Siglecs, short for sialic acid binding Ig-like lectins are cell surface receptors and members of the immunoglobulin superfamily

Immunoglobulin superfamily

The immunoglobulin superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins ; they all possess a...

 (IgSF) that recognize sugars. Their ability to recognize carbohydrate

Carbohydrate

A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

s using an immunoglobulin domain

Immunoglobulin domain

The immunoglobulin domain is a type of protein domain that consists of a 2-layer sandwich of between 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek key topology....

 places them in the group of I-type (Ig-type) lectin

Lectin

Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...

s. They are transmembrane protein

Transmembrane protein

A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...

s that contain an N-terminal V-like immunoglobulin (IgV) domain that binds sialic acid

Sialic acid

Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...

 and a variable number of C2-type Ig (IgC2) domains.

The first described Siglec is sialoadhesin

Sialoadhesin

Sialoadhesin is a cell adhesion molecule found on the surface of certain cells of the immune system called macrophages. It is found in especially high amounts on macrophages of the spleen, liver, lymph node, bone marrow, colon, and lungs. Also, in patients suffering from rheumatoid arthritis, the...

 (Siglec-1/CD169) that is a lectin-like adhesion molecule on macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s. Other Siglecs were later added to this family, including CD22

CD22

CD22 or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells...

 (Siglec-2), which is restricted to B cell

B cell

B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

s and has an important role in regulating their adhesion

Cell adhesion

Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...

 and activation, CD33

CD33

CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.It binds sialic acids, therefore is a member of the SIGLEC family of lectins....

 (Siglec-3) and myelin-associated glycoprotein

Myelin-associated glycoprotein

Myelin-associated glycoprotein is a cell membrane glycoprotein that is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO-66 receptor, NgR. MAG is believed to be involved in myelination during nerve regeneration....

 (MAG/Siglec-4). Several additional Siglecs (Siglecs 5–12) have been identified in humans that are highly similar in structure to CD33 so are collectively referred to as ‘CD33-related Siglecs’. CD33-related siglecs all have two conserved immunoreceptor tyrosine-based inhibitory motif

Immunoreceptor tyrosine-based inhibitory motif

An immunoreceptor tyrosine-based inhibition motif , is a conserved sequence of amino acids that is found in the cytoplasmic tails of many inhibitory receptors of the immune system...

 (ITIM)-like motifs in their cytoplasm

Cytoplasm

The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

ic tails suggesting their involvement in cellular activation.

External links

• Functional Glycomics Gateway, a collaboration between the Consortium for Functional Glycomics
  Consortium for Functional Glycomics
  The Consortium for Functional Glycomics is a large research initiative funded in 2001 by a glue grant from the National Institute of General Medical Sciences to “define paradigms by which protein-carbohydrate interactions mediate cell communication”...
  
   and Nature Publishing Group
  Nature Publishing Group
  Nature Publishing Group is an international publishing company that publishes academic journals, online databases, and services across the life, physical, chemical and applied sciences and clinical medicine...