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FLASH GENE
Symbol TRPC3 contributors: mct/pgu - updated : 28-08-2015
HGNC name transient receptor potential cation channel, subfamily C, member 3
HGNC id 12335
Corresponding disease
SCA41 spinocerebellar ataxia 41
Location 4q27      Physical location : 122.800.182 - 122.872.909
Synonym name short transient receptor potential channel 3
Synonym symbol(s) TRP3
DNA
TYPE functioning gene
STRUCTURE 72.70 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
MYOZ2 4q26-q27 myozenin 2 MRPL42P1 4q27 myozenin 2 KIAA1350 FABP2 4q28-q31 fatty acid binding protein 2, intestinal LOC201989 4q27 similar to Glycerol kinase, testis specific 1 (ATP:glycerol 3-phosphotransferase) (Glycerokinase) (GK) LOC389221 4 similar to hypothetical protein LOC349114 LOC389222 4 LOC389222 LOC152972 4q27 similar to bA291L22.2 (similar to CDC10 (cell division cycle 10, S. cerevisiae, homolog)) PDE5A 4q26 phosphodiesterase 5A, cGMP-specific LOC391691 4 similar to ARHGAP20 protein MAD2L1 4q27 MAD2 mitotic arrest deficient-like 1 (yeast) LOC344988 4q27 similar to GTP-binding protein SAR1a (COPII-associated small GTPase) PRDM5 4q27 PR domain containing 5 FLJ23191 4q27 hypothetical protein FLJ23191 TNIP3 4q27 TNFAIP3 interacting protein 3 GPR103 4q27 G protein-coupled receptor 103 LOC391692 4 similar to TUBULIN BETA CHAIN ANXA5 4q26-q27 annexin A5 FLJ30834 4q27 hypothetical protein FLJ30834 PMSCL1 4q27 polymyositis/scleroderma autoantigen 1, 75kDa CCNA2 4q27 cyclin A2 BBS7 4q27 Bardet-Biedl syndrome 7 TRPC3 4q25-q27 transient receptor potential cation channel, subfamily C, member 3 KIAA1109 4q28.1 hypothetical protein KIAA1109 Tenr 4q28.1 testis nuclear RNA-binding protein IL2 4q26-q27 interleukin 2 IL21 4q26-q27 interleukin 21 FLJ35630 4q28.1 hypothetical protein FLJ35630 FGF2 4q26 fibroblast growth factor 2 (basic) NUDT6 4q26 nudix (nucleoside diphosphate linked moiety X)-type motif 6 SPATA5 4q27 spermatogenesis associated 5 SPRY1 4q26-q27 sprouty homolog 1, antagonist of FGF signaling (Drosophila) LOC391693 4 similar to ribosomal protein L21 LOC391694 4 similar to Peptidylprolyl isomerase A (cyclophilin A) LOC391695 4 similar to Tubulin alpha-4 chain (Alpha-tubulin 4) LOC391696 4 similar to Synaptic glycoprotein SC2 KIAA1223 4q28.1 KIAA1223 protein
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 - 3548 105.4 921 - 2005 15728370
  • isoform a
  • 11 - 3330 97.2 848 - 2005 15728370
  • isoform b
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon lowly
    Hearing/Equilibriumearinnercochlea highly Homo sapiens
    Nervousbrainhindbraincerebellum predominantly Homo sapiens
     gangliasensory ganglia  lowly Homo sapiens
    Respiratorylung   lowly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumcochlea cell Homo sapiens
    Hearing / Equilibriumhair cell receptor Homo sapiens
    NervousPurkinje cell Homo sapiens
    Reproductivespermatocyte
    cell lineage
    cell lines megakaryocytes
    fluid/secretion sperm
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • cytoplasmic N terminus with ankyrin repeats and a coiled-coil structure, and the ankyrin repeat (AR) region (38-188 amino acids) forms extracellular Ca(2+)-entry channels by homo or heteromerization with other TRP subtypes in various cells including skeletal myotubes
  • six transmembrane segments
  • a cytoplasmic C terminus with a dystrophin (coiled-coil) domain and a highly conserved TRP (EWKFHR) domain
  • HOMOLOGY
    interspecies homolog to murine Trpc3 (96.4pc)
    homolog to rattus Trpc3 (95.9pc)
    Homologene
    FAMILY
  • transient receptor family
  • STrpC subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    text
  • colocalizing with TRPC4
  • mostly associated to the surface of the spermatogenic cells
  • a fraction of canonical transient receptor potential 3 (TRPC3) channels is localized to mitochondria
  • basic FUNCTION
  • receptor-activated non-selective calcium premeant cation channel
  • behaving in embryonic kidney as an inositol phosphate and diacylglycerol-gated channel
  • may influence sperm motility
  • mediating T-cell receptor-dependent calcium entry in human T- lymphocytes
  • required for BDNF-mediated neuronal protection and protects cerebellar granule neurons against serum deprivation-induced cell death
  • additional function of TRPC3, and TRPC7 may be to enhance secretion either by affecting transport through the Golgi stack or by increasing fusion at the plasma membrane
  • playing an essential role for angiotensin II-induced cardiac hypertrophy
  • regulating agonist-stimulated Ca2+ mobilization by selectively mediating interaction between ORAI1 and GNB2L1
  • necessary mediator of pathologic cardiac hypertrophy, in part through a calcineurin/NFAT signaling pathway
  • a subtle activation/inhibition of voltage-independent Ca2+ channels like TRPC3 could play a crucial role in Ca2+ homeostasis and consequently in regulation of electromechanical activity of the developing heart
  • TRPC3 and TRPC6 are thus required for the normal function of cells involved in touch and hearing, and are potential components of mechanotransducing complexes
  • regulate cardiac fibroblast proliferation and differentiation, likely by controlling the Ca(2+) influx that activates extracellular signal-regulated kinase signaling
  • likely plays an important role in atrial fibrillation by promoting fibroblast pathophysiology
  • TRPC3 channels contribute to mitochondrial Ca(2+) uptake
  • role of TRPC3 and Ca(2+) influx in the regulation of BDNF secretion by human airway smooth muscle and the enhancing effects of inflammation
  • heteromeric TRPC3/TRPC1 could participate in regulating the resting cytosolic Ca(2+) levels in skeletal muscle
  • obligatory requirement for a member of the TRPC family of cation channels in ER stress-induced apoptosis in macrophages, underscoring a rather selective role of the TRPC3 channel on mechanisms related to the UPR signaling in M1 macrophage
  • regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFKB1 pathway
  • role of TRPC3 channel in endoplasmic reticulum stress-induced apoptosis of human coronary artery endothelial cells
  • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component comprised of homo- or heterotetramers between TRPC3/6/7
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TRPC1, ITPR3, MX1, RNF24
  • PLCG1
  • interacting with TRPM4 (negatively modulated the channel activity of TRPC3 via the interaction between the two channel proteins)
  • interacting with RYR1 (TRPC3 and RYR1 are functionally engaged via linker proteins in skeletal muscle)
  • TRPC3 TRP domain and AMP-activated protein kinase binding site are required for TRPC3 activation by erythropoietin
  • TRPC3 channel activation dependent on ADORA1 activation and playing a predominant role in arrhythmogenesis
  • SYPL2 could be a new factor for regulating Ca(2+) transients during skeletal muscle contraction possibly via a correlation with TRPC3 and TRPC4
  • interaction between SYPL2 and TRPC3 participates in regulating Ca(2+) transients in skeletal muscle
  • cell & other
    REGULATION
    activated by diacylglycerol (DAG) generated by G protein-coupled receptors (GPCR)/Gαq/phospholipase C signaling
    N-linked protein glycosylation
    EPO, in a modulated manner by TRPC6
    ITPR with bound IP3
    Other may be activated by Ca2+ store depletion
    is probably operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors
    ASSOCIATED DISORDERS
    corresponding disease(s) SCA41
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    enhanced expression in type 2 diabete mellitus patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • as an emerging candidate protein implicated in various forms of ataxia in humans
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquiredheart failure
    pharmacologic inhibitors of TRPC channels might be a strategy for attenuating local Ca2+ signals involved in pathologic cardiac hypertrophy or failure
    cardiovascularrythm 
    TRPC3 represents a promising target to prevent conduction disturbances
    ANIMAL & CELL MODELS
  • gain-of-function mutation (T635A) in the transient receptor potential (TRP) channel Trpc3 results in abnormal channel gating and causes cerebellar ataxia in the dominant Moonwalker (Mwk) mouse mutant (
  • double Trpc3/Trpc6 knock-out mice showed hearing impairment, vestibular deficits and defective auditory brain stem responses to high-frequency sounds