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CXCL5 - Wikipedia

From Wikipedia, the free encyclopedia

CXCL5

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2MGS

Identifiers

Aliases

CXCL5, ENA-78, SCYB5, C-X-C motif chemokine ligand 5

External IDs

OMIM: 600324; MGI: 1096868; HomoloGene: 88672; GeneCards: CXCL5; OMA:CXCL5 - orthologs

Gene location (Human)

Chr.	Chromosome 4 (human)^[1]

Band	4q13.3	Start	73,995,642 bp^[1]
Band	4q13.3	End	73,998,677 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 5 (mouse)^[2]

Band	5 E1\|5 44.78 cM	Start	90,907,219 bp^[2]
Band	5 E1\|5 44.78 cM	End	90,909,483 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

monocyte

appendix

cartilage tissue

pancreatic epithelial cell

minor salivary glands

islet of Langerhans

testicle

pancreatic ductal cell

gallbladder

palpebral conjunctiva

Top expressed in

right lobe of liver

cervix

endothelial cell of lymphatic vessel

trachea

respiratory epithelium

olfactory epithelium

mandibular molars

embryo

embryo

conjunctival fornix

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	CXCR chemokine receptor binding cytokine activity chemokine activity identical protein binding
Cellular component	extracellular region extracellular space
Biological process	positive regulation of cell population proliferation inflammatory response response to lipopolysaccharide signal transduction cell-cell signaling immune response chemokine-mediated signaling pathway cell chemotaxis neutrophil mediated immunity chemotaxis defense response positive regulation of neutrophil chemotaxis regulation of signaling receptor activity G protein-coupled receptor signaling pathway neutrophil chemotaxis leukocyte chemotaxis antimicrobial humoral immune response mediated by antimicrobial peptide cellular response to lipopolysaccharide
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


6374


20311

Ensembl


ENSG00000163735


ENSMUSG00000029371

UniProt


P42830


P50228

RefSeq (mRNA)


NM_002994


NM_009141

RefSeq (protein)


NP_002985


NP_033167

Location (UCSC)

Chr 4: 74 – 74 Mb

Chr 5: 90.91 – 90.91 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

C-X-C motif chemokine 5 (CXCL5 or ENA78) is a protein that in humans is encoded by the CXCL5 gene.^[5]^[6]

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 (ENA-78). It is produced following stimulation of cells with the inflammatory cytokines interleukin-1 or tumor necrosis factor-alpha.^[7] Expression of CXCL5 has also been observed in eosinophils, and can be inhibited with the type II interferon IFN-γ.^[8] This chemokine stimulates the chemotaxis of neutrophils possessing angiogenic properties. It elicits these effects by interacting with the cell surface chemokine receptor CXCR2.^[8] The gene for CXCL5 has four exons and is located on human chromosome 4 amongst several other CXC chemokine genes.^[7]^[9] CXCL5 has been implicated in connective tissue remodelling.^[8] CXCL5 has been also described to regulate neutrophil homeostasis.^[10]

Clinical significance

CXCL5 plays a role in reducing sensitivity to sunburn pain in some subjects, and is a "potential target which can be utilized to understand more about pain in other inflammatory conditions like arthritis and cystitis.".^[11] CXCL5 is well known to have chemotactic and activating functions on neutrophil, mainly during acute inflammatory responses. However CXCL5 expression is also higher in atherosclerosis (a chronic inflammatory condition) but is not associated with neutrophil infiltration. Instead CXCL5 has a protective role in atherosclerosis by directly controlling macrophage foam cell formation.^[12]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000163735 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000029371 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Chang MS, McNinch J, Basu R, Simonet S (Nov 1994). "Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene". J Biol Chem. 269 (41): 25277–82. doi:10.1016/S0021-9258(18)47243-2. PMID 7929219.
^ "Entrez Gene: CXCL5 chemokine (C-X-C motif) ligand 5".
^ ^a ^b Chang MS, McNinch J, Basu R, Simonet S (1994). "Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene". J. Biol. Chem. 269 (41): 25277–82. doi:10.1016/S0021-9258(18)47243-2. PMID 7929219.
^ ^a ^b ^c Persson T, Monsef N, Andersson P, Bjartell A, Malm J, Calafat J, Egesten A (2003). "Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophils". Clin. Exp. Allergy. 33 (4): 531–7. doi:10.1046/j.1365-2222.2003.01609.x. PMID 12680872. S2CID 2449190.
^ O'Donovan N, Galvin M, Morgan JG (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet. Cell Genet. 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098. S2CID 8087808.
^ Mei J, Liu Y, Dai N, Hoffmann C, Hudock KM, Zhang P, Guttentag SH, Kolls JK, Oliver PM, Bushman FD, Worthen GS (2012). "Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice". Journal of Clinical Investigation. 122 (3): 974–986. doi:10.1172/JCI60588. PMC 3287232. PMID 22326959.
^
Dawes JM, Calvo M, Perkins JR, Paterson KJ, Kiesewetter H, Hobbs C, Kaan TK, Orengo C, Bennett DL, McMahon SB (July 2011). "CXCL5 Mediates UVB Irradiation-Induced Pain". Sci Transl Med. 3 (90): 90ra60. doi:10.1126/scitranslmed.3002193. PMC 3232447. PMID 21734176.
- Howard Lovy (July 11, 2011). "Sunburn pain discovery could lead to better arthritis treatments". FierceBiotech. Archived from the original on 2011-07-13.
^ Rousselle A, Qadri F, Leukel L, Yilmaz R, Fontaine JF, Sihn G, Bader M, Ahluwalia A, Duchene J (2013). "CXCL5 limits macrophage foam cell formation in atherosclerosis". Journal of Clinical Investigation. 123 (3): 1343–7. doi:10.1172/JCI66580. PMC 3582141. PMID 23376791.

External links

Human CXCL5 genome location and CXCL5 gene details page in the UCSC Genome Browser.

Duchene J, Lecomte F, Ahmed S, Cayla C, Pesquero J, Bader M, Perretti M, Ahluwalia A (2007). "A novel inflammatory pathway involved in leukocyte recruitment: role for the kinin B1 receptor and the chemokine CXCL5". J. Immunol. 179 (7): 4849–56. doi:10.4049/jimmunol.179.7.4849. PMC 3696729. PMID 17878384.
Walz A, Schmutz P, Mueller C, Schnyder-Candrian S (1997). "Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease". J. Leukoc. Biol. 62 (5): 604–11. doi:10.1002/jlb.62.5.604. PMID 9365115. S2CID 20141618.
Struyf S, Proost P, Van Damme J (2004). Regulation of the Immune Response by the Interaction of Chemokines and Proteases. Advances in Immunology. Vol. 81. pp. 1–44. doi:10.1016/S0065-2776(03)81001-5. ISBN 978-0-12-022481-4. PMID 14711052.
Walz A, Burgener R, Car B, et al. (1992). "Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8". J. Exp. Med. 174 (6): 1355–62. doi:10.1084/jem.174.6.1355. PMC 2119025. PMID 1744577.
Power CA, Furness RB, Brawand C, Wells TN (1995). "Cloning of a full-length cDNA encoding the neutrophil-activating peptide ENA-78 from human platelets". Gene. 151 (1–2): 333–4. doi:10.1016/0378-1119(94)90682-3. PMID 7828901.
Corbett MS, Schmitt I, Riess O, Walz A (1995). "Characterization of the gene for human neutrophil-activating peptide 78 (ENA-78)". Biochem. Biophys. Res. Commun. 205 (1): 612–7. doi:10.1006/bbrc.1994.2709. PMID 7999089.
Koch AE, Kunkel SL, Harlow LA, et al. (1994). "Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis". J. Clin. Invest. 94 (3): 1012–8. doi:10.1172/JCI117414. PMC 295150. PMID 8083342.
Power CA, Clemetson JM, Clemetson KJ, Wells TN (1996). "Chemokine and chemokine receptor mRNA expression in human platelets". Cytokine. 7 (6): 479–82. doi:10.1006/cyto.1995.0065. PMID 8580362.
Ahuja SK, Murphy PM (1996). "The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor". J. Biol. Chem. 271 (34): 20545–50. doi:10.1074/jbc.271.34.20545. PMID 8702798.
Keates S, Keates AC, Mizoguchi E, et al. (1997). "Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis". Am. J. Physiol. 273 (1 Pt 1): G75–82. doi:10.1152/ajpgi.1997.273.1.G75. PMID 9252512.
Wuyts A, Proost P, Lenaerts JP, et al. (1998). "Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78". Eur. J. Biochem. 255 (1): 67–73. doi:10.1046/j.1432-1327.1998.2550067.x. PMID 9692902.
Wyrick PB, Knight ST, Paul TR, et al. (1999). "Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis". J. Infect. Dis. 179 (4): 954–66. doi:10.1086/314676. PMID 10068592.
Wuyts A, Govaerts C, Struyf S, et al. (1999). "Isolation of the CXC chemokines ENA-78, GRO alpha and GRO gamma from tumor cells and leukocytes reveals NH2-terminal heterogeneity. Functional comparison of different natural isoforms". Eur. J. Biochem. 260 (2): 421–9. doi:10.1046/j.1432-1327.1999.00166.x. PMID 10095777.
Hogaboam CM, Bone-Larson CL, Steinhauser ML, et al. (1999). "Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines". FASEB J. 13 (12): 1565–74. doi:10.1096/fasebj.13.12.1565. hdl:2027.42/154508. PMID 10463948. S2CID 7043800.
Luu NT, Rainger GE, Nash GB (2000). "Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils". J. Immunol. 164 (11): 5961–9. doi:10.4049/jimmunol.164.11.5961. PMID 10820279.
Crane IJ, Wallace CA, McKillop-Smith S, Forrester JV (2000). "Control of chemokine production at the blood–retina barrier". Immunology. 101 (3): 426–33. doi:10.1046/j.0019-2805.2000.01105.x. PMC 2327097. PMID 11106948.
Zhang C, Thornton MA, Kowalska MA, et al. (2001). "Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus". Blood. 98 (3): 610–7. doi:10.1182/blood.V98.3.610. PMID 11468158.
Chandrasekar B, Melby PC, Sarau HM, et al. (2003). "Chemokine-cytokine cross-talk. The ELR+ CXC chemokine LIX (CXCL5) amplifies a proinflammatory cytokine response via a phosphatidylinositol 3-kinase-NF-kappa B pathway". J. Biol. Chem. 278 (7): 4675–86. doi:10.1074/jbc.M207006200. PMID 12468547.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

Cell signaling: cytokines

By family

Chemokine

CCL	CCL1 CCL2/MCP1 CCL3/MIP1α CCL4/MIP1β CCL5/RANTES CCL6 CCL7 CCL8 CCL9 CCL11 CCL12 CCL13 CCL14 CCL15 CCL16 CCL17 CCL18/PARC/DCCK1/AMAC1/MIP4 CCL19 CCL20 CCL21 CCL22 CCL23 CCL24 CCL25 CCL26 CCL27 CCL28
CXCL	CXCL1/KC CXCL2 CXCL3 CXCL4 CXCL5 CXCL6 CXCL7 CXCL8/IL8 CXCL9 CXCL10 CXCL11 CXCL12 CXCL13 CXCL14 CXCL15 CXCL16 CXCL17
CX3CL	CX3CL1
XCL	XCL1 XCL2

TNF

Interleukin

Type I
(grouped by
receptor
subunit)

γ chain	IL2/IL15 IL4/IL13 IL7 IL9 IL21
β chain	IL3 IL5 GMCSF
IL6 like/gp130	IL6 IL11 IL27 IL30 IL31 +non IL OSM LIF CNTF CTF1
IL12 family/IL12RB1	IL12 IL23 IL27 IL35
Other	IL14 IL16 IL32 IL34

Type II

IL10 family

IL10/IL22
IL19
IL20
IL24
IL26
Interferon type III
- IL28/IFNL2+3
- IL29/IFNL1

Interferon

I	IFNA1 IFNA2 IFNA4 IFNA5 IFNA6 IFNA7 IFNA8 IFNA10 IFNA13 IFNA14 IFNA16 IFNA17 IFNA21 IFNB1 IFNK IFNW1
II	IFNG

Ig superfamily

IL17 family

IL17/IL25 (IL17A)

Other

By function/
cell

proinflammatory cytokine
- IL1
- TNFA

Monokine
Lymphokine
- T_h1
  - IFNγ
  - TNFβ
- T_h2
  - IL4
  - IL5
  - IL6
  - IL10
  - IL13

Chemokine receptor modulators

CCR1	Agonists: CCL4 (MIP-1β) CCL5 (RANTES) CCL6 CCL9 (CCL10) CCL14 CCL15 CCL16 CCL23
CCR2	Agonists: CCL2 CCL8 CCL12 CCL16 NAMs: Cenicriviroc (TAK-652, TBR-652)
CCR3	Agonists: CCL5 (RANTES) CCL7 CCL11 CCL13 CCL15 CCL18 CCL24 CCL26 CCL28
CCR4	Agonists: CCL3 (MIP-1α) CCL5 (RANTES) CCL17 CCL22 Antibodies: Mogamulizumab (against CCR4)
CCR5	Agonists: CCL3 (MIP-1α) CCL4 (MIP-1β) CCL5 (RANTES) CCL8 CCL11 CCL13 CCL14 CCL16 NAMs: Aplaviroc Cenicriviroc (TAK-652, TBR-652) INCB009471 Maraviroc Vicriviroc Antibodies: PRO-140
CCR6	Agonists: CCL20
CCR7	Agonists: CCL19 CCL21
CCR8	Agonists: CCL1 CCL16
CCR9	Agonists: CCL25
CCR10	Agonists: CCL27 CCL28
CCR11	Agonists: CCL19 CCL21 CCL25
Ungrouped	Antibodies: Bertilimumab (against CCL11) Carlumab (against CCL2)

CXC

CXCR1 (IL-8Rα)	Agonists: CXCL6 Emoctakin Interleukin-8 (CXCL8, GCP-1) Antagonists: Navarixin NAMs: Ladarixin Reparixin (repertaxin)
CXCR2 (IL-8Rβ)	Agonists: CXCL1 (MGSA) CXCL2 CXCL3 CXCL5 CXCL6 CXCL7 Emoctakin Garnocestim Interleukin-8 (CXCL8, GCP-1) Antagonists: Danirixin Elubrixin Navarixin NAMs: Ladarixin Reparixin (repertaxin)
CXCR3	Agonists: CXCL4 (PF4) CXCL9 (MIG) CXCL10 (IP-10) CXCL11 (I-TAC) Iroplact Antibodies: Eldelumab (against CXCL10)
CXCR4	Agonists: MIF SDF-1 (CXCL12) Ubiquitin Antagonists: Mavorixafor Plerixafor (AMD3100) Antibodies: Ulocuplumab (against CXCR4)
CXCR5	Agonists: CXCL13
CXCR6	Agonists: CXCL16
CXCR7	Agonists: Conolidine CXCL11 (I-TAC) CCX771 LIH383 RTI-5152-12 SDF-1 (CXCL12) VUF15485 PAMs: Plerixafor (AMD3100)

C (XC)

XCR1	Agonists: Lymphotactin-α (XCL1) Lymphotactin-β (XCL2) Antibodies: Pateclizumab

CX3C

CX3CR1	Agonists: Fractalkine (CX3CL1)

Others

CCBP2	Agonists: CC (β) chemokines
CMKLR1	Agonists: Chemerin Resolvin E1

Categories:

Hidden categories:

Function

Clinical significance

References

External links

Further reading