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Q8TD43 (TRPM4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
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

Short name=hTRPM4
Alternative name(s):
Calcium-activated non-selective cation channel 1
Long transient receptor potential channel 4
Short name=LTrpC-4
Short name=LTrpC4
Melastatin-4
Gene names
Name:TRPM4
Synonyms:LTRPC4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1214 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. Ref.2 Ref.4 Ref.8 Ref.9 Ref.12 Ref.16 Ref.21 Ref.22

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). Ref.10 Ref.11 Ref.15 Ref.17 Ref.19

Subunit structure

Homomultimer. Ref.2

Subcellular location

Isoform 1: Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum. Golgi apparatus Ref.1 Ref.2 Ref.20.

Isoform 2: Endoplasmic reticulum. Golgi apparatus Ref.1 Ref.2 Ref.20.

Tissue specificity

Widely expressed with a high expression in intestine and prostate. In brain, it is both expressed in whole cerebral arteries and isolated vascular smooth muscle cells. Prominently expressed in Purkinje fibers. Expressed at higher levels in T-helper 2 (Th2) cells as compared to T-helper 1 (Th1) cells. Ref.1 Ref.2 Ref.4 Ref.8 Ref.18 Ref.22 Ref.23

Post-translational modification

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

Sumoylated. Desumoylated by SENP1. Ref.23

Involvement in disease

Progressive familial heart block 1B (PFHB1B) [MIM:604559]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24 Ref.25

Sequence similarities

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

Sequence caution

The sequence BAA90907.1 differs from that shown. Reason: Erroneous termination at position 1191. Translated as Glu.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Ion transport
Transport
   Cellular componentCell membrane
Endoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   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_processcalcium ion transmembrane transport

Traceable author statement. Source: Reactome

dendritic cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

ion transmembrane transport

Traceable author statement. Source: Reactome

positive regulation of canonical Wnt signaling pathway

Inferred from direct assay Ref.21. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay Ref.21. Source: UniProtKB

protein sumoylation

Inferred from direct assay Ref.23. Source: UniProtKB

regulation of T cell cytokine production

Inferred from direct assay Ref.22. Source: UniProtKB

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.20. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay Ref.20. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay Ref.20. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium activated cation channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

calcium channel activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8TD43-1)

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: Q8TD43-2)

Also known as: TRPM4a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-174: Missing.
Isoform 3 (identifier: Q8TD43-3)

Also known as: TRPM4c;

The sequence of this isoform differs from the canonical sequence as follows:
     738-882: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12141214Transient receptor potential cation channel subfamily M member 4
PRO_0000259529

Regions

Topological domain1 – 683683Cytoplasmic Potential
Transmembrane684 – 70421Helical; Potential
Topological domain705 – 77672Extracellular Potential
Transmembrane777 – 79721Helical; Potential
Topological domain798 – 86871Cytoplasmic Potential
Transmembrane869 – 88921Helical; Potential
Topological domain890 – 8923Extracellular Potential
Transmembrane893 – 91321Helical; Potential
Topological domain914 – 92916Cytoplasmic Potential
Transmembrane930 – 95021Helical; Potential
Topological domain951 – 96515Extracellular Potential
Intramembrane966 – 99328Pore-forming; Potential
Topological domain994 – 101926Extracellular Potential
Transmembrane1020 – 104021Helical; Potential
Topological domain1041 – 1214174Cytoplasmic Potential
Region1076 – 1176101Calmodulin-binding
Region1136 – 11416Mediates modulation by decavanadate and PIP2-binding
Coiled coil1134 – 118754 Potential
Motif981 – 9866Selectivity filter

Amino acid modifications

Modified residue11451Phosphoserine; by PKC Probable
Modified residue11521Phosphoserine; by PKC Probable

Natural variations

Alternative sequence1 – 174174Missing in isoform 2.
VSP_021442
Alternative sequence738 – 882145Missing in isoform 3.
VSP_021443
Natural variant71E → K in PFHB1B; attenuated desumoylation of TRPM4 resulting in constitutive sumoylation of the channel leading to impaired endocytosis and elevated channel density at the cell surface. Ref.23
VAR_064042
Natural variant1011A → T. Ref.25
Corresponds to variant rs113984787 [ dbSNP | Ensembl ].
VAR_066761
Natural variant1031Y → C. Ref.25
VAR_066762
Natural variant1311Q → H in PFHB1B; incomplete right bundle-branch block. Ref.25
VAR_066763
Natural variant1641R → W in PFHB1B. Ref.24
VAR_066764
Natural variant2521R → H. Ref.25
VAR_066765
Natural variant2931Q → R in PFHB1B; right bundle-branch block. Ref.25
Corresponds to variant rs172147855 [ dbSNP | Ensembl ].
VAR_066766
Natural variant4321A → T in PFHB1B; atrioventricular block. Ref.24 Ref.25
Corresponds to variant rs201907325 [ dbSNP | Ensembl ].
VAR_066767
Natural variant487 – 49812Missing. Ref.25
VAR_066768
Natural variant5611D → A. Ref.25
Corresponds to variant rs56355369 [ dbSNP | Ensembl ].
VAR_066769
Natural variant5821G → S in PFHB1B; atrioventricular block. Ref.25
Corresponds to variant rs172149856 [ dbSNP | Ensembl ].
VAR_066770
Natural variant7901Y → H in PFHB1B; atrioventricular block. Ref.25
VAR_066771
Natural variant8441G → D in PFHB1B; right bundle-branch block. Ref.24 Ref.25
Corresponds to variant rs200038418 [ dbSNP | Ensembl ].
VAR_066772
Natural variant8541Q → R. Ref.25
Corresponds to variant rs172155862 [ dbSNP | Ensembl ].
VAR_066773
Natural variant9141K → R in PFHB1B; atrioventricular block. Ref.25
VAR_066774
Natural variant9701P → S in PFHB1B; incomplete right bundle-branch block. Ref.25
VAR_066775
Natural variant12041P → L. Ref.25
Corresponds to variant rs150391806 [ dbSNP | Ensembl ].
VAR_066776

Experimental info

Mutagenesis2751L → A or C: Abolishes ability to restore sensitivity to Ca(2+) after desensitization. Ref.13
Mutagenesis2781I → N: No effect. Ref.13
Mutagenesis2791D → N: No effect. Ref.13
Mutagenesis3241G → A: No effect. Ref.13
Mutagenesis3251G → A: Abolishes ability to restore sensitivity to Ca(2+) after desensitization. Ref.13
Mutagenesis3271R → A: No effect. Ref.13
Mutagenesis9771Q → E: Alters the monovalent cation permeability sequence and results in a pore with moderate Ca(2+) permeability. Ref.14
Mutagenesis981 – 9866EDMDVA → TIIDGP: Induces a functional channel that combines the gating hallmarks of TRPM4 (activation by Ca(2+)) with TRPV6-like sensitivity to block by extracellular Ca(2+) and Mg(2+) as well as Ca(2+) permeation. Ref.14
Mutagenesis9811E → A: Results in a channel with normal permeability properties but with a reduced sensitivity to block by intracellular spermine. Ref.14
Mutagenesis9821D → A: Results in a functional channel that exhibits extremely fast desensitization, possibly indicating destabilization of the pore. Ref.14
Mutagenesis9841D → A: Results in a non-functional channel with a dominant negative phenotype. Ref.14
Mutagenesis10591K → Q: Does not affect PIP2-binding. Ref.17
Mutagenesis10721R → Q: Does not affect PIP2-binding. Ref.17
Mutagenesis1136 – 11416Missing: Results in a channel with very rapid desensitization and highly reduced sensitivity to PIP2. Ref.17
Mutagenesis11451S → A: Decreases the sensitivity to Ca(2+). Ref.13
Mutagenesis11521S → A: Decreases the sensitivity to Ca(2+). Ref.13
Sequence conflict11491K → E in BAA90907. Ref.6
Sequence conflict12071P → L in BAA90907. Ref.6
Sequence conflict12101P → H in BAA90907. Ref.6
Sequence conflict12141D → E in BAA90907. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TRPM4b) [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: 76ADA452690ED8F5

FASTA1,214134,301
        10         20         30         40         50         60 
MVVPEKEQSW IPKIFKKKTC TTFIVDSTDP GGTLCQCGRP RTAHPAVAME DAFGAAVVTV 

        70         80         90        100        110        120 
WDSDAHTTEK PTDAYGELDF TGAGRKHSNF LRLSDRTDPA AVYSLVTRTW GFRAPNLVVS 

       130        140        150        160        170        180 
VLGGSGGPVL QTWLQDLLRR GLVRAAQSTG AWIVTGGLHT GIGRHVGVAV RDHQMASTGG 

       190        200        210        220        230        240 
TKVVAMGVAP WGVVRNRDTL INPKGSFPAR YRWRGDPEDG VQFPLDYNYS AFFLVDDGTH 

       250        260        270        280        290        300 
GCLGGENRFR LRLESYISQQ KTGVGGTGID IPVLLLLIDG DEKMLTRIEN ATQAQLPCLL 

       310        320        330        340        350        360 
VAGSGGAADC LAETLEDTLA PGSGGARQGE ARDRIRRFFP KGDLEVLQAQ VERIMTRKEL 

       370        380        390        400        410        420 
LTVYSSEDGS EEFETIVLKA LVKACGSSEA SAYLDELRLA VAWNRVDIAQ SELFRGDIQW 

       430        440        450        460        470        480 
RSFHLEASLM DALLNDRPEF VRLLISHGLS LGHFLTPMRL AQLYSAAPSN SLIRNLLDQA 

       490        500        510        520        530        540 
SHSAGTKAPA LKGGAAELRP PDVGHVLRML LGKMCAPRYP SGGAWDPHPG QGFGESMYLL 

       550        560        570        580        590        600 
SDKATSPLSL DAGLGQAPWS DLLLWALLLN RAQMAMYFWE MGSNAVSSAL GACLLLRVMA 

       610        620        630        640        650        660 
RLEPDAEEAA RRKDLAFKFE GMGVDLFGEC YRSSEVRAAR LLLRRCPLWG DATCLQLAMQ 

       670        680        690        700        710        720 
ADARAFFAQD GVQSLLTQKW WGDMASTTPI WALVLAFFCP PLIYTRLITF RKSEEEPTRE 

       730        740        750        760        770        780 
ELEFDMDSVI NGEGPVGTAD PAEKTPLGVP RQSGRPGCCG GRCGGRRCLR RWFHFWGAPV 

       790        800        810        820        830        840 
TIFMGNVVSY LLFLLLFSRV LLVDFQPAPP GSLELLLYFW AFTLLCEELR QGLSGGGGSL 

       850        860        870        880        890        900 
ASGGPGPGHA SLSQRLRLYL ADSWNQCDLV ALTCFLLGVG CRLTPGLYHL GRTVLCIDFM 

       910        920        930        940        950        960 
VFTVRLLHIF TVNKQLGPKI VIVSKMMKDV FFFLFFLGVW LVAYGVATEG LLRPRDSDFP 

       970        980        990       1000       1010       1020 
SILRRVFYRP YLQIFGQIPQ EDMDVALMEH SNCSSEPGFW AHPPGAQAGT CVSQYANWLV 

      1030       1040       1050       1060       1070       1080 
VLLLVIFLLV ANILLVNLLI AMFSYTFGKV QGNSDLYWKA QRYRLIREFH SRPALAPPFI 

      1090       1100       1110       1120       1130       1140 
VISHLRLLLR QLCRRPRSPQ PSSPALEHFR VYLSKEAERK LLTWESVHKE NFLLARARDK 

      1150       1160       1170       1180       1190       1200 
RESDSERLKR TSQKVDLALK QLGHIREYEQ RLKVLEREVQ QCSRVLGWVA EALSRSALLP 

      1210 
PGGPPPPDLP GSKD 

« Hide

Isoform 2 (TRPM4a) [UniParc].

Checksum: 684A8C554B2B0F2E
Show »

FASTA1,040115,566
Isoform 3 (TRPM4c) [UniParc].

Checksum: 80DEBD935A55F200
Show »

FASTA1,069118,630

References

« Hide 'large scale' references
[1]"Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform."
Xu X.-Z.S., Moebius F., Gill D.L., Montell C.
Proc. Natl. Acad. Sci. U.S.A. 98:10692-10697(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization."
Launay P., Fleig A., Perraud A.-L., Scharenberg A.M., Penner R., Kinet J.-P.
Cell 109:397-407(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
[3]"TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel."
Hofmann T., Chubanov V., Gudermann T., Montell C.
Curr. Biol. 13:1153-1158(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[4]"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), FUNCTION, TISSUE SPECIFICITY.
Tissue: Prostate.
[5]Erratum
Nilius B., Prenen J., Droogmans G., Voets T., Vennekens R., Freichel M., Wissenbach U., Flockerzi V.
J. Biol. Chem. 278:42728-42728(2003)
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Trachea.
[7]"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).
Tissue: Brain.
[8]"Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries."
Earley S., Waldron B.J., Brayden J.E.
Circ. Res. 95:922-929(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[9]"Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes."
Guinamard R., Chatelier A., Demion M., Potreau D., Patri S., Rahmati M., Bois P.
J. Physiol. (Lond.) 558:75-83(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Decavanadate modulates gating of TRPM4 cation channels."
Nilius B., Prenen J., Janssens A., Voets T., Droogmans G.
J. Physiol. (Lond.) 560:753-765(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[11]"Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b."
Nilius B., Prenen J., Voets T., Droogmans G.
Pflugers Arch. 448:70-75(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ATP-BINDING, ENZYME REGULATION.
[12]"TRPM4 regulates calcium oscillations after T cell activation."
Launay P., Cheng H., Srivatsan S., Penner R., Fleig A., Kinet J.-P.
Science 306:1374-1377(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4."
Nilius B., Prenen J., Tang J., Wang C., Owsianik G., Janssens A., Voets T., Zhu M.X.
J. Biol. Chem. 280:6423-6433(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1145 AND SER-1152, ATP-BINDING, CALMODULIN-BINDING, MUTAGENESIS OF LEU-275; ILE-278; ASP-279; GLY-324; GLY-325; ARG-327; SER-1145 AND SER-1152.
[14]"The selectivity filter of the cation channel TRPM4."
Nilius B., Prenen J., Janssens A., Owsianik G., Wang C., Zhu M.X., Voets T.
J. Biol. Chem. 280:22899-22906(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SELECTIVITY FILTER MOTIF, MUTAGENESIS OF GLN-977; GLU-981; 981-GLU--ALA-986; ASP-982 AND ASP-984.
[15]"Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization."
Zhang Z., Okawa H., Wang Y., Liman E.R.
J. Biol. Chem. 280:39185-39192(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PIP2-BINDING.
[16]"TRPM4 controls insulin secretion in pancreatic beta-cells."
Cheng H., Beck A., Launay P., Gross S.A., Stokes A.J., Kinet J.-P., Fleig A., Penner R.
Cell Calcium 41:51-61(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate."
Nilius B., Mahieu F., Prenen J., Janssens A., Owsianik G., Vennekens R., Voets T.
EMBO J. 25:467-478(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PIP2-BINDING, MUTAGENESIS OF LYS-1059; ARG-1072 AND 1136-ARG--ARG-1141.
[18]"Tissue distribution profiles of the human TRPM cation channel family."
Fonfria E., Murdock P.R., Cusdin F.S., Benham C.D., Kelsell R.E., McNulty S.
J. Recept. Signal Transduct. 26:159-178(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[19]"A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity."
Takezawa R., Cheng H., Beck A., Ishikawa J., Launay P., Kubota H., Kinet J.-P., Fleig A., Yamada T., Penner R.
Mol. Pharmacol. 69:1413-1420(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[20]"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: SUBCELLULAR LOCATION.
[21]"TRPM4 enhances cell proliferation through up-regulation of the beta-catenin signaling pathway."
Armisen R., Marcelain K., Simon F., Tapia J.C., Toro J., Quest A.F., Stutzin A.
J. Cell. Physiol. 226:103-109(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[22]"Trpm4 differentially regulates Th1 and th2 function by altering calcium signaling and NFAT localization."
Weber K.S., Hildner K., Murphy K.M., Allen P.M.
J. Immunol. 185:2836-2846(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[23]"Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I."
Kruse M., Schulze-Bahr E., Corfield V., Beckmann A., Stallmeyer B., Kurtbay G., Ohmert I., Schulze-Bahr E., Brink P., Pongs O.
J. Clin. Invest. 119:2737-2744(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PFHB1B LYS-7, CHARACTERIZATION OF VARIANT PFHB1B LYS-7, SUMOYLATION, TISSUE SPECIFICITY.
[24]"Gain-of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease."
Liu H., El Zein L., Kruse M., Guinamard R., Beckmann A., Bozio A., Kurtbay G., Megarbane A., Ohmert I., Blaysat G., Villain E., Pongs O., Bouvagnet P.
Circ. Cardiovasc. Genet. 3:374-385(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PFHB1B TRP-164; THR-432 AND ASP-844.
[25]"Mutational spectrum in the Ca(2+) -activated cation channel gene TRPM4 in patients with cardiac conductance disturbances."
Stallmeyer B., Zumhagen S., Denjoy I., Duthoit G., Hebert J.L., Ferrer X., Maugenre S., Schmitz W., Kirchhefer U., Schulze-Bahr E., Guicheney P., Schulze-Bahr E.
Hum. Mutat. 33:109-117(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PFHB1B HIS-131; ARG-293; THR-432; SER-582; HIS-790; ASP-844; ARG-914 AND SER-970, VARIANTS THR-101; CYS-103; HIS-252; LYS-487 DEL; ALA-561; ARG-854 AND LEU-1204.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY046396 mRNA. Translation: AAL02142.1.
AF497623 mRNA. Translation: AAM18083.1.
AY297044 mRNA. Translation: AAP44473.1.
AY297045 mRNA. Translation: AAP44474.1.
AY297046 mRNA. Translation: AAP44475.1.
AJ575813 mRNA. Translation: CAE05941.1.
AK000048 mRNA. Translation: BAA90907.1. Sequence problems.
AK292862 mRNA. Translation: BAF85551.1.
BC132727 mRNA. Translation: AAI32728.1.
CCDSCCDS33073.1. [Q8TD43-1]
CCDS56098.1. [Q8TD43-3]
RefSeqNP_001182156.1. NM_001195227.1. [Q8TD43-3]
NP_060106.2. NM_017636.3. [Q8TD43-1]
UniGeneHs.467101.

3D structure databases

ProteinModelPortalQ8TD43.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120154. 1 interaction.
STRING9606.ENSP00000252826.

Chemistry

ChEMBLCHEMBL1628469.
GuidetoPHARMACOLOGY496.

Protein family/group databases

TCDB1.A.4.5.4. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

PhosphoSiteQ8TD43.

Polymorphism databases

DMDM74715868.

Proteomic databases

MaxQBQ8TD43.
PaxDbQ8TD43.
PRIDEQ8TD43.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252826; ENSP00000252826; ENSG00000130529. [Q8TD43-1]
ENST00000427978; ENSP00000407492; ENSG00000130529. [Q8TD43-3]
GeneID54795.
KEGGhsa:54795.
UCSCuc002pmw.3. human. [Q8TD43-1]
uc010emu.3. human. [Q8TD43-3]

Organism-specific databases

CTD54795.
GeneCardsGC19P049661.
HGNCHGNC:17993. TRPM4.
HPAHPA041169.
MIM604559. phenotype.
606936. gene.
neXtProtNX_Q8TD43.
Orphanet130. Brugada syndrome.
871. Familial progressive cardiac conduction defect.
PharmGKBPA38272.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG253824.
HOGENOMHOG000236350.
HOVERGENHBG108337.
InParanoidQ8TD43.
KOK04979.
OMARTWGFRA.
OrthoDBEOG725DH1.
PhylomeDBQ8TD43.
TreeFamTF314204.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ8TD43.
BgeeQ8TD43.
CleanExHS_TRPM4.
GenevestigatorQ8TD43.

Family and domain databases

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

Other

GeneWikiTRPM4.
GenomeRNAi54795.
NextBio57471.
PROQ8TD43.
SOURCESearch...

Entry information

Entry nameTRPM4_HUMAN
AccessionPrimary (citable) accession number: Q8TD43
Secondary accession number(s): A2RU25 expand/collapse secondary AC list , Q7Z5D9, Q96L84, Q9NXV1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: June 1, 2002
Last modified: July 9, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM