Metabotropic glutamate receptor 6

Mammalian protein found in humans

GRM6

Identifiers

Aliases

GRM6, CSNB1B, GPRC1F, MGLUR6, mGlu6, glutamate metabotropic receptor 6

External IDs

OMIM: 604096 MGI: 1351343 HomoloGene: 20232 GeneCards: GRM6

Gene location (Human)

Chr.	Chromosome 5 (human)^[1]

Band	5q35.3	Start	178,977,587 bp^[1]
Band	5q35.3	End	178,996,206 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 11 (mouse)^[2]

Band	11\|11 B1.3	Start	50,741,512 bp^[2]
Band	11\|11 B1.3	End	50,757,035 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

pancreatic ductal cell

tibialis anterior muscle

cerebellar hemisphere

ganglionic eminence

anterior pituitary

deltoid muscle

hypothalamus

Brodmann area 9

amygdala

putamen

Top expressed in

spleen

thymus

bone marrow

lens

islet of Langerhans

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	glutamate receptor activity G protein-coupled receptor activity protein homodimerization activity signal transducer activity adenylate cyclase inhibiting G protein-coupled glutamate receptor activity protein binding
Cellular component	integral component of membrane Golgi apparatus cell projection endoplasmic reticulum membrane membrane Golgi membrane plasma membrane integral component of plasma membrane dendrite endoplasmic reticulum presynaptic membrane new growing cell tip
Biological process	G protein-coupled glutamate receptor signaling pathway detection of visible light locomotory behavior response to stimulus sensory perception of light stimulus detection of light stimulus involved in visual perception positive regulation of calcium ion import retina development in camera-type eye signal transduction visual perception chemical synaptic transmission regulation of synaptic transmission, glutamatergic adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway G protein-coupled receptor signaling pathway
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


2916


108072

Ensembl


ENSG00000113262


ENSMUSG00000000617

UniProt


O15303


Q5NCH9

RefSeq (mRNA)


NM_000843


NM_173372

RefSeq (protein)


NP_000834


NP_775548

Location (UCSC)

Chr 5: 178.98 – 179 Mb

Chr 11: 50.74 – 50.76 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Glutamate receptor, metabotropic 6, also known as GRM6 or mGluR6, is a protein which in humans is encoded by the GRM6 gene.^[5]^[6]

Function

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.^[5]

mGluR6 is specifically expressed in the retina, in a subtype of bipolar cells that depolarize in response to light, known as ON bipolar cells. These cells form synapses with photoreceptor cells, and detect the neurotransmitter glutamate via a GPCR signal transduction cascade. The glutamate receptor mGluR6 is located post-synaptically at the tips of the bipolar cell dendrites, and is responsible for initiating a signaling cascade that ultimately controls gating of the TRPM1 channel.^[7]^[8] In human patients, mutations in the GRM6 gene are associated with congenital stationary night blindness.^[9]^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000113262 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000000617 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: GRM6 glutamate receptor, metabotropic 6".
^ Hashimoto T, Inazawa J, Okamoto N, Tagawa Y, Bessho Y, Honda Y, Nakanishi S (June 1997). "The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6". Eur. J. Neurosci. 9 (6): 1226–35. doi:10.1111/j.1460-9568.1997.tb01477.x. PMID 9215706. S2CID 25387864.
^ Nakajima Y, Iwakabe H, Akazawa C, Nawa H, Shigemoto R, Mizuno N, Nakanishi S (1993). "Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate". J Biol Chem. 268 (16): 11868–73. doi:10.1016/S0021-9258(19)50280-0. PMID 8389366.
^ Masu M, Iwakabe H, Tagawa Y, Miyoshi T, Yamashita M, Fukuda Y, Sasaki H, Hiroi K, Nakamura Y, Shigemoto R, Takada M, Nakamura K, Nakao K, Katsuki M, Nakanishi S (1995). "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene". Cell. 80 (5): 757–65. doi:10.1016/0092-8674(95)90354-2. PMID 7889569. S2CID 17081238.
^ Dryja TP, McGee TL, Berson EL, Fishman GA, Sandberg MA, Alexander KR, Derlacki DJ, Rajagopalan AS (2005). "Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6". Proc Natl Acad Sci U S A. 102 (13): 4884–9. Bibcode:2005PNAS..102.4884D. doi:10.1073/pnas.0501233102. PMC 555731. PMID 15781871.
^ Zeitz C, van Genderen M, Neidhardt J, Luhmann UF, Hoeben F, Forster U, Wycisk K, Mátyás G, Hoyng CB, Riemslag F, Meire F, Cremers FP, Berger W (2005). "Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram". Invest Ophthalmol Vis Sci. 46 (11): 4328–35. doi:10.1167/iovs.05-0526. PMID 16249515.

Hashimoto T, Inazawa J, Okamoto N, et al. (1997). "The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6". Eur. J. Neurosci. 9 (6): 1226–35. doi:10.1111/j.1460-9568.1997.tb01477.x. PMID 9215706. S2CID 25387864.
Dhingra A, Lyubarsky A, Jiang M, et al. (2001). "The light response of ON bipolar neurons requires G[alpha]o". J. Neurosci. 20 (24): 9053–8. doi:10.1523/JNEUROSCI.20-24-09053.2000. PMC 6773027. PMID 11124982.
Valerio A, Ferraboli S, Paterlini M, et al. (2001). "Identification of novel alternatively-spliced mRNA isoforms of metabotropic glutamate receptor 6 gene in rat and human retina". Gene. 262 (1–2): 99–106. doi:10.1016/S0378-1119(00)00547-3. PMID 11179672.
Dryja TP, McGee TL, Berson EL, et al. (2005). "Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6". Proc. Natl. Acad. Sci. U.S.A. 102 (13): 4884–9. Bibcode:2005PNAS..102.4884D. doi:10.1073/pnas.0501233102. PMC 555731. PMID 15781871.
Zeitz C, van Genderen M, Neidhardt J, et al. (2005). "Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram". Invest. Ophthalmol. Vis. Sci. 46 (11): 4328–35. doi:10.1167/iovs.05-0526. PMID 16249515.
Zeitz C, Forster U, Neidhardt J, et al. (2007). "Night blindness-associated mutations in the ligand-binding, cysteine-rich, and intracellular domains of the metabotropic glutamate receptor 6 abolish protein trafficking". Hum. Mutat. 28 (8): 771–80. doi:10.1002/humu.20499. PMID 17405131. S2CID 24946081.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin-like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3
Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)
Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)
Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin (1A 1B 1C) TAAR (1 2 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 1 2 FPRL1 OXE Prostaglandin DP (1 2), EP (1 2 3 4), FP Prostacyclin Thromboxane
Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Hydroxycarboxylic acids 1 2 3 Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide

B/W (1
2)
FF (1
2)
S
Y (1
2
4
5)
Neuromedin (B
U (1
2))
Neurotensin (1
2)

Other

Anaphylatoxin (C3a
C5a (1
2))
Angiotensin (1
2)
Apelin
Bombesin
- BRS3
- GRPR
- NMBR)
- Bradykinin (B1
- B2)
Chemokine
Cholecystokinin (A
B)
Endothelin
- A
- B
Formyl peptide (1
2
3)
FSH
Galanin (1
2
3)
Gonadotropin-releasing hormone (1
2)
Ghrelin
Kisspeptin
Luteinizing hormone/choriogonadotropin
MAS (1
1L
D
E
F
G
X1
X2
X3
X4)
Melanocortin (1
2
3
4
5)
MCHR (1
2)
Motilin
Opioid (Delta
Kappa
Mu
Nociceptin & Zeta, but not Sigma)
Orexin (1
2)
Oxytocin
Prokineticin (1
2)
Prolactin-releasing peptide
Relaxin (1
2
3
4)
Somatostatin (1
2
3
4
5)
Tachykinin (1
2
3)
Thyrotropin
Thyrotropin-releasing hormone
Urotensin-II
Vasopressin (1A
1B
2)

Miscellaneous

Taste, bitter	TAS2R 1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor type 1
Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)
Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin-like

Adhesion	ADGRB Brain-specific angiogenesis inhibitor 1 2 3 ADGRC Cadherin 1 2 3 ADGRE EMR 1 2 3 CD97 ADGRG 1 2 3 4 5 6 7 ADGRL Latrophilin 1 2 3 ELTD1
Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)
Other	Calcitonin CALCRL Corticotropin-releasing hormone (1 2) Glucagon (GR GIPR GLP1R GLP2R) Growth-hormone-releasing hormone PACAPR1 GPR Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste, sweet	TAS1R 1 2 3 Vomeronasal receptor, type 2
Other	Calcium-sensing receptor GABA_B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled & Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)
Smoothened	Smoothened

Metabotropic glutamate receptor modulators

Group I

mGluR₁Tooltip Metabotropic glutamate receptor 1	Agonists: ACPD DHPG Glutamate Ibotenic acid Quisqualic acid Ro01-6128 Ro67-4853 Ro67-7476 VU-71 Theanine Antagonists: BAY 36-7620 CPCCOEt Cyclothiazide LY-367,385 LY-456,236 MCPG NPS-2390
mGluR₅Tooltip Metabotropic glutamate receptor 5	Agonists: ACPD ADX-47273 CDPPB CHPG DFB DHPG Glutamate Ibotenic acid Quisqualic acid VU-1545 Antagonists: CTEP DMeOB LY-344,545 Mavoglurant MCPG NPS-2390 Remeglurant SIB-1757 SIB-1893; Negative allosteric modulators: AZD9272 Basimglurant Dipraglurant Fenobam GRN-529 MPEP MTEP Raseglurant

Group II

mGluR₂Tooltip Metabotropic glutamate receptor 2

Agonists: BINA
CBiPES
DCG-IV
Eglumegad
Glutamate
Ibotenic acid
LY-379,268
LY-404,039 (pomaglumetad)
LY-487,379
LY-566,332
MGS-0028
Pomaglumetad methionil (LY-2140023)
Talaglumetad; Positive allosteric modulators: JNJ-40411813 (ADX-71149)

Antagonists: APICA
CECXG
EGLU
HYDIA
LY-307,452
LY-341,495
MCPG
MGS-0039
PCCG-4; Negative allosteric modulators: Decoglurant
RO4491533

mGluR₃Tooltip Metabotropic glutamate receptor 3

Agonists: CBiPES
DCG-IV
Eglumegad
Glutamate
Ibotenic acid
LY-379,268
LY-404,039 (pomaglumetad)
LY-487,379
MGS-0028
Pomaglumetad methionil (LY-2140023)
Talaglumetad

Antagonists: APICA
CECXG
EGLU
HYDIA
LY-307,452
LY-341,495
MCPG
MGS-0039; Negative allosteric modulators: Decoglurant
RO4491533

Group III

mGluR₄Tooltip Metabotropic glutamate receptor 4	Agonists: Glutamate L-AP4 LSP2-9166 PHCCC VU-001,171 VU-0155,041; Positive allosteric modulators: Foliglurax MPEP Antagonists: CPPG MAP4 MPPG MSOP MTPG UBP-1112
mGluR₆Tooltip Metabotropic glutamate receptor 6	Agonists: Glutamate L-AP4 Antagonists: CPPG MAP4 MPPG MSOP MTPG UBP-1112
mGluR₇Tooltip Metabotropic glutamate receptor 7	Agonists: AMN082 Glutamate L-AP4 LSP2-9166 Antagonists: CPPG MAP4 MMPIP MPPG MSOP MTPG UBP-1112 XAP044; Negative allosteric modulators: ADX71743
mGluR₈Tooltip Metabotropic glutamate receptor 8	Agonists: DCPG Glutamate L-AP4; Positive allosteric modulators: AZ12216052 Antagonists: CPPG MAP4 MPPG MSOP MTPG UBP-1112