TRPM4
entrez
54795
canonical
uniprot
Q8TD43
canonical
ensembl
ENSG00000130529
resolver
ensp
ENSP00000252826
resolver
ensp
ENSP00000407492
resolver
genesymbol
TRPM4
resolver
genesymbol_syn
LTRPC4
resolver
hgnc
HGNC:17993
resolver
uniprot
A2RU25
resolver
uniprot
B4DIX5
resolver
uniprot
Q7Z5D9
resolver
uniprot
Q96L84
resolver
uniprot
Q9NXV1
resolver
uniprot_entry
B4DIX5_HUMAN
resolver
uniprot_entry
TRPM4_HUMAN
resolver
uniprot_sec
A2RU25
resolver
uniprot_sec
Q7Z5D9
resolver
uniprot_sec
Q96L84
resolver
uniprot_sec
Q9NXV1
resolver
activity_regulation
ACTIVITY REGULATION: Displays weak voltage dependence, and repressed by decavanadate (PubMed:12799367, PubMed:15331675, PubMed:29211723, PubMed:38750366). Calmodulin-binding confers the Ca(2+) sensitivity (PubMed:15590641). ATP is able to restore Ca(2+) sensitivity after desensitization (PubMed:15590641). ATP inhibits channel activity (PubMed:14758478, PubMed:15331675, PubMed:29211723, PubMed:38750366). Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca(2+) sensitivity and shifting its voltage dependence of activation towards negative potentials (PubMed:16186107, PubMed:16424899). Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (PubMed:16407466). Exhibits pronounced temperature sensitivity, with activities strongly intensifying near physiological temperatures (PubMed:38750366). {ECO:0000269|PubMed:14758478, ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15590641, ECO:0000269|PubMed:16186107, ECO:0000269|PubMed:16407466, ECO:0000269|PubMed:16424899, ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:38750366}.
uniprot
proteins
amino_acid_sequence
MVVPEKEQSWIPKIFKKKTCTTFIVDSTDPGGTLCQCGRPRTAHPAVAMEDAFGAAVVTVWDSDAHTTEKPTDAYGELDFTGAGRKHSNFLRLSDRTDPAAVYSLVTRTWGFRAPNLVVSVLGGSGGPVLQTWLQDLLRRGLVRAAQSTGAWIVTGGLHTGIGRHVGVAVRDHQMASTGGTKVVAMGVAPWGVVRNRDTLINPKGSFPARYRWRGDPEDGVQFPLDYNYSAFFLVDDGTHGCLGGENRFRLRLESYISQQKTGVGGTGIDIPVLLLLIDGDEKMLTRIENATQAQLPCLLVAGSGGAADCLAETLEDTLAPGSGGARQGEARDRIRRFFPKGDLEVLQAQVERIMTRKELLTVYSSEDGSEEFETIVLKALVKACGSSEASAYLDELRLAVAWNRVDIAQSELFRGDIQWRSFHLEASLMDALLNDRPEFVRLLISHGLSLGHFLTPMRLAQLYSAAPSNSLIRNLLDQASHSAGTKAPALKGGAAELRPPDVGHVLRMLLGKMCAPRYPSGGAWDPHPGQGFGESMYLLSDKATSPLSLDAGLGQAPWSDLLLWALLLNRAQMAMYFWEMGSNAVSSALGACLLLRVMARLEPDAEEAARRKDLAFKFEGMGVDLFGECYRSSEVRAARLLLRRCPLWGDATCLQLAMQADARAFFAQDGVQSLLTQKWWGDMASTTPIWALVLAFFCPPLIYTRLITFRKSEEEPTREELEFDMDSVINGEGPVGTADPAEKTPLGVPRQSGRPGCCGGRCGGRRCLRRWFHFWGAPVTIFMGNVVSYLLFLLLFSRVLLVDFQPAPPGSLELLLYFWAFTLLCEELRQGLSGGGGSLASGGPGPGHASLSQRLRLYLADSWNQCDLVALTCFLLGVGCRLTPGLYHLGRTVLCIDFMVFTVRLLHIFTVNKQLGPKIVIVSKMMKDVFFFLFFLGVWLVAYGVATEGLLRPRDSDFPSILRRVFYRPYLQIFGQIPQEDMDVALMEHSNCSSEPGFWAHPPGAQAGTCVSQYANWLVVLLLVIFLLVANILLVNLLIAMFSYTFGKVQGNSDLYWKAQRYRLIREFHSRPALAPPFIVISHLRLLLRQLCRRPRSPQPSSPALEHFRVYLSKEAERKLLTWESVHKENFLLARARDKRESDSERLKRTSQKVDLALKQLGHIREYEQRLKVLEREVQQCSRVLGWVAEALSRSALLPPGGPPPPDLPGSKD
uniprot
proteins
disease_involvement
DISEASE: Progressive familial heart block 1B (PFHB1B) [MIM:604559]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death. {ECO:0000269|PubMed:19726882, ECO:0000269|PubMed:20562447, ECO:0000269|PubMed:21887725}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Erythrokeratodermia variabilis et progressiva 6 (EKVP6) [MIM:618531]: A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP6 inheritance is autosomal dominant. {ECO:0000269|PubMed:30528822}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellular Ca(2+), it is impermeable to it (PubMed:12015988). Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane (PubMed:12015988). It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Plays a role in keratinocyte differentiation (PubMed:30528822). {ECO:0000269|PubMed:11535825, ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:12799367, ECO:0000269|PubMed:12842017, ECO:0000269|PubMed:14758478, ECO:0000269|PubMed:15121803, ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15472118, ECO:0000269|PubMed:15550671, ECO:0000269|PubMed:15590641, ECO:0000269|PubMed:15845551, ECO:0000269|PubMed:16186107, ECO:0000269|PubMed:16407466, ECO:0000269|PubMed:16424899, ECO:0000269|PubMed:16806463, ECO:0000269|PubMed:20625999, ECO:0000269|PubMed:20656926, ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:30528822}.; FUNCTION: [Isoform 2]: Lacks channel activity. {ECO:0000269|PubMed:12842017}.
uniprot
proteins
mass_dalton
134301
uniprot
proteins
mutagenesis
MUTAGEN 275; /note="L->A,C: Abolishes ability to restore sensitivity to Ca(2+) after desensitization."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 278; /note="I->N: No effect."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 279; /note="D->N: No effect."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 324; /note="G->A: No effect."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 325; /note="G->A: Abolishes ability to restore sensitivity to Ca(2+) after desensitization."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 327; /note="R->A: No effect."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 396; /note="E->A: Loss of the temperature-induced potentiation. Inability to activate at negative membrane potentials."; /evidence="ECO:0000269|PubMed:38750366"; MUTAGEN 597; /note="R->A: Becomes insensitive to decavanadate's voltage modulation effect."; /evidence="ECO:0000269|PubMed:38750366"; MUTAGEN 613; /note="K->A,M: Becomes insensitive to decavanadate's voltage modulation effect."; /evidence="ECO:0000269|PubMed:38750366"; MUTAGEN 664; /note="R->A: Becomes insensitive to decavanadate's voltage modulation effect."; /evidence="ECO:0000269|PubMed:38750366"; MUTAGEN 925; /note="K->A: Becomes insensitive to decavanadate's voltage modulation effect."; /evidence="ECO:0000269|PubMed:38750366"; MUTAGEN 977; /note="Q->E: Alters the monovalent cation permeability sequence and results in a pore with moderate Ca(2+) permeability."; /evidence="ECO:0000269|PubMed:15845551"; MUTAGEN 981..986; /note="EDMDVA->TIIDGP: Induces a functional channel that combines the gating hallmarks of TRPM4 (activation by Ca(2+)) with TRPV6-like sensitivity to block by extracellular Ca(2+) and Mg(2+) as well as Ca(2+) permeation."; /evidence="ECO:0000269|PubMed:15845551"; MUTAGEN 981; /note="E->A: Results in a channel with normal permeability properties but with a reduced sensitivity to block by intracellular spermine."; /evidence="ECO:0000269|PubMed:15845551"; MUTAGEN 982; /note="D->A: Results in a functional channel that exhibits extremely fast desensitization, possibly indicating destabilization of the pore."; /evidence="ECO:0000269|PubMed:15845551"; MUTAGEN 984; /note="D->A: Results in a non-functional channel with a dominant negative phenotype."; /evidence="ECO:0000269|PubMed:15845551"; MUTAGEN 1049; /note="K->A: Becomes insensitive to decavanadate's voltage modulation effect."; /evidence="ECO:0000269|PubMed:38750366"; MUTAGEN 1059; /note="K->Q: Does not affect PIP2-binding."; /evidence="ECO:0000269|PubMed:16424899"; MUTAGEN 1072; /note="R->Q: Does not affect PIP2-binding."; /evidence="ECO:0000269|PubMed:16424899"; MUTAGEN 1136..1141; /note="Missing: Results in a channel with very rapid desensitization and highly reduced sensitivity to PIP2."; /evidence="ECO:0000269|PubMed:16424899"; MUTAGEN 1145; /note="S->A: Decreases the sensitivity to Ca(2+)."; /evidence="ECO:0000269|PubMed:15590641"; MUTAGEN 1152; /note="S->A: Decreases the sensitivity to Ca(2+)."; /evidence="ECO:0000269|PubMed:15590641
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by PKC leads to increase the sensitivity to Ca(2+). {ECO:0000269|PubMed:15590641}.; PTM: Sumoylated. Desumoylated by SENP1. {ECO:0000269|PubMed:19726882}.
uniprot
proteins
protein_family
LTrpC subfamily
uniprot
proteins
protein_family
TRPM4 sub-subfamily
uniprot
proteins
protein_family
Transient receptor (TC 1.A.4) family
uniprot
proteins
pubmed
11535825
uniprot
proteins
pubmed
12015988
uniprot
proteins
pubmed
12799367
uniprot
proteins
pubmed
12842017
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14758478
uniprot
proteins
pubmed
15121803
uniprot
proteins
pubmed
15331675
uniprot
proteins
pubmed
15472118
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15550671
uniprot
proteins
pubmed
15590641
uniprot
proteins
pubmed
15845551
uniprot
proteins
pubmed
16186107
uniprot
proteins
pubmed
16407466
uniprot
proteins
pubmed
16424899
uniprot
proteins
pubmed
16777713
uniprot
proteins
pubmed
16806463
uniprot
proteins
pubmed
19726882
uniprot
proteins
pubmed
19945433
uniprot
proteins
pubmed
20562447
uniprot
proteins
pubmed
20625999
uniprot
proteins
pubmed
20656926
uniprot
proteins
pubmed
21887725
uniprot
proteins
pubmed
29211723
uniprot
proteins
pubmed
29217581
uniprot
proteins
pubmed
30528822
uniprot
proteins
pubmed
38750366
uniprot
proteins
sequence_length
1214
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15590641, ECO:0000269|PubMed:19945433, ECO:0000269|PubMed:29211723}; Multi-pass membrane protein {ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581}. Endoplasmic reticulum {ECO:0000269|PubMed:19945433}. Golgi apparatus {ECO:0000269|PubMed:19945433}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:11535825}. Endoplasmic reticulum. Golgi apparatus.
uniprot
proteins
transmembrane_region
TRANSMEM 783..803; /note="Helical"; /evidence="ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581"; TRANSMEM 815..835; /note="Helical"; /evidence="ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581"; TRANSMEM 864..884; /note="Helical"; /evidence="ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581"; TRANSMEM 887..910; /note="Helical"; /evidence="ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581"; TRANSMEM 931..951; /note="Helical"; /evidence="ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581"; TRANSMEM 1020..1040; /note="Helical"; /evidence="ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581
uniprot
proteins