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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1q23.2      Physical location : 159.682.079 - 159.684.379
Synonym name	pentraxin 1
Synonym symbol(s)	PTX1, MGC88244, MGC149895

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000567 2 - 2024 NP_000558 25 224 - 1992 1477104 NM_001329058 4 - 691 NP_001315987 - 91 - 1992 1477104 NM_001329057 3 - 1316 NP_001315986 - 224 - 1992 1477104

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       highly Urinary bladder       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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