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Protein

Transient receptor potential cation channel subfamily M member 2

Gene

Trpm2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Nonselective, voltage-independent cation channel that mediates Na+ and Ca2+ influx, leading to increased cytoplasmic Ca2+ levels (PubMed:16651700, PubMed:16260005, PubMed:11804595, PubMed:16601673, PubMed:19454650). 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:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca2+ levels (Probable). Besides, mediates the release of lysosomal Zn2+ stores in response to reactive oxygen species, leading to increased cytosolic Zn2+ levels (PubMed:25562606). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD+) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:16260005, PubMed:16601673, PubMed:25562606). 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). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca2+ levels (PubMed:16601673). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca2+ levels (By similarity). 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:16651700, PubMed:11804595, PubMed:19454650, PubMed:25562606).By similarityCurated6 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Ion channel, Sodium channel
Biological processCalcium transport, Ion transport, Sodium transport, Transport
LigandCalcium, Sodium

Enzyme and pathway databases

ReactomeiR-RNO-3295583 TRP channels
R-RNO-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily M member 2
Gene namesi
Name:Trpm2Imported
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi1311889 Trpm2

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 – 751CytoplasmicCuratedAdd BLAST751
Transmembranei752 – 772HelicalSequence analysisAdd BLAST21
Topological domaini773 – 793ExtracellularCuratedAdd BLAST21
Transmembranei794 – 814HelicalSequence analysisAdd BLAST21
Topological domaini815 – 870CytoplasmicCuratedAdd BLAST56
Transmembranei871 – 891HelicalSequence analysisAdd BLAST21
Topological domaini892 – 894ExtracellularCurated3
Transmembranei895 – 915HelicalSequence analysisAdd BLAST21
Topological domaini916 – 934CytoplasmicCuratedAdd BLAST19
Transmembranei935 – 955HelicalSequence analysisAdd BLAST21
Topological domaini956 – 1025ExtracellularCuratedAdd BLAST70
Transmembranei1026 – 1046HelicalSequence analysisAdd BLAST21
Topological domaini1047 – 1507CytoplasmicCuratedAdd BLAST461

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004381921 – 1507Transient receptor potential cation channel subfamily M member 2Add BLAST1507

Proteomic databases

PaxDbiE9PTA2
PeptideAtlasiE9PTA2
PRIDEiE9PTA2

Expressioni

Tissue specificityi

Detected in pancreas beta-cells (PubMed:16601673). Detected in fetal brain cortex neurons (at protein level) (PubMed:16651700).2 Publications

Gene expression databases

BgeeiENSRNOG00000001216 Expressed in 8 organ(s), highest expression level in spleen

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001631

Structurei

3D structure databases

ProteinModelPortaliE9PTA2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1351 – 1502Nudix hydrolasePROSITE-ProRule annotationAdd BLAST152

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1387 – 1408Nudix 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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3614 Eukaryota
KOG4195 Eukaryota
ENOG410XR5B LUCA
GeneTreeiENSGT00760000119127
HOGENOMiHOG000236350
HOVERGENiHBG055825
InParanoidiE9PTA2
KOiK04977
OMAiSHTGVMK
OrthoDBiEOG091G035A
PhylomeDBiE9PTA2
TreeFamiTF314204

Family and domain databases

InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR015797 NUDIX_hydrolase-like_dom_sf
IPR000086 NUDIX_hydrolase_dom
IPR029594 TRPM2
PANTHERiPTHR13800:SF2 PTHR13800:SF2, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
SUPFAMiSSF55811 SSF55811, 1 hit
PROSITEiView protein in PROSITE
PS51462 NUDIX, 1 hit

Sequencei

Sequence statusi: Complete.

E9PTA2-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEPLDQRRTD SDQEEGFGVQ SRRATDLGMV PNLRRSNSSL CKSRRLLCSF
60 70 80 90 100
SSEKQENLSS WIPENIKKKE CVYFVESSKL SDAGKVVCEC GYTHEQHIEV
110 120 130 140 150
AIKPHTFQGK EWDPKKHVHE MPTDAFGDIV FTGLSQKVGK YVRLSQDTSS
160 170 180 190 200
IVIYQLMTQH WGLDVPSLLI SVTGGAKNFN MKLRLKSIFR RGLVKVAQTT
210 220 230 240 250
GAWIITGGSH TGVMKQVGEA VRDFSLSSSC KEGDVITIGI ATWGTIHNRE
260 270 280 290 300
ALIHPMGGFP AEYMLDEEGQ GNLTCLDSNH SHFILVDDGT HGQYGVEIPL
310 320 330 340 350
RTKLEKFISE QTKERGGVAI KIPIVCVVLE GGPGTLHTIY NAITNGTPCV
360 370 380 390 400
IVEGSGRVAD VIAQVAALPV SEITISLIQQ KLSVFFQEMF ETFTENQIVE
410 420 430 440 450
WTKKIQDIVR RRQLLTVFRE GKDGQQDVDV AILQALLKAS RSQDHFGHEN
460 470 480 490 500
WDHQLKLAVA WNRVDIARSE IFTDEWQWKP SDLHPMMTAA LISNKPEFVR
510 520 530 540 550
LFLENGVRLK EFVTWDTLLC LYENLEPSCL FHSKLQKVLA EEHERLAYAS
560 570 580 590 600
ETPRLQMHHV AQVLRELLGD STQLLYPRPR YTDRPRLSLP MPHIKLNVQG
610 620 630 640 650
VSLRSLYKRS TGHVTFTIDP VRDLLIWAII QNHRELAGII WAQSQDCTAA
660 670 680 690 700
ALACSKILKE LSKEEEDTDS SEEMLALADE FEHRAIGVFT ECYRKDEERA
710 720 730 740 750
QKLLVRVSEA WGKTTCLQLA LEAKDMKFVS HGGIQAFLTK VWWGQLCVDN
760 770 780 790 800
GLWRIILCML AFPLLFTGFI SFREKRLQAL CRLARVRAFF NAPVVIFYLN
810 820 830 840 850
ILSYFAFLCL FAYVLMVDFQ PSPSWCEYLI YLWLFSLVCE ETRQLFYDPD
860 870 880 890 900
GCGLMKMASL YFSDFWNKLD VGAILLFIAG LTCRLIPATL YPGRIILSLD
910 920 930 940 950
FIMFCLRLMH IFTISKTLGP KIIIVKRMMK DVFFFLFLLA VWVVSFGVAK
960 970 980 990 1000
QAILIHNESR VDWIFRGVIY HSYLTIFGQI PTYIDGVNFS MDQCSPNGTD
1010 1020 1030 1040 1050
PYKPKCPESD WTGQAPAFPE WLTVTLLCLY LLFANILLLN LLIAMFNYTF
1060 1070 1080 1090 1100
QEVQEHTDQI WKFQRHDLIE EYHGRPPAPP PLILLSHLQL LIKRIVLKIP
1110 1120 1130 1140 1150
AKRHKQLKNK LEKNEEAALL SWELYLKENY LQNQQYQHKQ RPEQKIQDIS
1160 1170 1180 1190 1200
EKVDTMVDLL DMDRVKRSGS TEQRLASLEE QVTQMGRSLH WIVTTLKDSG
1210 1220 1230 1240 1250
FGSGAGALTL AQRAFDEPDA ELSIRKKGEE GGDGYHVSAR HLLYPDARIM
1260 1270 1280 1290 1300
RFPVPNEKVP WEAEFLIYDP PFYTAEKKDA TLTDPVGDTA EPLSKINYNV
1310 1320 1330 1340 1350
VDGLMDRCSF HGTYVVQYGF PLNPMGRTGL RGRGSLSWFG PNHTLQPVVT
1360 1370 1380 1390 1400
RWKRNQGGGI CRKSVRKMLE VLVVKLPQSE HWALPGGSRE PGKMLPRKLK
1410 1420 1430 1440 1450
QVLQQEYWVT FETLLRQGTE VYKGYVDDPR NTDNAWIETV AVSIHFQDQN
1460 1470 1480 1490 1500
DVELKRLEEN LQTHDPKESA RGLEMSTEWQ VVDRRIPLYV NHKKILQKVA

SLFGAHF
Length:1,507
Mass (Da):172,259
Last modified:July 22, 2015 - v3
Checksum:i3E54E154A0166F99
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti783L → P in AAW65801 (PubMed:16260005).Curated1
Sequence conflicti783L → P in BAE72117 (PubMed:16651700).Curated1
Sequence conflicti1210L → LA in AAW65801 (PubMed:16260005).Curated1
Sequence conflicti1374V → M in AAW65801 (PubMed:16260005).Curated1
Sequence conflicti1374V → M in BAE72117 (PubMed:16651700).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB193179 mRNA Translation: BAE72117.1
AY749166 mRNA Translation: AAW65801.1
AABR07044580 Genomic DNA No translation available.
AABR07044581 Genomic DNA No translation available.
AABR07072820 Genomic DNA No translation available.
AC109383 Genomic DNA No translation available.
RefSeqiNP_001011559.1, NM_001011559.1
XP_006256311.1, XM_006256249.3
UniGeneiRn.214495

Genome annotation databases

EnsembliENSRNOT00000001631; ENSRNOP00000001631; ENSRNOG00000001216
GeneIDi294329
KEGGirno:294329

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB193179 mRNA Translation: BAE72117.1
AY749166 mRNA Translation: AAW65801.1
AABR07044580 Genomic DNA No translation available.
AABR07044581 Genomic DNA No translation available.
AABR07072820 Genomic DNA No translation available.
AC109383 Genomic DNA No translation available.
RefSeqiNP_001011559.1, NM_001011559.1
XP_006256311.1, XM_006256249.3
UniGeneiRn.214495

3D structure databases

ProteinModelPortaliE9PTA2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001631

Proteomic databases

PaxDbiE9PTA2
PeptideAtlasiE9PTA2
PRIDEiE9PTA2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001631; ENSRNOP00000001631; ENSRNOG00000001216
GeneIDi294329
KEGGirno:294329

Organism-specific databases

CTDi7226
RGDi1311889 Trpm2

Phylogenomic databases

eggNOGiKOG3614 Eukaryota
KOG4195 Eukaryota
ENOG410XR5B LUCA
GeneTreeiENSGT00760000119127
HOGENOMiHOG000236350
HOVERGENiHBG055825
InParanoidiE9PTA2
KOiK04977
OMAiSHTGVMK
OrthoDBiEOG091G035A
PhylomeDBiE9PTA2
TreeFamiTF314204

Enzyme and pathway databases

ReactomeiR-RNO-3295583 TRP channels
R-RNO-6798695 Neutrophil degranulation

Miscellaneous databases

PROiPR:E9PTA2

Gene expression databases

BgeeiENSRNOG00000001216 Expressed in 8 organ(s), highest expression level in spleen

Family and domain databases

InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR015797 NUDIX_hydrolase-like_dom_sf
IPR000086 NUDIX_hydrolase_dom
IPR029594 TRPM2
PANTHERiPTHR13800:SF2 PTHR13800:SF2, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
SUPFAMiSSF55811 SSF55811, 1 hit
PROSITEiView protein in PROSITE
PS51462 NUDIX, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRPM2_RAT
AccessioniPrimary (citable) accession number: E9PTA2
Secondary accession number(s): Q2PH54, Q5G856
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 2, 2016
Last sequence update: July 22, 2015
Last modified: October 10, 2018
This is version 65 of the entry and version 3 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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Main funding by: National Institutes of Health

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