfunction
  • chronic elevation of CRP observed in obese subjects may worsen LEP resistance, contributing to the pathogenesis of cardiovascular disease
  • CRP induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of BTG2 expression
  • protective effects of BDNF against CRP-induced inflammation in women
  • CRP decreased likely ADIPOOQ expression and multimerization, while CRP-induced decline in ADIPOQ might be mediated through the PI3K/Akt pathway
  • CRP is a ligand for CFHR1, suggesting that CFHR1 enhances, rather than inhibits, complement activation
  • CFH can bind pro-inflammatory monomeric CRP (mCRP) as well as the circulating pentameric form
  • elevated expression of CRP was characteristic of M1 macrophages rather than M2 through NFKB1 activation
  • cell & other
    REGULATION
    induced by IL-1 and IL-6
    Other regulated by USF1
    proteolytic cleavage of CRP between AAs 146 and 147 within the Ca2+ binding region abolished the APCS-binding site; however, the intact subunits of the pentameric CRP were capable of binding APCS
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in cardiovascular disease
    constitutional     --over  
    in response to inflammation and is purported to be a risk factor for atherogenesis
    constitutional     --over  
    in drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome
    constitutional     --over  
    obstructive sleep apnea syndrome (OSAS)
    constitutional     --over  
    in a substantial proportion of asymptomatic Hereditary angioedema (HAE) patients and levels of CRP increase significantly during an abdominal attack
    Susceptibility
  • to systemic lupus erythematosus (SLE)
  • to cardiovascular disease
  • to variation of CRP level
  • Variant & Polymorphism SNP
  • increasing the risk of systemic lupus erythematosus (SLE)
  • SNP in the promoter increasing the risk of high CRP level and cardiovascular disease
  • individuals homozygous for rs181704186-G have a mean CRP level of 0.23 mg/L, in contrast to individuals heterozygous for rs181704186 with mean CRP of 2.97 mg/L and major allele homozygotes with mean CRP of 4.11 mg/L
  • Candidate gene
    Marker
  • one of the most important biomarker for cardiovascular diseases
  • CRP measurements during the first trimester of pregnancy are helpful in predicting pre-eclampsia
  • high CRP level is significantly associated with higher late mortality in patients with chronic obstructive pulmonary disease (COPD)
  • ADIPOQ/CRP, may be useful for detecting metabolic dysregulation
  • maternal serum and fetal cord CRP levels were higher in the IUGR group (
  • Therapy target
    ANIMAL & CELL MODELS