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MGP005325

UniProt Annotations

Entry Information

Gene Name	transient receptor potential cation channel, subfamily M, member 4
Protein Entry	TRPM4_HUMAN
UniProt ID	Q8TD43
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=TRPM4b; IsoId=Q8TD43-1; Sequence=Displayed; Name=2; Synonyms=TRPM4a; IsoId=Q8TD43-2; Sequence=VSP_021442; Name=3; Synonyms=TRPM4c; IsoId=Q8TD43-3; Sequence=VSP_021443;
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 mutations affecting the gene represented in this entry.
Enzyme Regulation	Gating is voltage-dependent and repressed by decavanadate. Calmodulin-binding confers the Ca(2+) sensitivity. ATP is able to restore Ca(2+) sensitivity after desensitization. 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. Activity is also enhanced by 3,5- bis(trifluoromethyl)pyrazole derivative (BTP2). {ECO:0000269\|PubMed:14758478, ECO:0000269\|PubMed:15331675, ECO:0000269\|PubMed:16186107, ECO:0000269\|PubMed:16407466, ECO:0000269\|PubMed:16424899}.
Function	Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. 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. {ECO:0000269\|PubMed:12015988, ECO:0000269\|PubMed:12799367, ECO:0000269\|PubMed:15121803, ECO:0000269\|PubMed:15472118, ECO:0000269\|PubMed:15550671, ECO:0000269\|PubMed:16806463, ECO:0000269\|PubMed:20625999, ECO:0000269\|PubMed:20656926}.
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}.
Sequence Caution	Sequence=BAA90907.1; Type=Erroneous termination; Positions=1191; Note=Translated as Glu.; Evidence={ECO:0000305};
Similarity	Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM4 sub-subfamily. {ECO:0000305}.
Subcellular Location	Isoform 1: Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum. Golgi apparatus.
Subcellular Location	Isoform 2: Endoplasmic reticulum. Golgi apparatus.
Subunit	Homomultimer. {ECO:0000269\|PubMed:12015988}.
Tissue Specificity	Widely expressed with a high expression in intestine and prostate. In brain, it is both expressed in whole cerebral arteries and isolated vascular smooth muscle cells. Prominently expressed in Purkinje fibers. Expressed at higher levels in T-helper 2 (Th2) cells as compared to T-helper 1 (Th1) cells. {ECO:0000269\|PubMed:11535825, ECO:0000269\|PubMed:12015988, ECO:0000269\|PubMed:12799367, ECO:0000269\|PubMed:15472118, ECO:0000269\|PubMed:16777713, ECO:0000269\|PubMed:19726882, ECO:0000269\|PubMed:20656926}.