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1.A.4.5.12
TrpM4 of 1213 aas and 6 TMSs. Calcium-activated non selective cation channel that mediates membrane depolarization. While it is activated by increases in intracellular Ca2+, it is impermeable to it. It does mediate transport of monovalent cations (Na+ > K+ > Cs+ > Li+), leading to depolarize the membrane. It thereby plays a central role in  the function of cardiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. It also participates in T-cell activation by modulating Ca2+ oscillations after T lymphocyte activation (Demion et al. 2007). The structure has been determined by cryo EM both with and without ATP (Guo et al. 2017). It consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain to inhibit channel activity. TRPM4 has an exceptionally wide filter although it is only permeable to monovalent cations; filter residue Gln973 is essential in defining monovalent selectivity. The S1-S4 domain and the post-S6 TRP domain form the central gating apparatus that probably houses the Ca2+- and PtdIns(4,5)P2-binding sites (Guo et al. 2017).

Accession Number:Q7TN37
Protein Name:Transient receptor potential cation channel subfamily M member 4
Length:1213
Molecular Weight:135760.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate

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FASTA formatted sequence
1:	MVGPEKEQSW IPKIFRKKVC TTFIVDLSDD AGGTLCQCGQ PRDAHPSVAV EDAFGAAVVT 
61:	EWNSDEHTTE KPTDAYGDLD FTYSGRKHSN FLRLSDRTDP ATVYSLVTRS WGFRAPNLVV 
121:	SVLGGSGGPV LQTWLQDLLR RGLVRAAQST GAWIVTGGLH TGIGRHVGVA VRDHQTASTG 
181:	SSKVVAMGVA PWGVVRNRDM LINPKGSFPA RYRWRGDPED GVEFPLDYNY SAFFLVDDGT 
241:	YGRLGGENRF RLRFESYVAQ QKTGVGGTGI DIPVLLLLID GDEKMLKRIE DATQAQLPCL 
301:	LVAGSGGAAD CLVETLEDTL APGSGGLRRG EARDRIRRYF PKGDPEVLQA QVERIMTRKE 
361:	LLTVYSSEDG SEEFETIVLR ALVKACGSSE ASAYLDELRL AVAWNRVDIA QSELFRGDIQ 
421:	WRSFHLEASL MDALLNDRPE FVRLLISHGL SLGHFLTPVR LAQLYSAVSP NSLIRNLLDQ 
481:	ASHASSSKSP PVNGTVELRP PNVGQVLRTL LGETCAPRYP ARNTRDSYLG QDHRENDSLL 
541:	MDWANKQPST DASFEQAPWS DLLIWALLLN RAQMAIYFWE KGSNSVASAL GACLLLRVMA 
601:	RLESEAEEAA RRKDLAATFE SMSVDLFGEC YHNSEERAAR LLLRRCPLWG EATCLQLAMQ 
661:	ADARAFFAQD GVQSLLTQKW WGEMDSTTPI WALLLAFFCP PLIYTNLIVF RKSEEEPTQK 
721:	DLDFDMDSSI NGAGPPGTVE PSAKVALERR QRRRPGRALC CGKFSKRWSD FWGAPVTAFL 
781:	GNVVSYLLFL LLFAHVLLVD FQPTKPSVSE LLLYFWAFTL LCEELRQGLG GGWGSLASGG 
841:	RGPDRAPLRH RLHLYLSDTW NQCDLLALTC FLLGVGCRLT PGLFDLGRTV LCLDFMIFTL 
901:	RLLHIFTVNK QLGPKIVIVS KMMKDVFFFL FFLCVWLVAY GVATEGILRP QDRSLPSILR 
961:	RVFYRPYLQI FGQIPQEEMD VALMIPGNCS MERGSWAHPE GPVAGSCVSQ YANWLVVLLL 
1021:	IVFLLVANIL LLNLLIAMFS YTFSKVHGNS DLYWKAQRYS LIREFHSRPA LAPPLIIISH 
1081:	VRLLIKWLRR CRRCRRANLP ASPVFEHFRV CLSKEAERKL LTWESVHKEN FLLAQARDKR 
1141:	DSDSERLKRT SQKVDTALKQ LGQIREYDRR LRGLEREVQH CSRVLTWMAE ALSHSALLPP 
1201:	GAPPPPSPTG SKD