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{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''Complement C4-A''' is a [[protein]] that in humans is encoded by the ''C4A'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: C4A complement component 4A (Rodgers blood group)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=720| accessdate = }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
{{GNF_Protein_box
| image = PBB_Protein_C4A_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1hzf.
| Name = Complement component 4A (Rodgers blood group)
| HGNCid = 1323
| Symbol = C4A
| AltSymbols =; C4; C4A2; C4A3; C4A4; C4A6; C4B; C4S; CO4; CPAMD2; RG; C4A; C4A13; C4A91; C4B1; C4B12; C4B2; C4B3; C4B5; C4F; CH; CPAMD3
| OMIM = 120810
| ECnumber = 
| Homologene = 36030
| MGIid = 88228
| GeneAtlas_image1 = PBB_GE_C4A_208451_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_C4A_214428_x_at_tn.png
| Function = {{GNF_GO|id=GO:0004866 |text = endopeptidase inhibitor activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}}
| Process = {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006956 |text = complement activation}} {{GNF_GO|id=GO:0006958 |text = complement activation, classical pathway}} {{GNF_GO|id=GO:0045087 |text = innate immune response}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 720
    | Hs_Ensembl = ENSG00000204319
    | Hs_RefseqProtein = NP_009224
    | Hs_RefseqmRNA = NM_007293
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 6
    | Hs_GenLoc_start = 32090517
    | Hs_GenLoc_end = 32111174
    | Hs_Uniprot = P0C0L4
    | Mm_EntrezGene = 12268
    | Mm_Ensembl =
    | Mm_RefseqmRNA = XM_001002697
    | Mm_RefseqProtein = XP_001002697
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
{{SI}}
{{CMG}}


== Function ==


This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic [[lupus]] erythematosus and type I diabetes mellitus.<ref>{{cite journal | vauthors = Dawkins RL, Uko G, Christiansen FT, Kay PH | title = Low C4 concentrations in insulin dependent diabetes mellitus | journal = British Medical Journal | volume = 287 | issue = 6395 | pages = 839 | date = Sep 1983 | pmid = 6412852 | pmc = 1549128 | doi = 10.1136/bmj.287.6395.839-b }}</ref><ref>{{cite journal | vauthors = Vergani D, Johnston C, B-Abdullah N, Barnett AH | title = Low serum C4 concentrations: an inherited predisposition to insulin dependent diabetes? | journal = British Medical Journal | volume = 286 | issue = 6369 | pages = 926–8 | date = Mar 1983 | pmid = 6403137 | pmc = 1547358 | doi = 10.1136/bmj.286.6369.926 }}</ref><ref>{{cite journal | vauthors = Mijovic CH, Fletcher JA, Bradwell AR, Barnett AH | title = Low C4 levels in type 1 (insulin-dependent) diabetes | journal = Diabetologia | volume = 30 | issue = 10 | pages = 824 | date = Oct 1987 | pmid = 3428499 | doi = 10.1007/bf00275752 }}</ref><ref>{{cite journal | vauthors = Thomsen M, Mølvig J, Zerbib A, de Preval C, Abbal M, Dugoujon JM, Ohayon E, Svejgaard A, Cambon-Thomsen A, Nerup J | title = The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes | journal = Immunogenetics | volume = 28 | issue = 5 | pages = 320–7 | year = 1988 | pmid = 3139557 | doi = 10.1007/BF00364230 }}</ref><ref>{{cite journal | vauthors = Jenhani F, Bardi R, Gorgi Y, Ayed K, Jeddi M | title = C4 polymorphism in multiplex families with insulin dependent diabetes in the Tunisian population: standard C4 typing methods and RFLP analysis | journal = Journal of Autoimmunity | volume = 5 | issue = 2 | pages = 149–60 | date = Apr 1992 | pmid = 1352685 | doi = 10.1016/0896-8411(92)90196-w }}</ref><ref>{{cite journal|vauthors=Lhotta K, Auinger M, Kronenberg F, Irsigler K, König P|title=Polymorphism of complement C4 and susceptibility to IDDM and microvascular complications|journal=Diabetes Care|year=1996|volume=19|issue=1|pages=53&ndash;55|doi=10.2337/diacare.19.1.53}}</ref> This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene.<ref name="entrez" />


'''Complement component 4A (Rodgers blood group)''', also known as '''C4A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: C4A complement component 4A (Rodgers blood group)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=720| accessdate = }}</ref>
== See also ==
* [[Complement component 4]]
** [[Complement component 4B]]
* [[HLA A1-B8-DR3-DQ2|HLA A1-B8-DR3-DQ2 haplotype]]
* [[Complement system]]
* [[Complement deficiency]]


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene.<ref name="entrez">{{cite web | title = Entrez Gene: C4A complement component 4A (Rodgers blood group)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=720| accessdate = }}</ref>
}}


==See also==
== References ==
* [[Complement component 4]]
{{reflist}}


==References==
==External links==
{{reflist}}
* {{UCSC gene info|C4A}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Hugli TE | title = Biochemistry and biology of anaphylatoxins | journal = Complement | volume = 3 | issue = 3 | pages = 111–27 | year = 1987 | pmid = 3542363 | doi =  }}
| citations =
* {{cite journal | vauthors = Yu CY | title = Molecular genetics of the human MHC complement gene cluster | journal = Experimental and Clinical Immunogenetics | volume = 15 | issue = 4 | pages = 213–30 | year = 1999 | pmid = 10072631 | doi = 10.1159/000019075 }}
*{{cite journal | author=Hugli TE |title=Biochemistry and biology of anaphylatoxins. |journal=Complement |volume=3 |issue= 3 |pages= 111-27 |year= 1987 |pmid= 3542363 |doi=  }}
* {{cite journal | vauthors = Anderson MJ, Milner CM, Cotton RG, Campbell RD | title = The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect | journal = Journal of Immunology | volume = 148 | issue = 9 | pages = 2795–802 | date = May 1992 | pmid = 1573268 | doi =  }}
*{{cite journal | author=Yu CY |title=Molecular genetics of the human MHC complement gene cluster. |journal=Exp. Clin. Immunogenet. |volume=15 |issue= 4 |pages= 213-30 |year= 1999 |pmid= 10072631 |doi= }}
* {{cite journal | vauthors = Hessing M, van 't Veer C, Hackeng TM, Bouma BN, Iwanaga S | title = Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein | journal = FEBS Letters | volume = 271 | issue = 1-2 | pages = 131–6 | date = Oct 1990 | pmid = 1699796 | doi = 10.1016/0014-5793(90)80389-Z }}
*{{cite journal | author=Anderson MJ, Milner CM, Cotton RG, Campbell RD |title=The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect. |journal=J. Immunol. |volume=148 |issue= 9 |pages= 2795-802 |year= 1992 |pmid= 1573268 |doi=  }}
* {{cite journal | vauthors = Yu CY | title = The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene | journal = Journal of Immunology | volume = 146 | issue = 3 | pages = 1057–66 | date = Feb 1991 | pmid = 1988494 | doi =  }}
*{{cite journal | author=Hessing M, van 't Veer C, Hackeng TM, ''et al.'' |title=Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein. |journal=FEBS Lett. |volume=271 |issue= 1-2 |pages= 131-6 |year= 1990 |pmid= 1699796 |doi= }}
* {{cite journal | vauthors = Ghiso J, Saball E, Leoni J, Rostagno A, Frangione B | title = Binding of cystatin C to C4: the importance of sense-antisense peptides in their interaction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 4 | pages = 1288–91 | date = Feb 1990 | pmid = 2304899 | pmc = 53459 | doi = 10.1073/pnas.87.4.1288 }}
*{{cite journal | author=Yu CY |title=The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene. |journal=J. Immunol. |volume=146 |issue= 3 |pages= 1057-66 |year= 1991 |pmid= 1988494 |doi=  }}
* {{cite journal | vauthors = Yu CY, Belt KT, Giles CM, Campbell RD, Porter RR | title = Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity | journal = The EMBO Journal | volume = 5 | issue = 11 | pages = 2873–81 | date = Nov 1986 | pmid = 2431902 | pmc = 1167237 | doi =  }}
*{{cite journal | author=Ghiso J, Saball E, Leoni J, ''et al.'' |title=Binding of cystatin C to C4: the importance of sense-antisense peptides in their interaction. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 4 |pages= 1288-91 |year= 1990 |pmid= 2304899 |doi= }}
* {{cite journal | vauthors = Speiser PW, White PC | title = Structure of the human RD gene: a highly conserved gene in the class III region of the major histocompatibility complex | journal = Dna | volume = 8 | issue = 10 | pages = 745–51 | date = Dec 1989 | pmid = 2612324 | doi = 10.1089/dna.1989.8.745 }}
*{{cite journal | author=Yu CY, Belt KT, Giles CM, ''et al.'' |title=Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. |journal=EMBO J. |volume=5 |issue= 11 |pages= 2873-81 |year= 1987 |pmid= 2431902 |doi=  }}
* {{cite journal | vauthors = Palsdottir A, Fossdal R, Arnason A, Edwards JH, Jensson O | title = Heterogeneity of human C4 gene size. A large intron (6.5 kb) is present in all C4A genes and some C4B genes | journal = Immunogenetics | volume = 25 | issue = 5 | pages = 299–304 | year = 1987 | pmid = 2883116 | doi = 10.1007/BF00404422 }}
*{{cite journal | author=Speiser PW, White PC |title=Structure of the human RD gene: a highly conserved gene in the class III region of the major histocompatibility complex. |journal=DNA |volume=8 |issue= 10 |pages= 745-51 |year= 1990 |pmid= 2612324 |doi= }}
* {{cite journal | vauthors = Kishore N, Shah D, Skanes VM, Levine RP | title = The fluid-phase binding of human C4 and its genetic variants, C4A3 and C4B1, to immunoglobulins | journal = Molecular Immunology | volume = 25 | issue = 9 | pages = 811–9 | date = Sep 1988 | pmid = 3264881 | doi = 10.1016/0161-5890(88)90117-4 }}
*{{cite journal | author=Palsdottir A, Fossdal R, Arnason A, ''et al.'' |title=Heterogeneity of human C4 gene size. A large intron (6.5 kb) is present in all C4A genes and some C4B genes. |journal=Immunogenetics |volume=25 |issue= 5 |pages= 299-304 |year= 1987 |pmid= 2883116 |doi= }}
* {{cite journal | vauthors = Chakravarti DN, Campbell RD, Porter RR | title = The chemical structure of the C4d fragment of the human complement component C4 | journal = Molecular Immunology | volume = 24 | issue = 11 | pages = 1187–97 | date = Nov 1987 | pmid = 3696167 | doi = 10.1016/0161-5890(87)90165-9 }}
*{{cite journal | author=Kishore N, Shah D, Skanes VM, Levine RP |title=The fluid-phase binding of human C4 and its genetic variants, C4A3 and C4B1, to immunoglobulins. |journal=Mol. Immunol. |volume=25 |issue= 9 |pages= 811-9 |year= 1989 |pmid= 3264881 |doi= }}
* {{cite journal | vauthors = Belt KT, Yu CY, Carroll MC, Porter RR | title = Polymorphism of human complement component C4 | journal = Immunogenetics | volume = 21 | issue = 2 | pages = 173–80 | year = 1985 | pmid = 3838531 | doi = 10.1007/BF00364869 }}
*{{cite journal | author=Chakravarti DN, Campbell RD, Porter RR |title=The chemical structure of the C4d fragment of the human complement component C4. |journal=Mol. Immunol. |volume=24 |issue= 11 |pages= 1187-97 |year= 1988 |pmid= 3696167 |doi= }}
* {{cite journal | vauthors = Hortin G, Sims H, Strauss AW | title = Identification of the site of sulfation of the fourth component of human complement | journal = The Journal of Biological Chemistry | volume = 261 | issue = 4 | pages = 1786–93 | date = Feb 1986 | pmid = 3944109 | doi =  }}
*{{cite journal | author=Belt KT, Yu CY, Carroll MC, Porter RR |title=Polymorphism of human complement component C4. |journal=Immunogenetics |volume=21 |issue= 2 |pages= 173-80 |year= 1985 |pmid= 3838531 |doi= }}
* {{cite journal | vauthors = Moon KE, Gorski JP, Hugli TE | title = Complete primary structure of human C4a anaphylatoxin | journal = The Journal of Biological Chemistry | volume = 256 | issue = 16 | pages = 8685–92 | date = Aug 1981 | pmid = 6167582 | doi =  }}
*{{cite journal | author=Hortin G, Sims H, Strauss AW |title=Identification of the site of sulfation of the fourth component of human complement. |journal=J. Biol. Chem. |volume=261 |issue= 4 |pages= 1786-93 |year= 1986 |pmid= 3944109 |doi=  }}
* {{cite journal | vauthors = Palsdottir A, Cross SJ, Edwards JH, Carroll MC | title = Correlation between a DNA restriction fragment length polymorphism and C4A6 protein | journal = Nature | volume = 306 | issue = 5943 | pages = 615–6 | year = 1984 | pmid = 6316164 | doi = 10.1038/306615a0 }}
*{{cite journal | author=Moon KE, Gorski JP, Hugli TE |title=Complete primary structure of human C4a anaphylatoxin. |journal=J. Biol. Chem. |volume=256 |issue= 16 |pages= 8685-92 |year= 1981 |pmid= 6167582 |doi=  }}
* {{cite journal | vauthors = Belt KT, Carroll MC, Porter RR | title = The structural basis of the multiple forms of human complement component C4 | journal = Cell | volume = 36 | issue = 4 | pages = 907–14 | date = Apr 1984 | pmid = 6546707 | doi = 10.1016/0092-8674(84)90040-0 }}
*{{cite journal | author=Palsdottir A, Cross SJ, Edwards JH, Carroll MC |title=Correlation between a DNA restriction fragment length polymorphism and C4A6 protein. |journal=Nature |volume=306 |issue= 5943 |pages= 615-6 |year= 1984 |pmid= 6316164 |doi= }}
* {{cite journal | vauthors = Carroll MC, Campbell RD, Bentley DR, Porter RR | title = A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B | journal = Nature | volume = 307 | issue = 5948 | pages = 237–41 | year = 1984 | pmid = 6559257 | doi = 10.1038/307237a0 }}
*{{cite journal | author=Belt KT, Carroll MC, Porter RR |title=The structural basis of the multiple forms of human complement component C4. |journal=Cell |volume=36 |issue= 4 |pages= 907-14 |year= 1984 |pmid= 6546707 |doi= }}
* {{cite journal | vauthors = Carroll MC, Porter RR | title = Cloning of a human complement component C4 gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 1 | pages = 264–7 | date = Jan 1983 | pmid = 6572000 | pmc = 393353 | doi = 10.1073/pnas.80.1.264 }}
*{{cite journal | author=Carroll MC, Campbell RD, Bentley DR, Porter RR |title=A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. |journal=Nature |volume=307 |issue= 5948 |pages= 237-41 |year= 1984 |pmid= 6559257 |doi= }}
* {{cite journal | vauthors = Whitehead AS, Goldberger G, Woods DE, Markham AF, Colten HR | title = Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 17 | pages = 5387–91 | date = Sep 1983 | pmid = 6577433 | pmc = 384261 | doi = 10.1073/pnas.80.17.5387 }}
*{{cite journal | author=Carroll MC, Porter RR |title=Cloning of a human complement component C4 gene. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 1 |pages= 264-7 |year= 1983 |pmid= 6572000 |doi= }}
*{{cite journal | author=Whitehead AS, Goldberger G, Woods DE, ''et al.'' |title=Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 17 |pages= 5387-91 |year= 1983 |pmid= 6577433 |doi= }}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=720}}


{{Complement system}}
{{Complement system}}


[[Category:Blood]]
[[Category:Hematology]]
[[Category:Transfusion medicine]]
[[Category:Transfusion medicine]]
[[Category:Hematology]]
[[Category:Blood antigen systems]]
[[Category:Blood antigen systems]]
[[Category:Complement system]]
[[Category:Complement system]]
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{{gene-6-stub}}

Latest revision as of 13:12, 23 October 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Complement C4-A is a protein that in humans is encoded by the C4A gene.[1]

Function

This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus.[2][3][4][5][6][7] This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene.[1]

See also


References

  1. ↑ 1.0 1.1 "Entrez Gene: C4A complement component 4A (Rodgers blood group)".
  2. ↑ Dawkins RL, Uko G, Christiansen FT, Kay PH (Sep 1983). "Low C4 concentrations in insulin dependent diabetes mellitus". British Medical Journal. 287 (6395): 839. doi:10.1136/bmj.287.6395.839-b. PMC 1549128. PMID 6412852.
  3. ↑ Vergani D, Johnston C, B-Abdullah N, Barnett AH (Mar 1983). "Low serum C4 concentrations: an inherited predisposition to insulin dependent diabetes?". British Medical Journal. 286 (6369): 926–8. doi:10.1136/bmj.286.6369.926. PMC 1547358. PMID 6403137.
  4. ↑ Mijovic CH, Fletcher JA, Bradwell AR, Barnett AH (Oct 1987). "Low C4 levels in type 1 (insulin-dependent) diabetes". Diabetologia. 30 (10): 824. doi:10.1007/bf00275752. PMID 3428499.
  5. ↑ Thomsen M, Mølvig J, Zerbib A, de Preval C, Abbal M, Dugoujon JM, Ohayon E, Svejgaard A, Cambon-Thomsen A, Nerup J (1988). "The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes". Immunogenetics. 28 (5): 320–7. doi:10.1007/BF00364230. PMID 3139557.
  6. ↑ Jenhani F, Bardi R, Gorgi Y, Ayed K, Jeddi M (Apr 1992). "C4 polymorphism in multiplex families with insulin dependent diabetes in the Tunisian population: standard C4 typing methods and RFLP analysis". Journal of Autoimmunity. 5 (2): 149–60. doi:10.1016/0896-8411(92)90196-w. PMID 1352685.
  7. ↑ Lhotta K, Auinger M, Kronenberg F, Irsigler K, König P (1996). "Polymorphism of complement C4 and susceptibility to IDDM and microvascular complications". Diabetes Care. 19 (1): 53&ndash, 55. doi:10.2337/diacare.19.1.53.

External links

Further reading


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