Chemokine
Encyclopedia
Chemokines are a family of small cytokine
s, or protein
s secreted by cell
s. Their name is derived from their ability to induce directed chemotaxis
in nearby responsive cells; they are chemotactic cytokines. 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. 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 recruit 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 vertebrate
s, some virus
es and some bacteria
, but none have been described for other invertebrate
s. These proteins exert their biological effects by interacting with G protein
-linked transmembrane receptors called chemokine receptor
s, 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 lymphocyte
s to the lymph node
s so they can screen for invasion of pathogens by interacting with antigen-presenting cell
s 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 vessel
s), 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 bacteria
l infection, virus
es and agents that cause physical damage such as silica or the urate crystal
s 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 monocyte
s, 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 acid
s that are important for creating their 3-dimensional or tertiary structure
, such as (in most cases) four cysteine
s that interact with each other in pairs to create a Greek key shape that is a characteristic of chemokines. Intramolecular disulfide bond
s 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.
Members of the chemokine family are divided into four groups depending on the spacing of their first two cysteine residues. Thus the nomenclature for chemokines is, e.g.: CCL1 for the ligand 1 of the CC-family of chemokines, and CCR1 for its respective receptor.
There have been at least 27 distinct members of this subgroup reported for mammals, called CC chemokine ligands
(CCL)-1 to -28; CCL10 is the same as CCL9
. Chemokines of this subfamily usually contain four cysteines (C4-CC chemokines), but a small number of CC chemokines possess six cysteines (C6-CC chemokines). C6-CC chemokines include CCL1, CCL15, CCL21, CCL23 and CCL28. CC chemokines induce the migration of monocyte
s and other cell types such as NK cells and dendritic cells.
Examples of CC chemokine include monocyte chemoattractant protein-1
(MCP-1 or CCL2) which induces monocytes to leave the bloodstream and enter the surrounding tissue to become tissue macrophage
s.
CCL5 (or RANTES
) attracts cells such as T cells, eosinophils and basophils that express the receptor CCR5.
-leucine
-arginine
(or ELR for short) immediately before the first cysteine of the CXC motif (ELR-positive), and those without an ELR motif (ELR-negative). ELR-positive CXC chemokines specifically induce the migration of neutrophils, and interact with chemokine receptors CXCR1 and CXCR2. An example of an ELR-positive CXC chemokine is interleukin-8 (IL-8), which induces neutrophils to leave the bloodstream and enter into the surrounding tissue. Other CXC chemokines that lack the ELR motif, such as CXCL13
, tend to be chemoattractant for lymphocytes. CXC chemokines bind to CXC chemokine receptors
, of which seven have been discovered to date, designated CXCR1-7.
.
s are G protein-coupled receptor
s containing 7 transmembrane domain
s that are found on the surface of leukocytes. Approximately 19 different chemokine receptors have been characterized to date, which are divided into four families depending on the type of chemokine they bind; CXCR
that bind CXC chemokines, CCR
that bind CC chemokines, CX3CR1
that binds the sole CX3C chemokine (CX3CL1), and XCR1
that binds the two XC chemokines (XCL1 and XCL2). They share many structural features; they are similar in size (with about 350 amino acid
s), have a short, acidic N-terminal end, seven helical transmembrane domains with three intracellular
and three extracellular
hydrophilic loops, and an intracellular C-terminus containing serine
and threonine
residues important for receptor regulation. The first two extracellular loops of chemokine receptors each has a conserved cysteine
residue that allow formation of a disulfide bridge between these loops. G proteins are coupled to the C-terminal end of the chemokine receptor to allow intracellular signaling after receptor activation, while the N-terminal domain of the chemokine receptor determines ligand binding specificity.
following ligand binding. Activation of G proteins, by chemokine receptors, causes the subsequent activation of an enzyme
known as phospholipase C
(PLC). PLC cleaves a molecule called phosphatidylinositol (4,5)-bisphosphate
(PIP2) into two second messenger molecules known as Inositol triphosphate
(IP3) and diacylglycerol
(DAG) that trigger intracellular signaling events; DAG activates another enzyme called protein kinase C
(PKC), and IP3 triggers the release of calcium
from intracellular stores. These events promote many signaling cascades (such as the MAP kinase pathway
) that generate responses like chemotaxis
, degranulation
, release of superoxide
anions and changes in the avidity of cell adhesion molecule
s called integrin
s within the cell harbouring the chemokine receptor.
, MIP (macrophage inflammatory protein
s) 1α and 1β (now known as CCL5, CCL3 and CCL4 respectively) suppress HIV
-1 provided the initial connection and indicated that these molecules might control infection as part of immune responses in vivo. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV
infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s, or protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s secreted by cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s. Their name is derived from their ability to induce directed chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
in nearby responsive cells; they are chemotactic cytokines. 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
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residues in conserved locations that are key to forming their 3-dimensional shape. 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
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and can be induced during an immune response to recruit cells of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to a site of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
. Chemokines are found in all vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s, some virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es and some bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, but none have been described for other invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s. These proteins exert their biological effects by interacting with G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
-linked transmembrane receptors called chemokine receptor
Chemokine receptor
Chemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. There have been 19 distinct chemokine receptors described in mammals...
s, that are selectively found on the surfaces of their target cells.
Function
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
during processes of immune surveillance, such as directing lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s to the lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s so they can screen for invasion of pathogens by interacting with antigen-presenting cell
Antigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
s 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
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
(the growth of new blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s), or guide cells to tissues that provide specific signals critical for cellular maturation. Other chemokines are inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and are released from a wide variety of cells in response to bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l infection, virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es and agents that cause physical damage such as silica or the urate crystal
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
s that occur in gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
. Their release is often stimulated by pro-inflammatory cytokines such as interleukin 1. Inflammatory chemokines function mainly as chemoattractants for leukocytes, recruiting monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s, neutrophils and other effector cells from the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
to sites of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
or tissue damage. Certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
. They are released by many different cell types and serve to guide cells of both innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
and adaptive immune system
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...
.
Structural characteristics
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...
of between 8 and 10 kDa
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...
. They are approximately 20-50% identical to each other; that is, they share gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
sequence
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
and amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
homology. They all also possess conserved amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s that are important for creating their 3-dimensional or tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
, such as (in most cases) four cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
s that interact with each other in pairs to create a Greek key shape that is a characteristic of chemokines. Intramolecular disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
s 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
Protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein that can be turned into an active form by posttranslational modification. The name of the precursor for a protein is often prefixed by pro...
, 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
N-terminal end
The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group . The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus...
of the mature protein, with the third cysteine residing in the centre of the molecule and the fourth close to the C-terminal end
C-terminal end
The C-terminus is the end of an amino acid chain , terminated by a free carboxyl group . When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus...
. 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
3 10 helix
A 310 helix is a type of secondary structure found in proteins.-Structure:The amino acids in a 310-helix are arranged in a right-handed helical structure...
, three β-strands and a C-terminal α-helix
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
. 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.
Types
 |
||||
| CC chemokines | ||||
|---|---|---|---|---|
| Name | Gene | Other name(s) | Receptor | Uniprot |
| CCL1 CCL1 Chemokine ligand 1 is a small glycoprotein secreted by activated T cells that belongs to a family inflammatory cytokines known as chemokines. CCL1 attracts monocytes, NK cells, and immature B cells and dendritic cells by interacting with a cell surface chemokine receptor called CCR8. This... |
Scya1 | I-309, TCA-3 | CCR8 | |
| CCL2 CCL2 For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.Chemokine ligand 2 also known as monocyte chemotactic protein-1 or small inducible cytokine A2 is a protein that in humans is encoded by the CCL2 gene. CCL2 is a small cytokine belonging to the CC... |
Scya2 | MCP-1 | CCR2 CCR2 CCR2, short for chemokine receptor 2, is a chemokine receptor.CCR2 has also recently been designated CD192 .-External links:* at... |
P13500 |
| CCL3 CCL3 Chemokine ligand 3 is a protein that in humans is encoded by the CCL3 gene.-Further reading:... |
Scya3 | MIP-1a | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... |
P10147 |
| CCL4 CCL4 Chemokine ligand 4, also known as CCL4, is a protein which in humans is encoded by the CCL4 gene.- Function :CCL4, also known as Macrophage inflammatory protein-1β is a CC chemokine with specificity for CCR5 receptors... |
Scya4 | MIP-1ß | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... , CCR5 CCR5 C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins... |
P13236 |
| CCL5 | Scya5 | RANTES | CCR5 CCR5 C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins... |
P13501 |
| CCL6 CCL6 Chemokine ligand 6 is a small cytokine belonging to the CC chemokine family that has only been identified in rodents.In mice, CCL6 is expressed in cells from neutrophil and macrophage lineages, and can be greatly induced under conditions suitable for myeloid cell differentiation... |
Scya6 | C10, MRP-2 | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... |
P27784 |
| CCL7 CCL7 Chemokine ligand 7 is a small cytokine known as a chemokine that was previously called monocyte-specific chemokine 3 . Due to CCL7 possessing two adjacent N-terminal cysteine residues in its mature protein, it is classified among the subfamily of chemokines known as CC chemokines. CCL7... |
Scya7 | MARC, MCP-3 | CCR2 CCR2 CCR2, short for chemokine receptor 2, is a chemokine receptor.CCR2 has also recently been designated CD192 .-External links:* at... |
P80098 |
| CCL8 CCL8 Chemokine ligand 8, also known as monocyte chemoattractant protein 2 , is a protein that in humans is encoded by the CCL8 gene.... |
Scya8 | MCP-2 | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... , CCR2B, CCR5 CCR5 C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins... |
P80075 |
| CCL9 CCL9 Chemokine ligand 9 is a small cytokine belonging to the CC chemokine family. It is also called macrophage inflammatory protein-1 gamma , macrophage inflammatory protein-related protein-2 and CCF18 , that has been described in rodents. CCL9 has also been previously designated CCL10, although... /CCL10 |
Scya9 | MRP-2, CCF18, MIP-1? | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... |
P51670 |
| CCL11 CCL11 Chemokine ligand 11 is a small cytokine belonging to the CC chemokine family that is also known as eotaxin-1. CCL11 selectively recruits eosinophils by inducing their chemotaxis, and therefore, is implicated in allergic responses. The effects of CCL11 are mediated by its binding to a... |
Scya11 | Eotaxin | CCR2 CCR2 CCR2, short for chemokine receptor 2, is a chemokine receptor.CCR2 has also recently been designated CD192 .-External links:* at... , CCR3 CCR3 (gene) C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.CCR3 has also recently been designated CD193 .-Interactions:CCR3 has been shown to interact with CCL5.... , CCR5 CCR5 C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins... |
P51671 |
| CCL12 CCL12 Chemokine ligand 12 is a small cytokine belonging to the CC chemokine family that has been described in mice. It is also known as monocyte chemotactic protein 5 and, due to its similarity with the human chemokine MCP-1, sometimes it is called MCP-1-related chemokine. CCL12 specifically... |
Scya12 | MCP-5 | Q62401 | |
| CCL13 CCL13 Chemokine ligand 13 is a small cytokine belonging to the CC chemokine family. Its gene is located on human chromosome 17 within a large cluster of other CC chemokines. CCL13 induces chemotaxis in monocytes, eosinophils, T lymphocytes, and basophils by binding cell surface G-protein linked... |
Scya13 | MCP-4, NCC-1, Ckß10 | CCR2 CCR2 CCR2, short for chemokine receptor 2, is a chemokine receptor.CCR2 has also recently been designated CD192 .-External links:* at... , CCR3 CCR3 (gene) C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.CCR3 has also recently been designated CD193 .-Interactions:CCR3 has been shown to interact with CCL5.... , CCR5 CCR5 C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins... |
Q99616 |
| CCL14 CCL14 Chemokine ligand 14 is a small cytokine belonging to the CC chemokine family. It is also commonly known as HCC-1. It is produced as a protein precursor that is processed to generate a mature active protein containing 74 amino acids that and is 46% identical in amino acid composition to CCL3 and... |
Scya14 | HCC-1, MCIF, Ckß1, NCC-2, CCL | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... |
Q16627 |
| CCL15 CCL15 Chemokine ligand 15 is a small cytokine belonging to the CC chemokine family that is also known as leukotactin-1, MIP5 and HCC-2. CCL15 is expressed in liver, small intestine, colon, and in certain leukocytes and macrophages of the lung... |
Scya15 | Leukotactin-1, MIP-5, HCC-2, NCC-3 | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... , CCR3 CCR3 (gene) C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.CCR3 has also recently been designated CD193 .-Interactions:CCR3 has been shown to interact with CCL5.... |
Q16663 |
| CCL16 CCL16 Chemokine ligand 16 is a small cytokine belonging to the CC chemokine family that is known under several pseudonyms, including Liver-expressed chemokine and Monotactin-1 . This chemokine is expressed by the liver, thymus, and spleen and is chemoattractive for monocytes and lymphocytes... |
Scya16 | LEC, NCC-4, LMC, Ckß12 | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... , CCR2 CCR2 CCR2, short for chemokine receptor 2, is a chemokine receptor.CCR2 has also recently been designated CD192 .-External links:* at... , CCR5 CCR5 C-C chemokine receptor type 5, also known as CCR5, is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins... , CCR8 |
O15467 |
| CCL17 CCL17 Chemokine ligand 17 is a small cytokine belonging to the CC chemokine family that is also known as thymus and activation regulated chemokine . CCL17 is expressed constitutively in thymus, but only transiently in phytohemagglutinin-stimulated peripheral blood mononuclear cells... |
Scya17 | TARC, dendrokine, ABCD-2 | CCR4 CCR4 C-C chemokine receptor type 4 is a protein that in humans is encoded by the CCR4 gene. CCR4 has also recently been designated CD194 .The protein encoded by this gene belongs to the G protein-coupled receptor family... |
Q92583 |
| CCL18 CCL18 Chemokine ligand 18 is a small cytokine belonging to the CC chemokine family that was previously called PARC . CCL18 is approximately 60% identical in amino acid sequence to CCL3... |
Scya18 | PARC, DC-CK1, AMAC-1, Ckß7, MIP-4 | P55774 | |
| CCL19 CCL19 C-C motif chemokine 19 is a protein that in humans is encoded by the CCL19 gene.Chemokine ligand 19 is a small cytokine belonging to the CC chemokine family that is also known as EBI1 ligand chemokine and macrophage inflammatory protein-3-beta... |
Scya19 | ELC, Exodus-3, Ckß11 | CCR7 | Q99731 |
| CCL20 CCL20 Chemokine ligand 20 or liver activation regulated chemokine or Macrophage Inflammatory Protein-3 is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils... |
Scya20 | LARC, Exodus-1, Ckß4 | CCR6 | P78556 |
| CCL21 CCL21 Chemokine ligand 21 is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine , exodus-2, and secondary lymphoid-tissue chemokine . The gene for CCL21 is located on human chromosome 9... |
Scya21 | SLC, 6Ckine, Exodus-2, Ckß9, TCA-4 | CCR7 | O00585 |
| CCL22 CCL22 C-C motif chemokine 22 is a protein that in humans is encoded by the CCL22 gene.The protein encoded by this gene is secreted by dendritic cells and macrophages, and elicits its effects on its target cells by interacting with cell surface chemokine receptors such as CCR4... |
Scya22 | MDC, DC/ß-CK | CCR4 CCR4 C-C chemokine receptor type 4 is a protein that in humans is encoded by the CCR4 gene. CCR4 has also recently been designated CD194 .The protein encoded by this gene belongs to the G protein-coupled receptor family... |
O00626 |
| CCL23 CCL23 Chemokine ligand 23 is a small cytokine belonging to the CC chemokine family that is also known as Macrophage inflammatory protein 3 and Myeloid progenitor inhibitory factor 1 . CCL23 is predominantly expressed in lung and liver tissue, but is also found in bone marrow and placenta. It is also... |
Scya23 | MPIF-1, Ckß8, MIP-3, MPIF-1 | CCR1 CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.CCR1 has also recently been designated CD191 .-External links:... |
P55773 |
| CCL24 CCL24 Chemokine ligand 24 also known as myeloid progenitor inhibitory factor 2 or eosinophil chemotactic protein 2 is a protein that in humans is encoded by the CCL24 gene. This gene is located on human chromosome 7.... |
Scya24 | Eotaxin-2, MPIF-2, Ckß6 | CCR3 CCR3 (gene) C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.CCR3 has also recently been designated CD193 .-Interactions:CCR3 has been shown to interact with CCL5.... |
O00175 |
| CCL25 CCL25 Chemokine ligand 25 is a small cytokine belonging to the CC chemokine family that is also known as TECK . CCL25 is believed to play a role in the development of T-cells. It is chemotactic for thymocytes, macrophages, and dendritic cells. CCL25 elicits its effects by binding the chemokine... |
Scya25 | TECK, Ckß15 | CCR9 CCR9 C-C chemokine receptor type 9 is a protein that in humans is encoded by the CCR9 gene.CCR9 has also recently been designated CDw199 .-Further reading:... |
O15444 |
| CCL26 CCL26 Chemokine ligand 26 is a small cytokine belonging to the CC chemokine family that is also called Eotaxin-3, Macrophage inflammatory protein 4-alpha... |
Scya26 | Eotaxin-3, MIP-4a, IMAC, TSC-1 | CCR3 CCR3 (gene) C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.CCR3 has also recently been designated CD193 .-Interactions:CCR3 has been shown to interact with CCL5.... |
Q9Y258 |
| CCL27 CCL27 Chemokine ligand 27 is a small cytokine belonging to the CC chemokine family also known under the names IL-11 R-alpha-locus chemokine , Skinkine, ESkine and Cutaneous T-cell-attracting chemokine . It is associated with homing of memory T lymphocytes to the skin, and plays a role in T... |
Scya27 | CTACK, ILC, Eskine, PESKY, skinkine | CCR10 CCR10 C-C chemokine receptor type 10 is a protein that in humans is encoded by the CCR10 gene.-Further reading:... |
Q9Y4X3 |
| CCL28 CCL28 CCL28, also known as mucosae-associated epithelial chemokine , CCK1 and SCYA28, is a chemokine. CCL28 regulates the chemotaxis of cells that express the chemokine receptors CCR3 and CCR10.... |
Scya28 | MEC | CCR3 CCR3 (gene) C-C chemokine receptor type 3 is a protein that in humans is encoded by the CCR3 gene.CCR3 has also recently been designated CD193 .-Interactions:CCR3 has been shown to interact with CCL5.... , CCR10 CCR10 C-C chemokine receptor type 10 is a protein that in humans is encoded by the CCR10 gene.-Further reading:... |
Q9NRJ3 |
| CXC chemokines | ||||
| Name | Gene | Other name(s) | Receptor | Uniprot |
| CXCL1 CXCL1 Chemokine ligand 1 is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, GROα, KC, Neutrophil-activating protein 3 and melanoma growth stimulating activity, alpha... |
Scyb1 | Gro-a, GRO1, NAP-3, KC | CXCR2 | P09341 |
| CXCL2 CXCL2 Chemokine ligand 2 is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha , Growth-regulated protein beta and Gro oncogene-2 . CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1... |
Scyb2 | Gro-ß, GRO2, MIP-2a | CXCR2 | P19875 |
| CXCL3 CXCL3 Chemokine ligand 3 is a small cytokine belonging to the CXC chemokine family that is also known as GRO3 oncogene , GRO protein gamma and macrophage inflammatory protein-2-beta... |
Scyb3 | Gro-?, GRO3, MIP-2ß | CXCR2 | P19876 |
| CXCL4 | Scyb4 | PF-4 | CXCR3B | P02776 |
| CXCL5 CXCL5 C-X-C motif chemokine 5 is a protein that in humans is encoded by the CXCL5 gene.- Function :The protein encoded by this gene, CXCL5 is a small cytokine belonging to the CXC chemokine family that is also known as epithelial-derived neutrophil-activating peptide 78... |
Scyb5 | ENA-78 | CXCR2 | P42830 |
| CXCL6 CXCL6 Chemokine ligand 6 is a small cytokine belonging to the CXC chemokine family that is also known as granulocyte chemotactic protein 2 . As its former name suggests, CXCL6 is a chemoattractant for neutrophilic granulocytes. It elicits its chemotactic effects by interacting with the chemokine... |
Scyb6 | GCP-2 | CXCR1, CXCR2 | P80162 |
| CXCL7 CXCL7 Chemokine ligand 7 is a human gene.The encoded protein, Chemokine ligand is a small cytokine belonging to the CXC chemokine family. It is an isoform of Beta-Thromboglobulin or Pro-Platelet basic protein .... |
Scyb7 | NAP-2, CTAPIII, ß-Ta, PEP | P02775 | |
| CXCL8 Interleukin 8 Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies... |
Scyb8 | IL-8, NAP-1, MDNCF, GCP-1 | CXCR1, CXCR2 | P10145 |
| CXCL9 CXCL9 Chemokine ligand 9 is a small cytokine belonging to the CXC chemokine family that is also known as Monokine induced by gamma interferon . CXCL9 is a T-cell chemoattractant, which is induced by IFN-γ. It is closely related to two other CXC chemokines called CXCL10 and CXCL11, whose genes are... |
Scyb9 | MIG, CRG-10 | CXCR3 CXCR3 Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 and CD183... |
Q07325 |
| CXCL10 CXCL10 C-X-C motif chemokine 10 also known as Interferon gamma-induced protein 10 or small-inducible cytokine B10 is an 8.7 kDa protein that in humans is encoded by the CXCL10 gene... |
Scyb10 | IP-10, CRG-2 | CXCR3 CXCR3 Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 and CD183... |
P02778 |
| CXCL11 CXCL11 Chemokine ligand 11 is a small cytokine belonging to the CXC chemokine family that is also called Interferon-inducible T-cell alpha chemoattractant and Interferon-gamma-inducible protein 9... |
Scyb11 | I-TAC, ß-R1, IP-9 | CXCR3 CXCR3 Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 and CD183... , CXCR7 CXCR7 C-X-C chemokine receptor type 7 is a protein that in humans is encoded by the CXCR7 gene.This gene encodes a member of the G-protein coupled receptor family. This protein was earlier thought to be a receptor for vasoactive intestinal peptide and was considered to be an orphan receptor... |
O14625 |
| CXCL12 | Scyb12 | SDF-1, PBSF | CXCR4 CXCR4 C-X-C chemokine receptor type 4 also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene.- Function :... , CXCR7 CXCR7 C-X-C chemokine receptor type 7 is a protein that in humans is encoded by the CXCR7 gene.This gene encodes a member of the G-protein coupled receptor family. This protein was earlier thought to be a receptor for vasoactive intestinal peptide and was considered to be an orphan receptor... |
P48061 |
| CXCL13 CXCL13 C-X-C motif chemokine 13 also known as B lymphocyte chemoattractant is a protein that in humans is encoded by the CXCL13 gene.- Function :CXCL13 is a small cytokine belonging to the CXC chemokine family... |
Scyb13 | BCA-1, BLC | CXCR5 CXCR5 C-X-C chemokine receptor type 5 also known as Burkitt lymphoma receptor 1 is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 and belongs to the CXC chemokine receptor family... |
O43927 |
| CXCL14 CXCL14 Chemokine ligand 14 is a small cytokine belonging to the CXC chemokine family that is also known as BRAK... |
Scyb14 | BRAK, bolekine | O95715 | |
| CXCL15 CXCL15 Chemokine ligand 15 is a small cytokine belonging to the CXC chemokine family that has been described in the mouse. This chemokine is also known under the name lungkine. CXCL15 is an ELR+ CXC chemokine that recruits neutrophils during inflammation of the lungs... |
Scyb15 | Lungkine, WECHE | Q9WVL7 | |
| CXCL16 CXCL16 Chemokine ligand 16 is a small cytokine belonging to the CXC chemokine family. Larger than other chemokines , CXCL16 is composed of a CXC chemokine domain, a mucin-like stalk, a transmembrane domain and a cytoplasmic tail containing a potential tyrosine phosphorylation site that may bind SH2... |
Scyb16 | SRPSOX | CXCR6 CXCR6 C-X-C chemokine receptor type 6 is a protein that in humans is encoded by the CXCR6 gene.CXCR6 has also recently been designated CD186 .-Further reading:... |
Q9H2A7 |
| CXCL17 CXCL17 Chemokine ligand 17 is a small cytokine belonging to the CXC chemokine family that has been identified in humans and mice. CXCL17 attracts dendritic cells and monocytes and is regulated in tumors. It is also known as VEGF co-regulated chemokine 1 and dendritic cell- and monocyte-attracting... |
VCC-1 | DMC, VCC-1 | Q6UXB2 | |
| C chemokines | ||||
| Name | Gene | Other name(s) | Receptor | Uniprot |
| XCL1 XCL1 Chemokine ligand is a small cytokine belonging to the XC chemokine family that is also known as lymphotactin. It is found in high levels in spleen, thymus, intestine and peripheral blood leukocytes, and at lower levels in lung, prostate gland and ovary. Cellular sources for XCL1 include... |
Scyc1 | Lymphotactin a, SCM-1a, ATAC | XCR1 XCR1 The "C" sub-family of chemokine receptors contains only one member: XCR1, the receptor for XCL1 and XCL2 .XCR1 is also known as GPR5.-External links:... |
P47992 |
| XCL2 XCL2 Chemokine ligand 2 is a small cytokine belonging to the XC chemokine family that is highly related to another chemokine called XCL1. It is predominantly expressed in activated T cells, but can also be found at low levels in unstimulated cells. XCL2 induces chemotaxis of cells expressing the... |
Scyc2 | Lymphotactin ß, SCM-1ß | XCR1 XCR1 The "C" sub-family of chemokine receptors contains only one member: XCR1, the receptor for XCL1 and XCL2 .XCR1 is also known as GPR5.-External links:... |
Q9UBD3 |
| CX3C chemokines | ||||
| Name | Gene | Other name(s) | Receptor | Uniprot |
| CX3CL1 CX3CL1 Chemokine ligand 1 is a large cytokine protein of 373 amino acids, it contains multiple domains and is the only known member of the CX3C chemokine family. It is also commonly known under the names fractalkine and neurotactin . The polypeptide structure of CXC3L1 differs from the typical... |
Scyd1 | Fractalkine, Neurotactin, ABCD-3 | CX3CR1 CX3CR1 CX3C chemokine receptor 1 also known as the fractalkine receptor or G-protein coupled receptor 13 is a protein that in humans is encoded by the CX3CR1 gene... |
P78423 |
Members of the chemokine family are divided into four groups depending on the spacing of their first two cysteine residues. Thus the nomenclature for chemokines is, e.g.: CCL1 for the ligand 1 of the CC-family of chemokines, and CCR1 for its respective receptor.
CC chemokines
The CC chemokine (or ß-chemokine) proteins have two adjacent cysteines (amino acids), near their amino terminus.There have been at least 27 distinct members of this subgroup reported for mammals, called CC chemokine ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
(CCL)-1 to -28; CCL10 is the same as CCL9
CCL9
Chemokine ligand 9 is a small cytokine belonging to the CC chemokine family. It is also called macrophage inflammatory protein-1 gamma , macrophage inflammatory protein-related protein-2 and CCF18 , that has been described in rodents. CCL9 has also been previously designated CCL10, although...
. Chemokines of this subfamily usually contain four cysteines (C4-CC chemokines), but a small number of CC chemokines possess six cysteines (C6-CC chemokines). C6-CC chemokines include CCL1, CCL15, CCL21, CCL23 and CCL28. CC chemokines induce the migration of monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s and other cell types such as NK cells and dendritic cells.
Examples of CC chemokine include monocyte chemoattractant protein-1
CCL2
For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.Chemokine ligand 2 also known as monocyte chemotactic protein-1 or small inducible cytokine A2 is a protein that in humans is encoded by the CCL2 gene. CCL2 is a small cytokine belonging to the CC...
(MCP-1 or CCL2) which induces monocytes to leave the bloodstream and enter the surrounding tissue to become tissue 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.
CCL5 (or RANTES
RANTES
Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. It is also known as RANTES .- Function :...
) attracts cells such as T cells, eosinophils and basophils that express the receptor CCR5.
CXC chemokines
The two N-terminal cysteines of CXC chemokines (or α-chemokines) are separated by one amino acid, represented in this name with an "X". There have been 17 different CXC chemokines described in mammals, that are subdivided into two categories, those with a specific amino acid sequence (or motif) of glutamic acidGlutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
-leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
-arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
(or ELR for short) immediately before the first cysteine of the CXC motif (ELR-positive), and those without an ELR motif (ELR-negative). ELR-positive CXC chemokines specifically induce the migration of neutrophils, and interact with chemokine receptors CXCR1 and CXCR2. An example of an ELR-positive CXC chemokine is interleukin-8 (IL-8), which induces neutrophils to leave the bloodstream and enter into the surrounding tissue. Other CXC chemokines that lack the ELR motif, such as CXCL13
CXCL13
C-X-C motif chemokine 13 also known as B lymphocyte chemoattractant is a protein that in humans is encoded by the CXCL13 gene.- Function :CXCL13 is a small cytokine belonging to the CXC chemokine family...
, tend to be chemoattractant for lymphocytes. CXC chemokines bind to CXC chemokine receptors
CXC chemokine receptors
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane proteins since they span the...
, of which seven have been discovered to date, designated CXCR1-7.
C chemokines
The third group of chemokines is known as the C chemokines (or γ chemokines), and is unlike all other chemokines in that it has only two cysteines; one N-terminal cysteine and one cysteine downstream. Two chemokines have been described for this subgroup and are called XCL1 (lymphotactin-α) and XCL2 (lymphotactin-ß). These chemokines attract T cell precursors to the thymusThymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
.
CX3C chemokines
A fourth group has also been discovered and members have three amino acids between the two cysteines and is termed CX3C chemokine (or d-chemokines). The only CX3C chemokine discovered to date is called fractalkine (or CX3CL1). It is both secreted and tethered to the surface of the cell that expresses it, thereby serving as both a chemoattractant and as an adhesion molecule.Receptors
Chemokine receptorChemokine receptor
Chemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. There have been 19 distinct chemokine receptors described in mammals...
s are G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
s containing 7 transmembrane domain
Transmembrane helix
Transmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called a "domain" because an alpha-helix in a membrane can fold independently from the rest of the protein, similar to domains of water-soluble proteins...
s that are found on the surface of leukocytes. Approximately 19 different chemokine receptors have been characterized to date, which are divided into four families depending on the type of chemokine they bind; CXCR
CXC chemokine receptors
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane proteins since they span the...
that bind CXC chemokines, CCR
CC chemokine receptors
CC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane proteins since they span the...
that bind CC chemokines, CX3CR1
CX3CR1
CX3C chemokine receptor 1 also known as the fractalkine receptor or G-protein coupled receptor 13 is a protein that in humans is encoded by the CX3CR1 gene...
that binds the sole CX3C chemokine (CX3CL1), and XCR1
XCR1
The "C" sub-family of chemokine receptors contains only one member: XCR1, the receptor for XCL1 and XCL2 .XCR1 is also known as GPR5.-External links:...
that binds the two XC chemokines (XCL1 and XCL2). They share many structural features; they are similar in size (with about 350 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s), have a short, acidic N-terminal end, seven helical transmembrane domains with three intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
and three extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
hydrophilic loops, and an intracellular C-terminus containing serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
and threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
residues important for receptor regulation. The first two extracellular loops of chemokine receptors each has a conserved cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residue that allow formation of a disulfide bridge between these loops. G proteins are coupled to the C-terminal end of the chemokine receptor to allow intracellular signaling after receptor activation, while the N-terminal domain of the chemokine receptor determines ligand binding specificity.
Signal transduction
Chemokine receptors associate with G-proteins to transmit cell signalsCell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
following ligand binding. Activation of G proteins, by chemokine receptors, causes the subsequent activation of an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
known as phospholipase C
Phospholipase C
Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...
(PLC). PLC cleaves a molecule called phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdInsP2, also known simply as PIP2, is a minor phospholipid component of cell membranes...
(PIP2) into two second messenger molecules known as Inositol triphosphate
Inositol triphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate , together with diacylglycerol , is a secondary messenger molecule used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell...
(IP3) and diacylglycerol
Diglyceride
A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....
(DAG) that trigger intracellular signaling events; DAG activates another enzyme called protein kinase C
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
(PKC), and IP3 triggers the release of calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
from intracellular stores. These events promote many signaling cascades (such as the MAP kinase pathway
MAPK/ERK pathway
The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...
) that generate responses like chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
, degranulation
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
, release of superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
anions and changes in the avidity of cell adhesion molecule
Cell adhesion molecule
Cell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
s called integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s within the cell harbouring the chemokine receptor.
Infection control
The discovery that the β chemokines RANTESRANTES
Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. It is also known as RANTES .- Function :...
, MIP (macrophage inflammatory protein
Macrophage Inflammatory Protein
Macrophage Inflammatory Proteins belong to the family of chemotactic cytokines known as chemokines. Macrophage inflammatory protein-1 , MIP-1 and MIP-1 are chemokines crucial for immune responses towards infection and inflammation. In humans, there are two major forms, MIP-1α and MIP-1β that are...
s) 1α and 1β (now known as CCL5, CCL3 and CCL4 respectively) suppress HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
-1 provided the initial connection and indicated that these molecules might control infection as part of immune responses in vivo. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.
External links
- List of chemokines and their receptors at nlm.nih.gov
- The cytokine family database - Chemokines at kumamoto-u.ac.jp
- The correct chemokine nomenclature at rndsystems.com