Protein: Transient receptor potential cation channel subfamily M member 4 (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4) (MLS2s) (Melastatin-like 2) (Q9ESQ5)
Organism: Rattus norvegicus (Rat)
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. Essential for the migration but not the maturation of dendritic cells (By similarity). Plays a role in keratinocyte differentiation (By similarity).
Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:19945433}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8TD43}. Endoplasmic reticulum {ECO:0000269|PubMed:19945433}. Golgi apparatus {ECO:0000269|PubMed:19945433}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:19945433}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8TD43}. Endoplasmic reticulum {ECO:0000269|PubMed:19945433}. Golgi apparatus {ECO:0000269|PubMed:19945433}. Note=Mainly integrated into the ER/Golgi complex and is rarely found in the plasma membrane. {ECO:0000269|PubMed:19945433}.
Sequence: MVGQEKEQSWIPKIFRKKVCTTFIVDLHDDAGGTLCQCGQPRDAHPSVAVEDAFGAAVVTEWNSDEHTTEKPTDAYGDLDFTYSGRKSSNFLRLSDRTDPATVYSLVTRSWGFRAPNLVVSVLGGSEGPVLQTWLQDLLRRGLVRAAQSTGAWIVTGGLHTGIGRHVGVAVRDHQTASTGGSKVVAMGVAPWGVVRNRDMLINPKGSFPARYRWRGDPEDGVEFPLDYNYSAFFLVDDGTYGRMGGENRFRLRFESYVAQQKTGVGGTGIDIPVLLLLIEGDEKMLKRIEDATQAQLPCLLVAGSGGAADCLVETLEDTLAPGSGGLRRGEARDRIRRYFPKGDPEVLQAQVERIMTRKELLTVYSSEDGSEEFETIVLRALVKACGSSEASAYLDELRLAVAWNRVDIAQSELFRGDIQWRSFHLEASLMDALLNDRPEFVRLLISHGLSLGHFLTPVRLAQLYSAVSPNSLIRNLLDQASHASSSKSPPANGAAELRPPNVGQVLRTLLGETCAPRYPARNTRHSLLGQDHRENDSLLMDWANMQQDASFEQAPWSDLLIWALLLNRAQMAIYFWEKGSNSVASALGACLLLRVMARLEWEAEEAARRKDLAAKFESMSVDLFGECYHNSEYRAARLLLRRCPLWGEATCLQLAMQADARAFFAQDGVQSLLTQKWWGEMDSTNPIWALLLTFFCPPLIYTNLILFRKSEEEPTQKDLDFDMDSSMNGAGPLGPAEPSAKVALERRRRRRPGHTLCCGGCSKRWSYFWGAPVTAFLGNVVSYLLFLLLFAHVLLVDFQPTKPGVFELLLYFWAFTLLCEELRQGLGGGWGTLANGGPGPGKAPLRHRLHLYLLDTWNQCDLLALTCFLLGVGCRLTPGLFDLGRTVLCLDFMIFTLRLLHIFTVNKQLGPKIVIVSKMMKDVFFFLFFLCVWLVAYGVATEGILRPQDRSLPSILRRVFYRPYLQIFGQIPQEEMDVALMNPSNCSAERGSWAHPEGPVAGSCVSQYANWLVVLLLIVFLLVANILLLNLLIAMFSYTFNKVHGNSDLYWKAQRYSLIREFHSRPALAPPLIIISHLRLLFKWLRRCHRTNLPASPVFEHFRVCLSKEAERTLLTWESVHKENFLLAQARDKRDSDSERLKRTSQKVDTALKQLGQIREYDRRLRGLEREVQHCSRVLTWMAEALSHSALLPPGGPPPPSPTGSKD
InterPro domains: - IPR050927: Transient receptor potential cation channel M (family) [7-1190]
- IPR057366: TRPM-like domain (domain) [413-667]
- IPR005821: Ion transport domain (domain) [784-1045]
- IPR041491: TRPM, SLOG domain (domain) [90-313]
Interaction partners: - ATP-binding cassette sub-family C member 8
- Sodium channel protein type 5 subunit alpha
- Transient receptor potential cation channel subfamily V member 2
- Sodium channel protein type 9 subunit alpha
- Short transient receptor potential channel 3
- Sodium channel protein type 3 subunit alpha
- Sodium channel regulatory subunit beta-1
- Transient receptor potential Ca2+ channel 6A
- Sodium channel regulatory subunit beta-3
- Transient receptor potential cation channel subfamily V member 4
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0005215 (transporter activity), GO:0016740 (transferase activity), GO:0022857 (transmembrane transporter activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:1901702 (salt transmembrane transporter activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0022803 (passive transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0005216 (monoatomic ion channel activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0016301 (kinase activity), GO:0015085 (calcium ion transmembrane transporter activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0015267 (channel activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0005261 (monoatomic cation channel activity), GO:0005262 (calcium channel activity), GO:0022839 (monoatomic ion gated channel activity), GO:0022836 (gated channel activity), GO:0046873 (metal ion transmembrane transporter activity), GO:0005227 (calcium activated cation channel activity)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0023056 (positive regulation of signaling), GO:0055085 (transmembrane transport), GO:0019222 (regulation of metabolic process), GO:0051234 (establishment of localization), GO:0003008 (system process), GO:0065008 (regulation of biological quality), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0048522 (positive regulation of cellular process), GO:0035556 (intracellular signal transduction), GO:0098660 (inorganic ion transmembrane transport), GO:0044057 (regulation of system process), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0034220 (monoatomic ion transmembrane transport), GO:0003013 (circulatory system process), GO:0098739 (import across plasma membrane), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0001919 (regulation of receptor recycling), GO:0042391 (regulation of membrane potential), GO:0006810 (transport), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0098655 (monoatomic cation transmembrane transport), GO:0003018 (vascular process in circulatory system), GO:0010562 (positive regulation of phosphorus metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0008015 (blood circulation), GO:0051246 (regulation of protein metabolic process), GO:1902075 (cellular response to salt), GO:0071702 (organic substance transport), GO:0090257 (regulation of muscle system process), GO:0099587 (inorganic ion import across plasma membrane), GO:0006811 (monoatomic ion transport), GO:0010468 (regulation of gene expression), GO:0019932 (second-messenger-mediated signaling), GO:0098657 (import into cell), GO:0098662 (inorganic cation transmembrane transport), GO:0031326 (regulation of cellular biosynthetic process), GO:0003015 (heart process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:1902533 (positive regulation of intracellular signal transduction), GO:1902531 (regulation of intracellular signal transduction), GO:0051174 (regulation of phosphorus metabolic process), GO:0043408 (regulation of MAPK cascade), GO:0006937 (regulation of muscle contraction), GO:0031399 (regulation of protein modification process), GO:0098659 (inorganic cation import across plasma membrane), GO:0045937 (positive regulation of phosphate metabolic process), GO:0019722 (calcium-mediated signaling), GO:0019220 (regulation of phosphate metabolic process), GO:0070588 (calcium ion transmembrane transport), GO:0097746 (blood vessel diameter maintenance), GO:0006812 (monoatomic cation transport), GO:0035296 (regulation of tube diameter), GO:0006816 (calcium ion transport), GO:0031401 (positive regulation of protein modification process), GO:0042325 (regulation of phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0006942 (regulation of striated muscle contraction), GO:0030001 (metal ion transport), GO:0042327 (positive regulation of phosphorylation), GO:0001934 (positive regulation of protein phosphorylation), GO:0097553 (calcium ion transmembrane import into cytosol), GO:0050731 (positive regulation of peptidyl-tyrosine phosphorylation), GO:0050730 (regulation of peptidyl-tyrosine phosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0036477 (somatodendritic compartment), GO:0042995 (cell projection), GO:0044297 (cell body), GO:0097447 (dendritic tree), GO:0043025 (neuronal cell body), GO:0120025 (plasma membrane bounded cell projection), GO:0030425 (dendrite), GO:0043005 (neuron projection)