leucine rich repeat containing 32

Target id: 2913

Nomenclature: leucine rich repeat containing 32

Abbreviated Name: GARP

Family: Leucine-rich repeat proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     leucine rich repeat containing 32 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 662 11q13.5-q14 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
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Antibody Comments
Anti-GARP monoclonal antibodies such as LHG-10.6 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. ARGX-115 is an Anti-GARP mAb in preclinical development by arGEN-X [1] as a novel anti-cancer therapeutic.
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 ID:  4
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of activated T cell proliferation (GO:0046007) IEA
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of activated T cell proliferation (GO:0046007) IEA
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of cytokine secretion (GO:0050710) IEA
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of activated T cell proliferation (GO:0046007) IEA
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  negative regulation of activated T cell proliferation (GO:0046007) IEA
References: 
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 Med7 (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]

How to cite this page

Leucine-rich repeat proteins: leucine rich repeat containing 32. Last modified on 08/05/2017. Accessed on 20/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2913.