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C1q deficiency 123 C2 and B genes
C1q deficiency
Deficiency of C1q may be found in association with
lupus-like syndromes. C1r deficiency, which is inherited
as an autosomal-recessive trait, may be associated with
respiratory tract infections, glomerulonephritis, and skin
manifestations that resemble a systemic lupus erythematosus
(SLE)-like disease. C1s deficiency is transmitted as
an autosomal-dominant trait, and patients may again show
SLE-like signs and symptoms. Their antigen–antibody
complexes can persist without resolution.
C1q receptor (C1q-R)
A receptor that binds the collagen segments of C1q fixed to
antigen–antibody complexes. The C1q globular head is the
site of binding of the Fc region of immunoglobulin. Thus,
the C1q-R can facilitate the attachment of antigen–antibody
complexes to cells expressing C1q-R and Fc receptors.
Neutrophils, B cells, monocytes, macrophages, natural
killer (NK) cells, endothelial cells, platelets, and fibroblasts
all express C1q-R. C1q-R stimulation on neutrophils may
lead to a respiratory burst.
C1r
A subcomponent of C1, the first component of complement
in the classical activation pathway. It is a serine esterase.
Ca 2+ binds C1r molecules to the stem of a C1q molecule.
Following binding of at least two globular regions of C1q
with immunoglobulin M (IgM) or IgG, C1r is split into a
463-amino acid residue α chain, the N terminal fragment,
and a 243-amino acid residue carboxyl-terminal β chain
fragment where the active site is situated. C1s becomes
activated when C1r splits its arginine–isoleucine bond.
Refer also to C1.
C1s
A serine esterase that is a subcomponent of C1, the first
component of complement in the classical activation
pathway. Ca 2+ binds two C1s molecules to the C1q stalk.
Following activation, C1r splits the single-chain, 85-kDa
C1s molecule into a 431-amino acid residue A chain and
a 243-amino acid residue B chain where the active site is
located. C1s splits a C4 arginine–alanine bond and a C2
arginine–lysine bond.
5'
123
SCR domains vWF Type A domain
456
7
C2 Gene
1kb
Serine
protease
domain
8 9 10 – 18
Schematic representation of the exon/intron organization of the human C2
gene. Exons, represented by vertical bars, are numbered.
Class II
3'
C2 (complement component 2)
The third complement protein to participate in the classical
complement pathway activation. C2 is a 110-kDa single
polypeptide chain that unites with C4b molecules on cell
surfaces in the presence of Mg 2+ . C1s splits C2 following
its combination with C4b at the cell surface. This yields
a 35-kDa C2b molecule and a 75-kDa C2a fragment.
Whereas C2b may leave the cell surface, C2a continues
to be associated with surface C4b. The complex of C4b2a
constitutes classical pathway C3 convertase. This enzyme is
able to bind and split C3. C4b facilitates combination with
C3. C2b catalyzes the enzymatic cleavage. C2a contains
the active site of classical pathway C3 convertase (C4b2a).
C2 is encoded by genes on the short arm of chromosome 6
in humans. C2A, C2B, and C2C alleles encode human C2.
Murine C2 is encoded by genes at the S region of chromosome
17.
C2a
The principal substance produced by C1s* cleavage of C2.
N-linked oligosaccharides may combine with C2a at six
sites. The 509 carboxyl terminal amino acid residues of C2
constitute C2a. The catalytic site for C3 and C5 cleavage
is located in the 287-residue carboxyl terminal sequence.
The association of C2a with C4b yields the C3 convertase
(C4b2a)* of the classical pathway.
C2b
A 223-amino acid terminal residue of C2 that represents
a lesser product of C1s cleavage of C2. Three abbreviated
68-amino acid residue homologous repeats in C2b are present
in C3- or C4-binding proteins. N-linked oligosaccharides
combine with C2b at two sites. A peptide split from
the carboxyl terminus of C2b by plasmin has been implicated
in the formation of edema in hereditary angioneurotic
edema patients.
C2 and B genes
The C2 and B genes are situated within the major histocompatibility
complex (MHC) locus on the short arm of
chromosome 6. They are termed MHC class III genes.
TNFα and TNFβ genes are situated between the C2 and
HLA-B genes. Another gene designated FD lies between the
Bf and C4a genes. C2 and B complete primary structures
have been deduced from cDNA and protein sequences.
C2 is comprised of 732 residues and is an 81-kDa molecule,
whereas B contains 739 residues and is an 83-kDa
molecule. Both proteins have a three-domain globular
structure. During C3 convertase formation, the amino
terminal domains, C2b or Ba, are split off. They contain
consensus repeats that are present in CR1, CR2, H, DAF,
and C4bp, which all combine with C3 and/or C4 fragments
and regulate C3 convertases. The amino acid sequences of
the C2 and B consensus repeats are known. C2b contains
site(s) significant for C2 binding to C4b. Ba, resembling
C2b, manifests binding site(s) significant in C3 convertase
Class III
DP DQ DR 21-OH C4 C2 Bf B
C
Class I
C2 and B genes are situated within the major histocompatibility complex (MHC) locus on the short arm of chromosome 6.
A
C