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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

Activity 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

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 Expressed in 184 organ(s), highest expression level in jejunum
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

3D structure databases

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
OMAiQMALYFW
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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1B0GS49A0A1B0GS49_MOUSE
Transient receptor potential cation...
Trpm4
1,066Annotation score:
A0A1B0GT86A0A1B0GT86_MOUSE
Transient receptor potential cation...
Trpm4
128Annotation score:
A0A1B0GRR7A0A1B0GRR7_MOUSE
Transient receptor potential cation...
Trpm4
85Annotation score:
A0A1B0GSM7A0A1B0GSM7_MOUSE
Transient receptor potential cation...
Trpm4
65Annotation score:
A0A1B0GRQ4A0A1B0GRQ4_MOUSE
Transient receptor potential cation...
Trpm4
97Annotation score:

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

Cross-referencesi

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

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...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040367

Chemistry databases

GuidetoPHARMACOLOGYi496

Protein family/group databases

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

PTM databases

iPTMnetiQ7TN37
PhosphoSitePlusiQ7TN37

Proteomic databases

PaxDbiQ7TN37
PeptideAtlasiQ7TN37
PRIDEiQ7TN37

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi54795
MGIiMGI:1915917 Trpm4

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Miscellaneous databases

ChiTaRSiTrpm4 mouse
PROiPR:Q7TN37
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038260 Expressed in 184 organ(s), highest expression level in jejunum
ExpressionAtlasiQ7TN37 baseline and differential
GenevisibleiQ7TN37 MM

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
ProtoNetiSearch...

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: November 7, 2018
This is version 108 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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