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Protein

Transient receptor potential cation channel subfamily M member 4

Gene

Trpm4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca2+, it is impermeable to it (PubMed:17188667, PubMed:29211714). 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 Ca2+ 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 Ca2+ 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 (By similarity). Essential for the migration but not the maturation of dendritic cells (PubMed:18758465).By similarity3 Publications

Enzyme regulationi

Gating is voltage-dependent and repressed by decavanadate. Calmodulin-binding confers the Ca2+ sensitivity. ATP is able to restore Ca2+ sensitivity after desensitization. Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca2+ sensitivity and shifting its voltage dependence of activation towards negative potentials. Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (By similarity). Inhibited by flufenamic acid and glibenclamide (PubMed:17188667).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei172ATP; shared with neighboring subunitCombined sources1 Publication1
Binding sitei422ATPCombined sources1 Publication1
Binding sitei449ATP; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi824CalciumBy similarity1
Metal bindingi827CalciumBy similarity1
Metal bindingi861CalciumBy similarity1
Metal bindingi864CalciumBy similarity1

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • calcium activated cation channel activity Source: UniProtKB
  • calcium channel activity Source: MGI
  • calcium ion binding Source: UniProtKB
  • calmodulin binding Source: UniProtKB-KW
  • voltage-gated ion channel activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Ion channel
Biological processAdaptive immunity, Immunity, Ion transport, Transport
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Protein family/group databases

TCDBi1.A.4.5.12 the transient receptor potential ca(2+) channel (trp-cc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily M member 4
Alternative name(s):
Calcium-activated non-selective cation channel 1
Long transient receptor potential channel 4
Short name:
LTrpC-4
Short name:
LTrpC4
Gene namesi
Name:Trpm4
Synonyms:Ltrpc4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1915917 Trpm4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 778Cytoplasmic1 PublicationAdd BLAST778
Transmembranei779 – 799Helical1 PublicationAdd BLAST21
Topological domaini800 – 810Extracellular1 PublicationAdd BLAST11
Transmembranei811 – 831Helical1 PublicationAdd BLAST21
Topological domaini832 – 859Cytoplasmic1 PublicationAdd BLAST28
Transmembranei860 – 880Helical1 PublicationAdd BLAST21
Topological domaini881 – 882Extracellular1 Publication2
Transmembranei883 – 906Helical1 PublicationAdd BLAST24
Topological domaini907 – 926Cytoplasmic1 PublicationAdd BLAST20
Transmembranei927 – 947Helical1 PublicationAdd BLAST21
Topological domaini948 – 959Extracellular1 PublicationAdd BLAST12
Intramembranei960 – 980Pore-forming1 PublicationAdd BLAST21
Topological domaini981 – 1015Extracellular1 PublicationAdd BLAST35
Transmembranei1016 – 1036Helical1 PublicationAdd BLAST21
Topological domaini1037 – 1213Cytoplasmic1 PublicationAdd BLAST177

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice have fewer dendritic cells in lymphoid organs and impaired migration of dendritic cells is seen.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi160H → A: Near loss of channel sensitivity to inhibition by ATP. 1 Publication1
Mutagenesisi214W → A: Decreases channel sensitivity to inhibition by ATP. 1 Publication1
Mutagenesisi228Y → A: Strongly decreases channel sensitivity to inhibition by ATP. 1 Publication1
Mutagenesisi973Q → D or N: Strongly decreased selectivity for monovalent cations and increased permeability for Ca(2+). 1 Publication1
Mutagenesisi973Q → E: Decreased selectivity for monovalent cations and increased permeability for Ca(2+). 1 Publication1

Chemistry databases

GuidetoPHARMACOLOGYi496

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002595301 – 1213Transient receptor potential cation channel subfamily M member 4Add BLAST1213

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei527PhosphoserineBy similarity1
Modified residuei538PhosphoserineCombined sources1
Disulfide bondi989 ↔ 1007Combined sources1 Publication
Modified residuei1144Phosphoserine; by PKCBy similarity1
Modified residuei1151Phosphoserine; by PKCBy similarity1

Post-translational modificationi

Phosphorylation by PKC leads to increase the sensitivity to Ca2+.By similarity
Sumoylated. Desumoylated by SENP1.By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ7TN37
PeptideAtlasiQ7TN37
PRIDEiQ7TN37

PTM databases

iPTMnetiQ7TN37
PhosphoSitePlusiQ7TN37

Expressioni

Tissue specificityi

Sino-atrial nodes (at protein level). Widely expressed.3 Publications

Gene expression databases

BgeeiENSMUSG00000038260
ExpressionAtlasiQ7TN37 baseline and differential
GenevisibleiQ7TN37 MM

Interactioni

Subunit structurei

Homotetramer.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040367

Structurei

Secondary structure

11213
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 19Combined sources5
Beta strandi21 – 23Combined sources3
Beta strandi70 – 72Combined sources3
Beta strandi76 – 81Combined sources6
Beta strandi89 – 97Combined sources9
Helixi100 – 109Combined sources10
Beta strandi119 – 123Combined sources5
Helixi133 – 141Combined sources9
Helixi144 – 150Combined sources7
Beta strandi153 – 157Combined sources5
Beta strandi159 – 161Combined sources3
Helixi163 – 176Combined sources14
Beta strandi186 – 191Combined sources6
Helixi192 – 194Combined sources3
Turni196 – 199Combined sources4
Beta strandi205 – 207Combined sources3
Beta strandi231 – 237Combined sources7
Beta strandi241 – 243Combined sources3
Helixi248 – 258Combined sources11
Beta strandi264 – 267Combined sources4
Beta strandi274 – 278Combined sources5
Helixi283 – 293Combined sources11
Beta strandi299 – 301Combined sources3
Beta strandi303 – 305Combined sources3
Helixi306 – 316Combined sources11
Helixi332 – 337Combined sources6
Turni338 – 341Combined sources4
Helixi345 – 358Combined sources14
Beta strandi360 – 364Combined sources5
Beta strandi366 – 368Combined sources3
Beta strandi370 – 372Combined sources3
Helixi373 – 384Combined sources12
Helixi391 – 403Combined sources13
Helixi407 – 413Combined sources7
Beta strandi415 – 419Combined sources5
Helixi423 – 435Combined sources13
Helixi439 – 447Combined sources9
Helixi452 – 455Combined sources4
Helixi458 – 464Combined sources7
Helixi473 – 481Combined sources9
Helixi503 – 511Combined sources9
Beta strandi513 – 515Combined sources3
Helixi558 – 568Combined sources11
Helixi572 – 581Combined sources10
Beta strandi582 – 584Combined sources3
Helixi585 – 601Combined sources17
Helixi606 – 633Combined sources28
Helixi635 – 642Combined sources8
Turni647 – 651Combined sources5
Helixi654 – 660Combined sources7
Helixi664 – 667Combined sources4
Helixi670 – 681Combined sources12
Helixi690 – 698Combined sources9
Helixi700 – 703Combined sources4
Beta strandi704 – 708Combined sources5
Helixi766 – 771Combined sources6
Helixi775 – 798Combined sources24
Beta strandi803 – 805Combined sources3
Helixi808 – 829Combined sources22
Helixi849 – 856Combined sources8
Helixi860 – 879Combined sources20
Helixi881 – 883Combined sources3
Helixi884 – 900Combined sources17
Helixi902 – 905Combined sources4
Helixi906 – 908Combined sources3
Turni910 – 912Combined sources3
Helixi913 – 919Combined sources7
Helixi920 – 922Combined sources3
Helixi923 – 947Combined sources25
Helixi955 – 968Combined sources14
Helixi969 – 971Combined sources3
Turni977 – 979Combined sources3
Helixi981 – 983Combined sources3
Beta strandi984 – 987Combined sources4
Beta strandi990 – 994Combined sources5
Beta strandi996 – 998Combined sources3
Beta strandi1000 – 1004Combined sources5
Beta strandi1006 – 1009Combined sources4
Turni1011 – 1013Combined sources3
Helixi1014 – 1028Combined sources15
Helixi1030 – 1066Combined sources37
Helixi1073 – 1075Combined sources3
Helixi1077 – 1089Combined sources13
Helixi1114 – 1140Combined sources27
Helixi1143 – 1161Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6BCJelectron microscopy3.14A/B/C/D1-1213[»]
6BCLelectron microscopy3.54A/B/C/D1-1213[»]
6BCOelectron microscopy2.88A/B/C/D1-1213[»]
6BCQelectron microscopy3.25A/B/C/D1-1213[»]
ProteinModelPortaliQ7TN37
SMRiQ7TN37
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1072 – 1175Calmodulin-bindingBy similarityAdd BLAST104
Regioni1135 – 1140Mediates modulation by decavanadate and PIP2-bindingBy similarity6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1133 – 1185Sequence analysisAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi971 – 973Selectivity filter1 Publication3

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3614 Eukaryota
ENOG410XR5B LUCA
GeneTreeiENSGT00760000119127
HOVERGENiHBG108337
InParanoidiQ7TN37
KOiK04979
OMAiGQAPWSD
OrthoDBiEOG091G017C
PhylomeDBiQ7TN37
TreeFamiTF314204

Family and domain databases

InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR029581 TRPM4
PANTHERiPTHR13800:SF6 PTHR13800:SF6, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7TN37-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVGPEKEQSW IPKIFRKKVC TTFIVDLSDD AGGTLCQCGQ PRDAHPSVAV
60 70 80 90 100
EDAFGAAVVT EWNSDEHTTE KPTDAYGDLD FTYSGRKHSN FLRLSDRTDP
110 120 130 140 150
ATVYSLVTRS WGFRAPNLVV SVLGGSGGPV LQTWLQDLLR RGLVRAAQST
160 170 180 190 200
GAWIVTGGLH TGIGRHVGVA VRDHQTASTG SSKVVAMGVA PWGVVRNRDM
210 220 230 240 250
LINPKGSFPA RYRWRGDPED GVEFPLDYNY SAFFLVDDGT YGRLGGENRF
260 270 280 290 300
RLRFESYVAQ QKTGVGGTGI DIPVLLLLID GDEKMLKRIE DATQAQLPCL
310 320 330 340 350
LVAGSGGAAD CLVETLEDTL APGSGGLRRG EARDRIRRYF PKGDPEVLQA
360 370 380 390 400
QVERIMTRKE LLTVYSSEDG SEEFETIVLR ALVKACGSSE ASAYLDELRL
410 420 430 440 450
AVAWNRVDIA QSELFRGDIQ WRSFHLEASL MDALLNDRPE FVRLLISHGL
460 470 480 490 500
SLGHFLTPVR LAQLYSAVSP NSLIRNLLDQ ASHASSSKSP PVNGTVELRP
510 520 530 540 550
PNVGQVLRTL LGETCAPRYP ARNTRDSYLG QDHRENDSLL MDWANKQPST
560 570 580 590 600
DASFEQAPWS DLLIWALLLN RAQMAIYFWE KGSNSVASAL GACLLLRVMA
610 620 630 640 650
RLESEAEEAA RRKDLAATFE SMSVDLFGEC YHNSEERAAR LLLRRCPLWG
660 670 680 690 700
EATCLQLAMQ ADARAFFAQD GVQSLLTQKW WGEMDSTTPI WALLLAFFCP
710 720 730 740 750
PLIYTNLIVF RKSEEEPTQK DLDFDMDSSI NGAGPPGTVE PSAKVALERR
760 770 780 790 800
QRRRPGRALC CGKFSKRWSD FWGAPVTAFL GNVVSYLLFL LLFAHVLLVD
810 820 830 840 850
FQPTKPSVSE LLLYFWAFTL LCEELRQGLG GGWGSLASGG RGPDRAPLRH
860 870 880 890 900
RLHLYLSDTW NQCDLLALTC FLLGVGCRLT PGLFDLGRTV LCLDFMIFTL
910 920 930 940 950
RLLHIFTVNK QLGPKIVIVS KMMKDVFFFL FFLCVWLVAY GVATEGILRP
960 970 980 990 1000
QDRSLPSILR RVFYRPYLQI FGQIPQEEMD VALMIPGNCS MERGSWAHPE
1010 1020 1030 1040 1050
GPVAGSCVSQ YANWLVVLLL IVFLLVANIL LLNLLIAMFS YTFSKVHGNS
1060 1070 1080 1090 1100
DLYWKAQRYS LIREFHSRPA LAPPLIIISH VRLLIKWLRR CRRCRRANLP
1110 1120 1130 1140 1150
ASPVFEHFRV CLSKEAERKL LTWESVHKEN FLLAQARDKR DSDSERLKRT
1160 1170 1180 1190 1200
SQKVDTALKQ LGQIREYDRR LRGLEREVQH CSRVLTWMAE ALSHSALLPP
1210
GAPPPPSPTG SKD
Length:1,213
Mass (Da):135,760
Last modified:October 1, 2003 - v1
Checksum:iE4959F53ED35FB66
GO
Isoform 2 (identifier: Q7TN37-2) [UniParc]FASTAAdd to basket
Also known as: A

The sequence of this isoform differs from the canonical sequence as follows:
     1-725: Missing.

Show »
Length:488
Mass (Da):55,446
Checksum:i2289051A44B57F81
GO
Isoform 3 (identifier: Q7TN37-3) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     1-725: Missing.
     812-877: Missing.

Show »
Length:422
Mass (Da):48,155
Checksum:iCC899781256E6660
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1119 – 1120KL → NV in AAH46537 (PubMed:15489334).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0214441 – 725Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST725
Alternative sequenceiVSP_021445812 – 877Missing in isoform 3. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB112657 mRNA Translation: BAC81769.1
AB112658 mRNA Translation: BAC81770.1
AB112667 Genomic DNA Translation: BAC81771.1
AJ575814 mRNA Translation: CAE05940.1
BC046472 mRNA Translation: AAH46472.1
BC046537 mRNA Translation: AAH46537.1
BC049993 mRNA Translation: AAH49993.1
BC058632 mRNA Translation: AAH58632.1
BC096475 mRNA Translation: AAH96475.1
CCDSiCCDS52245.1 [Q7TN37-1]
RefSeqiNP_780339.2, NM_175130.4 [Q7TN37-1]
UniGeneiMm.439890

Genome annotation databases

EnsembliENSMUST00000042194; ENSMUSP00000040367; ENSMUSG00000038260 [Q7TN37-1]
GeneIDi68667
KEGGimmu:68667
UCSCiuc009gun.2 mouse [Q7TN37-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRPM4_MOUSE
AccessioniPrimary (citable) accession number: Q7TN37
Secondary accession number(s): Q6PDM0
, Q769E2, Q769E4, Q80Y94, Q80YB3, Q811E2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 1, 2003
Last modified: May 23, 2018
This is version 106 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health