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, res ...

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 on the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

surface. It recognizes C4b and C3b fragments that are created during activation of C4 ( classical or lectin pathway) or C3 (

alternative Alternative or alternate may refer to: Arts, entertainment and media * Alternative (''Kamen Rider''), a character in the Japanese TV series ''Kamen Rider Ryuki'' * ''The Alternative'' (film), a 1978 Australian television film * ''The 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 conv ...

, 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 The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector ...

. This glycoprotein is broadly distributed among hematopoietic and non-hematopoietic cells. It is a determinant for the Cromer blood group system.

Structure

DAF is a 70

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...

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 residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of the alternate complement pathway. 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 Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occu ...

(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 CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the ''CD59'' gene. It is an LU domain and belongs to the LY6/uPAR/ alpha-ne ...

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 coxsackieviruses 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 ...

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 or rat 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 The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...

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 ...

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