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FLASH GENE
Symbol TRPC4 contributors: mct/pgu - updated : 22-01-2015
HGNC name transient receptor potential cation channel, subfamily C, member 4
HGNC id 12336
Location 13q13.3      Physical location : 38.210.774 - 38.443.939
Synonym name
  • transient receptor potential 4
  • short transient receptor potential channel 4
  • Synonym symbol(s) TRP4, HTRP4, CCE1, MGC119570, MGC119571, MGC119572
    DNA
    TYPE functioning gene
    STRUCTURE 233.16 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    NBEA 13q13 neurobeachin MAB21L1 13q13.1-q13.2 mab-21-like 1 (C. elegans) DCAMKL1 13q12.3-q13 doublecortin and CaM kinase-like 1 FLJ20449 13q13.2 hypothetical protein FLJ20449 LOC387919 13 similar to RIKEN cDNA A730037C10 gene SPG20 13q13.1 spastic paraplegia 20, spartin (Troyer syndrome) LOC387920 13 similar to bA251J8.3.1 (novel protein, isoform 1) CCNA1 13q12.3-q13 cyclin A1 LOC390393 13 similar to glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)  (EC 1.2.1.12) - mouse RFXAP 13q14 regulatory factor X-associated protein MADH9 13q12-q14 MAD, mothers against decapentaplegic homolog 9 (Drosophila) LOC390394 13 similar to eukaryotic translation initiation factor 4A1; initiation factor eIF-4A long form ALG5 13q13.2 asparagine-linked glycosylation 5 homolog (yeast, dolichyl-phosphate beta-glucosyltransferase) OIP2 13q13.1 Opa-interacting protein 2 P38IP 13q13.2 transcription factor (p38 interacting protein) MGC33182 13q13.2 casein kinase I alpha S-like OSF-2 TRPC4 13q13.1-q13.2 transient receptor potential cation channel, subfamily C, member 4 LOC390395 13 similar to 60 kDa heat shock protein, mitochondrial precursor (Hsp60) (60 kDa chaperonin) (CPN60) (Heat shock protein 60) (HSP-60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) (HuCHA60) BM-002 13q13.3 hypothetical protein BM-002 DKFZp686J0811 13q13.3 hypothetical protein DKFZp686J0811 LOC390396 13 similar to KIAA1074 protein STOML3 13q13.2 stomatin (EPB72)-like 3 FLJ12661 13q13.3 hypothetical protein FLJ12661 LOC387921 13 similar to RIKEN cDNA 8030451K01 LOC390397 13 similar to NTF2-related export protein 1 (p15 protein) LHFP 13q12 lipoma HMGIC fusion partner COG6 13q13.3 component of oligomeric golgi complex 6 FOXO1A 13q14.1 forkhead box O1A (rhabdomyosarcoma) MRPS31 13q13.2 mitochondrial ribosomal protein S31 SLC25A15 13q14 solute carrier family 25 (mitochondrial carrier; ornithine transporter) member 15 HCP34 13q14.11 cytochrome c, somatic pseudogene ELF1 13q13 E74-like factor 1 (ets domain transcription factor) WBP4 13q13.3 WW domain binding protein 4 (formin binding protein 21) KBTBD6 13q13.3 kelch repeat and BTB (POZ) domain containing 6 LOC390398 13 similar to calmodulin 1; Calmodulin 1 (phosphorylase kinase, delta)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3534 112.1 977 - 2002 11713258
    also called variant alpha
    12 splicing 3282 102.7 893 not in pancreas and brain, but in smooth muscle and endothelial cells where they regulate membrane potential and Ca(2+) influx 2002 11713258
  • also called variant beta
  • interacting with inositol 1, 4, 5-triphosphate receptor
  • 11 splicing 3111 96.4 836 - 2002 11713258
    also called variant delta
    11 splicing 3087 95.5 828 - 2002 11713258
    also called variant gamma
    11 - 3549 - 982 - 2002 11713258
    also called variant epsilon
    - - 2657 - 323 - 2002 11713258
    10 - 3015 - 804 - 2002 11713258
    also called variant zeta
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessels    
    Nervousbrain   specific Homo sapiens
    Reproductivefemale systemuterus   
    Respiratoryrespiratory tracttrachea   
    Visualeyeanterior segmentcornea  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE) highly Homo sapiensFetal
    Epithelialbarrier/liningendothelium  
    Muscularsmoothvessel   Homo sapiens
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion sperm
    at STAGE
    physiological period fetal, pregnancy
    Text highly in placenta, kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • cytoplasmic N terminus with two ankyrin repeats and a coiled-coil structure, that can self-associate and form a tetramer
  • six transmembrane segments
  • a PDZ-interacting domain controling its cell surface localization
  • a cytoplasmic C terminus with a dystrophin (coiled-coil) domain and a highly conserved TRP (EWKFHR) domain
  • HOMOLOGY
    interspecies homolog to murine Trrp4
    ortholog to Drosophila store operated channel (Soc)
    intraspecies paralog to TRPC5
    Homologene
    FAMILY
  • TRP superfamily of Ca2+ cation channels
  • classic subfamily
  • CATEGORY receptor membrane , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    text
  • colocalizing with TRPC3
  • mostly associated to the surface of the cells
  • TRPC4 and TRPM3 localized to apical tight junctions
  • basic FUNCTION
  • behaving in human embryonic kidney as an inositol phosphate and diacylglycerol-gated channel
  • suppressing epidermal growth factor-induced store-operated channel activation and growth in human corneal epithelial cells
  • implicated in the regulation of calcium homeostasis in astrocytes, particularly as part of a signaling complex that forms at junctional sites between astrocytes
  • necessary mediator of pathologic cardiac hypertrophy, in part through a calcineurin
  • NFAT signaling pathway
  • prominent cation channel in the vascular endothelium
  • potential key player in endothelial phenotype switching and tuning of cellular growth factor signaling
  • TRPC4 and TRPC5 are implicated in important physiological functions, such as growth cone guidance and smooth muscle contraction
  • both TRPC1 and TRPC4 are essential for an intrinsic membrane conductance mediating the plateau potential in lateral septal neurons, possibly as heteromeric channels
  • 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
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of store-operated channel in human corneal epithelial cells
  • comprised of homo- or heterotetramers between either TRPC1/4/5
  • 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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • calmodulin (signaling complex involved in agonist, induced calcium entry)
  • interacted with the PDZ1 domain of TJP1 and this was also dependent on the TRL motif
  • SESTD1 associated with TRPC4 and TRPC5 via the channel calmodulin- and inositol 1,4,5-trisphosphate receptor-binding domain
  • SYPL2 could be a new factor for regulating Ca(2+) transients during skeletal muscle contraction possibly via a correlation with TRPC3 and TRPC4
  • cell & other
    REGULATION
    activated by receptor-tyrosine-kinase or G protein coupled receptors
    depletion of intracellular Ca2+ stores (store-operated Ca2+ entry) or by stretch
    GNAI2, that is involved specifically in the activation of TRPC4
    Other Ca(2+) entry channel that is regulated by cell-cell contact formation and interaction with beta-catenin
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to myocardial infarction
    Variant & Polymorphism SNP
  • higher Ca(2+) signals generated by TRPC4-I957V may ultimately facilitate the generation of endothelium- and nitric oxide-dependent vasorelaxation, thereby explaining its protective effect at the vasculature for myocardial infarction
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyepilepsy 
    TRPC channels could be an unsuspected but critical molecular target for clinical intervention for excitotoxicity
    ANIMAL & CELL MODELS