Chemokines are a family of small cytokines, or proteins secreted by cells. Proteins are classified as chemokines according to shared structural characteristics such as small size (they are all approximately 8-10 kilodaltons in size), and the presence of four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines. However, these proteins have historically been known under several other names including the SIS family of cytokines, SIG family of cytokines, SCY family of cytokines, Platelet factor-4 superfamily or intercrines. Some chemokines are considered pro-inflammatory and can be induced during an immune response to promote cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates, some viruses and some bacteria, but none have been described for other invertebrates. These proteins exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors, that are selectively found on the surfaces of their target cells.
The major role of chemokines is to act as a chemoattractant to guide the migration of cells. Cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine. Some chemokines control cells of the immune system during processes of immune surveillance, such as directing lymphocytes to the lymph nodes so they can screen for invasion of pathogens by interacting with antigen-presenting cells residing in these tissues. These are known as homeostatic chemokines and are produced and secreted without any need to stimulate their source cell(s). Some chemokines have roles in development; they promote angiogenesis (the growth of new blood vessels), or guide cells to tissues that provide specific signals critical for cellular maturation. Other chemokines are inflammatory and are released from a wide variety of cells in response to bacterial infection, viruses and agents that cause physical damage such as silica or the urate crystals that occur in gout. Their release is often stimulated by pro-inflammatory cytokines such as interleukin 1. Inflammatory chemokines function mainly as chemoattractants for leukocytes, recruiting monocytes, neutrophils and other effector cells from the blood to sites of infection or tissue damage. Certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing. They are released by many different cell types and serve to guide cells of both innate immune system and adaptive immune system.
Proteins are classified into the chemokine family based on their structural characteristics, not just their ability to attract cells. All chemokines are small, with a molecular mass of between 8 and 10 kDa. They are approximately 20-50% identical to each other; that is, they share gene sequence and amino acid sequence homology. They all also possess conserved amino acids that are important for creating their 3-dimensional or tertiary structure, such as (in most cases) four cysteines that interact with each other in pairs to create a Greek key shape that is a characteristic of chemokines. Intramolecular disulfide bonds typically join the first to third, and the second to fourth cysteine residues, numbered as they appear in the protein sequence of the chemokine. Typical chemokine proteins are produced as pro-peptides, beginning with a signal peptide of approximately 20 amino acids that gets cleaved from the active (mature) portion of the molecule during the process of its secretion from the cell. The first two cysteines, in a chemokine, are situated close together near the N-terminal end of the mature protein, with the third cysteine residing in the centre of the molecule and the fourth close to the C-terminal end. A loop of approximately ten amino acids follows the first two cysteines and is known as the N-loop. This is followed by a single-turn helix, called a 310-helix, three β-strands and a C-terminal α-helix. These helices and strands are connected by turns called 30s, 40s and 50s loops; the third and fourth cysteines are located in the 30s and 50s loops.
|CCL8||Scya8||MCP-2||CCR1, CCR2B, CCR5||P80075|
|CCL9/CCL10||Scya9||MRP-2, CCF18, MIP-1γ||CCR1||P51670|
|CCL11||Scya11||Eotaxin||CCR2, CCR3, CCR5||P51671|
|CCL13||Scya13||MCP-4, NCC-1, Ckβ10||CCR2, CCR3, CCR5||Q99616|
|CCL14||Scya14||HCC-1, MCIF, Ckβ1, NCC-2, CCL||CCR1||Q16627|
|CCL15||Scya15||Leukotactin-1, MIP-5, HCC-2, NCC-3||CCR1, CCR3||Q16663|
|CCL16||Scya16||LEC, NCC-4, LMC, Ckβ12||CCR1, CCR2, CCR5, CCR8||O15467|
|CCL17||Scya17||TARC, dendrokine, ABCD-2||CCR4||Q92583|
|CCL18||Scya18||PARC, DC-CK1, AMAC-1, Ckβ7, MIP-4||P55774|
|CCL19||Scya19||ELC, Exodus-3, Ckβ11||CCR7||Q99731|
|CCL20||Scya20||LARC, Exodus-1, Ckβ4||CCR6||P78556|
|CCL21||Scya21||SLC, 6Ckine, Exodus-2, Ckβ9, TCA-4||CCR7||O00585|
|CCL23||Scya23||MPIF-1, Ckβ8, MIP-3, MPIF-1||CCR1||P55773|
|CCL24||Scya24||Eotaxin-2, MPIF-2, Ckβ6||CCR3||O00175|
|CCL26||Scya26||Eotaxin-3, MIP-4α, IMAC, TSC-1||CCR3||Q9Y258|
|CCL27||Scya27||CTACK, ILC, Eskine, PESKY, skinkine||CCR10||Q9Y4X3|
|CXCL1||Scyb1||Gro-α, GRO1, NAP-3, KC||CXCR2||P09341|
|CXCL2||Scyb2||Gro-β, GRO2, MIP-2α||CXCR2||P19875|
|CXCL3||Scyb3||Gro-γ, GRO3, MIP-2β||CXCR2||P19876|
|CXCL7||Scyb7||NAP-2, CTAPIII, β-Ta, PEP||P02775|
|CXCL8||Scyb8||IL-8, NAP-1, MDNCF, GCP-1||CXCR1, CXCR2||P10145|
|CXCL11||Scyb11||I-TAC, β-R1, IP-9||CXCR3||O14625|
|XCL1||Scyc1||Lymphotactin α, SCM-1α, ATAC||XCR1||P47992|
|XCL2||Scyc2||Lymphotactin β, SCM-1β||XCR1||Q9UBD3|
|CX3CL1||Scyd1||Fractalkine, Neurotactin, ABCD-3||CX3CR1||P78423|
Members of the chemokine family are categorized into four groups depending on the spacing of their first two cysteine residues.