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target has curated data in GtoImmuPdb
Target id: 2913
Nomenclature: leucine rich repeat containing 32
Abbreviated Name: GARP
Family: Leucine-rich repeat proteins
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 1 | 662 | 11q13.5 | LRRC32 | leucine rich repeat containing 32 | 4 |
| Mouse | 1 | 663 | 7 E2 | Lrrc32 | leucine rich repeat containing 32 | 5 |
| Rat | 1 | 663 | 1q32 | Lrrc32 | leucine rich repeat containing 32 | |
| Gene and Protein Information Comments | ||||||
| Two transcripts of the human gene are reported, which differ in their 5' untranslated regions but encode the same length protein [4]. | ||||||
| Previous and Unofficial Names |
| glycoprotein A repetitions predominant |
| Database Links |
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| Alphafold | Q14392 (Hs) |
| CATH/Gene3D | 3.80.10.10 |
| Ensembl Gene | ENSG00000137507 (Hs), ENSMUSG00000090958 (Mm), ENSRNOG00000015310 (Rn) |
| Entrez Gene | 2615 (Hs), 434215 (Mm), 293135 (N/A) |
| Human Protein Atlas | ENSG00000137507 (Hs) |
| KEGG Gene | hsa:2615 (Hs), mmu:434215 (Mm) |
| Pharos | Q14392 (Hs) |
| RefSeq Nucleotide | NM_001128922 (Hs), NM_005512 (Hs), NM_001113379 (Mm), NM_001170434 (Rn) |
| RefSeq Protein | NP_005503 (Hs), NP_001106850 (Mm), NP_001163905 (Rn) |
| UniProtKB | Q14392 (Hs) |
| Wikipedia | LRRC32 (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Antibody Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Anti-GARP monoclonal antibodies such as LHG-10.6 and livmoniplimab (ABBV-151, formerly ARGX-115 and MHG-8) have been developed [2]. These mAbs are reported to bind to a conformational epitope within GARP/TGF-β1 complexes on Treg cells, and block the production of active TGF-β1, and subsequently block immunosuppressive Treg activity. It is hypothesised that anti-GARP, Treg-inhibiting mAbs could be used to combat chronic infection and cancer with less serious autommune side effects than anti-CTLA4 and anti-PD1 mAbs. Livmoniplimab (ABBV-151) was developed by arGEN-X [1] as a novel anti-cancer therapeutic, and is being progressed into clinical trial by AbbVie. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| GARP is expressed on the surface of T regulatory (Treg) cells and binds latent (inactive) TGF-β1. GARP is also involved in the activation of TGF-β1 [2]. Anti-GARP antibodies block release of active TGF-β1, and are predicted to boost immune responses to infection and cancer [2]. GARP is a marker of activated human Treg cells. Th17 differentiation is induced by activated Tregs expressing GARP/latent TGF-β1 complexes in the presence of exogenous IL-6 [3]. |
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| General Comments |
| LRRC32 encodes a type I transmembrane protein (known as GARP) which contains 20 leucine-rich repeats in its extracellular domain [4] to which latent TGF-β1 binds. |
1. arGEN-X. ARGX-115. Accessed on 07/09/2016. Modified on 07/09/2016. http://www.argen-x.com, http://www.argen-x.com/en-GB/content/argx-115/20/
2. Cuende J, Liénart S, Dedobbeleer O, van der Woning B, De Boeck G, Stockis J, Huygens C, Colau D, Somja J, Delvenne P et al.. (2015) Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo. Sci Transl Med, 7 (284): 284ra56. [PMID:25904740]
3. Edwards JP, Fujii H, Zhou AX, Creemers J, Unutmaz D, Shevach EM. (2013) Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J Immunol, 190 (11): 5506-15. [PMID:23645881]
4. Ollendorff V, Noguchi T, deLapeyriere O, Birnbaum D. (1994) The GARP gene encodes a new member of the family of leucine-rich repeat-containing proteins. Cell Growth Differ, 5 (2): 213-9. [PMID:8180135]
5. Roubin R, Pizette S, Ollendorff V, Planche J, Birnbaum D, Delapeyriere O. (1996) Structure and developmental expression of mouse Garp, a gene encoding a new leucine-rich repeat-containing protein. Int J Dev Biol, 40 (3): 545-55. [PMID:8840187]
6. Van Der Woning S, Borgions F, Dreier T, Mariën L, De Boeck G, Liénart S, Lucas S, Coulie P. (2019) GARP-TGF-beta 1 antibodies. Patent number: US10479829B2. Assignee: argenx BVBA' Université Catholique de Louvian. Priority date: 11/05/2018. Publication date: 19/11/2019.
Leucine-rich repeat proteins: leucine rich repeat containing 32. Last modified on 20/10/2021. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2913.
