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FLASH GENE

Symbol

TRPC1

contributors: mct/npt/pgu - updated : 22-01-2015

HGNC name	transient receptor potential cation channel, subfamily C, member 1
HGNC id	12333

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	83.46 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence
text structure	TATA box and CCAAT sequence close to the transcription initiation site
	four nuclear factor-kappaB (NF-kappaB)-binding sites in the 5'-regulatory region

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001251845 12 - 4179 NP_001238774 91 793 - 1996 8646775 long form NM_003304 12 - 4077 NP_003295 90 759 - 2009 19193631 short form

EXPRESSION

Type

widely

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 Cardiovascular heart       predominantly Digestive liver         Nervous brain       highly Homo sapiens Reproductive female system ovary         male system testis       Urinary kidney         Visual eye retina

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell Reproductive spermatocyte

cell lineage
cell lines
fluid/secretion	sperm

at STAGE

physiological period

fetal, pregnancy

Text	predominantly in brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	cytoplasmic N terminus
	ankyrin repeats and a coiled coil structure
	six transmembrane segments
	a cytoplasmic C terminus with a dystrophin (coiled-coil) domain
	a highly conserved TRP (EWKFHR) domain

conjugated

GlycoP

mono polymer

homomer , heteromer , tetramer , heptamer

HOMOLOGY

interspecies

ortholog to Drosophila store-operated channel (Soc)

Homologene

FAMILY	TRP superfamily of Ca2+ cation channels, classic subfamily
	transient receptor family
	STrpC subfamily

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm
text	perisynaptic region of the cerebellar parallel fibre-purkinje cell synapse
	mostly associated to the surface of spermatogenic cells
	co-localizes and could be co-immunoprecipitated with beta-tubulin
	forms functional endoplasmic reticulum (ER) homotetrameric channels, and is localized exclusively in the sarcoplasmic reticulum

basic FUNCTION	transient receptor potential non voltage-channel
	involved in calcium homeostasis in megakaryocytes and platelets
	plays fundamental roles in processes ranging from sensory physiology to male fertility
	may influence flagellar movement
	encoding a non-selective cation channel involved directly or indirectly in the regulation of cell volume
	having a function in retinal epithelium cells, dependent on its interaction with beta-tubulin
	showing a pattern of single-channel conductance, amiloride sensitivity and ion permeability distinct from that of TRPC1 alone
	operates as a sarcoplasmic reticulum Ca2+ leak channel in skeletal muscle
	deeply involved in intracellular Ca2+ homeostasis at rest and during muscle activation by potentially regulating SR Ca2+ content, resting cytosolic Ca2+ and kinetics of the voltage-evoked Ca2+ transients
	necessary mediator of pathologic cardiac hypertrophy, in part through a calcineurin/NFAT signaling pathway
	critical aspects of the TRPC1 channelosome that are involved in the regulation of TRPC1 function and TRPC1-SOC-generated Ca2+ signals
	cationic channel with functional effects that include stimulation of cardiovascular remodelling
	is potentially a molecular mediator for postsynaptic Ca2+ elevation required for BDNF-induced synaptic plasticity
	TRPC1 and TRPC5 have critical roles in neurite outgrowth
	acts as a scaffold at the cell surface to assemble a signaling complex to stimulate neurite outgrowth
	both TRPC1 and TRPC4 are essential for an intrinsic membrane conductance mediating the plateau potential in lateral septal neurons, possibly as heteromeric channels
	reduces calcium permeability in heteromeric channel complexes
	TRPC1-mediated Ca2+ influx enhances PI3K/Akt pathway during muscle regeneration
	regulates cell proliferation and motility, two processes underlying cancer progression
	TRPC1-mediated increase in store-operated Ca2+ entry is required for the proliferation of adult hippocampal neural progenitor cells
	down-regulation of TRPV6 currents by TRPC1 may increase the cellular diversity to fine-tune Ca2+ homeostasis
	TRPC1 is able to suppress TRPV6 dependent currents/entry because of a reduction of TRPV6 plasma membrane expression
	TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms
	heteromeric TRPC3/TRPC1 could participate in regulating the resting cytosolic Ca(2+) levels in skeletal muscle
	contribution of heteromultimeric channels from TRPC1, TRPC4, and TRPC5 subunits to the regulation of mechanisms underlying spatial working memory and flexible relearning by facilitating proper synaptic transmission in hippocampal neurons

CELLULAR PROCESS

cell migration & motility

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	forming with PKD2 a channel with a unique constellation of new and TRPP2/TRPC1-specific properties, activated in response to G-protein-coupled receptor activation
	in glomerular mesangial cells, the TRPC1/TRPC4 complexes constitute the functional subunits of UBXN11 and the interaction between STIM1 and TRPC4 may be the mechanism for the activation of the channels
	comprised of homo- or heterotetramers between either TRPC1/4/5
	is a component of a Ca(2+)-dependent amplification of EGF-dependent cell proliferation

INTERACTION

DNA

RNA

small molecule

protein	HOMER and ITPR1 (interaction TRPC1/ITPR1 regulated by HOMER)
	interacting with C10orf63
	interacting with STIM1
	CAV1 interacts with TRPC1 and ITPR3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells
	interacting with PKD2(form homotetramers, with distinct functional and regulatory properties, among which there are the presence of four subconductance states in PKD2)
	binds directly to KL and KDR and strengthens the association to promote their cointernalization (
	functional interaction of TRPC1 with TRPV6 that negatively regulates Ca2+ influx (
	MARCKS coordinates native TRPC1 channel activation in VSMCs by acting as a reversible PI(4,5)P2 buffer, which is regulated by PRKCA-mediated TRPC1 phosphorylation

cell & other

REGULATION

activated by	by depletion of intracellular Ca2+ stores (store-operated Ca2+ entry) or by stretch
	GRM1

induced by

TNF-alpha through an NF-kappaB-dependent pathway in endothelial cells, which can trigger augmented Ca2+ entry following Ca2+ store depletion

Other	stimulated by a G protein coupled receptor from extracellular space by a process called calcium capacitative entry (CCE)
	regulated by REST
	at least in certain cell types, TRPC1 is regulated during cell cycle progression

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology epilepsy   TRPC channels could be an unsuspected but critical molecular target for clinical intervention for excitotoxicity

ANIMAL & CELL MODELS