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Q7TN37

- TRPM4_MOUSE

UniProt

Q7TN37 - TRPM4_MOUSE

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
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    • History
      Entry version 83 (01 Oct 2014)
      Sequence version 1 (01 Oct 2003)
      Previous versions | rss
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    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. dendritic cell chemotaxis Source: UniProtKB
    4. positive regulation of canonical Wnt signaling pathway Source: UniProtKB
    5. positive regulation of cell proliferation Source: UniProtKB
    6. protein sumoylation Source: UniProtKB
    7. regulation of ion transmembrane transport Source: GOC
    8. regulation of membrane potential Source: MGI
    9. regulation of T cell cytokine production Source: UniProtKB

    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

    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

    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

    Structurei

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 689689CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini711 – 77868ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini800 – 86364CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini885 – 8884ExtracellularSequence Analysis
    Topological domaini910 – 92617CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini948 – 96114ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini990 – 101526ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1037 – 1213177CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei962 – 98928Pore-formingSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei690 – 71021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei779 – 79921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei864 – 88421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei889 – 90921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei927 – 94721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei1016 – 103621HelicalSequence AnalysisAdd
    BLAST

    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.
    GeneTreeiENSGT00650000093200.
    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

    MVGPEKEQSW IPKIFRKKVC TTFIVDLSDD AGGTLCQCGQ PRDAHPSVAV     50
    EDAFGAAVVT EWNSDEHTTE KPTDAYGDLD FTYSGRKHSN FLRLSDRTDP 100
    ATVYSLVTRS WGFRAPNLVV SVLGGSGGPV LQTWLQDLLR RGLVRAAQST 150
    GAWIVTGGLH TGIGRHVGVA VRDHQTASTG SSKVVAMGVA PWGVVRNRDM 200
    LINPKGSFPA RYRWRGDPED GVEFPLDYNY SAFFLVDDGT YGRLGGENRF 250
    RLRFESYVAQ QKTGVGGTGI DIPVLLLLID GDEKMLKRIE DATQAQLPCL 300
    LVAGSGGAAD CLVETLEDTL APGSGGLRRG EARDRIRRYF PKGDPEVLQA 350
    QVERIMTRKE LLTVYSSEDG SEEFETIVLR ALVKACGSSE ASAYLDELRL 400
    AVAWNRVDIA QSELFRGDIQ WRSFHLEASL MDALLNDRPE FVRLLISHGL 450
    SLGHFLTPVR LAQLYSAVSP NSLIRNLLDQ ASHASSSKSP PVNGTVELRP 500
    PNVGQVLRTL LGETCAPRYP ARNTRDSYLG QDHRENDSLL MDWANKQPST 550
    DASFEQAPWS DLLIWALLLN RAQMAIYFWE KGSNSVASAL GACLLLRVMA 600
    RLESEAEEAA RRKDLAATFE SMSVDLFGEC YHNSEERAAR LLLRRCPLWG 650
    EATCLQLAMQ ADARAFFAQD GVQSLLTQKW WGEMDSTTPI WALLLAFFCP 700
    PLIYTNLIVF RKSEEEPTQK DLDFDMDSSI NGAGPPGTVE PSAKVALERR 750
    QRRRPGRALC CGKFSKRWSD FWGAPVTAFL GNVVSYLLFL LLFAHVLLVD 800
    FQPTKPSVSE LLLYFWAFTL LCEELRQGLG GGWGSLASGG RGPDRAPLRH 850
    RLHLYLSDTW NQCDLLALTC FLLGVGCRLT PGLFDLGRTV LCLDFMIFTL 900
    RLLHIFTVNK QLGPKIVIVS KMMKDVFFFL FFLCVWLVAY GVATEGILRP 950
    QDRSLPSILR RVFYRPYLQI FGQIPQEEMD VALMIPGNCS MERGSWAHPE 1000
    GPVAGSCVSQ YANWLVVLLL IVFLLVANIL LLNLLIAMFS YTFSKVHGNS 1050
    DLYWKAQRYS LIREFHSRPA LAPPLIIISH VRLLIKWLRR CRRCRRANLP 1100
    ASPVFEHFRV CLSKEAERKL LTWESVHKEN FLLAQARDKR DSDSERLKRT 1150
    SQKVDTALKQ LGQIREYDRR LRGLEREVQH CSRVLTWMAE ALSHSALLPP 1200
    GAPPPPSPTG SKD 1213
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ENSGT00650000093200.
    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

    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: October 1, 2014
    This is version 83 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