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Q7TN37

- TRPM4_MOUSE

UniProt

Q7TN37 - TRPM4_MOUSE

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Protein

Transient receptor potential cation channel subfamily M member 4

Gene

Trpm4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- 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. 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.By similarity2 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.By similarity1 Publication

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calcium activated cation channel activity Source: UniProtKB
  3. calcium channel activity Source: MGI
  4. voltage-gated ion channel activity Source: MGI

GO - Biological processi

  1. calcium ion transmembrane transport Source: GOC
  2. calcium ion transport Source: MGI
  3. cardiac conduction Source: InterPro
  4. cation transmembrane transport Source: GOC
  5. dendritic cell chemotaxis Source: UniProtKB
  6. positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  7. positive regulation of cell proliferation Source: UniProtKB
  8. protein sumoylation Source: UniProtKB
  9. regulation of ion transmembrane transport Source: GOC
  10. regulation of membrane potential Source: MGI
  11. regulation of T cell cytokine production Source: UniProtKB
  12. vasoconstriction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Adaptive immunity, Immunity, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Calcium, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_227861. TRP channels.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1915917. Trpm4.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Endoplasmic reticulum By similarity. Golgi apparatus By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 689689CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei690 – 71021HelicalSequence AnalysisAdd
BLAST
Topological domaini711 – 77868ExtracellularSequence AnalysisAdd
BLAST
Transmembranei779 – 79921HelicalSequence AnalysisAdd
BLAST
Topological domaini800 – 86364CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei864 – 88421HelicalSequence AnalysisAdd
BLAST
Topological domaini885 – 8884ExtracellularSequence Analysis
Transmembranei889 – 90921HelicalSequence AnalysisAdd
BLAST
Topological domaini910 – 92617CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei927 – 94721HelicalSequence AnalysisAdd
BLAST
Topological domaini948 – 96114ExtracellularSequence AnalysisAdd
BLAST
Intramembranei962 – 98928Pore-formingSequence AnalysisAdd
BLAST
Topological domaini990 – 101526ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1016 – 103621HelicalSequence AnalysisAdd
BLAST
Topological domaini1037 – 1213177CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. Golgi apparatus Source: UniProtKB
  3. integral component of membrane Source: MGI
  4. plasma membrane Source: MGI
Complete GO annotation...

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12131213Transient receptor potential cation channel subfamily M member 4PRO_0000259530Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1144 – 11441Phosphoserine; by PKCBy similarity
Modified residuei1151 – 11511Phosphoserine; by PKCBy similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ7TN37.
PRIDEiQ7TN37.

PTM databases

PhosphoSiteiQ7TN37.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ7TN37.
GenevestigatoriQ7TN37.

Interactioni

Subunit structurei

Homomultimer.By similarity

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1072 – 1175104Calmodulin-bindingBy similarityAdd
BLAST
Regioni1135 – 11406Mediates modulation by decavanadate and PIP2-bindingBy similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1133 – 118553Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi977 – 9826Selectivity filterBy similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG253824.
GeneTreeiENSGT00760000119127.
HOVERGENiHBG108337.
InParanoidiQ7TN37.
KOiK04979.
OMAiRTWGFRA.
OrthoDBiEOG725DH1.
PhylomeDBiQ7TN37.
TreeFamiTF314204.

Family and domain databases

InterProiIPR005821. Ion_trans_dom.
IPR029581. TRPM4.
[Graphical view]
PANTHERiPTHR13800:SF6. PTHR13800:SF6. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1119 – 11202KL → NV in AAH46537. (PubMed:15489334)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 725725Missing in isoform 2 and isoform 3. 1 PublicationVSP_021444Add
BLAST
Alternative sequencei812 – 87766Missing in isoform 3. 1 PublicationVSP_021445Add
BLAST

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

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 .
CCDSi CCDS52245.1. [Q7TN37-1 ]
RefSeqi NP_780339.2. NM_175130.4. [Q7TN37-1 ]
UniGenei Mm.439890.

3D structure databases

ModBasei Search...
MobiDBi Search...

Chemistry

GuidetoPHARMACOLOGYi 496.

PTM databases

PhosphoSitei Q7TN37.

Proteomic databases

PaxDbi Q7TN37.
PRIDEi Q7TN37.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000042194 ; ENSMUSP00000040367 ; ENSMUSG00000038260 . [Q7TN37-1 ]
GeneIDi 68667.
KEGGi mmu:68667.
UCSCi uc009gun.2. mouse. [Q7TN37-1 ]

Organism-specific databases

CTDi 54795.
MGIi MGI:1915917. Trpm4.

Phylogenomic databases

eggNOGi NOG253824.
GeneTreei ENSGT00760000119127.
HOVERGENi HBG108337.
InParanoidi Q7TN37.
KOi K04979.
OMAi RTWGFRA.
OrthoDBi EOG725DH1.
PhylomeDBi Q7TN37.
TreeFami TF314204.

Enzyme and pathway databases

Reactomei REACT_227861. TRP channels.

Miscellaneous databases

ChiTaRSi Trpm4. mouse.
NextBioi 327656.
PROi Q7TN37.
SOURCEi Search...

Gene expression databases

Bgeei Q7TN37.
Genevestigatori Q7TN37.

Family and domain databases

InterProi IPR005821. Ion_trans_dom.
IPR029581. TRPM4.
[Graphical view ]
PANTHERi PTHR13800:SF6. PTHR13800:SF6. 1 hit.
Pfami PF00520. Ion_trans. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and characterization of the murine TRPM4 channel."
    Murakami M., Xu F., Miyoshi I., Sato E., Ono K., Iijima T.
    Biochem. Biophys. Res. Commun. 307:522-528(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Strain: 129/SvJ.
    Tissue: Heart.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Colon and Salivary gland.
  4. "TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node cells."
    Demion M., Bois P., Launay P., Guinamard R.
    Cardiovasc. Res. 73:531-538(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, ENZYME REGULATION.
  5. "The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells."
    Barbet G., Demion M., Moura I.C., Serafini N., Leger T., Vrtovsnik F., Monteiro R.C., Guinamard R., Kinet J.P., Launay P.
    Nat. Immunol. 9:1148-1156(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiTRPM4_MOUSE
AccessioniPrimary (citable) accession number: Q7TN37
Secondary accession number(s): Q6PDM0
, Q769E2, Q769E4, Q80Y94, Q80YB3, Q811E2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 1, 2003
Last modified: November 26, 2014
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3