Q9ESQ5 (TRPM4_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Trpm4
Synonyms:	Ltrpc4

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1208 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Essential for the migration but not the maturation of dendritic cells By similarity. Ref.2 Ref.5
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.
Subunit structure	Homomultimer By similarity.
Subcellular location	Isoform 1: Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum. Golgi apparatus Ref.2. Isoform 2: Endoplasmic reticulum. Golgi apparatus Ref.2.
Tissue specificity	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. Ref.2
Post-translational modification	Sumoylated. Desumoylated by SENP1 By similarity. Phosphorylation by PKC leads to increase the sensitivity to Ca2+.
Sequence similarities	Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM4 sub-subfamily. [View classification]
Sequence caution	The sequence BAB15808.1 differs from that shown. Reason: Chimeric cDNA.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Ion transport Transport
Cellular component	Cell membrane Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Transmembrane Transmembrane helix
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Ion channel
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	dendritic cell chemotaxis Inferred from sequence or structural similarity. 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
Cellular_component	Golgi apparatus Inferred from direct assay Ref.2. Source: UniProtKB endoplasmic reticulum Inferred from direct assay Ref.2. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium activated cation channel activity Inferred from direct assay Ref.2. Source: UniProtKB calcium channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms may exist.

Isoform 1 (identifier: Q9ESQ5-1)

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.

Isoform 2 (identifier: Q9ESQ5-2)

Also known as: TRPM4a;

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

Note: Probably non-functional.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1208	1208	Transient receptor potential cation channel subfamily M member 4		PRO_0000259531
Regions
	Topological domain	1 – 687	687	Cytoplasmic Potential
	Transmembrane	688 – 708	21	Helical; Potential
	Topological domain	709 – 776	68	Extracellular Potential
	Transmembrane	777 – 797	21	Helical; Potential
	Topological domain	798	1	Cytoplasmic Potential
	Transmembrane	799 – 819	21	Helical; Potential
	Topological domain	820 – 886	67	Extracellular Potential
	Transmembrane	887 – 907	21	Helical; Potential
	Topological domain	908 – 924	17	Cytoplasmic Potential
	Transmembrane	925 – 945	21	Helical; Potential
	Topological domain	946 – 959	14	Extracellular Potential
	Intramembrane	960 – 987	28	Pore-forming; Potential
	Topological domain	988 – 1013	26	Extracellular Potential
	Transmembrane	1014 – 1034	21	Helical; Potential
	Topological domain	1035 – 1208	174	Cytoplasmic Potential
	Region	1070 – 1170	101	Calmodulin-binding By similarity
	Region	1130 – 1135	6	Mediates modulation by decavanadate and PIP2-binding By similarity
	Coiled coil	1128 – 1180	53	Potential
	Motif	975 – 980	6	Selectivity filter By similarity
Amino acid modifications
	Modified residue	1139	1	Phosphoserine; by PKC By similarity
	Modified residue	1146	1	Phosphoserine; by PKC By similarity
Natural variations
	Alternative sequence	1 – 186	186	Missing in isoform 2.		VSP_040337

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (TRPM4b) [UniParc]. Last modified October 31, 2006. Version 2. Checksum: 324CEC9A6B9F7EA6	FASTA	1,208	135,341
	10 20 30 40 50 60 MVGQEKEQSW IPKIFRKKVC TTFIVDLHDD AGGTLCQCGQ PRDAHPSVAV EDAFGAAVVT 70 80 90 100 110 120 EWNSDEHTTE KPTDAYGDLD FTYSGRKSSN FLRLSDRTDP ATVYSLVTRS WGFRAPNLVV 130 140 150 160 170 180 SVLGGSEGPV LQTWLQDLLR RGLVRAAQST GAWIVTGGLH TGIGRHVGVA VRDHQTASTG 190 200 210 220 230 240 GSKVVAMGVA PWGVVRNRDM LINPKGSFPA RYRWRGDPED GVEFPLDYNY SAFFLVDDGT 250 260 270 280 290 300 YGRMGGENRF RLRFESYVAQ QKTGVGGTGI DIPVLLLLIE 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 PANGAAELRP PNVGQVLRTL LGETCAPRYP ARNTRHSLLG QDHRENDSLL 550 560 570 580 590 600 MDWANMQQDA SFEQAPWSDL LIWALLLNRA QMAIYFWEKG SNSVASALGA CLLLRVMARL 610 620 630 640 650 660 EWEAEEAARR KDLAAKFESM SVDLFGECYH NSEYRAARLL LRRCPLWGEA TCLQLAMQAD 670 680 690 700 710 720 ARAFFAQDGV QSLLTQKWWG EMDSTNPIWA LLLTFFCPPL IYTNLILFRK SEEEPTQKDL 730 740 750 760 770 780 DFDMDSSMNG AGPLGPAEPS AKVALERRRR RRPGHTLCCG GCSKRWSYFW GAPVTAFLGN 790 800 810 820 830 840 VVSYLLFLLL FAHVLLVDFQ PTKPGVFELL LYFWAFTLLC EELRQGLGGG WGTLANGGPG 850 860 870 880 890 900 PGKAPLRHRL HLYLLDTWNQ CDLLALTCFL LGVGCRLTPG LFDLGRTVLC LDFMIFTLRL 910 920 930 940 950 960 LHIFTVNKQL GPKIVIVSKM MKDVFFFLFF LCVWLVAYGV ATEGILRPQD RSLPSILRRV 970 980 990 1000 1010 1020 FYRPYLQIFG QIPQEEMDVA LMNPSNCSAE RGSWAHPEGP VAGSCVSQYA NWLVVLLLIV 1030 1040 1050 1060 1070 1080 FLLVANILLL NLLIAMFSYT FNKVHGNSDL YWKAQRYSLI REFHSRPALA PPLIIISHLR 1090 1100 1110 1120 1130 1140 LLFKWLRRCH RTNLPASPVF EHFRVCLSKE AERTLLTWES VHKENFLLAQ ARDKRDSDSE 1150 1160 1170 1180 1190 1200 RLKRTSQKVD TALKQLGQIR EYDRRLRGLE REVQHCSRVL TWMAEALSHS ALLPPGGPPP PSPTGSKD
	Isoform 2 (TRPM4a) [UniParc]. Checksum: 68246240BDC5FECB	FASTA	1,022	115,277
	10 20 30 40 50 60 MGVAPWGVVR NRDMLINPKG SFPARYRWRG DPEDGVEFPL DYNYSAFFLV DDGTYGRMGG 70 80 90 100 110 120 ENRFRLRFES YVAQQKTGVG GTGIDIPVLL LLIEGDEKML KRIEDATQAQ LPCLLVAGSG 130 140 150 160 170 180 GAADCLVETL EDTLAPGSGG LRRGEARDRI RRYFPKGDPE VLQAQVERIM TRKELLTVYS 190 200 210 220 230 240 SEDGSEEFET IVLRALVKAC GSSEASAYLD ELRLAVAWNR VDIAQSELFR GDIQWRSFHL 250 260 270 280 290 300 EASLMDALLN DRPEFVRLLI SHGLSLGHFL TPVRLAQLYS AVSPNSLIRN LLDQASHASS 310 320 330 340 350 360 SKSPPANGAA ELRPPNVGQV LRTLLGETCA PRYPARNTRH SLLGQDHREN DSLLMDWANM 370 380 390 400 410 420 QQDASFEQAP WSDLLIWALL LNRAQMAIYF WEKGSNSVAS ALGACLLLRV MARLEWEAEE 430 440 450 460 470 480 AARRKDLAAK FESMSVDLFG ECYHNSEYRA ARLLLRRCPL WGEATCLQLA MQADARAFFA 490 500 510 520 530 540 QDGVQSLLTQ KWWGEMDSTN PIWALLLTFF CPPLIYTNLI LFRKSEEEPT QKDLDFDMDS 550 560 570 580 590 600 SMNGAGPLGP AEPSAKVALE RRRRRRPGHT LCCGGCSKRW SYFWGAPVTA FLGNVVSYLL 610 620 630 640 650 660 FLLLFAHVLL VDFQPTKPGV FELLLYFWAF TLLCEELRQG LGGGWGTLAN GGPGPGKAPL 670 680 690 700 710 720 RHRLHLYLLD TWNQCDLLAL TCFLLGVGCR LTPGLFDLGR TVLCLDFMIF TLRLLHIFTV 730 740 750 760 770 780 NKQLGPKIVI VSKMMKDVFF FLFFLCVWLV AYGVATEGIL RPQDRSLPSI LRRVFYRPYL 790 800 810 820 830 840 QIFGQIPQEE MDVALMNPSN CSAERGSWAH PEGPVAGSCV SQYANWLVVL LLIVFLLVAN 850 860 870 880 890 900 ILLLNLLIAM FSYTFNKVHG NSDLYWKAQR YSLIREFHSR PALAPPLIII SHLRLLFKWL 910 920 930 940 950 960 RRCHRTNLPA SPVFEHFRVC LSKEAERTLL TWESVHKENF LLAQARDKRD SDSERLKRTS 970 980 990 1000 1010 1020 QKVDTALKQL GQIREYDRRL RGLEREVQHC SRVLTWMAEA LSHSALLPPG GPPPPSPTGS KD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[2]	"Cloning and characterization of rat transient receptor potential-melastatin 4 (TRPM4)." Yoo J.C., Yarishkin O.V., Hwang E.M., Kim E., Kim D.G., Park N., Hong S.G., Park J.Y. Biochem. Biophys. Res. Commun. 391:806-811(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"Cloning of novel Ca-permeable channels." Ohki G., Ishibashi K., Suzuki M. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 717-1208. Tissue: Brain.
[4]	"Activation of the Ca(2+)-activated nonselective cation channel by diacylglycerol analogues in rat cardiomyocytes." Guinamard R., Chatelier A., Lenfant J., Bois P. J. Cardiovasc. Electrophysiol. 15:342-348(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[5]	"Functional expression of the TRPM4 cationic current in ventricular cardiomyocytes from spontaneously hypertensive rats." Guinamard R., Demion M., Magaud C., Potreau D., Bois P. Hypertension 48:587-594(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AABR03000917 Genomic DNA. No translation available. AABR03004552 Genomic DNA. No translation available. AB040807 mRNA. Translation: BAB15808.1. Sequence problems.
IPI	IPI00192252. IPI00973653.
RefSeq	NP_001129701.1. NM_001136229.1.
UniGene	Rn.205004.
3D structure databases
ModBase	Search...
Proteomic databases
PaxDb	Q9ESQ5.
PRIDE	Q9ESQ5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000041513; ENSRNOP00000041387; ENSRNOG00000020714.
GeneID	171143.
KEGG	rno:171143.
UCSC	RGD:620244. rat.
Organism-specific databases
CTD	54795.
RGD	620244. Trpm4.
Phylogenomic databases
eggNOG	NOG253824.
GeneTree	ENSGT00650000093200.
HOGENOM	HOG000236350.
HOVERGEN	HBG108337.
InParanoid	Q9ESQ5.
KO	K04979.
OrthoDB	EOG4WM4T2.
Gene expression databases
ArrayExpress	Q9ESQ5.
Genevestigator	Q9ESQ5.
GermOnline	ENSRNOG00000020714. Rattus norvegicus.
Family and domain databases
InterPro	IPR005821. Ion_trans_dom. [Graphical view]
Pfam	PF00520. Ion_trans. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	621940.

Entry information

Entry name

TRPM4_RAT

Accession

Primary (citable) accession number: Q9ESQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 31, 2006
Last modified:	April 3, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program