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Protein

Transient receptor potential cation channel subfamily M member 2

Gene

Trpm2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nonselective, voltage-independent cation channel that mediates Na+ and Ca2+ influx, leading to increased cytoplasmic Ca2+ levels (PubMed:11804595, PubMed:19454650, PubMed:21753080, PubMed:22493272). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (By similarity). Also contributes to Ca2+ release from intracellular stores in response to ADP-ribose (PubMed:21753080). Plays a role in numerous processes that involve signaling via intracellular Ca2+ levels (PubMed:21753080). Besides, mediates the release of lysosomal Zn2+ stores in response to reactive oxygen species, leading to increased cytosolic Zn2+ levels (By similarity). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:27533035, PubMed:27562954). Activated by intracellular ADP-ribose, beta-NAD (NAD+) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:19454650, PubMed:21753080, PubMed:22493272). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate. Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (By similarity). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272, PubMed:25817999). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis (PubMed:27533035, PubMed:27562954). Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca2+ levels (PubMed:20921208, PubMed:25817999). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection (PubMed:21709234). Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro) (PubMed:22493272). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca2+ levels (PubMed:21753080). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its function in increasing cytoplasmic Ca2+ and Zn2+ levels (By similarity). Confers susceptibility to cell death following oxidative stress (PubMed:25562606).By similarity8 Publications

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • calcium-release channel activity Source: UniProtKB
  • cation channel activity Source: UniProtKB
  • ligand-gated calcium channel activity Source: UniProtKB
  • manganese ion transmembrane transporter activity Source: MGI
  • sodium channel activity Source: UniProtKB-KW

GO - Biological processi

  • calcium ion import across plasma membrane Source: UniProtKB
  • calcium ion transmembrane import into cytosol Source: UniProtKB
  • calcium-mediated signaling using intracellular calcium source Source: UniProtKB
  • cellular response to calcium ion Source: UniProtKB
  • cellular response to hydrogen peroxide Source: UniProtKB
  • cellular response to purine-containing compound Source: UniProtKB
  • cellular response to temperature stimulus Source: UniProtKB
  • dendritic cell chemotaxis Source: UniProtKB
  • dendritic cell differentiation Source: UniProtKB
  • manganese ion transport Source: MGI
  • regulation of actin cytoskeleton reorganization Source: UniProtKB
  • regulation of filopodium assembly Source: UniProtKB
  • release of sequestered calcium ion into cytosol Source: UniProtKB
  • response to heat Source: UniProtKB
  • response to hydroperoxide Source: MGI
  • response to purine-containing compound Source: MGI
  • temperature homeostasis Source: UniProtKB
  • zinc II ion transmembrane transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel, Sodium channel

Keywords - Biological processi

Calcium transport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calcium, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-3295583. TRP channels.
R-MMU-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily M member 2
Alternative name(s):
Long transient receptor potential channel 2
Short name:
LTrpC-2
Short name:
LTrpC2
Transient receptor potential channel 7
Short name:
TrpC7
Gene namesi
Name:Trpm2
Synonyms:Ltrpc2, Trpc7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1351901. Trpm2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 750CytoplasmicSequence analysisAdd BLAST750
Transmembranei751 – 771HelicalSequence analysisAdd BLAST21
Topological domaini772 – 792ExtracellularSequence analysisAdd BLAST21
Transmembranei793 – 813HelicalSequence analysisAdd BLAST21
Topological domaini814 – 869CytoplasmicSequence analysisAdd BLAST56
Transmembranei870 – 890HelicalSequence analysisAdd BLAST21
Topological domaini891 – 893ExtracellularSequence analysis3
Transmembranei894 – 914HelicalSequence analysisAdd BLAST21
Topological domaini915 – 933CytoplasmicSequence analysisAdd BLAST19
Transmembranei934 – 954HelicalSequence analysisAdd BLAST21
Topological domaini955 – 1024ExtracellularSequence analysisAdd BLAST70
Transmembranei1025 – 1045HelicalSequence analysisAdd BLAST21
Topological domaini1046 – 1506CytoplasmicSequence analysisAdd BLAST461

GO - Cellular componenti

  • cell projection Source: UniProtKB-SubCell
  • cytoplasmic vesicle membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: MGI
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Lysosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice display no obvious phenotype, but display increased blood glucose levels when fed ad libitum (PubMed:20921208). After oral or intraperitoneal glucose administration, they display increased blood glucose and lower plasma insulin levels; basal fasting glucose and insulin levels are not altered (PubMed:20921208). Ca2+ influx into beta-cells is unchanged under basal conditions or upon stimulation with glucose up to 8.3 mM; Ca2+ influx is decreased upon stimulation with high glucose levels (16.7 mM) (PubMed:20921208). Likewise, insulin secretion is decreased only upon stimulation with 11.2 or 16.7 mM glucose, but not in response to more moderate glucose levels (PubMed:20921208). Mutant mice have a reduced number of neurons that are activated by warm temperature (34 to 43 degrees Celsius) in their dorsal root ganglia and superior cervical ganglia (PubMed:27533035). Mutant mice show altered behavorial responses to environmental temperature; contrary to wild-type they show no preference for a cooler environment when exposed to 38 degrees Celsius (PubMed:27533035). Besides, they spend less time than wild-type in a cooler environment (23 degrees Celsius) (PubMed:27533035). Mutant mice develop higher fever in response to prostaglandin E2 injection into the preoptic area of the hypothalamus, a brain area involved in body temperature control (PubMed:27562954). Mutant mice display a defective innate immune response and are highly susceptible to infection by L.monocytogenes (PubMed:21709234). They are unable to contain the bacterial infection; contrary to wild-type, they die within a few days after infection (PubMed:21709234). The defective immune response is due to impaired secretion of Il12b and IFNG; mice are rescued by treatment with recombinant IFNG (PubMed:21709234).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi214M → A: Abolishes lowering of temperature threshold for activation in response to reactive oxygen species. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153271 – 1506Transient receptor potential cation channel subfamily M member 2Add BLAST1506

Proteomic databases

EPDiQ91YD4.
MaxQBiQ91YD4.
PaxDbiQ91YD4.
PRIDEiQ91YD4.

PTM databases

iPTMnetiQ91YD4.
PhosphoSitePlusiQ91YD4.

Expressioni

Tissue specificityi

Detected in the preoptic area of the hypothalamus, a brain area involved in body temperature control (PubMed:27562954). Detected in beta-cells in pancreas islets (at protein level) (PubMed:16601673, PubMed:20921208). Detected in brain cortex, striatum, hippocampus CA1, CA2 and CA3 layers, and in the Purkinje cell layer in cerebellum (PubMed:15708008). Widely expressed, with highest levels in lung, spleen, eye and brain (PubMed:11804595). Detected in dendritic cells and in polymorphonuclear neutrophils (PubMed:21753080).6 Publications

Gene expression databases

BgeeiENSMUSG00000009292.

Interactioni

Protein-protein interaction databases

MINTiMINT-4997883.
STRINGi10090.ENSMUSP00000101040.

Structurei

3D structure databases

ProteinModelPortaliQ91YD4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1350 – 1501Nudix hydrolasePROSITE-ProRule annotationAdd BLAST152

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1386 – 1407Nudix boxPROSITE-ProRule annotationAdd BLAST22

Domaini

The cytosolic nudix box binds ADP-ribose and is required for channel activation by ADP-ribose.By similarity

Sequence similaritiesi

Contains 1 nudix hydrolase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3614. Eukaryota.
KOG4195. Eukaryota.
ENOG410XR5B. LUCA.
GeneTreeiENSGT00760000119127.
HOGENOMiHOG000236350.
HOVERGENiHBG055825.
InParanoidiQ91YD4.
KOiK04977.
OMAiITGGSHT.
OrthoDBiEOG091G035A.
PhylomeDBiQ91YD4.
TreeFamiTF314204.

Family and domain databases

Gene3Di3.90.79.10. 1 hit.
InterProiIPR005821. Ion_trans_dom.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
IPR029594. TRPM2.
[Graphical view]
PANTHERiPTHR13800:SF2. PTHR13800:SF2. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]
SUPFAMiSSF55811. SSF55811. 1 hit.
PROSITEiPS51462. NUDIX. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q91YD4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESLDRRRTG SEQEEGFGVQ SRRATDLGMV PNLRRSNSSL CKSRRFLCSF
60 70 80 90 100
SSEKQENLSS WIPENIKKKE CVYFVESSKL SDAGKVVCAC GYTHEQHLEV
110 120 130 140 150
AIKPHTFQGK EWDPKKHVQE MPTDAFGDIV FTDLSQKVGK YVRVSQDTPS
160 170 180 190 200
SVIYQLMTQH WGLDVPNLLI SVTGGAKNFN MKLRLKSIFR RGLVKVAQTT
210 220 230 240 250
GAWIITGGSH TGVMKQVGEA VRDFSLSSSC KEGEVITIGV ATWGTIHNRE
260 270 280 290 300
GLIHPMGGFP AEYMLDEEGQ GNLTCLDSNH SHFILVDDGT HGQYGVEIPL
310 320 330 340 350
RTKLEKFISE QTKERGGVAI KIPIVCVVLE GGPGTLHTIY NAINNGTPCV
360 370 380 390 400
IVEGSGRVAD VIAQVATLPV SEITISLIQQ KLSIFFQEMF ETFTENQIVE
410 420 430 440 450
WTKKIQDIVR RRQLLTIFRE GKDGQQDVDV AILQALLKAS RSQDHFGHEN
460 470 480 490 500
WDHQLKLAVA WNRVDIARSE IFTDEWQWKP ADLHPMMTAA LISNKPEFVR
510 520 530 540 550
LFLENGVRLK EFVTWDTLLC LYENLEPSCL FHSKLQKVLA EEQRLAYASA
560 570 580 590 600
TPRLHMHHVA QVLRELLGDS TQLLYPRPRY TDRPRLSMTV PHIKLNVQGV
610 620 630 640 650
SLRSLYKRST GHVTFTIDPV RDLLIWAVIQ NHRELAGIIW AQSQDCTAAA
660 670 680 690 700
LACSKILKEL SKEEEDTDSS EEMLALADEF EHRAIGVFTE CYRKDEERAQ
710 720 730 740 750
KLLVRVSEAW GKTTCLQLAL EAKDMKFVSH GGIQAFLTKV WWGQLCVDNG
760 770 780 790 800
LWRIILCMLA FPLLFTGFIS FREKRLQALC RPARVRAFFN APVVIFHMNI
810 820 830 840 850
LSYFAFLCLF AYVLMVDFQP SPSWCEYLIY LWLFSLVCEE TRQLFYDPDG
860 870 880 890 900
CGLMKMASLY FSDFWNKLDV GAILLFIVGL TCRLIPATLY PGRIILSLDF
910 920 930 940 950
IMFCLRLMHI FTISKTLGPK IIIVKRMMKD VFFFLFLLAV WVVSFGVAKQ
960 970 980 990 1000
AILIHNESRV DWIFRGVVYH SYLTIFGQIP TYIDGVNFSM DQCSPNGTDP
1010 1020 1030 1040 1050
YKPKCPESDW TGQAPAFPEW LTVTLLCLYL LFANILLLNL LIAMFNYTFQ
1060 1070 1080 1090 1100
EVQEHTDQIW KFQRHDLIEE YHGRPPAPPP LILLSHLQLL IKRIVLKIPA
1110 1120 1130 1140 1150
KRHKQLKNKL EKNEETALLS WELYLKENYL QNQQYQQKQR PEQKIQDISE
1160 1170 1180 1190 1200
KVDTMVDLLD MDQVKRSGST EQRLASLEEQ VTQVTRALHW IVTTLKDSGF
1210 1220 1230 1240 1250
GSGAGALTLA PQRAFDEPDA ELSIRRKVEE PGDGYHVSAR HLLYPNARIM
1260 1270 1280 1290 1300
RFPVPNEKVP WAAEFLIYDP PFYTAEKDVA LTDPVGDTAE PLSKISYNVV
1310 1320 1330 1340 1350
DGPTDRRSFH GVYVVEYGFP LNPMGRTGLR GRGSLSWFGP NHTLQPVVTR
1360 1370 1380 1390 1400
WKRNQGGAIC RKSVRKMLEV LVMKLPRSEH WALPGGSREP GEMLPRKLKR
1410 1420 1430 1440 1450
VLRQEFWVAF ETLLMQGTEV YKGYVDDPRN TDNAWIETVA VSIHFQDQND
1460 1470 1480 1490 1500
MELKRLEENL HTHDPKELTR DLKLSTEWQV VDRRIPLYAN HKTILQKVAS

LFGAHF
Length:1,506
Mass (Da):172,202
Last modified:November 2, 2016 - v2
Checksum:iE340C2F4DED121F4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti843Q → QY in CAC69081 (Ref. 1) 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ344343 mRNA. Translation: CAC69081.1.
AB166747 mRNA. Translation: BAD83707.1.
AJ878415 mRNA. Translation: CAI47592.1.
AC153507 Genomic DNA. No translation available.
AC158612 Genomic DNA. No translation available.
CH466553 Genomic DNA. Translation: EDL31768.1.
BC141391 mRNA. Translation: AAI41392.1.
RefSeqiNP_612174.2. NM_138301.2.
UniGeneiMm.276762.

Genome annotation databases

EnsembliENSMUST00000105401; ENSMUSP00000101040; ENSMUSG00000009292.
GeneIDi28240.
KEGGimmu:28240.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ344343 mRNA. Translation: CAC69081.1.
AB166747 mRNA. Translation: BAD83707.1.
AJ878415 mRNA. Translation: CAI47592.1.
AC153507 Genomic DNA. No translation available.
AC158612 Genomic DNA. No translation available.
CH466553 Genomic DNA. Translation: EDL31768.1.
BC141391 mRNA. Translation: AAI41392.1.
RefSeqiNP_612174.2. NM_138301.2.
UniGeneiMm.276762.

3D structure databases

ProteinModelPortaliQ91YD4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4997883.
STRINGi10090.ENSMUSP00000101040.

PTM databases

iPTMnetiQ91YD4.
PhosphoSitePlusiQ91YD4.

Proteomic databases

EPDiQ91YD4.
MaxQBiQ91YD4.
PaxDbiQ91YD4.
PRIDEiQ91YD4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000105401; ENSMUSP00000101040; ENSMUSG00000009292.
GeneIDi28240.
KEGGimmu:28240.

Organism-specific databases

MGIiMGI:1351901. Trpm2.

Phylogenomic databases

eggNOGiKOG3614. Eukaryota.
KOG4195. Eukaryota.
ENOG410XR5B. LUCA.
GeneTreeiENSGT00760000119127.
HOGENOMiHOG000236350.
HOVERGENiHBG055825.
InParanoidiQ91YD4.
KOiK04977.
OMAiITGGSHT.
OrthoDBiEOG091G035A.
PhylomeDBiQ91YD4.
TreeFamiTF314204.

Enzyme and pathway databases

ReactomeiR-MMU-3295583. TRP channels.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiQ91YD4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000009292.

Family and domain databases

Gene3Di3.90.79.10. 1 hit.
InterProiIPR005821. Ion_trans_dom.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
IPR029594. TRPM2.
[Graphical view]
PANTHERiPTHR13800:SF2. PTHR13800:SF2. 1 hit.
PfamiPF00520. Ion_trans. 1 hit.
[Graphical view]
SUPFAMiSSF55811. SSF55811. 1 hit.
PROSITEiPS51462. NUDIX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRPM2_MOUSE
AccessioniPrimary (citable) accession number: Q91YD4
Secondary accession number(s): Q5KTC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: November 2, 2016
Last modified: November 30, 2016
This is version 111 of the entry and version 2 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.