Search results for C4A

Showing 19 results out of 26

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Protein (5 results from a total of 12)

C4A

Identifier: R-HSA-8956717
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Primary external reference: UniProt: C4A: P0C0L4
Identifier: R-HSA-166737
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: C4A: P0C0L4
C4 alpha chain has a thioester bond between Cys 1010 and Gln 1013
Identifier: R-HSA-981503
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: C4A: P0C0L4
Identifier: R-HSA-981506
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: C4A: P0C0L4
Identifier: R-HSA-166734
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: C4A: P0C0L4

Set (2 results from a total of 2)

C4a

Identifier: R-HSA-981725
Species: Homo sapiens
Compartment: extracellular region

C4b

Identifier: R-HSA-981700
Species: Homo sapiens
Compartment: extracellular region

Reaction (4 results from a total of 4)

Identifier: R-HSA-166753
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
The alpha chain of C4 is cleaved, releasing an N-terminal portion of this chain as C4a. The beta and gamma chains are not cleaved and remain linked to the alpha chain by disulfide bonds (Nagasawa et al. 1976, 1980). The resulting C4b heterotrimer undergoes a gross conformational change; the internal thioester in C4b becomes exposed and able to form covalent bonds with surrounding molecules (Law and Dodds 1997). A large proportion of the bonds formed are with water, but some will attach C4b to biological surfaces (Rother et al. 1998). This irreversible reaction can be catalyzed by activated MBL, generated through the lectin pathway of complement activation (Fujita et al. 2004; Hajela et al. 2002), and by activated C1, generated through the classical pathway (Muller-Eberhard and Lepow 1965).

N.B. Humans have two highly polymorphic loci for Complement factor 4, C4A and C4B. C4A alleles carry the Rodgers (Rg) blood group antigens while the C4B alleles carry the Chido (Ch) blood group antigens. The two loci encode non identical C4 peptides; C4 derived from C4A reacts more rapidly with the amino groups of peptide antigens while C4B allotypes react more rapidly with the hydroxyl group of carbohydrate antigens. The names of the two loci are always represented in uppercase. C4a and C4b refer to the peptide products of Complement Factor 4 cleavage.
Identifier: R-HSA-981713
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
The cleavage of C4 into C4a and C4b releases an acyl group from the intrachain thioester bond, allowing C4b to bond covalently to any adjacent biological substrates (Dodds & Law 1998). C4 is encoded at two loci, C4A and C4B. The C4b proteins derived from these genes are not identical and have different binding preferences (Law et al 1984, Sepp et al. 1993); C4A-derived C4b binds more efficiently than C4B-derived C4b to amino groups, while C4B-derived C4b is more effective than C4A in binding to hydroxyl groups. The site of C4b deposition is not clearly established (Møller-Kristensen et al. 2003) but generally accepted to be the activating cell membrane surface, though it may be the activating complex itself.
Identifier: R-HSA-964811
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
C5AR2 (GPR77, C5L2) has been described as a receptor for the chemotactic and inflammatory peptides anaphylatoxin C5a, C4a and C3a and even their des-arginated derivatives. Highest binding affinity was for C3a-desArg, also called Acylation Stimulating Protein (ASP), produced from C3a following arginine removal by carboxypeptidases. Binding of C3a and its derivatives has been disputed (Johswich et al. 2006) leading to suggestions that this receptor may be a C5a scavenger. It is weakly coupled to G(i)-mediated signaling pathways and believed to function primarily as a decoy receptor though it can interact with beta arrestin (Van Lith et al. 2009).
Identifier: R-HSA-8852809
Species: Homo sapiens
Compartment: extracellular region
Carboxypeptidase N (CPN) is able to inactivate the complement anaphylatoxins C3a, C4a, and C5a (Bokisch & Müller-Eberhard 1970), 74-77 amino acid peptides that are released during complement activation. They mediate smooth muscle contraction, vasodilation, release of histamine from mast cells, and chemotaxis of selective bone marrow derived myeloid cells. C3a and C5a mediate their activities by binding the C3a receptor (C3AR1) and C5a receptor (C5AR1), respectively. CPN regulates these anaphylatoxins by removing their carboxy-terminal arginines, which reduces their biological activities 10-100-fold (Ember et al. 1998).
Carboxypeptidase B2 (Plasma carboxypeptidase B, Thrombin-activable fibrinolysis inhibitor, TAF1, CPB2) also can convert C3a and C5a to C3a-desArg and C5a-desArg (Campbell et al. 2002). C3a-desArg cannot bind C3AR1, and C5a-desArg has a 90% decrease in pro-inflammatory activity compared to C5a (Sayah et al. 2003).

CPN is a tetramer comprised of two heterodimers each consisting of a CPN1 and CPN2 subunit (Levin et al. 1982, Keil et al. 2007). The catalytic CPN1 subunit ranges in size from 48 kDa to 55 kDa. This reflects processing by trypsin or plasmin, which can remove a C-terminal segment to produce the 48 kDa form, and cleave at Arg218-Arg219 to produce two peptide chains held together in an active conformation by non-covalent bonds (Levin et al. 1982, Quagraine et al. 2005). This step increases the catalytic activity of CPN towards chromogenic substrates.

Complex (4 results from a total of 4)

Identifier: R-HSA-981502
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-981643
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-2855050
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-166732
Species: Homo sapiens
Compartment: extracellular region
Circulates in blood as a disulfide-linked trimer of an alpha, beta and gamma chain.

Pathway (1 results from a total of 1)

Identifier: R-HSA-166662
Species: Homo sapiens
Activation of the lectin pathway (LP) is initiated by Mannose-binding lectin (MBL), the hetero-complex CL-LK formed from COLEC11 (Collectin liver 1, CL-L1) and COLEC10 (Collectin kidney 1, CL-K1), and the ficolins (FCN1, FCN2, FCN3). All are Ca-dependent (C-type) lectins that initiate the complement cascade after binding to specific carbohydrate patterns on the target cell surface. All form trimers and larger oligomers (Jensen et al. 2005, Dommett et al. 2006, Garlatti et al. 2010). MBL and ficolins circulate in plasma as complexes with homodimers of MBL-associated serine proteases (MASP) (Fujita et al. 2004, Hajela et al. 2002). MASP1, MASP2 and MASP3 have all been reported to mediate complement activation. Upon binding of human lectin to the target surface, the complex of lectin:MASP undergoes conformational changes that result in MASP cleavage and activation (Matsushita M et al. 2000, Fujita et al. 2004). Active MASP2 cleaves C4 to generate C4a and C4b. C4b binds to the target cell surface via its thioester bond, then binds circulating C2 (Law and Dodds 1997). Bound C2 is cleaved by MASP2 to yield the C3 convertase C4b:C2a. The active form of MASP1 was reported to cleave C2 in a manner similar to MASP2 (Matsushita et al. 2000, Chen & Wallis 2004). MASP1 can cleave proenzyme MASP2, leading to complement activation (Heja et al. 2012). MASP1 can also cleave fibrinogen to yield fibrinopeptide B, and activates factor XIII. MASP1 may have a role in removal of 'dead C3', i.e. C3(H2O) (Hajela et al. 2002). In addition to MASP1 to 3, two alternatively-slpiced forms of MASP1 (MAp44) and MASP2 (sMAP) have been implicated in complement cascade signaling (Takahashi et al. 1999, Degn et al. 2010). The functions of MASP3, sMAP and MAp44 in the lectin pathway remain to be clarified.

Icon (3 results from a total of 3)

C4a

Species: Homo sapiens
The alpha chain of C4 is cleaved, releasing an N-terminal portion of this chain as C4a

C4b

Species: Homo sapiens
C4b is derived from native C4 upon cleavage and release of C4a. It is prepared by cleavage of purified C4 with the classical pathway activated protease C1s enzyme

C4

Species: Homo sapiens
Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens
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