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leucine rich repeat containing 32

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Target id: 2913

Nomenclature: leucine rich repeat containing 32

Abbreviated Name: GARP

Family: Leucine-rich repeat proteins

Contents:

Gene and Protein Information Click here for help
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 Click here for help
glycoprotein A repetitions predominant
Database Links Click here for help
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)

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Antibodies
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Antibody Sp. Action Value Parameter Reference
livmoniplimab Peptide Primary target of this compound Hs Binding 9.1 pKd 6
⤷ pKd 9.1 (Kd 7.6x10-10 M) [6]
Description: Binding affinity of antibody for GARP-TGF-β1 complex, using Biacore assay.
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].
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
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.

References

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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.

How to cite this page

Leucine-rich repeat proteins: leucine rich repeat containing 32. Last modified on 20/10/2021. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2913.