XCL1

Last updated
XCL1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases XCL1 , ATAC, LPTN, LTN, SCM-1, SCM-1a, SCM1, SCM1A, SCYC1, X-C motif chemokine ligand 1
External IDs OMIM: 600250; MGI: 104593; HomoloGene: 2250; GeneCards: XCL1; OMA:XCL1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6375

16963

Ensembl

ENSG00000143184

ENSMUSG00000026573

UniProt

P47992

P47993

RefSeq (mRNA)

NM_002995

NM_008510

RefSeq (protein)

NP_002986

NP_032536

Location (UCSC) Chr 1: 168.58 – 168.58 Mb Chr 1: 164.76 – 164.76 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Chemokine (C motif) ligand (XCL1) is a small cytokine belonging to the C chemokine family that is also known as lymphotactin. Chemokines are known for their function in inflammatory and immunological responses. This family C chemokines differs in structure and function from most chemokines. [5] [6] There are only two chemokines in this family and what separated them from other chemokines is that they only have two cysteines; one N-terminal cysteine and one cysteine downstream. These both are called Lymphotactin, alpha and beta form, and claim special characteristics only found between the two. Lymphotactins can go through a reversible conformational change which changes its binding shifts. [7]

Contents

In normal tissues, XCL1 is found in high levels in spleen, thymus, small intestine and peripheral blood leukocytes, and at lower levels in lung, prostate gland and ovary. Secretion of XCL1 is responsible for the increase of intracellular calcium in peripheral blood lymphocytes. [8] Cellular sources for XCL1 include activated thymic and peripheral blood CD8+ T cells. [9] [10] [11] NK cells also secrete XCL1 along with other chemokines early in infections. [12] XCR1 expressing dendritic cells (DC) are a major target of XCL1. [12]

In humans, XCL1 is closely related to another chemokine called XCL2, whose gene is found at the same locus on chromosome 1. [11] Both of these chemokines share many genetic and functional similarities; however XCL2 has only been known to be observed in humans and not in mice. [12] XCL1 induces its chemotactic function by binding to a chemokine receptor called XCR1. [13] XCL1 is expressed on macrophages, fibroblasts, and specific lymphocytes. [6]

XCL1 is found in two metamorphic states: a monomer at 10°C, Ltn10, and a dimer at 40°C, Ltn40. [14]

Genomics

XCL1's gene is found on the long arm of chromosome 1, located on cytogenetic band q24.2 as seen in the infobox. The encoding gene is made of 6,017 DNA bases to encode for the protein XCL1. [15] This gene contains three exons and two introns as well as several transcription initiation sites. [8] This gene encodes for the 114-amino acid protein called XCL1 which is similar to other chemokines except that it lacks the first and third cysteine characteristics. This means that XCL1 only contains one cysteine creating a disulfide bond instead of two or three like the other chemokines. [5]

The genetic differences between XCL1 and XCL2 are very small. Both proteins are from the same family containing the C motif structure containing one disulfide bond and have almost identical tertiary structures. [8] These C chemokines also have the same flanking regions, meaning regions of the gene including the promoter and other places of protein binging that do not contribute to the RNA transcribed gene. [8] Gene mapping of this chemokine family shows similarities in their intron and exon locations with only one distinct difference. XCL1 has only one difference in its first intron that encodes for a large ribosomal subunit called L7a. In XCL2 have of the region encoding for L7a is cut off. [8] The only other genetic difference between the two mature proteins is the different amino acid in positions 7 and 8. [8] [12] This amino acid difference may account for some biological differences. Some difficulties with comparing these two chemokines is that XCL2 has never been observed in a mouse. [12]

Structure

One thing that sets XCL1 apart from other cytokines is its structure. [7] While most chemokines have two disulfide bonds that connect the N-terminus to the core of the structure, XCL1 only has one. [5] This simple difference in disulfide bonds changes the overall tertiary structure of XCL1 from other chemokines. There are two parts of the lymphotactin protein, structures Ltn10 and Ltn40, that folds into each other, which make it biologically active. [7] This conformational change alters the binding structures on the chemokine. This understanding of the interfolding provides more of a basis to understanding to the lymphotactin kinetics. [7]

Biological significance

The pair of XCL1 and XCR1 are known to be involved in cross-presentation, antigen uptake, and induction of innate as well as adaptive cytotoxic immunity. [12] XCR1, the receptor for XCL1, is exclusively expressed in conventional dendritic cells. [12] XCL1 is secreted by NK cells and by antigen-specific CD8+ T-cells, along with other chemokines including IFN-gamma. [12] This process likely facilitates the cross-presentation of antigens by the dendritic cells.

XCL1 is also known to increase T cells in joints that are effected with rheumatoid arthritis. [6] They are also expressed on RA synovial lymphocytes. [6]

Related Research Articles

<span class="mw-page-title-main">Chemokine</span> Small cytokines or signaling proteins secreted by cells

Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.

<span class="mw-page-title-main">Macrophage inflammatory protein</span> Protein family

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β, renamed CCL3 and CCL4 respectively, since 2000. However, other names are sometimes encountered in older literature, such as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.

<span class="mw-page-title-main">Interleukin 16</span> Protein-coding gene in the species Homo sapiens

Interleukin 16 is a pro-inflammatory pleiotropic cytokine. Its precursor, pro-interleukin-16 is a protein that in humans is encoded by the IL16 gene. This gene was discovered in 1982 at Boston University by Dr. David Center and Dr. William Cruikshank.

Chemokine ligands 4 previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the CCL4 gene. CCL4 belongs to a cluster of genes located on 17q11-q21 of the chromosomal region. Identification and localization of the gene on the chromosome 17 was in 1990 although the discovery of MIP-1 was initiated in 1988 with the purification of a protein doublet corresponding to inflammatory activity from supernatant of endotoxin-stimulated murine macrophages. At that time, it was also named as "macrophage inflammatory protein-1" (MIP-1) due to its inflammatory properties.

<span class="mw-page-title-main">CCL20</span> Mammalian protein found in Homo sapiens

Chemokine ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils. CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.

<span class="mw-page-title-main">CCL18</span> Mammalian protein found in Homo sapiens

Chemokine ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. The functions of CCL18 have been well studied in laboratory settings, however the physiological effects of the molecule in living organisms have been difficult to characterize because there is no similar protein in rodents that can be studied. The receptor for CCL18 has been identified in humans only recently, which will help scientists understand the molecule's role in the body.

<span class="mw-page-title-main">CCL21</span> Mammalian protein found in Homo sapiens

Chemokine ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine, exodus-2, and secondary lymphoid-tissue chemokine (SLC). CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7. The main function of CCL21 is to guide CCR7 expressing leukocytes to the secondary lymphoid organs, such as lymph nodes and Peyer´s patches.

<span class="mw-page-title-main">CCL22</span> Mammalian protein found in Homo sapiens

C-C motif chemokine 22 is a protein that in humans is encoded by the CCL22 gene.

<span class="mw-page-title-main">CCL17</span> Mammalian protein found in Homo sapiens

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.

<span class="mw-page-title-main">CX3CL1</span> Protein-coding gene in the species Homo sapiens

Fractalkine, also known as chemokine ligand 1, is a protein that in humans is encoded by the CX3CL1 gene.

<span class="mw-page-title-main">CCL19</span> Mammalian protein found in Homo sapiens

Chemokine ligand 19 (CCL19) is a protein that in humans is encoded by the CCL19 gene.

<span class="mw-page-title-main">XCR1</span> Protein-coding gene in the species Homo sapiens

The "C" sub-family of chemokine receptors contains only one member: XCR1, the receptor for XCL1 and XCL2.

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 (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.

<span class="mw-page-title-main">XCL2</span> Protein-coding gene in the species Homo sapiens

Chemokine ligand 2 (XCL2) 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 chemokine receptor XCR1. Its gene is located on chromosome 1 in humans.

<span class="mw-page-title-main">C-C chemokine receptor type 7</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21). The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals. CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs by detecting specific chemokines, which these tissues secrete.

<span class="mw-page-title-main">C-C chemokine receptor type 6</span> Mammalian protein found in Homo sapiens

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.

<span class="mw-page-title-main">CCR4</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">CCR9</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 9 is a protein that in humans is encoded by the CCR9 gene. This gene is mapped to the chemokine receptor gene cluster region. Two alternatively spliced transcript variants have been described.

Ly6 also known as lymphocyte antigen 6 or urokinase-type plasminogen activator receptor (uPAR) is family of proteins that share a common structure but differ in their tissue expression patterns and function. Ly6 are cysteine-rich proteins that form disulfide bridges and contain a LU domain. These proteins are GPI-anchored to the cell membrane or are secreted. A total of 35 human and 61 mouse Ly6 family members have been identified. Depending on which tissues they are expressed in, LY6 family members have different roles. They are expressed in various types of tissues and their expression dependent on the stage of cell differentiation. For example, they are involved in cell proliferation, cell migration, cell–cell interactions, immune cell maturation, macrophage activation, and cytokine production. Their overexpression or dysregulation, for example due to point mutations, is associated with tumorogenesis and autoimmune diseases. This family was discovered in the 1970s, and these proteins are still used as markers of distinct stage of leukocyte differentiation.

<span class="mw-page-title-main">C-C motif chemokine ligand 27</span> Mammalian protein found in Homo sapiens

C-C motif chemokine ligand 27 is a protein that in humans is encoded by the CCL27 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000143184 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026573 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Wang X, Sharp JS, Handel TM, Prestegard JH (2013). "Chemokine oligomerization in cell signaling and migration". In Giraldo J, Ciruela F (eds.). Progress in Molecular Biology and Translational Science. Vol. 117. pp. 531–578. doi:10.1016/B978-0-12-386931-9.00020-9. ISBN   978-0-12-386931-9. PMC   3937849 . PMID   23663982.
  6. 1 2 3 4 Szekanecz Z, Koch AE (2017). "Cell Recruitment and Angiogenesis". In Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR (eds.). Kelly and Firestein's Textbook of Rheumatology. Elsevier. pp. 384–395. doi:10.1016/B978-0-323-31696-5.00025-5. ISBN   978-0-323-31696-5.
  7. 1 2 3 4 Hundeiker M (2009). "[The clinical picture of the effects of radiation on the skin]". Strahlenschutz in Forschung und Praxis. 28: 160–4. doi:10.1016/S0076-6879(09)05403-2. PMC   3686570 . PMID   19480914.
  8. 1 2 3 4 5 6 Yoshida T, Imai T, Takagi S, Nishimura M, Ishikawa I, Yaoi T, Yoshie O (October 14, 1996). "Structure and expression of two highly related genes encoding SCM-1/human lymphotactin". FEBS Letters. 395 (1): 82–88. Bibcode:1996FEBSL.395...82Y. doi: 10.1016/0014-5793(96)01004-6 . PMID   8849694.
  9. ↑ Kelner GS, Kennedy J, Bacon KB, Kleyensteuber S, Largaespada DA, Jenkins NA, Copeland NG, Bazan JF, Moore KW, Schall TJ (November 1994). "Lymphotactin: a cytokine that represents a new class of chemokine". Science. 266 (5189): 1395–9. Bibcode:1994Sci...266.1395K. doi:10.1126/science.7973732. PMID   7973732.
  10. ↑ Kennedy J, Kelner GS, Kleyensteuber S, Schall TJ, Weiss MC, Yssel H, Schneider PV, Cocks BG, Bacon KB, Zlotnik A (July 1995). "Molecular cloning and functional characterization of human lymphotactin". Journal of Immunology. 155 (1): 203–9. doi: 10.4049/jimmunol.155.1.203 . PMID   7602097.
  11. 1 2 Yoshida T, Imai T, Takagi S, Nishimura M, Ishikawa I, Yaoi T, Yoshie O (October 1996). "Structure and expression of two highly related genes encoding SCM-1/human lymphotactin". FEBS Letters. 395 (1): 82–8. Bibcode:1996FEBSL.395...82Y. doi: 10.1016/0014-5793(96)01004-6 . PMID   8849694.
  12. 1 2 3 4 5 6 7 8 Kroczek RA, Henn V (February 10, 2012). "The role of XCR1 and its Ligand XCL1 in antigen cross-presentation by murine and human dendritic cells". Front. Immunol. 3 (14): 14. doi: 10.3389/fimmu.2012.00014 . PMC   3342032 . PMID   22566900.
  13. ↑ Yoshida T, Imai T, Kakizaki M, Nishimura M, Takagi S, Yoshie O (June 1998). "Identification of single C motif-1/lymphotactin receptor XCR1". The Journal of Biological Chemistry. 273 (26): 16551–4. doi: 10.1074/jbc.273.26.16551 . PMID   9632725.
  14. ↑ Tyler RC, Murray NJ, Peterson FC, Volkman BF (August 2011). "Native-state interconversion of a metamorphic protein requires global unfolding". Biochemistry. 50 (33): 7077–9. doi:10.1021/bi200750k. PMC   3160782 . PMID   21776971.
  15. ↑ "XCL1 Gene(Protein Coding)". GeneCards human gene database.
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