regulator of G-protein signaling 13

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 2805

Nomenclature: regulator of G-protein signaling 13

Abbreviated Name: RGS13

Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Immunopharmacology Comments
Immuno Cell Type Associations
Tissue Distribution
Functional Assays
Physiological Functions
Xenobiotics Influencing Gene Expression
Clinically-Relevant Mutations and Pathophysiology
Gene Expression and Pathophysiology
References
Contributors
How to cite this page

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	159	1q31.2	RGS13	regulator of G protein signaling 13	10
Mouse	-	158	1 62.56 cM	Rgs13	regulator of G-protein signaling 13	17
Rat	-	158	13q21	Rgs13	regulator of G-protein signaling 13

Database Links
Alphafold	O14921 (Hs), Q8K443 (Mm)
CATH/Gene3D	1.10.196.10
Ensembl Gene	ENSG00000127074 (Hs), ENSMUSG00000051079 (Mm), ENSRNOG00000003888 (Rn)
Entrez Gene	6003 (Hs), 246709 (Mm), 54293 (Rn)
Human Protein Atlas	ENSG00000127074 (Hs)
KEGG Gene	hsa:6003 (Hs), mmu:246709 (Mm), rno:54293 (Rn)
OMIM	607190 (Hs)
Pharos	O14921 (Hs)
RefSeq Nucleotide	NM_002927 (Hs), NM_153171 (Mm)
RefSeq Protein	NP_002918 (Hs), NP_694811 (Mm)
UniProtKB	O14921 (Hs), Q8K443 (Mm)
Wikipedia	RGS13 (Hs)

Associated Proteins

G Proteins
Name	References
Gαi/0
Gαq/11

Interacting Proteins
Name	Effect	References
phosphoinositide-3-kinase regulatory subunit 2	Inhibits PI3 kinase signaling.	2
phosphoCREB	Inhibits CREB transcription.	22

Immunopharmacology Comments
RGS13 is involved in a range of immune system and inflammatory processes [13,15,18]. For example, RGS13 inhibits CXCL12- and CXCL13-induced MAPK activation, and chemotaxis [17]. In contrast RGS13 knockdown enhances CXCL12 and CXCL13 responsiveness [6].

Immunopharmacology Comments

RGS13 is involved in a range of immune system and inflammatory processes [13,15,18]. For example, RGS13 inhibits CXCL12- and CXCL13-induced MAPK activation, and chemotaxis [17]. In contrast RGS13 knockdown enhances CXCL12 and CXCL13 responsiveness [6].

Cell Type Associations

Immuno Cell Type:	B cells
Cell Ontology Term:	B cell (CL:0000236)
References:	1-2

Immuno Cell Type:	Dendritic cells
Cell Ontology Term:	dendritic cell (CL:0000451)
Comment:	NB mouse dendritic cells.
References:	17

Immuno Cell Type:	Mast cells
Cell Ontology Term:	mast cell (CL:0000097)
References:	1-2

Tissue Distribution

Tonsil, thymus, lung, lymph node, spleen, lymph node and lymphocytes.

Species:	Human
Technique:	RT-PCR.
References:	8,10,12

EBV-infected B cells.

Species:	Human
Technique:	Microarray analysis.
References:	3

B cells, mast cells.

Species:	Human
Technique:	Western blot.
References:	1-2,6,11

Spleen, stomach, small intestine, thymus.

Species:	Mouse
Technique:	Northen blot.
References:	17

Dendritic cells.

Species:	Mouse
Technique:	RT-PCR.
References:	16

Midbrain.

Species:	Rat
Technique:	In situ hybridisation.
References:	5

Functional Assays

RGS13 blunts carbachol-induced MAPK activation in cells expressing the muscarinic M₂ receptor.

Species:	Human
Tissue:	293T and A9L cells expressing muscarinic receptor.
Response measured:	Decreased MAPK phosphorylation (as ERK phosphorylation level).
References:	10

RGS13 inhibits CXCL12- and CXCL13-induced MAPK activation, and chemotaxis.

Species:	Mouse
Tissue:	COS or CHO cells expressing CXCR4 or CXCR5 receptors and RGS13.
Response measured:	Decreased MAPK phosphorylation (as ERK phosphorylation level), inhibition of chemotaxis.
References:	17

Knockdown of RGS13 in a Burkitt's lymphoma cell line enhances responsiveness to the chemokines CXCL12 and CXCL13 and increases chemoattraction.

Species:	Human
Tissue:	HS-Sultan B cell lymphoma cell line.
Response measured:	Increased Ca²⁺ mobilization, polarization.
References:	6

Knockdown of RGS13 in mast cells enhances responsiveness to several natural GPCR ligands and increases chemotaxis.

Species:	Human
Tissue:	Mast cells.
Response measured:	Increased Ca²⁺ molilization, Akt phosphorylation and chemotaxis.
References:	1

Physiological Functions

RGS13 suppresses IgE-mediated mast cell degranulation and systemic anaphylaxis.

Species:	Mouse
Tissue:	Mast cells, multiorgan effects.
References:	2

RGS13 inhibits early antibody responses, plasma cell expansion, and germinal center formation in lymphoid organs following immunization.

Species:	Mouse
Tissue:	Lymph node.
References:	7

RGS13 promotes autoantibody formation in autoimmune-prone mice.

Species:	Mouse
Tissue:	Lymph node.
References:	21

Xenobiotics Influencing Gene Expression

Doxorubicin reduces RGS13 expression in mast cells.

Species:	Human
Tissue:	LAD2 human mast cell line.
Technique:	Quantitative PCR, immunoblotting.
References:	9

Clinically-Relevant Mutations and Pathophysiology

Disease:

Mantle cell lymphoma

Description:	MCL is an aggressive form of non-Hodgkin’s lymphoma (NHL; median survival of 3-4 years) that arises from B-cells originating within the mantle zone of lymphatic follicles. In the US, around six percent of all new NHL cases are MCL.
Disease Ontology:	DOID:0050746
Orphanet:	ORPHA52416

References:

8

Disease:

Non-allergic (intrinsic) asthma

Description:

Although characteristic symptoms are the same as for allergic asthma, non-allergic asthma is triggered by factors not related to allergies (e.g. anxiety, stress, exercise, cold air, dry air, hyperventilation, smoke, viruses or other irritants) and the immune system is not involved in the reaction.

References:

14

Disease:

Squamous cell carcinoma, head and neck

Synonyms:	HNSCC
OMIM:	275355
Orphanet:	ORPHA67037

References:

20

Gene Expression and Pathophysiology

Transcription factor T-bet downregulates Rgs13 in mouse germinal center (GC) B cells, increasing responsiveness to chemokines

Tissue or cell type:
Pathophysiology:
Species:	Mouse
Technique:
References:	13

IL-38 upregulates RGS13 in primary human bronchial epithelial cells

Tissue or cell type:
Pathophysiology:
Species:	Human
Technique:
References:	18

miR-452-5p and miR-139-5p downregulate Rgs13 in Raji B cells

Tissue or cell type:
Pathophysiology:
Species:	Human
Technique:
References:	15

RGS13 expression is upregulated in B cells from SLE patients compared to. healthy controls.

Tissue or cell type:
Pathophysiology:
Species:	Human
Technique:
References:	4

The baseline expression level of RGS13 in colon tissues from IBD patients associates with endoscopic remission after vedolizumab, but not anti-TNF, treatment

Tissue or cell type:
Pathophysiology:
Species:	Human
Technique:
References:	19

References

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1. Bansal G, DiVietro JA, Kuehn HS, Rao S, Nocka KH, Gilfillan AM, Druey KM. (2008) RGS13 controls g protein-coupled receptor-evoked responses of human mast cells. J Immunol, 181 (11): 7882-90. [PMID:19017978]

2. Bansal G, Xie Z, Rao S, Nocka KH, Druey KM. (2008) Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat Immunol, 9 (1): 73-80. [PMID:18026105]

3. Cahir-McFarland ED, Carter K, Rosenwald A, Giltnane JM, Henrickson SE, Staudt LM, Kieff E. (2004) Role of NF-kappa B in cell survival and transcription of latent membrane protein 1-expressing or Epstein-Barr virus latency III-infected cells. J Virol, 78 (8): 4108-19. [PMID:15047827]

4. Fan H, Zhao G, Ren D, Liu F, Dong G, Hou Y. (2017) Gender differences of B cell signature related to estrogen-induced IFI44L/BAFF in systemic lupus erythematosus. Immunol Lett, 181: 71-78. [PMID:27923569]

5. Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ. (2001) Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res, 88 (1-2): 113-23. [PMID:11295237]

6. Han JI, Huang NN, Kim DU, Kehrl JH. (2006) RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization. J Leukoc Biol, 79 (6): 1357-68. [PMID:16565322]

7. Hwang IY, Hwang KS, Park C, Harrison KA, Kehrl JH. (2013) Rgs13 constrains early B cell responses and limits germinal center sizes. PLoS ONE, 8 (3): e60139. [PMID:23533672]

8. Islam TC, Asplund AC, Lindvall JM, Nygren L, Liden J, Kimby E, Christensson B, Smith CI, Sander B. (2003) High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma. Leukemia, 17 (9): 1880-90. [PMID:12970790]

9. Iwaki S, Lu Y, Xie Z, Druey KM. (2011) p53 negatively regulates RGS13 protein expression in immune cells. J Biol Chem, 286 (25): 22219-26. [PMID:21531726]

10. Johnson EN, Druey KM. (2002) Functional characterization of the G protein regulator RGS13. J Biol Chem, 277 (19): 16768-74. [PMID:11875076]

11. Kauppila A, Mäkilä UM, Mäkäräinen L, Puolakka J, Seppälä A. (1986) Tiaprofenic acid in the treatment of primary dysmenorrhoea. Eur J Obstet Gynecol Reprod Biol, 22 (5-6): 359-63. [PMID:3533672]

12. Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M. (2004) Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system. Brain Res Mol Brain Res, 122 (1): 24-34. [PMID:14992813]

13. Ly A, Liao Y, Pietrzak H, Ioannidis LJ, Sidwell T, Gloury R, Doerflinger M, Triglia T, Qin RZ, Groom JR et al.. (2019) Transcription Factor T-bet in B Cells Modulates Germinal Center Polarization and Antibody Affinity Maturation in Response to Malaria. Cell Rep, 29 (8): 2257-2269.e6. [PMID:31747599]

14. Raedler D, Ballenberger N, Klucker E, Böck A, Otto R, Prazeres da Costa O, Holst O, Illig T, Buch T, von Mutius E et al.. (2015) Identification of novel immune phenotypes for allergic and nonallergic childhood asthma. J Allergy Clin Immunol, 135 (1): 81-91. [PMID:25226851]

15. Sengupta M, Wang BD, Lee NH, Marx A, Kusner LL, Kaminski HJ. (2018) MicroRNA and mRNA expression associated with ectopic germinal centers in thymus of myasthenia gravis. PLoS One, 13 (10): e0205464. [PMID:30308012]

16. Shi GX, Harrison K, Han SB, Moratz C, Kehrl JH. (2004) Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: implications for G protein-coupled receptor signaling. J Immunol, 172 (9): 5175-84. [PMID:15100254]

17. Shi GX, Harrison K, Wilson GL, Moratz C, Kehrl JH. (2002) RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13. J Immunol, 169 (5): 2507-15. [PMID:12193720]

18. Sun X, Hou T, Cheung E, Iu TN, Tam VW, Chu IM, Tsang MS, Chan PK, Lam CW, Wong CK. (2020) Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma. Cell Mol Immunol, 17 (6): 631-646. [PMID:31645649]

19. Verstockt B, Verstockt S, Veny M, Dehairs J, Arnauts K, Van Assche G, De Hertogh G, Vermeire S, Salas A, Ferrante M. (2020) Expression Levels of 4 Genes in Colon Tissue Might Be Used to Predict Which Patients Will Enter Endoscopic Remission After Vedolizumab Therapy for Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol, 18 (5): 1142-1151.e10. [PMID:31446181]

20. Wang J, Lippman SM, Lee JJ, Yang H, Khuri FR, Kim E, Lin J, Chang DW, Lotan R, Hong WK et al.. (2010) Genetic variations in regulator of G-protein signaling genes as susceptibility loci for second primary tumor/recurrence in head and neck squamous cell carcinoma. Carcinogenesis, 31 (10): 1755-61. [PMID:20627871]

21. Wang JH, New JS, Xie S, Yang P, Wu Q, Li J, Luo B, Ding Y, Druey KM, Hsu HC et al.. (2013) Extension of the germinal center stage of B cell development promotes autoantibodies in BXD2 mice. Arthritis Rheum, 65 (10): 2703-12. [PMID:23818250]

22. Xie Z, Geiger TR, Johnson EN, Nyborg JK, Druey KM. (2008) RGS13 acts as a nuclear repressor of CREB. Mol Cell, 31 (5): 660-70. [PMID:18775326]