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Q7TN37 (TRPM4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Trpm4
Synonyms:Ltrpc4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length1213 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Enzyme regulation

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. Ref.5

Subunit structure

Homomultimer By similarity.

Subcellular location

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

Tissue specificity

Sino-atrial nodes (at protein level). Widely expressed. Ref.1 Ref.2 Ref.5

Post-translational modification

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

Sumoylated. Desumoylated by SENP1 By similarity.

Disruption phenotype

Mice have fewer dendritic cells in lymphoid organs and impaired migration of dendritic cells is seen. Ref.6

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM4 sub-subfamily. [View classification]

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Ion transport
Transport
   Cellular componentCell membrane
Endoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Transmembrane
Transmembrane helix
   LigandATP-binding
Calcium
Calmodulin-binding
Nucleotide-binding
   Molecular functionIon channel
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdendritic cell chemotaxis

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of canonical Wnt receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

protein sumoylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of T cell cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of membrane potential

Inferred from sequence orthology Ref.2. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

integral to membrane

Inferred from sequence orthology Ref.2. Source: MGI

plasma membrane

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium activated cation channel activity

Inferred from direct assay Ref.5. Source: UniProtKB

calcium channel activity

Inferred from direct assay Ref.1. Source: MGI

voltage-gated ion channel activity

Inferred from sequence orthology Ref.2. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7TN37-1)

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.
Isoform 2 (identifier: Q7TN37-2)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-725: Missing.
Isoform 3 (identifier: Q7TN37-3)

Also known as: B;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12131213Transient receptor potential cation channel subfamily M member 4
PRO_0000259530

Regions

Topological domain1 – 689689Cytoplasmic Potential
Transmembrane690 – 71021Helical; Potential
Topological domain711 – 77868Extracellular Potential
Transmembrane779 – 79921Helical; Potential
Topological domain800 – 86364Cytoplasmic Potential
Transmembrane864 – 88421Helical; Potential
Topological domain885 – 8884Extracellular Potential
Transmembrane889 – 90921Helical; Potential
Topological domain910 – 92617Cytoplasmic Potential
Transmembrane927 – 94721Helical; Potential
Topological domain948 – 96114Extracellular Potential
Intramembrane962 – 98928Pore-forming; Potential
Topological domain990 – 101526Extracellular Potential
Transmembrane1016 – 103621Helical; Potential
Topological domain1037 – 1213177Cytoplasmic Potential
Region1072 – 1175104Calmodulin-binding By similarity
Region1135 – 11406Mediates modulation by decavanadate and PIP2-binding By similarity
Coiled coil1133 – 118553 Potential
Motif977 – 9826Selectivity filter By similarity

Amino acid modifications

Modified residue11441Phosphoserine; by PKC By similarity
Modified residue11511Phosphoserine; by PKC By similarity

Natural variations

Alternative sequence1 – 725725Missing in isoform 2 and isoform 3.
VSP_021444
Alternative sequence812 – 87766Missing in isoform 3.
VSP_021445

Experimental info

Sequence conflict1119 – 11202KL → NV in AAH46537. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2003. Version 1.
Checksum: E4959F53ED35FB66

FASTA1,213135,760
        10         20         30         40         50         60 
MVGPEKEQSW IPKIFRKKVC TTFIVDLSDD AGGTLCQCGQ PRDAHPSVAV EDAFGAAVVT 

        70         80         90        100        110        120 
EWNSDEHTTE KPTDAYGDLD FTYSGRKHSN FLRLSDRTDP ATVYSLVTRS WGFRAPNLVV 

       130        140        150        160        170        180 
SVLGGSGGPV LQTWLQDLLR RGLVRAAQST GAWIVTGGLH TGIGRHVGVA VRDHQTASTG 

       190        200        210        220        230        240 
SSKVVAMGVA PWGVVRNRDM LINPKGSFPA RYRWRGDPED GVEFPLDYNY SAFFLVDDGT 

       250        260        270        280        290        300 
YGRLGGENRF RLRFESYVAQ QKTGVGGTGI DIPVLLLLID GDEKMLKRIE DATQAQLPCL 

       310        320        330        340        350        360 
LVAGSGGAAD CLVETLEDTL APGSGGLRRG EARDRIRRYF PKGDPEVLQA QVERIMTRKE 

       370        380        390        400        410        420 
LLTVYSSEDG SEEFETIVLR ALVKACGSSE ASAYLDELRL AVAWNRVDIA QSELFRGDIQ 

       430        440        450        460        470        480 
WRSFHLEASL MDALLNDRPE FVRLLISHGL SLGHFLTPVR LAQLYSAVSP NSLIRNLLDQ 

       490        500        510        520        530        540 
ASHASSSKSP PVNGTVELRP PNVGQVLRTL LGETCAPRYP ARNTRDSYLG QDHRENDSLL 

       550        560        570        580        590        600 
MDWANKQPST DASFEQAPWS DLLIWALLLN RAQMAIYFWE KGSNSVASAL GACLLLRVMA 

       610        620        630        640        650        660 
RLESEAEEAA RRKDLAATFE SMSVDLFGEC YHNSEERAAR LLLRRCPLWG EATCLQLAMQ 

       670        680        690        700        710        720 
ADARAFFAQD GVQSLLTQKW WGEMDSTTPI WALLLAFFCP PLIYTNLIVF RKSEEEPTQK 

       730        740        750        760        770        780 
DLDFDMDSSI NGAGPPGTVE PSAKVALERR QRRRPGRALC CGKFSKRWSD FWGAPVTAFL 

       790        800        810        820        830        840 
GNVVSYLLFL LLFAHVLLVD FQPTKPSVSE LLLYFWAFTL LCEELRQGLG GGWGSLASGG 

       850        860        870        880        890        900 
RGPDRAPLRH RLHLYLSDTW NQCDLLALTC FLLGVGCRLT PGLFDLGRTV LCLDFMIFTL 

       910        920        930        940        950        960 
RLLHIFTVNK QLGPKIVIVS KMMKDVFFFL FFLCVWLVAY GVATEGILRP QDRSLPSILR 

       970        980        990       1000       1010       1020 
RVFYRPYLQI FGQIPQEEMD VALMIPGNCS MERGSWAHPE GPVAGSCVSQ YANWLVVLLL 

      1030       1040       1050       1060       1070       1080 
IVFLLVANIL LLNLLIAMFS YTFSKVHGNS DLYWKAQRYS LIREFHSRPA LAPPLIIISH 

      1090       1100       1110       1120       1130       1140 
VRLLIKWLRR CRRCRRANLP ASPVFEHFRV CLSKEAERKL LTWESVHKEN FLLAQARDKR 

      1150       1160       1170       1180       1190       1200 
DSDSERLKRT SQKVDTALKQ LGQIREYDRR LRGLEREVQH CSRVLTWMAE ALSHSALLPP 

      1210 
GAPPPPSPTG SKD

« Hide

Isoform 2 (A) [UniParc].

Checksum: 2289051A44B57F81
Show »

FASTA48855,446
Isoform 3 (B) [UniParc].

Checksum: CC899781256E6660
Show »

FASTA42248,155

References

« Hide 'large scale' references
[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]"Voltage dependence of the Ca2+-activated cation channel TRPM4."
Nilius B., Prenen J., Droogmans G., Voets T., Vennekens R., Freichel M., Wissenbach U., Flockerzi V.
J. Biol. Chem. 278:30813-30820(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Strain: 129/SvJ.
Tissue: Heart.
[3]Erratum
Nilius B., Prenen J., Droogmans G., Voets T., Vennekens R., Freichel M., Wissenbach U., Flockerzi V.
J. Biol. Chem. 278:42728-42728(2003)
[4]"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.
[5]"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.
[6]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00409286.
IPI00798524.
IPI00798543.
RefSeqNP_780339.2. NM_175130.4.
UniGeneMm.439890.

3D structure databases

ProteinModelPortalQ7TN37.
ModBaseSearch...

PTM databases

PhosphoSiteQ7TN37.

Proteomic databases

PaxDbQ7TN37.
PRIDEQ7TN37.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000042194; ENSMUSP00000040367; ENSMUSG00000038260.
GeneID68667.
KEGGmmu:68667.
UCSCuc009gun.2. mouse.

Organism-specific databases

CTD54795.
MGIMGI:1915917. Trpm4.

Phylogenomic databases

eggNOGNOG253824.
GeneTreeENSGT00650000093200.
HOVERGENHBG108337.
InParanoidQ7TN37.
KOK04979.
OMATWESVHK.
OrthoDBEOG4WM4T2.

Gene expression databases

BgeeQ7TN37.
GenevestigatorQ7TN37.
GermOnlineENSMUSG00000038260. Mus musculus.

Family and domain databases

InterProIPR005821. Ion_trans_dom.
[Graphical view]
PfamPF00520. Ion_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRPM4. mouse.
NextBio327656.
SOURCESearch...

Entry information

Entry nameTRPM4_MOUSE
AccessionPrimary (citable) accession number: Q7TN37
Secondary accession number(s): Q6PDM0 expand/collapse secondary AC list , Q769E2, Q769E4, Q80Y94, Q80YB3, Q811E2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 1, 2003
Last modified: April 3, 2013
This is version 71 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

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