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FLASH GENE
Symbol TRPM4 contributors: mct/npt - updated : 30-06-2015
HGNC name transient receptor potential cation channel, subfamily M, member 4
HGNC id 17993
Corresponding disease
PFHB1 progressive familial heart block, type I
Location 19q13.33      Physical location : 49.661.015 - 49.715.098
Synonym name
  • transient receptor potential (TRP) channel-related, melastatin class 4
  • calcium-activated non-selective cation channel 1
  • melastatin-4
  • Synonym symbol(s) TRPM4B, FLJ20041, LTRPC4
    DNA
    TYPE functioning gene
    STRUCTURE 54.08 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    FTL 19q13.3 ferritin, light polypeptide GYS1 19q13.3 glycogen synthase 1 (muscle) RUVBL2 19q13.3 RuvB-like 2 (E. coli) LHB 19q13.3 luteinizing hormone beta polypeptide CGB 19q13.3 chorionic gonadotropin, beta polypeptide NTF6A 19q13.3 neurotrophin 6, alpha pseudogene NTF6G 19q13.3 neurotrophin 6, gamma pseudogene CGB2 19q13.32 chorionic gonadotropin, beta polypeptide 2 CGB1 19q13.32 chorionic gonadotropin, beta polypeptide 1 NTF6B 19q13.3 neurotrophin 6, beta pseudogene CGB5 19q13.32 chorionic gonadotropin, beta polypeptide 5 CGB8 19q13.32 chorionic gonadotropin, beta polypeptide 8 CGB7 19q13.32 chorionic gonadotropin, beta polypeptide 7 NTF5 19q13.3 neurotrophin 5 (neurotrophin 4/5) KCNA7 19q13.4 potassium voltage-gated channel, shaker-related subfamily, member 7 SNRP70 19q13.3 small nuclear ribonucleoprotein 70kDa polypeptide (RNP antigen) LIN7B 19q13.3 lin-7 homolog B (C. elegans) FLJ10490 19q13.33 hypothetical protein FLJ10490 PPFIA3 19q13.3 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 3 HRC 19q13.3 histidine rich calcium binding protein TRPM4 19q13.32 transient receptor potential cation channel, subfamily M, member 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 4103 134 1214 - Xu, Park (2008)
    TRPM4-1 or TRPM4b
    24 - 3668 - 1069 - Xu, Park (2008)
  • TRPM4-2, or TRPM4a
  • lacks 174 amino acid residues at the N terminus
  • - - 2400 - 677 testis Xu, Park (2008)
    lacks 537 N-terminal amino acids
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon highly
    Lymphoid/Immunetonsils   highly
    Nervousnerve   highly
    Reproductivemale systemprostate  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • six putative transmembrane segments 6TM, that are pivotal in the protein-protein interaction with TRPC3
  • a C terminal TRP domain (EWKFHR), with a role as a site responsible for maintaining the normal Ca(2+) sensitivity
  • HOMOLOGY
    intraspecies homolog to TRPM5
    Homologene
    FAMILY
  • transient receptor potential family of non-selective cation channels
  • TRP-melastatin subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • Ca2+-activated and voltage-dependent Ca2+-impermeable cation channel
  • implicated in physiological processes including T-cell activation, myogenic vasoconstriction, and cardiac function
  • playing a pivotal role in modulation of store-operated Ca2+ via interaction with TRPC3
  • exceptional in that it is one of only two ion channels known in the mammalian genome that conduct monovalent cations exclusively and nonselectively
  • controls insulin secretion in pancreatic beta-cells, and may regulate calcium influx by causing the depolarization that drives the activation of voltage-dependent calcium channels
  • is a critical mediator of pressure-induced membrane depolarization and arterial constriction
  • TRPM4 is an important regulator of smooth muscle cell membrane depolarization and arterial constriction in response to intraluminal pressure
  • TRPM2, TRPM4 and TRPM5 control insulin secretion levels by sensing intracellular Ca2+ increase, NAD metabolites, or hormone receptor activation
  • ABCC8 and TRPM4 have an intrinsic capacity for stable co-association
  • TRPM4 and TRPM5 are both N-linked glycosylated at a unique site and also suggest that TRPM4/5 glycosylation seems not to be involved in channel trafficking, but mainly in their functional regulation
  • is potentially an important regulator of Ca2+ signals generated by histamine in adipose-derived stem cells (hASCs) and is required for adipogenesis
  • cell surface expression of TRPM4 channels is mediated by YWHAG binding, and the specific inhibition of this trafficking process can be a potential therapeutic target for glutamate-induced neuronal cell death
  • functions as a Ca(2+)-activated non-selective cation channel and constitutes a novel regulator of ventricular contractility
  • contributes to the regulation of driving force for store-operated calcium entry and thereby the activation of the calcineurin-NFAT pathway and the development of pathological cardiac hypertrophy
  • PLCB3, INPP5J interact with N-terminus region of TRPM4 channel
  • is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC) that conducts monovalent but not divalent cations
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • ABCC8 and TRPM4 co-assemble to form the unique ABCC8-TRPM4 channel
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with TRPC3 (regulates negatively the channel activity, in turn suppressing store-operated Ca2+ entry through the TRPC3 channel)
  • ABCC8 controls K(ATP) channel activity but not TRPM4 channels
  • is a binding partner for TRPM4
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PFHB1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    up-regulated in several types of injury involving the central nervous system (CNS), including cerebral ischemia, traumatic brain injury, subarachnoid hemorrhage, germinal matrix hemorrhage, and spinal cord injury
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquiredheart failure
    pharmacological or genetic down-regulation of TRPM4 function might be a novel strategy in the management of HF
    cardiovascularrythm 
    potential target for pharmacological approaches against atrial arrhythmias
    ANIMAL & CELL MODELS