CXCL14

chemokine (C-X-C motif) ligand 14
Identifiers
Symbol	CXCL14
Alt. symbols	SCYB14, BRAK, NJAC, bolekine, Kec, MIP-2g, BMAC, KS1
Entrez	9547
HUGO	10640
OMIM	604186
PDB	2HDL
RefSeq	NM_004887
UniProt	O95715
Other data
Locus	Chr. 5 q31

Last updated June 30, 2019

Chemokine (C-X-C motif) ligand 14 (CXCL14) is a small cytokine belonging to the CXC chemokine family that is also known as BRAK (for breast and kidney-expressed chemokine).^[1] Mature CXCL14 has many of the conserved features of the CXC chemokine subfamily but has some differences too, such as a shorter N-terminus and five extra amino acids in the region between its third and fourth cysteines.^[1] CXCL14 is constitutively expressed at high levels in many normal tissues, where its cellular source is thought to be fibroblasts.^[2] However, it is reduced or absent from most cancer cells.^[1]^[3] This chemokine is chemotactic for monocytes and can activate these cells in the presence of an inflammatory mediator called prostaglandin-E2 (PGE2).^[2] It is also a potent chemoattractant and activator of dendritic cells, is implicated in homing of these cells,^[4] and can stimulate the migration of activated NK cells.^[5] CXCL14 also inhibits angiogenesis, possibly as a result of its ability to block endothelial cell chemotaxis.^[6] The gene for CXCL14 contains four exons and is located on chromosome 5 in humans.^[1]

Cytokines are a broad and loose category of small proteins that are important in cell signaling. Cytokines are peptides, and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine signaling, paracrine signaling and endocrine signaling as immunomodulating agents. Their definite distinction from hormones is still part of ongoing research. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell.

Chemokines are a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines.

The N-terminus (also known as the amino-terminus, NH₂-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide referring to the free amine group (-NH₂) located at the end of a polypeptide. Normally the amine group is bonded to another carboxylic group in a protein to make it a chain, but since the end of a protein has only 1 out of 2 areas chained, the free amine group is referred to the N-terminus. By convention, peptide sequences are written N-terminus to C-terminus, left to right in LTR languages. This correlates the translation direction to the text direction (because when a protein is translated from messenger RNA, it is created from N-terminus to C-terminus - amino acids are added to the carbonyl end).

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Monocytes are a type of leukocyte, or white blood cell. They are the largest type of leukocyte and can differentiate into macrophages and myeloid lineage dendritic cells. As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

The stromal cell-derived factor 1 (SDF1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in humans is encoded by the CXCL12 gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types. Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the chemokine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The chemokines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, the cysteine residues are adjacent to each other. In the CXC subfamily, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group. CXCL12 signaling has been observed in several cancers. The CXCL12 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.

Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine ligand 4 (CXCL4). This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation. It is usually found in a complex with proteoglycan.

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as Monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

C-X-C motif chemokine 10 (CXCL10) also known as Interferon gamma-induced protein 10 (IP-10) or small-inducible cytokine B10 is an 8.7 kDa protein that in humans is encoded by the CXCL10 gene. C-X-C motif chemokine 10 is a small cytokine belonging to the CXC chemokine family.

C-X-C motif chemokine 11 (CXCL11) is a protein that in humans is encoded by the CXCL11 gene.

The chemokine ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, GROα, KC, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). In humans, this protein is encoded by the Cxcl1.

Chemokine ligand 2 (CXCL2) is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha (MIP2-alpha), Growth-regulated protein beta (Gro-beta) and Gro oncogene-2 (Gro-2). CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1. This chemokine is secreted by monocytes and macrophages and is chemotactic for polymorphonuclear leukocytes and hematopoietic stem cells. The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines. CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.

Chemokine ligand 3 (CXCL3) is a small cytokine belonging to the CXC chemokine family that is also known as GRO3 oncogene (GRO3), GRO protein gamma (GROg) and macrophage inflammatory protein-2-beta (MIP2b). CXCL3 controls migration and adhesion of monocytes and mediates its effects on its target cell by interacting with a cell surface chemokine receptor called CXCR2. More recently, it has been shown that Cxcl3 regulates cell autonomously the migration of the precursors of cerebellar granule neurons toward the internal layers of cerebellum, during the morphogenesis of cerebellum. Moreover, if the expression of Cxcl3 is reduced in cerebellar granule neuron precursors, this highly enhances the frequency of the medulloblastoma, the tumor of cerebellum. In fact, the reduced expression of Cxcl3 forces the cerebellar granule neuron precursors to remain at the surface of the cerebellum, where they highly proliferate under the stimulus of Sonic hedgehog, becoming target of transforming insults. Remarkably, the treatment with CXCL3 completely prevents the growth of medulloblastoma lesions in a Shh-type mouse model of medulloblastoma. Thus, CXCL3 is a target for medulloblastoma therapy. Cxcl3 is directly regulated transcriptionally by BTG2

CXCL5 protein-coding gene in the species Homo sapiens

C-X-C motif chemokine 5 is a protein that in humans is encoded by the CXCL5 gene.

chemokine ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the CXCL13 gene.

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 (7-TM) proteins, since they span the cell membrane seven times. There are currently seven known CXC chemokine receptors in mammals, named CXCR1 through CXCR7.

Chemokine ligand 6 (CXCL6) is a small cytokine belonging to the CXC chemokine family that is also known as granulocyte chemotactic protein 2 (GCP-2). As its former name suggests, CXCL6 is a chemoattractant for neutrophilic granulocytes. It elicits its chemotactic effects by interacting with the chemokine receptors CXCR1 and CXCR2. The gene for CXCL6 is located on human chromosome 4 in a cluster with other CXC chemokine genes.

Chemokine ligand 16 (CXCL16) 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. These are unusual features for a chemokine, and allow CXCL16 to be expressed as a cell surface bound molecule, as well as a soluble chemokine. CXCL16 is produced by dendritic cells found in the T cell zones of lymphoid organs, and by cells found in the red pulp of the spleen. Cells that bind and migrate in response to CXCL16 include several subsets of T cells, and natural killer T (NKT) cells. CXCL16 interacts with the chemokine receptor CXCR6, also known as Bonzo. Expression of CXCL16 is induced by the inflammatory cytokines IFN-gamma and TNF-alpha. The gene for human CXCL16 is located on chromosome 17.

Chemokine ligand 17 (CXCL17) 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 (VCC-1) and dendritic cell- and monocyte-attracting chemokine-like protein (DMC). This chemokine is constitutively expressed in the lung. The gene for human CXCL17 is located on chromosome 19.

Chemokine ligand 15 (CXCL15) 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. It is highly abundant in epithelial cells of the lung, and can also be found in other mucosal organs such as the urogenital and gastrointestinal tracts, and in endocrine organs like the adrenal gland. The gene for CXCL15 is found on mouse chromosome 5.

Chemokine receptor CXCR3 is a Gα_i protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11.

C-X-C chemokine receptor type 5 (CXC-R5) also known as CD185 or Burkitt lymphoma receptor 1 (BLR1) is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 and belongs to the CXC chemokine receptor family. It enables T cells to migrate to lymph node B cell zones. In humans, the CXC-R5 protein is encoded by the CXCR5 gene.

References

1 2 3 4 Hromas R, Broxmeyer HE, Kim C, Nakshatri H, Christopherson K, Azam M, Hou YH (February 1999). "Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells". Biochemical and Biophysical Research Communications. 255 (3): 703–6. doi:10.1006/bbrc.1999.0257. PMID 10049774.
1 2 Kurth I, Willimann K, Schaerli P, Hunziker T, Clark-Lewis I, Moser B (September 2001). "Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development". The Journal of Experimental Medicine. 194 (6): 855–61. doi:10.1084/jem.194.6.855. PMC 2195966 . PMID 11561000.
↑ Frederick MJ, Henderson Y, Xu X, Deavers MT, Sahin AA, Wu H, Lewis DE, El-Naggar AK, Clayman GL (June 2000). "In vivo expression of the novel CXC chemokine BRAK in normal and cancerous human tissue". The American Journal of Pathology. 156 (6): 1937–50. doi:10.1016/S0002-9440(10)65067-5. PMC 1850081 . PMID 10854217.
↑ Shurin GV, Ferris RL, Ferris R, Tourkova IL, Perez L, Lokshin A, Balkir L, Collins B, Chatta GS, Shurin MR (May 2005). "Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo". Journal of Immunology. 174 (9): 5490–8. doi:10.4049/jimmunol.174.9.5490. PMID 15843547.
↑ Starnes T, Rasila KK, Robertson MJ, Brahmi Z, Dahl R, Christopherson K, Hromas R (August 2006). "The chemokine CXCL14 (BRAK) stimulates activated NK cell migration: implications for the downregulation of CXCL14 in malignancy". Experimental Hematology. 34 (8): 1101–5. doi:10.1016/j.exphem.2006.05.015. PMID 16863917.
↑ Shellenberger TD, Wang M, Gujrati M, Jayakumar A, Strieter RM, Burdick MD, Ioannides CG, Efferson CL, El-Naggar AK, Roberts D, Clayman GL, Frederick MJ (November 2004). "BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells". Cancer Research. 64 (22): 8262–70. doi:10.1158/0008-5472.CAN-04-2056. PMID 15548693.

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[hromas-1] 1 2 3 4 Hromas R, Broxmeyer HE, Kim C, Nakshatri H, Christopherson K, Azam M, Hou YH (February 1999). "Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells". Biochemical and Biophysical Research Communications. 255 (3): 703–6. doi:10.1006/bbrc.1999.0257. PMID 10049774.

[kurth-2] 1 2 Kurth I, Willimann K, Schaerli P, Hunziker T, Clark-Lewis I, Moser B (September 2001). "Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development". The Journal of Experimental Medicine. 194 (6): 855–61. doi:10.1084/jem.194.6.855. PMC 2195966 . PMID 11561000.

[3] Frederick MJ, Henderson Y, Xu X, Deavers MT, Sahin AA, Wu H, Lewis DE, El-Naggar AK, Clayman GL (June 2000). "In vivo expression of the novel CXC chemokine BRAK in normal and cancerous human tissue". The American Journal of Pathology. 156 (6): 1937–50. doi:10.1016/S0002-9440(10)65067-5. PMC 1850081 . PMID 10854217.

[4] Shurin GV, Ferris RL, Ferris R, Tourkova IL, Perez L, Lokshin A, Balkir L, Collins B, Chatta GS, Shurin MR (May 2005). "Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo". Journal of Immunology. 174 (9): 5490–8. doi:10.4049/jimmunol.174.9.5490. PMID 15843547.

[5] Starnes T, Rasila KK, Robertson MJ, Brahmi Z, Dahl R, Christopherson K, Hromas R (August 2006). "The chemokine CXCL14 (BRAK) stimulates activated NK cell migration: implications for the downregulation of CXCL14 in malignancy". Experimental Hematology. 34 (8): 1101–5. doi:10.1016/j.exphem.2006.05.015. PMID 16863917.

[6] Shellenberger TD, Wang M, Gujrati M, Jayakumar A, Strieter RM, Burdick MD, Ioannides CG, Efferson CL, El-Naggar AK, Roberts D, Clayman GL, Frederick MJ (November 2004). "BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells". Cancer Research. 64 (22): 8262–70. doi:10.1158/0008-5472.CAN-04-2056. PMID 15548693.