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Protein

Transient receptor potential cation channel subfamily M member 2

Gene

TRPM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nonselective, voltage-independent cation channel mediating sodium and calcium ion influx in response to oxidative stress. Extracellular calcium passes through the channel and acts from the intracellular side as a positive regulator in channel activation. Activated by ADP-ribose, nicotinamide adenine dinucleotide (NAD+), reactive nitrogen species and arachidonic acid. Inactivated by intracellular ATP. Confers susceptibility to cell death following oxidative stress. Isoform 2 does not seem to be regulated by ADPR. Has ADP-ribose pyrophosphatase activity.1 Publication

Catalytic activityi

ADP-D-ribose + H2O = AMP + D-ribose 5-phosphate.1 Publication

Kineticsi

  1. KM=100 µM for ADP-ribose
  1. Vmax=0.1 µmol/min/mg enzyme

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1390 – 141223NADAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Hydrolase, Ion channel, Sodium channel

Keywords - Biological processi

Calcium transport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calcium, NAD, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-3295583. TRP channels.

Protein family/group databases

TCDBi1.A.4.5.5. the transient receptor potential ca(2+) channel (trp-cc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily M member 2 (EC:3.6.1.13)
Alternative name(s):
Estrogen-responsive element-associated gene 1 protein
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:EREG1, KNP3, LTRPC2, TRPC7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:12339. TRPM2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 752752CytoplasmicSequence analysisAdd
BLAST
Transmembranei753 – 77321HelicalSequence analysisAdd
BLAST
Topological domaini774 – 79522ExtracellularSequence analysisAdd
BLAST
Transmembranei796 – 81621HelicalSequence analysisAdd
BLAST
Topological domaini817 – 87256CytoplasmicSequence analysisAdd
BLAST
Transmembranei873 – 89321HelicalSequence analysisAdd
BLAST
Topological domaini894 – 8963ExtracellularSequence analysis
Transmembranei897 – 91721HelicalSequence analysisAdd
BLAST
Topological domaini918 – 93619CytoplasmicSequence analysisAdd
BLAST
Transmembranei937 – 95721HelicalSequence analysisAdd
BLAST
Topological domaini958 – 102568ExtracellularSequence analysisAdd
BLAST
Transmembranei1026 – 104621HelicalSequence analysisAdd
BLAST
Topological domaini1047 – 1503457CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • intracellular Source: Ensembl
  • neuronal cell body Source: Ensembl
  • neuron projection Source: Ensembl
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1397 – 13971M → I: Only slight effect on activity. 1 Publication

Organism-specific databases

PharmGKBiPA37012.

Chemistry

ChEMBLiCHEMBL1250402.
GuidetoPHARMACOLOGYi494.

Polymorphism and mutation databases

BioMutaiTRPM2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15031503Transient receptor potential cation channel subfamily M member 2PRO_0000215326Add
BLAST

Proteomic databases

PaxDbiO94759.
PeptideAtlasiO94759.
PRIDEiO94759.

PTM databases

iPTMnetiO94759.
PhosphoSiteiO94759.

Expressioni

Tissue specificityi

Highly expressed in brain and peripheral blood cells, such as neutrophils. Also detected in bone marrow, spleen, heart, liver and lung. Isoform 2 is found in neutrophil granulocytes.2 Publications

Inductioni

NAD+.

Gene expression databases

BgeeiENSG00000142185.
CleanExiHS_TRPC7.
HS_TRPM2.
ExpressionAtlasiO94759. baseline and differential.
GenevisibleiO94759. HS.

Organism-specific databases

HPAiHPA030976.
HPA035260.

Interactioni

Subunit structurei

Isoform 1 can interact with isoform 3. This interaction decreases calcium influx through isoform 1 and suppresses susceptibility to oxidative stress-induced cell death.

Protein-protein interaction databases

STRINGi9606.ENSP00000300482.

Chemistry

BindingDBiO94759.

Structurei

3D structure databases

ProteinModelPortaliO94759.
SMRiO94759. Positions 1236-1503.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1354 – 1498145Nudix hydrolasePROSITE-ProRule annotationAdd
BLAST

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.
InParanoidiO94759.
KOiK04977.
PhylomeDBiO94759.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94759-1) [UniParc]FASTAAdd to basket
Also known as: TRPM2-L

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
MEPSALRKAG SEQEEGFEGL PRRVTDLGMV SNLRRSNSSL FKSWRLQCPF
60 70 80 90 100
GNNDKQESLS SWIPENIKKK ECVYFVESSK LSDAGKVVCQ CGYTHEQHLE
110 120 130 140 150
EATKPHTFQG TQWDPKKHVQ EMPTDAFGDI VFTGLSQKVK KYVRVSQDTP
160 170 180 190 200
SSVIYHLMTQ HWGLDVPNLL ISVTGGAKNF NMKPRLKSIF RRGLVKVAQT
210 220 230 240 250
TGAWIITGGS HTGVMKQVGE AVRDFSLSSS YKEGELITIG VATWGTVHRR
260 270 280 290 300
EGLIHPTGSF PAEYILDEDG QGNLTCLDSN HSHFILVDDG THGQYGVEIP
310 320 330 340 350
LRTRLEKFIS EQTKERGGVA IKIPIVCVVL EGGPGTLHTI DNATTNGTPC
360 370 380 390 400
VVVEGSGRVA DVIAQVANLP VSDITISLIQ QKLSVFFQEM FETFTESRIV
410 420 430 440 450
EWTKKIQDIV RRRQLLTVFR EGKDGQQDVD VAILQALLKA SRSQDHFGHE
460 470 480 490 500
NWDHQLKLAV AWNRVDIARS EIFMDEWQWK PSDLHPTMTA ALISNKPEFV
510 520 530 540 550
KLFLENGVQL KEFVTWDTLL YLYENLDPSC LFHSKLQKVL VEDPERPACA
560 570 580 590 600
PAAPRLQMHH VAQVLRELLG DFTQPLYPRP RHNDRLRLLL PVPHVKLNVQ
610 620 630 640 650
GVSLRSLYKR SSGHVTFTMD PIRDLLIWAI VQNRRELAGI IWAQSQDCIA
660 670 680 690 700
AALACSKILK ELSKEEEDTD SSEEMLALAE EYEHRAIGVF TECYRKDEER
710 720 730 740 750
AQKLLTRVSE AWGKTTCLQL ALEAKDMKFV SHGGIQAFLT KVWWGQLSVD
760 770 780 790 800
NGLWRVTLCM LAFPLLLTGL ISFREKRLQD VGTPAARARA FFTAPVVVFH
810 820 830 840 850
LNILSYFAFL CLFAYVLMVD FQPVPSWCEC AIYLWLFSLV CEEMRQLFYD
860 870 880 890 900
PDECGLMKKA ALYFSDFWNK LDVGAILLFV AGLTCRLIPA TLYPGRVILS
910 920 930 940 950
LDFILFCLRL MHIFTISKTL GPKIIIVKRM MKDVFFFLFL LAVWVVSFGV
960 970 980 990 1000
AKQAILIHNE RRVDWLFRGA VYHSYLTIFG QIPGYIDGVN FNPEHCSPNG
1010 1020 1030 1040 1050
TDPYKPKCPE SDATQQRPAF PEWLTVLLLC LYLLFTNILL LNLLIAMFNY
1060 1070 1080 1090 1100
TFQQVQEHTD QIWKFQRHDL IEEYHGRPAA PPPFILLSHL QLFIKRVVLK
1110 1120 1130 1140 1150
TPAKRHKQLK NKLEKNEEAA LLSWEIYLKE NYLQNRQFQQ KQRPEQKIED
1160 1170 1180 1190 1200
ISNKVDAMVD LLDLDPLKRS GSMEQRLASL EEQVAQTAQA LHWIVRTLRA
1210 1220 1230 1240 1250
SGFSSEADVP TLASQKAAEE PDAEPGGRKK TEEPGDSYHV NARHLLYPNC
1260 1270 1280 1290 1300
PVTRFPVPNE KVPWETEFLI YDPPFYTAER KDAAAMDPMG DTLEPLSTIQ
1310 1320 1330 1340 1350
YNVVDGLRDR RSFHGPYTVQ AGLPLNPMGR TGLRGRGSLS CFGPNHTLYP
1360 1370 1380 1390 1400
MVTRWRRNED GAICRKSIKK MLEVLVVKLP LSEHWALPGG SREPGEMLPR
1410 1420 1430 1440 1450
KLKRILRQEH WPSFENLLKC GMEVYKGYMD DPRNTDNAWI ETVAVSVHFQ
1460 1470 1480 1490 1500
DQNDVELNRL NSNLHACDSG ASIRWQVVDR RIPLYANHKT LLQKAAAEFG

AHY
Length:1,503
Mass (Da):171,198
Last modified:October 23, 2007 - v2
Checksum:i02338437501ABFAB
GO
Isoform 2 (identifier: O94759-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     538-557: Missing.
     1291-1325: DTLEPLSTIQYNVVDGLRDRRSFHGPYTVQAGLPL → E

Show »
Length:1,449
Mass (Da):165,273
Checksum:iCFFA7E256DABB60B
GO
Isoform 3 (identifier: O94759-3) [UniParc]FASTAAdd to basket
Also known as: TRPM2-S

The sequence of this isoform differs from the canonical sequence as follows:
     847-1503: Missing.

Show »
Length:846
Mass (Da):95,699
Checksum:i70B0B29CADE26939
GO

Sequence cautioni

The sequence BAB64300 differs from that shown. Reason: Frameshift at positions 1227 and 1237. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1088 – 10881S → N in CAD01139 (PubMed:11960981).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti52 – 521N → K.1 Publication
Corresponds to variant rs45625933 [ dbSNP | Ensembl ].
VAR_025216
Natural varianti166 – 1661V → I.1 Publication
Corresponds to variant rs45544142 [ dbSNP | Ensembl ].
VAR_025217
Natural varianti385 – 3851V → M.1 Publication
Corresponds to variant rs45485992 [ dbSNP | Ensembl ].
VAR_025218
Natural varianti543 – 5431D → E.1 Publication
Corresponds to variant rs1556314 [ dbSNP | Ensembl ].
VAR_020032
Natural varianti780 – 7801D → E.1 Publication
Corresponds to variant rs9974927 [ dbSNP | Ensembl ].
VAR_025219
Natural varianti1189 – 11891Q → R.5 Publications
Corresponds to variant rs9978351 [ dbSNP | Ensembl ].
VAR_025220
Natural varianti1199 – 11991R → W.1 Publication
Corresponds to variant rs45611537 [ dbSNP | Ensembl ].
VAR_025221
Natural varianti1201 – 12011S → G.1 Publication
Corresponds to variant rs45519835 [ dbSNP | Ensembl ].
VAR_025222
Natural varianti1249 – 12491N → S.1 Publication
Corresponds to variant rs45513700 [ dbSNP | Ensembl ].
VAR_025223
Natural varianti1347 – 13471T → M.1 Publication
Corresponds to variant rs45589233 [ dbSNP | Ensembl ].
VAR_025224
Natural varianti1359 – 13591E → K.1 Publication
Corresponds to variant rs45570639 [ dbSNP | Ensembl ].
VAR_025225
Natural varianti1368 – 13681I → M.1 Publication
Corresponds to variant rs45613636 [ dbSNP | Ensembl ].
VAR_025226
Natural varianti1438 – 14381A → S.1 Publication
Corresponds to variant rs45578242 [ dbSNP | Ensembl ].
VAR_025227

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei538 – 55720Missing in isoform 2. 1 PublicationVSP_006574Add
BLAST
Alternative sequencei847 – 1503657Missing in isoform 3. 1 PublicationVSP_013018Add
BLAST
Alternative sequencei1291 – 132535DTLEP…AGLPL → E in isoform 2. 1 PublicationVSP_006575Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB001535 mRNA. Translation: BAA34700.1.
AJ417076 mRNA. Translation: CAD01139.1.
AY603182 mRNA. Translation: AAT12288.1.
AB166745 mRNA. Translation: BAD83705.1.
AJ878416 mRNA. Translation: CAI47593.1.
DQ012935 Genomic DNA. Translation: AAY22174.1.
AP001754 Genomic DNA. Translation: BAA95563.1.
CH471079 Genomic DNA. Translation: EAX09426.1.
CH471079 Genomic DNA. Translation: EAX09427.1.
AB017549 mRNA. Translation: BAB64300.1. Frameshift.
CCDSiCCDS13710.1. [O94759-1]
RefSeqiNP_001307279.1. NM_001320350.1.
NP_001307280.1. NM_001320351.1.
NP_003298.1. NM_003307.3.
XP_005261228.1. XM_005261171.3. [O94759-1]
UniGeneiHs.369759.

Genome annotation databases

EnsembliENST00000300481; ENSP00000300481; ENSG00000142185. [O94759-2]
ENST00000300482; ENSP00000300482; ENSG00000142185. [O94759-1]
ENST00000397928; ENSP00000381023; ENSG00000142185. [O94759-1]
GeneIDi7226.
KEGGihsa:7226.
UCSCiuc002zet.1. human. [O94759-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB001535 mRNA. Translation: BAA34700.1.
AJ417076 mRNA. Translation: CAD01139.1.
AY603182 mRNA. Translation: AAT12288.1.
AB166745 mRNA. Translation: BAD83705.1.
AJ878416 mRNA. Translation: CAI47593.1.
DQ012935 Genomic DNA. Translation: AAY22174.1.
AP001754 Genomic DNA. Translation: BAA95563.1.
CH471079 Genomic DNA. Translation: EAX09426.1.
CH471079 Genomic DNA. Translation: EAX09427.1.
AB017549 mRNA. Translation: BAB64300.1. Frameshift.
CCDSiCCDS13710.1. [O94759-1]
RefSeqiNP_001307279.1. NM_001320350.1.
NP_001307280.1. NM_001320351.1.
NP_003298.1. NM_003307.3.
XP_005261228.1. XM_005261171.3. [O94759-1]
UniGeneiHs.369759.

3D structure databases

ProteinModelPortaliO94759.
SMRiO94759. Positions 1236-1503.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000300482.

Chemistry

BindingDBiO94759.
ChEMBLiCHEMBL1250402.
GuidetoPHARMACOLOGYi494.

Protein family/group databases

TCDBi1.A.4.5.5. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

iPTMnetiO94759.
PhosphoSiteiO94759.

Polymorphism and mutation databases

BioMutaiTRPM2.

Proteomic databases

PaxDbiO94759.
PeptideAtlasiO94759.
PRIDEiO94759.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300481; ENSP00000300481; ENSG00000142185. [O94759-2]
ENST00000300482; ENSP00000300482; ENSG00000142185. [O94759-1]
ENST00000397928; ENSP00000381023; ENSG00000142185. [O94759-1]
GeneIDi7226.
KEGGihsa:7226.
UCSCiuc002zet.1. human. [O94759-1]

Organism-specific databases

CTDi7226.
GeneCardsiTRPM2.
HGNCiHGNC:12339. TRPM2.
HPAiHPA030976.
HPA035260.
MIMi603749. gene.
neXtProtiNX_O94759.
PharmGKBiPA37012.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3614. Eukaryota.
KOG4195. Eukaryota.
ENOG410XR5B. LUCA.
GeneTreeiENSGT00760000119127.
HOGENOMiHOG000236350.
HOVERGENiHBG055825.
InParanoidiO94759.
KOiK04977.
PhylomeDBiO94759.
TreeFamiTF314204.

Enzyme and pathway databases

ReactomeiR-HSA-3295583. TRP channels.

Miscellaneous databases

GeneWikiiTRPM2.
GenomeRNAii7226.
PROiO94759.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142185.
CleanExiHS_TRPC7.
HS_TRPM2.
ExpressionAtlasiO94759. baseline and differential.
GenevisibleiO94759. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O94759
Secondary accession number(s): D3DSL6
, Q5KTC2, Q6J3P5, Q96KN6, Q96Q93
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 23, 2007
Last modified: September 7, 2016
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.