Mammalian protein found in Homo sapiens
RNASE3
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Available structures
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PDB
| Ortholog search:
PDBe
RCSB
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List of PDB id codes
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4A2O
,
4X08
,
1DYT
,
4OXB
,
2LVZ
,
2KB5
,
4OXF
,
1QMT
,
4OWZ
,
1H1H
,
4A2Y
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Identifiers
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Aliases
| RNASE3
, ECP, RNS3, RAF1, ribonuclease A family member 3
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External IDs
| OMIM
:
131398
;
MGI
:
3528616
;
HomoloGene
:
136763
;
GeneCards
:
RNASE3
;
OMA
:
RNASE3 - orthologs
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Wikidata
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Eosinophil cationic protein (ECP)
also known as
ribonuclease 3
is a basic protein located in the
eosinophil
primary matrix.
[4]
In humans, the eosinophil cationic protein is encoded by the
RNASE3
gene
.
[5]
ECP is released during degranulation of
eosinophils
. This protein is related to inflammation and asthma because in these cases, there are increased levels of ECP in the body.
There are three
glycosylated
forms of ECP and consequently ECP has a range of molecular weights from 18-22 kDa.
[6]
Function
[
edit
]
Eosinophil cationic protein and the sequence related
eosinophil-derived neurotoxin
(
RNASE2
) are both members of the
Ribonuclease A
superfamily. Both proteins possess
neurotoxic
,
helmintho
-toxic, and
ribonucleo
-lytic activities. Eosinophil cationic protein is localized to the
granule
matrix of the
eosinophil
.
[7]
Ribonuclease activity and cytotoxicity
[
edit
]
The ribonuclease activity of ECP is not essential for cytotoxicity.
[8]
When the two known
ribonuclease
active-site residues are modified to non-functional counterparts (Lysine at position 38 to Arginine and Histidine at position 128 to Aspartate)
[9]
and compared to the wild-type ECP, the mutated ECP retains its cytotoxicity but no longer has its ribonuclease activity. The experiment confirmed that converting the two amino acids to non-functional counterparts did inhibit ECP’s ribonuclease activity. However, ECP retained its anti-parasitic activity. Also, it did not change the production and transportation of ECP in bacteria.
ECP is a potent cytotoxic protein capable of killing cells of guinea pig tracheal epithelium,
[10]
mammalian leukemia,
[11]
epidermis carcinoma,
[10]
and breast carcinoma,
[12]
as well as non-mammalian cells such as parasites, bacteria, and viruses.
[13]
Mature ECP is cytotoxic to human
bronchial
epithelial (
BEAS-2B
) cells by specific binding to cell surface heparan sulfate proteoglycans (HSPGs) followed by endocytosis.
[14]
ECP-induced apoptosis
[
edit
]
Studies show that ECP, along with other RNases including EDN, had been reported to induce
apoptosis
in cells. A latest study indicated that ECP caused cytotoxicity in HL-60 and HeLa cells via caspase-3 like activity.
[16]
Accordingly, cytotoxic RNases play an important role in cell death. However, the mechanism of ECP-induced apoptosis is still not fully verified. Recent studies have shown that eosinophils can induce epithelial cell death via apoptosis and
necrosis
.
[17]
ECP triggers apoptosis by caspase-8 activation through mitochondria-independent pathway.
[15]
Increases in chromatin condensation, sub-G1 population, PARP cleavage, and DNA fragmentation indicate that ECP induces apoptosis in human bronchial epithelial (BEAS-2B) cells.
[15]
Clinical significance
[
edit
]
Eosinophil granulocytes
appear in large numbers in inflammation sites and in response to certain parasitic infections. These cytoplasmic granules contain positively charged proteins that characterize the cells. ECP is one of the four highly basic proteins that enter the surrounding tissues when activated eosinophils degranulate. Although circulating ECP levels can vary widely among patients, some studies show that serum ECP measurements are useful in monitoring many active inflammatory diseases.
[18]
ECP concentrations in plasma and other body fluids increase during inflammatory reactions marked by activated eosinophils.
[19]
Serum ECP levels are also a useful, objective measurement for asthma severity. Increased ECP levels correspond to symptom onset. In seasonal asthmatic patients, ECP measurement reflected changes in disease activity throughout the year.
[20]
There are several mechanisms that can be combined to generate an
asthma
attack, including specific
IgE
antibodies, activated inflammatory cells, neurogenic mechanisms, hyperresponsiveness and individual hormonal imbalances. Allergic reactions in the lung typically have two phases. The late phase typically occurs several hours after exposure, upon which
eosinophils
accumulate in the
bronchus
and release granule proteins that cause bronchial irritability. ECP is also toxic to neurons, some epithelial cell lines, and isolated myocardial cells.
[21]
This could be a reason for itching disorders of the skin.
Serum ECP concentrations have also been linked to
atopic dermatitis
(AD) activity. ECP correlates with the symptoms (
lichenification
,
sleep deprivation
,
erythema
,
papules
,
pruritus
and
excoriations
) for AD and also correlates with the total clinical score.
[21]
Serum ECP measurement for assessing asthma severity, monitoring therapy, and indicating severity of certain inflammatory skin conditions present an advantage over subjective clinical measures that are prone to inconsistencies due to broad variability of individual investigator and patient assessments, especially in young children.
The normal
reference range for blood tests
for eosinophil cationic protein is between 2.3 and 16 μg/L.
[22]
See also
[
edit
]
References
[
edit
]
- ^
a
b
c
GRCh38: Ensembl release 89: ENSG00000169397
–
Ensembl
, May 2017
- ^
"Human PubMed Reference:"
.
National Center for Biotechnology Information, U.S. National Library of Medicine
.
- ^
"Mouse PubMed Reference:"
.
National Center for Biotechnology Information, U.S. National Library of Medicine
.
- ^
Boix E, Carreras E, Nikolovski Z, Cuchillo CM, Nogues MV (June 2001). "Identification and characterization of human eosinophil cationic protein by an epitope-specific antibody".
J. Leukoc. Biol
.
69
(6): 1027?35.
doi
:
10.1189/jlb.69.6.1027
.
PMID
11404391
.
S2CID
11326107
.
- ^
Mastrianni DM, Eddy RL, Rosenberg HF, Corrette SE, Shows TB, Tenen DG, Ackerman SJ (May 1992). "Localization of the human eosinophil Charcot-Leyden crystal protein (lysophospholipase) gene (CLC) to chromosome 19 and the human ribonuclease 2 (eosinophil-derived neurotoxin) and ribonuclease 3 (eosinophil cationic protein) genes (RNS2 and RNS3) to chromosome 14".
Genomics
.
13
(1): 240?2.
doi
:
10.1016/0888-7543(92)90237-M
.
PMID
1577491
.
- ^
Lee BioSolutions, Inc.
http://www.leebio.com/eosinophil-cationic-protein-human-P359.html
Archived
2012-03-06 at the
Wayback Machine
- ^
Hamann KJ, Ten RM, Loegering DA, Jenkins RB, Heise MT, Schad CR, Pease LR, Gleich GJ, Barker RL (August 1990). "Structure and chromosome localization of the human eosinophil-derived neurotoxin and eosinophil cationic protein genes: evidence for intronless coding sequences in the ribonuclease gene superfamily".
Genomics
.
7
(4): 535?46.
doi
:
10.1016/0888-7543(90)90197-3
.
PMID
2387583
.
- ^
Rosenberg HF (April 1995).
"Recombinant human eosinophil cationic protein. Ribonuclease activity is not essential for cytotoxicity"
.
J. Biol. Chem
.
270
(14): 7876?81.
doi
:
10.1074/jbc.270.14.7876
.
PMID
7713881
.
- ^
Lehrer RI, Szklarek D, Barton A, Ganz T, Hamann KJ, Gleich GJ (June 1989).
"Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein"
.
Journal of Immunology
.
142
(12): 4428?34.
doi
:
10.4049/jimmunol.142.12.4428
.
PMID
2656865
.
S2CID
46456095
.
- ^
a
b
Motojima S, Frigas E, Loegering DA, Gleich GJ (March 1989). "Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro".
Am. Rev. Respir. Dis
.
139
(3): 801?5.
doi
:
10.1164/ajrccm/139.3.801
.
PMID
2923379
.
- ^
Carreras E, Boix E, Navarro S, Rosenberg HF, Cuchillo CM, Nogues MV (April 2005). "Surface-exposed amino acids of eosinophil cationic protein play a critical role in the inhibition of mammalian cell proliferation".
Mol. Cell. Biochem
.
272
(1?2): 1?7.
doi
:
10.1007/s11010-005-4777-2
.
PMID
16010966
.
S2CID
41675640
.
- ^
Ali S, Kaur J, Patel KD (July 2000).
"Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation"
.
Am. J. Pathol
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157
(1): 313?21.
doi
:
10.1016/S0002-9440(10)64542-7
.
PMC
1850201
.
PMID
10880401
.
- ^
Venge P (January 2004).
"Monitoring the allergic inflammation"
.
Allergy
.
59
(1): 26?32.
doi
:
10.1046/j.1398-9995.2003.00386.x
.
PMID
14674929
.
- ^
Fan TC, Chang HT, Chen IW, Wang HY, Chang MD (December 2007).
"A heparan sulfate-facilitated and raft-dependent macropinocytosis of eosinophil cationic protein"
.
Traffic
.
8
(12): 1778?95.
doi
:
10.1111/j.1600-0854.2007.00650.x
.
PMID
17944807
.
S2CID
23093550
.
- ^
a
b
c
Chang KC, Lo CW, Fan TC, Chang MD, Shu CW, Chang CH, Chung CT, Fang SL, Chao CC, Tsai JJ, Lai YK (2010).
"TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B Cells"
.
BMC Cell Biol
.
11
: 6.
doi
:
10.1186/1471-2121-11-6
.
PMC
2819994
.
PMID
20089176
.
- ^
Navarro S, Aleu J, Jimenez M, Boix E, Cuchillo CM, Nogues MV (January 2008).
"The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane"
.
Cell. Mol. Life Sci
.
65
(2): 324?37.
doi
:
10.1007/s00018-007-7499-7
.
PMC
11131711
.
PMID
18087674
.
S2CID
30746145
.
- ^
Trautmann A, Schmid-Grendelmeier P, Kruger K, Crameri R, Akdis M, Akkaya A, Brocker EB, Blaser K, Akdis CA (February 2002).
"T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma"
.
The Journal of Allergy and Clinical Immunology
.
109
(2): 329?37.
doi
:
10.1067/mai.2002.121460
.
PMID
11842305
.
- ^
Wardlaw AJ (August 1994).
"Eosinophils in the 1990s: new perspectives on their role in health and disease"
.
Postgrad Med J
.
70
(826): 536?52.
doi
:
10.1136/pgmj.70.826.536
.
PMC
2397687
.
PMID
7937446
.
- ^
D'Amato G, Liccardi G, Russo M, Saggese M, D'Amato M (April 1996). "Measurement of serum levels of eosinophil cationic protein to monitor patients with seasonal respiratory allergy induced by Parietaria pollen (treated and untreated with specific immunotherapy)".
Allergy
.
51
(4): 245?50.
doi
:
10.1111/j.1398-9995.1996.tb00075.x
.
PMID
8792921
.
- ^
Tomassini M, Magrini L, De Petrillo G, Adriani E, Bonini S, Balsano F, Bonini S (June 1996).
"Serum levels of eosinophil cationic protein in allergic diseases and natural allergen exposure"
.
The Journal of Allergy and Clinical Immunology
.
97
(6): 1350?5.
doi
:
10.1016/S0091-6749(96)70204-X
.
PMID
8648032
.
- ^
a
b
Czech W, Krutmann J, Schopf E, Kapp A (April 1992). "Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis".
Br. J. Dermatol
.
126
(4): 351?5.
doi
:
10.1111/j.1365-2133.1992.tb00677.x
.
PMID
1571256
.
S2CID
23425301
.
- ^
Reference range list from Uppsala University Hospital ("Laborationslista"). Artnr 40284 Sj74a. Issued on April 22, 2008
Further reading
[
edit
]
- Plager DA, Davis MD, Andrews AG, et al. (2009).
"Eosinophil Ribonucleases and Their Cutaneous Lesion-Forming Activity"
.
Journal of Immunology
.
183
(6): 4013?20.
doi
:
10.4049/jimmunol.0900055
.
PMC
2852253
.
PMID
19717523
.
- Nielsen LP, Peterson CG, Dahl R (2009).
"Serum eosinophil granule proteins predict asthma risk in allergic rhinitis"
.
Allergy
.
64
(5): 733?7.
doi
:
10.1111/j.1398-9995.2008.01869.x
.
PMID
19133919
.
S2CID
17857088
.
- Behnecke A, Mayr S, Schick B, et al. (2008). "Evaluation of ECP release from intact tissue biopsies from patients with nasal polyps".
Inflamm. Res
.
57
(Suppl 1): S65?6.
doi
:
10.1007/s00011-007-0632-0
.
PMID
18345486
.
S2CID
28257312
.
- Eberlein B, Gulyas A, Schultz K, et al. (2009). "Benefits of alpine mountain climate of Bavaria in patients with allergic diseases and chronic obstructive pulmonary disease: results from the AURA* study".
J Investig Allergol Clin Immunol
.
19
(2): 159?61.
PMID
19476022
.
- Torrent M, Navarro S, Moussaoui M, et al. (2008). "Eosinophil cationic protein high-affinity binding to bacteria-wall lipopolysaccharides and peptidoglycans".
Biochemistry
.
47
(11): 3544?55.
doi
:
10.1021/bi702065b
.
PMID
18293932
.
- Parwez Q, Stemmler S, Epplen JT, Hoffjan S (2008).
"Variation in genes encoding eosinophil granule proteins in atopic dermatitis patients from Germany"
.
J Negat Results Biomed
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7
: 9.
doi
:
10.1186/1477-5751-7-9
.
PMC
2596079
.
PMID
19014520
.
- Zagai U, Lundahl J, Klominek J, et al. (2009).
"Eosinophil cationic protein stimulates migration of human lung fibroblasts in vitro"
.
Scand. Journal of Immunology
.
69
(4): 381?6.
doi
:
10.1111/j.1365-3083.2009.02233.x
.
PMID
19284504
.
- Torrent M, de la Torre BG, Nogues VM, et al. (2009).
"Bactericidal and membrane disruption activities of the eosinophil cationic protein are largely retained in an N-terminal fragment"
(PDF)
.
Biochem. J
.
421
(3): 425?34.
doi
:
10.1042/BJ20082330
.
PMID
19450231
.
S2CID
15170520
.
- Fukuda T, Iwata M, Kitazoe M, et al. (2009). "Human eosinophil cationic protein enhances stress fiber formation in Balb/c 3T3 fibroblasts and differentiation of rat neonatal cardiomyocytes".
Growth Factors
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27
(4): 228?36.
doi
:
10.1080/08977190902987149
.
PMID
19521893
.
S2CID
13245523
.
- Torrent M, Sanchez D, Buzan V, et al. (2009).
"Comparison of the membrane interaction mechanism of two antimicrobial RNases: RNase 3/ECP and RNase 7"
.
Biochim. Biophys. Acta
.
1788
(5): 1116?25.
doi
:
10.1016/j.bbamem.2009.01.013
.
PMID
19366593
.
- Dominguez-Ortega J, Perez-Bedmar J, Rodriguez-Jimenez B, et al. (2009). "Eosinophilic esophagitis due to profilin allergy".
J Investig Allergol Clin Immunol
.
19
(4): 338?9.
PMID
19639743
.
- Fan TC, Fang SL, Hwang CS, et al. (2008).
"Characterization of molecular interactions between eosinophil cationic protein and heparin"
.
J. Biol. Chem
.
283
(37): 25468?74.
doi
:
10.1074/jbc.M803516200
.
PMID
18593710
.
- Kang I, An XH, Oh YK, et al. (2010). "Identification of polymorphisms in the RNase3 gene and the association with allergic rhinitis".
Eur Arch Otorhinolaryngol
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267
(3): 391?5.
doi
:
10.1007/s00405-009-1103-8
.
PMID
19760211
.
S2CID
8311866
.
- Yuksel H, Yilmaz O, Sogut A, et al. (2009). "Correlation of quality of life with clinical parameters and eosinophilic cation protein levels in children with allergic rhinoconjunctivitis".
Int. Arch. Allergy Immunol
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148
(1): 18?22.
doi
:
10.1159/000151501
.
PMID
18716399
.
S2CID
24634035
.
- Rubin J, Zagai U, Blom K, et al. (2009).
"The coding ECP 434(G>C) gene polymorphism determines the cytotoxicity of ECP but has minor effects on fibroblast-mediated gel contraction and no effect on RNase activity"
.
Journal of Immunology
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183
(1): 445?51.
doi
:
10.4049/jimmunol.0803912
.
PMID
19542456
.
- Laurents DV, Bruix M, Jimenez MA, et al. (2009). "The (1)H, (13)C, (15)N resonance assignment, solution structure, and residue level stability of eosinophil cationic protein/RNase 3 determined by NMR spectroscopy".
Biopolymers
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91
(12): 1018?28.
doi
:
10.1002/bip.21152
.
PMID
19189375
.
S2CID
205493978
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- Peona V, De Amici M, Quaglini S, et al. (2010). "Serum eosinophilic cationic protein: is there a role in respiratory disorders?".
J Asthma
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47
(2): 131?4.
doi
:
10.3109/02770900903497170
.
PMID
20170318
.
S2CID
28187167
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- Shin SY, Choi SJ, Hur GY, et al. (2009).
"Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue"
(PDF)
.
Pediatr Allergy Immunol
.
20
(2): 134?41.
doi
:
10.1111/j.1399-3038.2008.00756.x
.
PMID
18657051
.
S2CID
205415552
.
- Woschnagg C, Rubin J, Venge P (2009).
"Eosinophil cationic protein (ECP) is processed during secretion"
.
Journal of Immunology
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183
(6): 3949?54.
doi
:
10.4049/jimmunol.0900509
.
PMID
19692640
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External links
[
edit
]
PDB gallery
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-
1dyt
: X-RAY CRYSTAL STRUCTURE OF ECP (RNASE 3) AT 1.75 A
-
1h1h
: CRYSTAL STRUCTURE OF EOSINOPHIL CATIONIC PROTEIN IN COMPLEX WITH 2',5'-ADP AT 2.0 A RESOLUTION REVEALS THE DETAILS OF THE RIBONUCLEOLYTIC ACTIVE SITE
-
1qmt
: RECOMBINANT HUMAN EOSINOPHIL CATIONIC PROTEIN
|