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1.A.4.5.4
Intracellular Ca2+-activated nonselective monovalent cation (Na+ and K+) channel (non-permeable to Ca2+), TRPM4b. Forms a protein-protein interaction with the TRPC3 channel and suppresses store-operated Ca+ entry (Park et al., 2008).  Contributes to the mammalian atrial action potential (Simard et al. 2013). TRPM4 is widely expressed and is associated with a variety of cardiovascular disorders. Autzen et al. 2018 presented two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3-angstrom resolution, as determined by single-particle cryo-electron microscopy. These structures, with and without calcium bound, reveal the general architecture for this major subfamily of TRP channels and a well-defined calcium-binding site within the intracellular side of the S1-S4 domain. The structures correspond to two distinct closed states. Calcium binding induces conformational changes that likely prime the channel for voltage-dependent opening (Autzen et al. 2018). TRPM4 functions as a limiting factor for antigen evoked calcium rise in connective tissue type mast cells, and concurrent translocation of TRPM4 into the plasma membrane is part of this mechanism (Rixecker et al. 2016).

Accession Number:Q8TD43
Protein Name:TRPM4B
Length:1214
Molecular Weight:134301.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Na+, K+

Cross database links:

Genevestigator: Q8TD43
HEGENOM: HBG443937
RefSeq: NP_060106.2   
Entrez Gene ID: 54795   
Pfam: PF00520   
OMIM: 606936  gene
KEGG: hsa:54795   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0005524 F:ATP binding
GO:0005516 F:calmodulin binding
GO:0006955 P:immune response
GO:0055085 P:transmembrane transport

References (18)

[1] “Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform.”  Xu X.-Z.S.et.al.   11535825
[2] “TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.”  Launay P.et.al.   12015988
[3] “TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel.”  Hofmann T.et.al.   12842017
[4] “Voltage dependence of the Ca2+-activated cation channel TRPM4.”  Nilius B.et.al.   12799367
[5] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries.”  Earley S.et.al.   15472118
[8] “Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes.”  Guinamard R.et.al.   15121803
[9] “Decavanadate modulates gating of TRPM4 cation channels.”  Nilius B.et.al.   15331675
[10] “Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b.”  Nilius B.et.al.   14758478
[11] “TRPM4 regulates calcium oscillations after T cell activation.”  Launay P.et.al.   15550671
[12] “Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4.”  Nilius B.et.al.   15590641
[13] “The selectivity filter of the cation channel TRPM4.”  Nilius B.et.al.   15845551
[14] “Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization.”  Zhang Z.et.al.   16186107
[15] “TRPM4 controls insulin secretion in pancreatic beta-cells.”  Cheng H.et.al.   16806463
[16] “The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate.”  Nilius B.et.al.   16424899
[17] “Tissue distribution profiles of the human TRPM cation channel family.”  Fonfria E.et.al.   16777713
[18] “A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity.”  Takezawa R.et.al.   16407466

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FASTA formatted sequence
1:	MVVPEKEQSW IPKIFKKKTC TTFIVDSTDP GGTLCQCGRP RTAHPAVAME DAFGAAVVTV 
61:	WDSDAHTTEK PTDAYGELDF TGAGRKHSNF LRLSDRTDPA AVYSLVTRTW GFRAPNLVVS 
121:	VLGGSGGPVL QTWLQDLLRR GLVRAAQSTG AWIVTGGLHT GIGRHVGVAV RDHQMASTGG 
181:	TKVVAMGVAP WGVVRNRDTL INPKGSFPAR YRWRGDPEDG VQFPLDYNYS AFFLVDDGTH 
241:	GCLGGENRFR LRLESYISQQ KTGVGGTGID IPVLLLLIDG DEKMLTRIEN ATQAQLPCLL 
301:	VAGSGGAADC LAETLEDTLA PGSGGARQGE ARDRIRRFFP KGDLEVLQAQ VERIMTRKEL 
361:	LTVYSSEDGS EEFETIVLKA LVKACGSSEA SAYLDELRLA VAWNRVDIAQ SELFRGDIQW 
421:	RSFHLEASLM DALLNDRPEF VRLLISHGLS LGHFLTPMRL AQLYSAAPSN SLIRNLLDQA 
481:	SHSAGTKAPA LKGGAAELRP PDVGHVLRML LGKMCAPRYP SGGAWDPHPG QGFGESMYLL 
541:	SDKATSPLSL DAGLGQAPWS DLLLWALLLN RAQMAMYFWE MGSNAVSSAL GACLLLRVMA 
601:	RLEPDAEEAA RRKDLAFKFE GMGVDLFGEC YRSSEVRAAR LLLRRCPLWG DATCLQLAMQ 
661:	ADARAFFAQD GVQSLLTQKW WGDMASTTPI WALVLAFFCP PLIYTRLITF RKSEEEPTRE 
721:	ELEFDMDSVI NGEGPVGTAD PAEKTPLGVP RQSGRPGCCG GRCGGRRCLR RWFHFWGAPV 
781:	TIFMGNVVSY LLFLLLFSRV LLVDFQPAPP GSLELLLYFW AFTLLCEELR QGLSGGGGSL 
841:	ASGGPGPGHA SLSQRLRLYL ADSWNQCDLV ALTCFLLGVG CRLTPGLYHL GRTVLCIDFM 
901:	VFTVRLLHIF TVNKQLGPKI VIVSKMMKDV FFFLFFLGVW LVAYGVATEG LLRPRDSDFP 
961:	SILRRVFYRP YLQIFGQIPQ EDMDVALMEH SNCSSEPGFW AHPPGAQAGT CVSQYANWLV 
1021:	VLLLVIFLLV ANILLVNLLI AMFSYTFGKV QGNSDLYWKA QRYRLIREFH SRPALAPPFI 
1081:	VISHLRLLLR QLCRRPRSPQ PSSPALEHFR VYLSKEAERK LLTWESVHKE NFLLARARDK 
1141:	RESDSERLKR TSQKVDLALK QLGHIREYEQ RLKVLEREVQ QCSRVLGWVA EALSRSALLP 
1201:	PGGPPPPDLP GSKD