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FLASH GENE

Symbol

TRPM1

contributors: mct/shn - updated : 14-06-2016

HGNC name	transient receptor potential cation channel, subfamily M, member 1
HGNC id	7146

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CSNB1C blindness night congenital, stationary 1C
Location	15q13.3      Physical location : 31.293.552 - 31.393.924
Synonym name	melastatin 1
	melastatin-1
	long transient receptor potential channel 1
	transient receptor potential cation channel subfamily M member 1
	transient receptor potential melastatin family
Synonym symbol(s)	MLSN1, LTRPC1, MLSN, CSNB1C

DNA

TYPE	functioning gene
STRUCTURE	160.21 kb     27 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	four consensus binding sites for MITF
	654 bp upstream sequence, containing four E boxes (E1-E4), including an 11 bp M box (E4), sufficient for melanocyte-specific transcription and activation by MITF
	an exon (exon 11) that is present in all TRPM1 cDNA clones but has no corresponding homologous region neither in TRPM3 nor in any other TRPM channel encoding 57 amino acids in the N-terminal cytosolic region of TRPM1

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D15S1043 - D15S165 - TRPM1 - D15S976 - D15S1013 - qter

RNA

TRANSCRIPTS	type	messenger

text	alternatively spliced, resulting in the production of a long form (TRPM1-L) and a short N-terminal form devoid of transmembrane segments (TRPM1-S) (PMID: 19966281)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002420 27 splicing 5724 NP_002411 - 1603 ON-bipolar cell dendrites and synaptic ribbons of a subclass of rods of the retinal (PMID:21896854) 2010 19966281 NM_001252024 28 splicing 5810 NP_001238953 - 1625 - 2010 19966281 also called 92+TRPM1 contains 22 additional amino acids NM_001252020 28 splicing 6022 NP_001238949 - 1642 - 2010 19966281 also called 109+TRPM1 or TRPM1L contains 39 additional amino acids is a component of the transduction cation channel in the GRM6 cascade of retinal ON bipolar cells NM_001252030 4 - 1002 NP_001238959 - 136 - 2010 19966281

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous nerve cranial nerve     highly Reproductive male system testis       Skin/Tegument skin       highly Homo sapiens Visual eye retina     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining retinal pigment epithelium (RPE)   highly Homo sapiens Fetal

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument melanocyte Homo sapiens Visual bipolar cell Homo sapiens Visual cone photoreceptor Homo sapiens Visual rod photoreceptor Homo sapiens

cell lineage	melanoma cell lineage
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ankyrin repeats at the N terminus, and basic N-terminal AA K464 of TRPM1 suggests that it is part of putative pleckstrin homology (PH) domain and is involved in the interactions with INPP5J
	a core of six transmembrane segments (6TM)
	a TRP (EWKFHR) domain
	a small putative transmembrane domain
	a larger domain with a hollow cavity
	a C terminal cytoplasmic tail

mono polymer

dimer

HOMOLOGY

interspecies	ortholog to Mlsn1, mus musculus
	ortholog to Trpm1, Rattus norvegicus

Homologene

FAMILY

TRP-melastatin subfamily

CATEGORY

antigen , receptor , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm
text	long form may be sequestered by MLN-S in the cytoplasm
	located on the dendrites and soma of retina ON-bipolar cells
	tips of retina ON-bipolar cell dendrites and rod spherules ribbons

basic FUNCTION	potential melanoma suppressor
	involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands
	role for TRPM1-mediated Ca(2+) homeostasis, which is also regulated by ultraviolet B, in melanogenesis
	ion channel whose function is critical to normal melanocyte pigmentation
	important role for the normal function of ON bipolar cells in the human retina
	GRM6-coupled cation channel in rod-bipolar cells, and is essential for the normal response of cone ON-bipolar cells
	functional ion-conducting plasma membrane channels
	expressed on the synaptic ribbons of a subclass of rods, suggesting a dual function for TRPM1 in the ON-pathway
	is a cation-selective channel, and will therefore depolarize ON bipolar cells when it opens
	light indirectly opens TRPM1 by reducing transmitter release from presynaptic photoreceptors, resulting in a decrease in GRM6 activation
	is not essential for development of hearing or balance and it is unlikely that TRPM1 is a component of the hair cell MET channel
	is essential for the light-induced depolarization of retinal ON bipolar cells
	the underlying transduction cascade in the dendritic tips of ON-bipolar cells involves GRM6 signaling to TRPM1 proteins that are an indispensable part of the transduction channel
	calcium channel that is essential for the depolarization of photo-responsive retinal bipolar cells
	in retinal ON bipolar cells, Go couples the metabotropic receptor GRM6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	ion transport

PATHWAY

metabolism

signaling

a component

TRPM1 and TRPM3 form heteromultimeric channels

INTERACTION

DNA

RNA

small molecule

protein	TRPM1
	GNB3 participates in the G-protein heterotrimer that couples GRM6 to TRPM1
	in the retina, TRPM1 activity is negatively coupled to metabotropic GRM6 signaling through Galphao
	GPR179 along with RGS7 and RGS11 controls the ability of the GRM6 cascade to gate TRPM1
	LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation

cell & other

REGULATION

activated by

HIS1 (regulation of both transcription and mRNA processing)

inhibited by

by low micromolar concentrations of Zn2+

Other	downregulated in murine melanoma cell line with an agressive phenotype
	regulated by MITF
	regulated by multiple mechanisms in melanocytes and melanoma cells

ASSOCIATED DISORDERS

corresponding disease(s)

CSNB1C

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in melanoma with high metastatic potential

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	potential target for pigmentation disorders

ANIMAL & CELL MODELS

	decreased expression of TRPM1 in the eye and the skin may alter bipolar cell signaling as well as melanocyte function, thus causing both congenital stationary night blindness and coat spotting patterns in horses
	ON bipolar cell function was absent or severely impaired in a mouse model that lacked Trpm1 expression