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CCR9

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Target id: 66

Nomenclature: CCR9

Family: Chemokine receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 369 3p21.31 CCR9 C-C motif chemokine receptor 9 17
Mouse 7 369 9 74.33 cM Ccr9 C-C motif chemokine receptor 9 17
Rat 6 369 8q32 Ccr9 C-C motif chemokine receptor 9
Previous and Unofficial Names Click here for help
GPR 9-6 [17] | GPR28
Database Links Click here for help
Specialist databases
GPCRdb ccr9_human (Hs), ccr9_mouse (Mm), q8ch33_rat (Rn)
Other databases
Alphafold P51686 (Hs), Q9WUT7 (Mm), Q8CH33 (Rn)
ChEMBL Target CHEMBL5815 (Hs)
Ensembl Gene ENSG00000173585 (Hs), ENSMUSG00000029530 (Mm), ENSRNOG00000006311 (Rn)
Entrez Gene 10803 (Hs), 12769 (Mm), 282832 (Rn)
Human Protein Atlas ENSG00000173585 (Hs)
KEGG Gene hsa:10803 (Hs), mmu:12769 (Mm), rno:282832 (Rn)
OMIM 604738 (Hs)
Pharos P51686 (Hs)
RefSeq Nucleotide NM_006641 (Hs), NM_009913 (Mm), NM_172329 (Rn)
RefSeq Protein NP_006632 (Hs), NP_034043 (Mm), NP_758832 (Rn)
UniProtKB P51686 (Hs), Q9WUT7 (Mm), Q8CH33 (Rn)
Wikipedia CCR9 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human CC chemokine receptor type 9 (CCR9) in complex with vercirnon.
PDB Id:  5LWE
Ligand:  vercirnon
Resolution:  2.8Å
Species:  Human
References:  7
Natural/Endogenous Ligands Click here for help
CCL25 {Sp: Human} , CCL25 {Sp: Mouse}

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Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 24 [PMID: 26987013 ] Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 8.2 pKi 5
⤷ pKi 8.2 (Ki 6x10-9 M) [5]
Description: FLIPR calcium assay using MOLT4 cells
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
vercirnon Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 8.2 pIC50 12
⤷ pIC50 8.2 (IC50 6x10-9 M) [12]
Description: Measuring inhibition of antagonist tracer [3H]CCX807 binding to human Molt-4 cells.
Immunopharmacology Comments
CCR9 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Activation of CCR9 by CCL25 plays a key role in leukocyte recruitment to the gut and CCR9 antagonists are being pursued as therapeutic agents for inflammatory bowel disease [13].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  T cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cellular signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Calcium channel
References:  15,17-18
Tissue Distribution Click here for help
Glomerular podocytes.
Species:  Human
Technique:  RT-PCR.
References:  4
Small bowel lamina propria mononuclear cells > colonic lamina propria mononuclear cells and peripheral blood leukocytes.
Species:  Human
Technique:  Flow cytometry.
References:  9
Intraepithelial lymphocytes and lamina propria lymphocytes.
Species:  Human
Technique:  Flow cytometry.
References:  18
Bone marrow stromal cells (BMSCs).
Species:  Human
Technique:  Flow cytometry and RT-PCR.
References:  2
Thymus: CD4+ and CD8+ thymocytes.
Species:  Human
Technique:  RT-PCR.
References:  16
Intraepithelial lymphocytes and lamina propria lymphocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  3
Thymus: CD4+ and CD8+ thymocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  1
Antibody-secreting plasma cells in the mesenteric lymph node and Peyer's patches.
Species:  Mouse
Technique:  Immunohistology.
References:  8
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of chemotaxis of human thymocytes endogenously expressing the CCR9 receptor.
Species:  Human
Tissue:  Thymocytes.
Response measured:  Chemotaxis.
References:  15
Measurement of Ca2+ levels in HEK 293 cells transfected with the human CCR9 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Ca2+ mobilisation.
References:  15-17
Measurement of chemotaxis of HEK 293 cells transfected with the human CCR9 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Chemotaxis.
References:  17
Measurement of chemotaxis of L1.2 cells transfected with the human CCR9 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Chemotaxis.
References:  18
Measurement of Ca2+ levels in Molt-4 cells endogenously expressing the CCR9 receptor.
Species:  Human
Tissue:  Molt-4 cells.
Response measured:  Ca2+ mobilisation.
References:  18
Physiological Functions Click here for help
Migration of T lymphocytes.
Species:  Mouse
Tissue:  In vivo.
References:  11
Migration of plasma cells to the small intestine.
Species:  Mouse
Tissue:  In vivo.
References:  8
T lymphocyte interaction with microvessels.
Species:  Mouse
Tissue:  Small intestine and colonic mucosa.
References:  3
T lymphocyte migration to the small-intestinal mucosa.
Species:  Mouse
Tissue:  In vivo (small intestine).
References:  10
Formation of gut cryptopatches.
Species:  Mouse
Tissue:  Small intestine.
References:  6
Physiological Consequences of Altering Gene Expression Click here for help
CCR9 receptor knockout mice exhibit reduced T cell receptor γδ+ gut intraepithelial lymphocytes.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
CCR9 receptor knockout mice exhibit reduced antibody-secreting plasma cell migration into the small intestine.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ccr9tm1.1Mal|Tnf+|Tnftm2Gkl Ccr9tm1.1Mal/Ccr9tm1.1Mal,Tnftm2Gkl/Tnf+
involves: 129S/SvEv * 129S2/SvPas * C57BL/6		 MGI:104798  MGI:1341902  MP:0008399 abnormal alpha-beta intraepithelial T cell morphology PMID: 18439426 
Ccr9tm1Lov Ccr9tm1Lov/Ccr9tm1Lov
Not Specified		 MGI:1341902  MP:0008349 abnormal gamma-delta intraepithelial T cell morphology PMID: 11884450 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas		 MGI:1341902  MP:0008345 abnormal gamma-delta T cell number PMID: 17548595 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas * C57BL/6		 MGI:1341902  MP:0000217 abnormal leukocyte cell number PMID: 11675330 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas		 MGI:1341902  MP:0005232 abnormal mesenteric lymph node morphology PMID: 17548595 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas * C57BL/6		 MGI:1341902  MP:0002145 abnormal T cell differentiation PMID: 11675330 
Ccr9tm1Ccb Ccr9tm1Ccb/Ccr9tm1Ccb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341902  MP:0002145 abnormal T cell differentiation PMID: 15484191 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas		 MGI:1341902  MP:0003944 abnormal T cell subpopulation ratio PMID: 17548595 
Ccr9tm1.1Mal|Tnf+|Tnftm2Gkl Ccr9tm1.1Mal/Ccr9tm1.1Mal,Tnftm2Gkl/Tnf+
involves: 129S/SvEv * 129S2/SvPas * C57BL/6		 MGI:104798  MGI:1341902  MP:0003944 abnormal T cell subpopulation ratio PMID: 18439426 
Ccr9tm1Lov Ccr9tm1Lov/Ccr9tm1Lov
Not Specified		 MGI:1341902  MP:0008363 decreased CD8-positive, gamma-delta intraepithelial T cell number PMID: 11884450 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas * C57BL/6		 MGI:1341902  MP:0005092 decreased double-positive T cell number PMID: 11675330 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas		 MGI:1341902  MP:0008351 decreased gamma-delta intraepithelial T cell number PMID: 17548595 
Ccr9tm1.1Mal|Tnf+|Tnftm2Gkl Ccr9tm1.1Mal/Ccr9tm1.1Mal,Tnftm2Gkl/Tnf+
involves: 129S/SvEv * 129S2/SvPas * C57BL/6		 MGI:104798  MGI:1341902  MP:0008351 decreased gamma-delta intraepithelial T cell number PMID: 18439426 
Ccr9tm1Lov Ccr9tm1Lov/Ccr9tm1Lov
Not Specified		 MGI:1341902  MP:0005016 decreased lymphocyte cell number PMID: 11884450 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas * C57BL/6		 MGI:1341902  MP:0008208 decreased pro-B cell number PMID: 11675330 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas * C57BL/6		 MGI:1341902  MP:0005018 decreased T cell number PMID: 11675330 
Ccr9tm1Ccb Ccr9tm1Ccb/Ccr9tm1Ccb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341902  MP:0000715 decreased thymocyte number PMID: 15484191 
Ccr9tm1Lov Ccr9tm1Lov/Ccr9tm1Lov
Not Specified		 MGI:1341902  MP:0008346 increased gamma-delta T cell number PMID: 11884450 
Ccr9tm1.1Mal Ccr9tm1.1Mal/Ccr9tm1.1Mal
involves: 129S2/SvPas * C57BL/6		 MGI:1341902  MP:0005015 increased T cell number PMID: 11675330 
Ccr9tm1.1Mal|Tnf+|Tnftm2Gkl Ccr9tm1.1Mal/Ccr9tm1.1Mal,Tnftm2Gkl/Tnf+
involves: 129S/SvEv * 129S2/SvPas * C57BL/6		 MGI:104798  MGI:1341902  MP:0001858 intestinal inflammation PMID: 18439426 
Biologically Significant Variants Click here for help
Type:  Splice variants
Species:  Human
Description:  Two splice variants of the CCR9 gene have been isolated, with the CCR9-A isoform having 12 additional amino acids at its N-terminus. They both are functional receptors but have different ligand selectivities.
References:  16

References

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1. Carramolino L, Zaballos A, Kremer L, Villares R, Martín P, Ardavín C, Martínez-A C, Márquez G. (2001) Expression of CCR9 beta-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8(+) T cells from secondary lymphoid organs. Blood, 97 (4): 850-7. [PMID:11159507]

2. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. (2006) Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells, 24 (4): 1030-41. [PMID:16253981]

3. Hosoe N, Miura S, Watanabe C, Tsuzuki Y, Hokari R, Oyama T, Fujiyama Y, Nagata H, Ishii H. (2004) Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa. Am J Physiol Gastrointest Liver Physiol, 286 (3): G458-66. [PMID:14592943]

4. Huber TB, Reinhardt HC, Exner M, Burger JA, Kerjaschki D, Saleem MA, Pavenstädt H. (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol, 168 (12): 6244-52. [PMID:12055238]

5. Kalindjian SB, Kadnur SV, Hewson CA, Venkateshappa C, Juluri S, Kristam R, Kulkarni B, Mohammed Z, Saxena R, Viswanadhan VN et al.. (2016) A New Series of Orally Bioavailable Chemokine Receptor 9 (CCR9) Antagonists; Possible Agents for the Treatment of Inflammatory Bowel Disease. J Med Chem, 59 (7): 3098-111. [PMID:26987013]

6. Onai N, Kitabatake M, Zhang YY, Ishikawa H, Ishikawa S, Matsushima K. (2002) Pivotal role of CCL25 (TECK)-CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes. Int Immunol, 14 (7): 687-94. [PMID:12096027]

7. Oswald C, Rappas M, Kean J, Doré AS, Errey JC, Bennett K, Deflorian F, Christopher JA, Jazayeri A, Mason JS et al.. (2016) Intracellular allosteric antagonism of the CCR9 receptor. Nature, 540 (7633): 462-465. [PMID:27926729]

8. Pabst O, Ohl L, Wendland M, Wurbel MA, Kremmer E, Malissen B, Förster R. (2004) Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine. J Exp Med, 199 (3): 411-6. [PMID:14744993]

9. Papadakis KA, Prehn J, Nelson V, Cheng L, Binder SW, Ponath PD, Andrew DP, Targan SR. (2000) The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. J Immunol, 165 (9): 5069-76. [PMID:11046037]

10. Svensson M, Marsal J, Ericsson A, Carramolino L, Brodén T, Márquez G, Agace WW. (2002) CCL25 mediates the localization of recently activated CD8alphabeta(+) lymphocytes to the small-intestinal mucosa. J Clin Invest, 110 (8): 1113-21. [PMID:12393847]

11. Uehara S, Grinberg A, Farber JM, Love PE. (2002) A role for CCR9 in T lymphocyte development and migration. J Immunol, 168 (6): 2811-9. [PMID:11884450]

12. Walters MJ, Wang Y, Lai N, Baumgart T, Zhao BN, Dairaghi DJ, Bekker P, Ertl LS, Penfold ME, Jaen JC et al.. (2010) Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. J Pharmacol Exp Ther, 335 (1): 61-9. [PMID:20660125]

13. Wendt E, Keshav S. (2015) CCR9 antagonism: potential in the treatment of Inflammatory Bowel Disease. Clin Exp Gastroenterol, 8: 119-30. [PMID:25897254]

14. Wurbel MA, Malissen M, Guy-Grand D, Meffre E, Nussenzweig MC, Richelme M, Carrier A, Malissen B. (2001) Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes. Blood, 98 (9): 2626-32. [PMID:11675330]

15. Youn BS, Kim CH, Smith FO, Broxmeyer HE. (1999) TECK, an efficacious chemoattractant for human thymocytes, uses GPR-9-6/CCR9 as a specific receptor. Blood, 94 (7): 2533-6. [PMID:10498628]

16. Yu CR, Peden KW, Zaitseva MB, Golding H, Farber JM. (2000) CCR9A and CCR9B: two receptors for the chemokine CCL25/TECK/Ck beta-15 that differ in their sensitivities to ligand. J Immunol, 164 (3): 1293-305. [PMID:10640743]

17. Zaballos A, Gutiérrez J, Varona R, Ardavín C, Márquez G. (1999) Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK. J Immunol, 162 (10): 5671-5. [PMID:10229797]

18. Zabel BA, Agace WW, Campbell JJ, Heath HM, Parent D, Roberts AI, Ebert EC, Kassam N, Qin S, Zovko M, LaRosa GJ, Yang LL, Soler D, Butcher EC, Ponath PD, Parker CM, Andrew DP. (1999) Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J Exp Med, 190: 1241-1256. [PMID:10544196]

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