Complement decay-accelerating factor, also known as CD55 or DAF, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that, in humans, is encoded by the ''CD55''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. DAF regulates the

complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and ...

on the cell surface. It recognizes C4b and C3b fragments that are created during activation of C4 ( classical or

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...

pathway) or C3 ( alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2a

C3-convertase C3 convertase (''C4bC2b'', formerly ''C4b2a'') belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 conver ...

, and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane attack complex. This

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as g ...

is broadly distributed among

hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells ...

and non-hematopoietic cells. It is a determinant for the Cromer blood group system.

Structure

DAF is a 70 kDa

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

that attaches to the cell membrane via a

glycophosphatidylinositol Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles i ...

(GPI) anchor. DAF contains four

complement control protein Complement control protein are proteins that interact with components of the complement system. The complement system is tightly regulated by a network of proteins known as "regulators of complement activation (RCA)" that help distinguish target ...

(CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2, CCP3, CCP4 and three consecutive

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated &minu ...

residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of the

alternate complement pathway The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections. The alternative pathway is one of three complement pathways that opsonize and ki ...

. CCP2 and CCP3 alone are involved in its inhibition of the classical pathway.

Pathology

Paroxysmal nocturnal hemoglobinuria

Because DAF is a GPI-anchored protein, its expression is reduced in persons with mutations that reduce GPI levels such as those with paroxysmal nocturnal hemoglobinuria (PNH). In PNH disorder,

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s with very low levels of DAF and CD59 undergo

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...

-mediated hemolysis. Symptoms include low red blood cell count (anemia), fatigue, and episodes of dark colored urine and other complications.

Infectious diseases

DAF is used as a receptor by some

coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovirus and echoviru ...

es and other

enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic s ...

es. Recombinant soluble DAF- Fc has been tested in mice as an anti-enterovirus therapy for heart damage; however, the human enterovirus that was tested binds much more strongly to human DAF than to

mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...

DAF. Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF. and DAF-Fc has yet to be tested in humans. Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement mediated lysis.

References

External links

*
Cromer blood group system
at BGMUT Blood Group Antigen Gene Mutation Database at NCBI,

NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1 ...

* {{Clusters of differentiation Blood Transfusion medicine Hematology Blood antigen systems