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Protein

Transient receptor potential cation channel subfamily M member 4

Gene

Trpm4

Organism
Rattus norvegicus (Rat)
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. 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. Essential for the migration but not the maturation of dendritic cells (By similarity).By similarity2 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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei172ATP; shared with neighboring subunitBy similarity1
Binding sitei422ATPBy similarity1
Binding sitei449ATP; via carbonyl oxygenBy similarity1
Metal bindingi822CalciumBy similarity1
Metal bindingi825CalciumBy similarity1
Metal bindingi859CalciumBy similarity1
Metal bindingi862CalciumBy 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

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
MLS2s
Melastatin-like 2
Gene namesi
Name:Trpm4
Synonyms:Ltrpc4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620244 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 – 776CytoplasmicBy similarityAdd BLAST776
Transmembranei777 – 797HelicalBy similarityAdd BLAST21
Topological domaini798 – 808ExtracellularBy similarityAdd BLAST11
Transmembranei809 – 829HelicalBy similarityAdd BLAST21
Topological domaini830 – 857CytoplasmicBy similarityAdd BLAST28
Transmembranei858 – 878HelicalBy similarityAdd BLAST21
Topological domaini879 – 880ExtracellularBy similarity2
Transmembranei881 – 904HelicalBy similarityAdd BLAST24
Topological domaini905 – 924CytoplasmicBy similarityAdd BLAST20
Transmembranei925 – 945HelicalBy similarityAdd BLAST21
Topological domaini946 – 957ExtracellularBy similarityAdd BLAST12
Intramembranei958 – 978Pore-formingBy similarityAdd BLAST21
Topological domaini979 – 1013ExtracellularBy similarityAdd BLAST35
Transmembranei1014 – 1034HelicalBy similarityAdd BLAST21
Topological domaini1035 – 1208CytoplasmicBy similarityAdd BLAST174

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002595311 – 1208Transient receptor potential cation channel subfamily M member 4Add BLAST1208

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei527PhosphoserineCombined sources1
Modified residuei538PhosphoserineBy similarity1
Disulfide bondi987 ↔ 1005By similarity
Modified residuei1139Phosphoserine; by PKCBy similarity1
Modified residuei1146Phosphoserine; 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

PaxDbiQ9ESQ5
PRIDEiQ9ESQ5

PTM databases

iPTMnetiQ9ESQ5
PhosphoSitePlusiQ9ESQ5

Expressioni

Tissue specificityi

Isoform 1 is highly expressed in the testis with a moderate expression in the brain, spleen and thymus. Isoform 2 is only expressed in the brain and spleen.1 Publication

Gene expression databases

GenevisibleiQ9ESQ5 RN

Interactioni

Subunit structurei

Homotetramer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000041387

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1070 – 1170Calmodulin-bindingBy similarityAdd BLAST101
Regioni1130 – 1135Mediates modulation by decavanadate and PIP2-bindingBy similarity6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1128 – 1180Sequence analysisAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi969 – 971Selectivity filterBy similarity3

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3614 Eukaryota
ENOG410XR5B LUCA
HOGENOMiHOG000236350
HOVERGENiHBG108337
InParanoidiQ9ESQ5
KOiK04979
OrthoDBiEOG091G017C
PhylomeDBiQ9ESQ5
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 (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms may exist.

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9ESQ5-1) [UniParc]FASTAAdd to basket
Also known as: TRPM4b

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
MVGQEKEQSW IPKIFRKKVC TTFIVDLHDD AGGTLCQCGQ PRDAHPSVAV
60 70 80 90 100
EDAFGAAVVT EWNSDEHTTE KPTDAYGDLD FTYSGRKSSN FLRLSDRTDP
110 120 130 140 150
ATVYSLVTRS WGFRAPNLVV SVLGGSEGPV LQTWLQDLLR RGLVRAAQST
160 170 180 190 200
GAWIVTGGLH TGIGRHVGVA VRDHQTASTG GSKVVAMGVA PWGVVRNRDM
210 220 230 240 250
LINPKGSFPA RYRWRGDPED GVEFPLDYNY SAFFLVDDGT YGRMGGENRF
260 270 280 290 300
RLRFESYVAQ QKTGVGGTGI DIPVLLLLIE 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 PANGAAELRP
510 520 530 540 550
PNVGQVLRTL LGETCAPRYP ARNTRHSLLG QDHRENDSLL MDWANMQQDA
560 570 580 590 600
SFEQAPWSDL LIWALLLNRA QMAIYFWEKG SNSVASALGA CLLLRVMARL
610 620 630 640 650
EWEAEEAARR KDLAAKFESM SVDLFGECYH NSEYRAARLL LRRCPLWGEA
660 670 680 690 700
TCLQLAMQAD ARAFFAQDGV QSLLTQKWWG EMDSTNPIWA LLLTFFCPPL
710 720 730 740 750
IYTNLILFRK SEEEPTQKDL DFDMDSSMNG AGPLGPAEPS AKVALERRRR
760 770 780 790 800
RRPGHTLCCG GCSKRWSYFW GAPVTAFLGN VVSYLLFLLL FAHVLLVDFQ
810 820 830 840 850
PTKPGVFELL LYFWAFTLLC EELRQGLGGG WGTLANGGPG PGKAPLRHRL
860 870 880 890 900
HLYLLDTWNQ CDLLALTCFL LGVGCRLTPG LFDLGRTVLC LDFMIFTLRL
910 920 930 940 950
LHIFTVNKQL GPKIVIVSKM MKDVFFFLFF LCVWLVAYGV ATEGILRPQD
960 970 980 990 1000
RSLPSILRRV FYRPYLQIFG QIPQEEMDVA LMNPSNCSAE RGSWAHPEGP
1010 1020 1030 1040 1050
VAGSCVSQYA NWLVVLLLIV FLLVANILLL NLLIAMFSYT FNKVHGNSDL
1060 1070 1080 1090 1100
YWKAQRYSLI REFHSRPALA PPLIIISHLR LLFKWLRRCH RTNLPASPVF
1110 1120 1130 1140 1150
EHFRVCLSKE AERTLLTWES VHKENFLLAQ ARDKRDSDSE RLKRTSQKVD
1160 1170 1180 1190 1200
TALKQLGQIR EYDRRLRGLE REVQHCSRVL TWMAEALSHS ALLPPGGPPP

PSPTGSKD
Length:1,208
Mass (Da):135,341
Last modified:October 31, 2006 - v2
Checksum:i324CEC9A6B9F7EA6
GO
Isoform 2 (identifier: Q9ESQ5-2) [UniParc]FASTAAdd to basket
Also known as: TRPM4a

The sequence of this isoform differs from the canonical sequence as follows:
     1-186: Missing.

Note: Probably non-functional.
Show »
Length:1,022
Mass (Da):115,277
Checksum:i68246240BDC5FECB
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0H2UHX0A0A0H2UHX0_RAT
Transient receptor potential cation...
Trpm4
1,296Annotation score:

Sequence cautioni

The sequence BAB15808 differs from that shown. Chimeric cDNA.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0403371 – 186Missing in isoform 2. 1 PublicationAdd BLAST186

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03000917 Genomic DNA No translation available.
AABR03004552 Genomic DNA No translation available.
AB040807 mRNA Translation: BAB15808.1 Sequence problems.
RefSeqiNP_001129701.1, NM_001136229.1 [Q9ESQ5-1]
UniGeneiRn.205004

Genome annotation databases

GeneIDi171143
KEGGirno:171143
UCSCiRGD:620244 rat [Q9ESQ5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03000917 Genomic DNA No translation available.
AABR03004552 Genomic DNA No translation available.
AB040807 mRNA Translation: BAB15808.1 Sequence problems.
RefSeqiNP_001129701.1, NM_001136229.1 [Q9ESQ5-1]
UniGeneiRn.205004

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000041387

PTM databases

iPTMnetiQ9ESQ5
PhosphoSitePlusiQ9ESQ5

Proteomic databases

PaxDbiQ9ESQ5
PRIDEiQ9ESQ5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi171143
KEGGirno:171143
UCSCiRGD:620244 rat [Q9ESQ5-1]

Organism-specific databases

CTDi54795
RGDi620244 Trpm4

Phylogenomic databases

eggNOGiKOG3614 Eukaryota
ENOG410XR5B LUCA
HOGENOMiHOG000236350
HOVERGENiHBG108337
InParanoidiQ9ESQ5
KOiK04979
OrthoDBiEOG091G017C
PhylomeDBiQ9ESQ5
TreeFamiTF314204

Miscellaneous databases

PROiPR:Q9ESQ5

Gene expression databases

GenevisibleiQ9ESQ5 RN

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_RAT
AccessioniPrimary (citable) accession number: Q9ESQ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 31, 2006
Last modified: September 12, 2018
This is version 115 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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