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Symbol TRPC5 contributors: mct - updated : 15-11-2017
HGNC name transient receptor potential cation channel, subfamily C, member 5
HGNC id 12337
Location Xq23      Physical location : 111.017.541 - 111.326.004
Synonym name
  • transient receptor potential channel 5
  • short transient receptor potential channel 5
  • protein phosphatase 1, regulatory subunit 159
  • Synonym symbol(s) TRP5, Htrp-5, PPP1R159
    TYPE functioning gene
    STRUCTURE 308.46 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - PAK3 - DCX DCX - DXS7356 - DXS8239 - [DXS7012E - DXS8204 - DXS7354 - DXS8110 ] - DXS1059 - DXS7360 - DXS7298 - qter
    Text [TRPC5 ]
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 5840 111.3 973 - 2009 19815560
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel     Homo sapiens
    Nervousbrain   predominantly Homo sapiens
     brainlimbic systemhippocampus predominantly Homo sapiens
     gangliasensory gangliadorsal root   Homo sapiens
     spinal cordposterior horn    Homo sapiens
    Reproductivefemale systemplacenta   
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis
    at STAGE
    physiological period fetal, perinatal, pregnancy
    Text predominantly in brain
  • two ankyrin repeats at the N terminus
  • two conserved CAMP/GMP dependent phosphorylation sites
  • eight transmembrane segments (TM1 to TM8) with a pore (TM7) between TM6 and TM8
  • a CaM-binding site is important for the Ca2+/CaM-mediated facilitation
  • a CIRB domain critical for the overall response of receptor-induced TRPC5 channel activation
  • a cytoplasmic C terminus with another potential phosphorylation site and a VTRRL (PDZ-like) motif
  • mono polymer homomer , heteromer , tetramer , polymer
    interspecies ortholog to Drosophila store-operated calcium channel (Soc)
    intraspecies homolog to TRPC4
  • canonical TRP subfamily
  • STrpC subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • transient receptor potential non voltage-channel, Ca2+-permeable nonselective cation channels important for neurite outgrowth and growth cone morphology of hippocampal neurons
  • non-specific cation channels activated through phospholipase C-dependent pathways
  • having gating properties that can switch reversibly between voltage-dependent and voltage-independent states
  • activated via G protein-coupled neuronal receptors and has an essential function in innate fear
  • involved in the control of fear-related behaviors, both learned and innate
  • forms Ca2+-activated cation channels that are functionally coupled to Ca2+-selective ion channels through local Ca2+ increases beneath the plasma membrane
  • enriched in the brain, where it is believed to control neurite extension and growth cone morphology
  • TRPC4 and TRPC5 are implicated in important physiological functions, such as growth cone guidance and smooth muscle contraction
  • necessary mediator of pathologic cardiac hypertrophy, in part through a calcineurin–NFAT signaling pathway
  • important components of the mechanism controlling neurite extension and growth cone morphology
  • forms cationic channels either through homomultimeric assembly or heteromultimeric coordination with other TRPC proteins
  • calcium regulation by TRPC5 would play a key role as a switch between proliferation and neuronal differentiation from neural progenitor cells
  • TRPC5 and TRPC6 are antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes
  • TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for nonselective, cationic current in podocytes
  • potential TRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings
  • specific role of TRPC5 in the innocuous range of cold temperature (37–25 °C) that is distinct from noxious cold sensing
  • essential function in the regulation of dendrite patterning in the mammalian brain
  • novel function for TRPC5 that couples calcium signaling to a ubiquitin ligase pathway at the centrosome and thereby orchestrates dendrite patterning and connectivity in the brain
  • TRPC1 and TRPC5 have critical roles in neurite outgrowth
  • suppression of neurite outgrowth by TRPC5 requires the channel function of TRPC5
  • acts downstream of semaphorin signaling to cause changes in neuronal growth cone morphology and nervous system development
  • TRPC4 and TRPC5 channels are important regulators of electrical excitability in both gastrointestinal myocytes and neurons
  • TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms
  • TRPC4 and TRPC5 proteins share 65p100 amino acid sequence identity and form Ca(2+)-permeable nonselective cation channels
  • Ca2+-permeable channel TRPC5 is an important determinant of albuminuria
  • receptor-operated cation channel, has been well recognized as a regulator in the central nervous system
  • functions of TRPC5 in regulating vascular aging
  • 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
    a component
  • heterotetrameric complexes with TRPC1 and TRPC4 channel subunits
    small molecule
  • interacting with C10orf63
  • interacting with the growth cone-enriched protein stathmin 2 (packaged into vesicles and are carried to newly forming growth cones and synapses)
  • SESTD1 is essential for efficient receptor-mediated activation of TRPC5
  • is in a molecular complex with RAC1
  • TRPC1 and TRPC5 have critical roles in neurite outgrowth
  • CAPN1 and CAPN2 cleave and functionally activate TRPC5
  • SEMA3A initiates growth cone collapse via activation of calpain that in turn potentiates TRPC5 activity
  • lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical TRPC6 channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation
  • cell & other
    activated by extracellular thioredoxin
    Ca2+ (Ca2+-dependent activation of TRPC5 channels is coupled to the opening of Ca2+-selective ion channels, and the simultaneous stimulation of membrane receptors leads to a further modulation of the TRPC5 channel currents)
    Other stimulated by a G protein coupled receptor from extracellular space by a process called calcium capacitative entry (CCE)
    intracellular calcium store depletion
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in focal cortical dysplasias (FCDs), and the cell-specific distribution patterns of TRPC5 in the misshapen neurons in FCDs could potentially contribute to the epileptogenesis of FCDs
    Variant & Polymorphism
    Candidate gene
    Therapy target
    cardiovascularaquiredheart failure
    pharmacologic inhibitors of TRPC channels might be a strategy for attenuating local Ca2+ signals involved in pathologic cardiac hypertrophy or failure
    promising novel molecular target for new therapy
    miscelleaneousurinarychronic kidney disease
    TRPC5 inhibition is a therapeutic strategy for the prevention or treatment of proteinuric kidney disease
  • TRPC5 -/- mice exhibit diminished innate fear levels in response to innately aversive stimuli
  • TRPC5 knockout mice harbor long, highly branched granule neuron dendrites with impaired dendritic claw differentiation in the cerebellar cortex