TRPM1 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

TRPM1

Target id: 493

Nomenclature: TRPM1

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     TRPM1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 1603 15q13-q14 TRPM1 transient receptor potential cation channel subfamily M member 1 7-8,17
Mouse 6 0 1506 7 C Trpm1 transient receptor potential cation channel, subfamily M, member 1 11
Rat 6 0 1628 1q22 Trpm1 transient receptor potential cation channel, subfamily M, member 1
Previous and Unofficial Names
LTRPC1 | melastatin 1 | MLSN1 | transient receptor potential cation channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics
Conducts mono- and di-valent cations non-selectively, dual rectification (inward and outward)
Ion Selectivity and Conductance Comments
Nonselective, outward rectifying [13,18,20].

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
pregnenolone sulphate Hs - - - - - 15
[15]
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Zn2+ Hs - 6.0 pIC50 - -
pIC50 6.0 (IC50 1x10-6 M)
Immunopharmacology Comments
Expressed on mouse B cells and rat mast cells [21].
Tissue Distribution
Skin: melanocytes (also reported in horse).
Species:  Human
Technique:  Immunocytochemistry, RT-PCR, western blot, northern blot.
References:  2,5,7-8,17,20
Retina: ON-bipolar cells (Note that the same pattern of expression is observed in human, mouse and monkey).
Species:  Human
Technique:  Immunohistochemistry, RT-PCR, northern blot
References:  3,10,12-13,18
Functional Assays
Ca2+ imaging.
Species:  Human
Tissue:  Heterologous overexpression in HEK 293 cells.
Response measured:  Ca2+ influx.
References:  23
Electrophysiology (Note that equivalent experiments in mouse produce the same results).
Species:  Human
Tissue:  Epidermal melanocytes, rod and cone ON-bipolar cells
Response measured:  Ionic current
References:  13,18,20
Physiological Functions
Putative tumour suppressor: in human melanocytic primary neoplasms, an inverse correlation with melanoma exists, i.e. loss of TRPM1 expression correlates with melanoma thickness.
Species:  Human
Tissue:  Skin.
References:  4,7-9,17
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpm1tm1Lex Trpm1tm1Lex/Trpm1tm1Lex
involves: 129S/SvEvBrd
MGI:1330305  MP:0004022 abnormal cone electrophysiology PMID: 19861548 
Trpm1tm1Tfur Trpm1tm1Tfur/Trpm1tm1Tfur
involves: 129S6/SvEvTac
MGI:1330305  MP:0004022 abnormal cone electrophysiology PMID: 19966281 
Trpm1tm1Lex Trpm1tm1Lex/Trpm1tm1Lex
involves: 129S/SvEvBrd
MGI:1330305  MP:0005551 abnormal eye electrophysiology PMID: 19861548 
Trpm1tm1Lex Trpm1tm1Lex/Trpm1tm1Lex
involves: 129S/SvEvBrd
MGI:1330305  MP:0005253 abnormal eye physiology PMID: 19861548 
Trpm1tm1Lex Trpm1tm1Lex/Trpm1tm1Lex
involves: 129S/SvEvBrd
MGI:1330305  MP:0004021 abnormal rod electrophysiology PMID: 19861548 
Trpm1tm1Tfur Trpm1tm1Tfur/Trpm1tm1Tfur
involves: 129S6/SvEvTac
MGI:1330305  MP:0004021 abnormal rod electrophysiology PMID: 19966281 
Trpm1tm1Lex Trpm1tm1Lex/Trpm1tm1Lex
involves: 129S/SvEvBrd
MGI:1330305  MP:0002090 abnormal vision PMID: 19861548 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Night blindness, congenital stationary, type 1C; CSNB1C
Synonyms: Congenital stationary night blindness [Orphanet: ORPHA215] [Disease Ontology: DOID:0050534]
Disease Ontology: DOID:0050534
OMIM: 613216
Orphanet: ORPHA215
References:  1,16,19,22
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human Y72C 1
Missense Human R74C 16,22
Missense Human L99P 1,16,22
Missense Human L354R 16,22
Missense Human R473P 1
Missense Human G534R 16,22
Missense Human M541K 1
Missense Human P611H 16,22
Missense Human R624C 19
Missense Human W856X 1
Missense Human I1002F 16
Missense Human F1075S 19
Missense Human Q1164R 1
Nonsense Human Q11X 1
Nonsense Human G138fs 16
Nonsense Human Y774X 1
Nonsense Human W856X 1
Nonsense Human S882X 19
Nonsense Human Y1035X 16
Gene Expression and Pathophysiology
Downregulation of expression is correlated with metastasis and poor prognosis in melanoma.
Tissue or cell type:  Pigmented melanoma cell lines.
Pathophysiology: 
Species:  Human
Technique:  Immunocytochemistry, RT-PCR, western blot, northern blot.
References:  4,7-9,17
Gene Expression and Pathophysiology Comments
In melanoma or cancer-associated retinopathy, autoantibodies target TRPM1 in retinal ON-bipolar cells and cause ON-bipolar cell dysfunction [6,14].
General Comments
TRPM1 is a constitutively open, non-selective ion channel that is negatively regulated by activation of mGluR6 receptors in the ON-bipolar cells [13,18].

Microphthalmia-associated transcription factor (MITF) induces expression of TRPM1 in melanocytes [17,24].

It has been reported that membrane insertion ot TRPM1 may be regulated by a short isoform (MLSN-S, 500 aa) [23], but note that the data supporting this report is weak and has not been reproduced or confirmed by any subsequent publication.

References

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1. Audo I, Kohl S, Leroy BP, Munier FL, Guillonneau X, Mohand-Saïd S, Bujakowska K, Nandrot EF, Lorenz B, Preising M et al.. (2009) TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. Am. J. Hum. Genet., 85 (5): 720-9. [PMID:19896113]

2. Bellone RR, Forsyth G, Leeb T, Archer S, Sigurdsson S, Imsland F, Mauceli E, Engensteiner M, Bailey E, Sandmeyer L et al. (2010) Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. Brief Functional Genomics, 9 (3): 193-207. [PMID:20353955]

3. Cao Y, Posokhova E, Martemyanov KA. (2011) TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner. J. Neurosci., 31 (32): 11521-6. [PMID:21832182]

4. Deeds J, Cronin F, Duncan LM. (2000) Patterns of melastatin mRNA expression in melanocytic tumors. Hum. Pathol., 31 (11): 1346-56. [PMID:11112208]

5. Devi S, Markandeya Y, Maddodi N, Dhingra A, Vardi N, Balijepalli RC, Setaluri V. (2013) Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes. Pigment Cell Melanoma Res, 26 (3): 348-56. [PMID:23452348]

6. Dhingra A, Fina ME, Neinstein A, Ramsey DJ, Xu Y, Fishman GA, Alexander KR, Qian H, Peachey NS, Gregg RG et al.. (2011) Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells. J. Neurosci., 31 (11): 3962-7. [PMID:21411639]

7. Duncan LM, Deeds J, Cronin FE, Donovan M, Sober AJ, Kauffman M, McCarthy JJ. (2001) Melastatin expression and prognosis in cutaneous malignant melanoma. J. Clin. Oncol., 19 (2): 568-76. [PMID:11208852]

8. Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW. (1998) Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res., 58 (7): 1515-20. [PMID:9537257]

9. Erickson LA, Letts GA, Shah SM, Shackelton JB, Duncan LM. (2009) TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas. Mod. Pathol., 22 (7): 969-76. [PMID:19396153]

10. Gilliam JC, Wensel TG. (2011) TRP channel gene expression in the mouse retina. Vision Res., 51 (23-24): 2440-52. [PMID:22037305]

11. Hunter JJ, Shao J, Smutko JS, Dussault BJ, Nagle DL, Woolf EA, Holmgren LM, Moore KJ, Shyjan AW. (1998) Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1). Genomics, 54 (1): 116-23. [PMID:9806836]

12. Klooster J, Blokker J, Ten Brink JB, Unmehopa U, Fluiter K, Bergen AA, Kamermans M. (2011) Ultrastructural localization and expression of TRPM1 in the human retina. Invest. Ophthalmol. Vis. Sci., 52 (11): 8356-62. [PMID:21896854]

13. Koike C, Obara T, Uriu Y, Numata T, Sanuki R, Miyata K, Koyasu T, Ueno S, Funabiki K, Tani A et al. (2010) TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc Natl Acad Sci U S A, 107 (1): 332-337. [PMID:19966281]

14. Kondo M, Sanuki R, Ueno S, Nishizawa Y, Hashimoto N, Ohguro H, Yamamoto S, Machida S, Terasaki H, Adamus G et al.. (2011) Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction. PLoS ONE, 6 (5): e19911. [PMID:21611200]

15. Lambert S, Drews A, Rizun O, Wagner TF, Lis A, Mannebach S, Plant S, Portz M, Meissner M, Philipp SE et al.. (2011) Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc ions. J. Biol. Chem., 286 (14): 12221-33. [PMID:21278253]

16. Li Z, Sergouniotis PI, Michaelides M, Mackay DS, Wright GA, Devery S, Moore AT, Holder GE, Robson AG, Webster AR. (2009) Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. Am. J. Hum. Genet., 85 (5): 711-9. [PMID:19878917]

17. Miller AJ, Du J, Rowan S, Hershey CL, Widlund HR, Fisher DE. (2004) Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma. Cancer Res., 64 (2): 509-16. [PMID:14744763]

18. Morgans CW, Zhang J, Jeffrey BG, Nelson SM, Burke NS, Duvoisin RM, Brown RL. (2009) TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proc Natl Acad Sci U S A, 106 (45): 19174-8. [PMID:19861548]

19. Nakamura M, Sanuki R, Yasuma TR, Onishi A, Nishiguchi KM, Koike C, Kadowaki M, Kondo M, Miyake Y, Furukawa T. (2010) TRPM1 mutations are associated with the complete form of congenital stationary night blindness. Mol. Vis., 16: 425-37. [PMID:20300565]

20. Oancea E, Vriens J, Brauchi S, Jun J, Splawski I, Clapham DE. (2009) TRPM1 forms ion channels associated with melanin content in melanocytes. Sci Signal, 2 (70): ra21. [PMID:19436059]

21. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br. J. Pharmacol., 173 (6): 953-69. [PMID:26603538]

22. van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA et al.. (2009) Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. Am. J. Hum. Genet., 85 (5): 730-6. [PMID:19896109]

23. Xu XZ, Moebius F, Gill DL, Montell C. (2001) Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proc. Natl. Acad. Sci. U.S.A., 98 (19): 10692-7. [PMID:11535825]

24. Zhiqi S, Soltani MH, Bhat KM, Sangha N, Fang D, Hunter JJ, Setaluri V. (2004) Human melastatin 1 (TRPM1) is regulated by MITF and produces multiple polypeptide isoforms in melanocytes and melanoma. Melanoma Res., 14 (6): 509-16. [PMID:15577322]

Contributors

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How to cite this page

Elena Oancea, David E. Clapham.
Transient Receptor Potential channels: TRPM1. Last modified on 18/08/2016. Accessed on 13/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=493.