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O94759 (TRPM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TRPM2
Synonyms:EREG1, KNP3, LTRPC2, TRPC7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1503 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.12

Catalytic activity

ADP-D-ribose + H2O = AMP + D-ribose 5-phosphate. Ref.10

Subunit structure

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

Subcellular location

Membrane; Multi-pass membrane protein Ref.3 Ref.10.

Tissue specificity

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. Ref.10 Ref.11

Induction

NAD+. Ref.2 Ref.10 Ref.11

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM2 sub-subfamily. [View classification]

Contains 1 nudix hydrolase domain.

Biophysicochemical properties

Kinetic parameters:

KM=100 µM for ADP-ribose

Vmax=0.1 µmol/min/mg enzyme

Sequence caution

The sequence BAB64300.1 differs from that shown. Reason: Frameshift at positions 1227 and 1237.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O94759-1)

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.
Isoform 2 (identifier: O94759-2)

The sequence of this isoform differs from the canonical sequence as follows:
     538-557: Missing.
     1291-1325: DTLEPLSTIQYNVVDGLRDRRSFHGPYTVQAGLPL → E
Isoform 3 (identifier: O94759-3)

Also known as: TRPM2-S;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15031503Transient receptor potential cation channel subfamily M member 2
PRO_0000215326

Regions

Topological domain1 – 752752Cytoplasmic Potential
Transmembrane753 – 77321Helical; Potential
Topological domain774 – 79522Extracellular Potential
Transmembrane796 – 81621Helical; Potential
Topological domain817 – 87256Cytoplasmic Potential
Transmembrane873 – 89321Helical; Potential
Topological domain894 – 8963Extracellular Potential
Transmembrane897 – 91721Helical; Potential
Topological domain918 – 93619Cytoplasmic Potential
Transmembrane937 – 95721Helical; Potential
Topological domain958 – 102568Extracellular Potential
Transmembrane1026 – 104621Helical; Potential
Topological domain1047 – 1503457Cytoplasmic Potential
Domain1354 – 1498145Nudix hydrolase
Nucleotide binding1390 – 141223NAD

Natural variations

Alternative sequence538 – 55720Missing in isoform 2.
VSP_006574
Alternative sequence847 – 1503657Missing in isoform 3.
VSP_013018
Alternative sequence1291 – 132535DTLEP…AGLPL → E in isoform 2.
VSP_006575
Natural variant521N → K. Ref.6
Corresponds to variant rs45625933 [ dbSNP | Ensembl ].
VAR_025216
Natural variant1661V → I. Ref.6
Corresponds to variant rs45544142 [ dbSNP | Ensembl ].
VAR_025217
Natural variant3851V → M. Ref.6
Corresponds to variant rs45485992 [ dbSNP | Ensembl ].
VAR_025218
Natural variant5431D → E. Ref.6
Corresponds to variant rs1556314 [ dbSNP | Ensembl ].
VAR_020032
Natural variant7801D → E. Ref.6
Corresponds to variant rs9974927 [ dbSNP | Ensembl ].
VAR_025219
Natural variant11891Q → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
Corresponds to variant rs9978351 [ dbSNP | Ensembl ].
VAR_025220
Natural variant11991R → W. Ref.6
Corresponds to variant rs45611537 [ dbSNP | Ensembl ].
VAR_025221
Natural variant12011S → G. Ref.6
Corresponds to variant rs45519835 [ dbSNP | Ensembl ].
VAR_025222
Natural variant12491N → S. Ref.6
Corresponds to variant rs45513700 [ dbSNP | Ensembl ].
VAR_025223
Natural variant13471T → M. Ref.6
Corresponds to variant rs45589233 [ dbSNP | Ensembl ].
VAR_025224
Natural variant13591E → K. Ref.6
Corresponds to variant rs45570639 [ dbSNP | Ensembl ].
VAR_025225
Natural variant13681I → M. Ref.6
Corresponds to variant rs45613636 [ dbSNP | Ensembl ].
VAR_025226
Natural variant14381A → S. Ref.6
Corresponds to variant rs45578242 [ dbSNP | Ensembl ].
VAR_025227

Experimental info

Mutagenesis13971M → I: Only slight effect on activity. Ref.12
Sequence conflict10881S → N in CAD01139. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TRPM2-L) [UniParc].

Last modified October 23, 2007. Version 2.
Checksum: 02338437501ABFAB

FASTA1,503171,198
        10         20         30         40         50         60 
MEPSALRKAG SEQEEGFEGL PRRVTDLGMV SNLRRSNSSL FKSWRLQCPF GNNDKQESLS 

        70         80         90        100        110        120 
SWIPENIKKK ECVYFVESSK LSDAGKVVCQ CGYTHEQHLE EATKPHTFQG TQWDPKKHVQ 

       130        140        150        160        170        180 
EMPTDAFGDI VFTGLSQKVK KYVRVSQDTP SSVIYHLMTQ HWGLDVPNLL ISVTGGAKNF 

       190        200        210        220        230        240 
NMKPRLKSIF RRGLVKVAQT TGAWIITGGS HTGVMKQVGE AVRDFSLSSS YKEGELITIG 

       250        260        270        280        290        300 
VATWGTVHRR EGLIHPTGSF PAEYILDEDG QGNLTCLDSN HSHFILVDDG THGQYGVEIP 

       310        320        330        340        350        360 
LRTRLEKFIS EQTKERGGVA IKIPIVCVVL EGGPGTLHTI DNATTNGTPC VVVEGSGRVA 

       370        380        390        400        410        420 
DVIAQVANLP VSDITISLIQ QKLSVFFQEM FETFTESRIV EWTKKIQDIV RRRQLLTVFR 

       430        440        450        460        470        480 
EGKDGQQDVD VAILQALLKA SRSQDHFGHE NWDHQLKLAV AWNRVDIARS EIFMDEWQWK 

       490        500        510        520        530        540 
PSDLHPTMTA ALISNKPEFV KLFLENGVQL KEFVTWDTLL YLYENLDPSC LFHSKLQKVL 

       550        560        570        580        590        600 
VEDPERPACA PAAPRLQMHH VAQVLRELLG DFTQPLYPRP RHNDRLRLLL PVPHVKLNVQ 

       610        620        630        640        650        660 
GVSLRSLYKR SSGHVTFTMD PIRDLLIWAI VQNRRELAGI IWAQSQDCIA AALACSKILK 

       670        680        690        700        710        720 
ELSKEEEDTD SSEEMLALAE EYEHRAIGVF TECYRKDEER AQKLLTRVSE AWGKTTCLQL 

       730        740        750        760        770        780 
ALEAKDMKFV SHGGIQAFLT KVWWGQLSVD NGLWRVTLCM LAFPLLLTGL ISFREKRLQD 

       790        800        810        820        830        840 
VGTPAARARA FFTAPVVVFH LNILSYFAFL CLFAYVLMVD FQPVPSWCEC AIYLWLFSLV 

       850        860        870        880        890        900 
CEEMRQLFYD PDECGLMKKA ALYFSDFWNK LDVGAILLFV AGLTCRLIPA TLYPGRVILS 

       910        920        930        940        950        960 
LDFILFCLRL MHIFTISKTL GPKIIIVKRM MKDVFFFLFL LAVWVVSFGV AKQAILIHNE 

       970        980        990       1000       1010       1020 
RRVDWLFRGA VYHSYLTIFG QIPGYIDGVN FNPEHCSPNG TDPYKPKCPE SDATQQRPAF 

      1030       1040       1050       1060       1070       1080 
PEWLTVLLLC LYLLFTNILL LNLLIAMFNY TFQQVQEHTD QIWKFQRHDL IEEYHGRPAA 

      1090       1100       1110       1120       1130       1140 
PPPFILLSHL QLFIKRVVLK TPAKRHKQLK NKLEKNEEAA LLSWEIYLKE NYLQNRQFQQ 

      1150       1160       1170       1180       1190       1200 
KQRPEQKIED ISNKVDAMVD LLDLDPLKRS GSMEQRLASL EEQVAQTAQA LHWIVRTLRA 

      1210       1220       1230       1240       1250       1260 
SGFSSEADVP TLASQKAAEE PDAEPGGRKK TEEPGDSYHV NARHLLYPNC PVTRFPVPNE 

      1270       1280       1290       1300       1310       1320 
KVPWETEFLI YDPPFYTAER KDAAAMDPMG DTLEPLSTIQ YNVVDGLRDR RSFHGPYTVQ 

      1330       1340       1350       1360       1370       1380 
AGLPLNPMGR TGLRGRGSLS CFGPNHTLYP MVTRWRRNED GAICRKSIKK MLEVLVVKLP 

      1390       1400       1410       1420       1430       1440 
LSEHWALPGG SREPGEMLPR KLKRILRQEH WPSFENLLKC GMEVYKGYMD DPRNTDNAWI 

      1450       1460       1470       1480       1490       1500 
ETVAVSVHFQ DQNDVELNRL NSNLHACDSG ASIRWQVVDR RIPLYANHKT LLQKAAAEFG 


AHY 

« Hide

Isoform 2 [UniParc].

Checksum: CFFA7E256DABB60B
Show »

FASTA1,449165,273
Isoform 3 (TRPM2-S) [UniParc].

Checksum: 70B0B29CADE26939
Show »

FASTA84695,699

References

« Hide 'large scale' references
[1]"Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain."
Nagamine K., Kudoh J., Minoshima S., Kawasaki K., Asakawa S., Ito F., Shimizu N.
Genomics 54:124-131(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-1189.
Tissue: Brain.
[2]"Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose."
Wehage E., Eisfeld J., Heiner I., Juengling E., Zitt C., Lueckhoff A.
J. Biol. Chem. 277:23150-23156(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-1189, REGULATION BY OXIDATIVE STRESS.
Tissue: Promyelocytic leukemia.
[3]"A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death."
Zhang W., Chu X., Tong Q., Cheung J.Y., Conrad K., Masker K., Miller B.A.
J. Biol. Chem. 278:16222-16229(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT ARG-1189, INTERACTION BETWEEN ISOFORMS 1 AND 3, SUBCELLULAR LOCATION.
Tissue: Bone marrow.
[4]"Characterization of human and mouse TRPM2 genes: identification of a novel N-terminal truncated protein specifically expressed in human striatum."
Uemura T., Kudoh J., Noda S., Kanba S., Shimizu N.
Biochem. Biophys. Res. Commun. 328:1232-1243(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-1189.
Tissue: Brain.
[5]"Cloning of the human TRPM2."
Hayes P.D.
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-1189.
[6]NIEHS SNPs program
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-52; ILE-166; MET-385; GLU-543; GLU-780; TRP-1199; GLY-1201; SER-1249; MET-1347; LYS-1359; MET-1368 AND SER-1438.
[7]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"Molecular cloning of a novel estrogen responsive gene, estrogen responsive element associated gene 1 (EREG1), which contains MutT like domain."
Hiroi H., Muramatsu M., Inoue S.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1190-1503.
[10]"ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology."
Perraud A.-L., Fleig A., Dunn C.A., Bagley L.A., Launay P., Schmitz C., Stokes A.J., Zhu Q., Bessman M.J., Penner R., Kinet J.-P., Scharenberg A.M.
Nature 411:595-599(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, REGULATION BY ADP-RIBOSE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]"Immunocyte Ca2+ influx system mediated by LTRPC2."
Sano Y., Inamura K., Miyake A., Mochizuki S., Yokoi H., Matsushime H., Furuichi K.
Science 293:1327-1330(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY PYRIMIDINE NUCLEOTIDES, TISSUE SPECIFICITY.
[12]"LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death."
Hara Y., Wakamori M., Ishii M., Maeno E., Nishida M., Yoshida T., Yamada H., Shimizu S., Mori E., Kudoh J., Shimizu N., Kurose H., Okada Y., Imoto K., Mori Y.
Mol. Cell 9:163-173(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF MET-1397.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS13710.1. [O94759-1]
RefSeqNP_003298.1. NM_003307.3.
XP_005261228.1. XM_005261171.1. [O94759-1]
UniGeneHs.369759.

3D structure databases

ProteinModelPortalO94759.
SMRO94759. Positions 1236-1503.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113077. 1 interaction.
STRING9606.ENSP00000300482.

Chemistry

ChEMBLCHEMBL1250402.
GuidetoPHARMACOLOGY494.

Protein family/group databases

TCDB1.A.4.5.5. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

PhosphoSiteO94759.

Proteomic databases

PaxDbO94759.
PRIDEO94759.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300481; ENSP00000300481; ENSG00000142185. [O94759-2]
ENST00000300482; ENSP00000300482; ENSG00000142185. [O94759-1]
ENST00000397928; ENSP00000381023; ENSG00000142185. [O94759-1]
GeneID7226.
KEGGhsa:7226.
UCSCuc002zet.1. human. [O94759-1]
uc002zey.1. human. [O94759-2]

Organism-specific databases

CTD7226.
GeneCardsGC21P045770.
HGNCHGNC:12339. TRPM2.
HPAHPA030974.
MIM603749. gene.
neXtProtNX_O94759.
PharmGKBPA37012.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG253824.
HOGENOMHOG000236350.
HOVERGENHBG055825.
KOK04977.
OrthoDBEOG725DH1.
PhylomeDBO94759.
TreeFamTF314204.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO94759.
BgeeO94759.
CleanExHS_TRPC7.
HS_TRPM2.
GenevestigatorO94759.

Family and domain databases

Gene3D3.90.79.10. 1 hit.
InterProIPR005821. Ion_trans_dom.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]
PfamPF00520. Ion_trans. 1 hit.
[Graphical view]
SUPFAMSSF55811. SSF55811. 1 hit.
PROSITEPS51462. NUDIX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTRPM2.
GenomeRNAi7226.
NextBio28299.
PROO94759.
SOURCESearch...

Entry information

Entry nameTRPM2_HUMAN
AccessionPrimary (citable) accession number: O94759
Secondary accession number(s): D3DSL6 expand/collapse secondary AC list , Q5KTC2, Q6J3P5, Q96KN6, Q96Q93
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 23, 2007
Last modified: July 9, 2014
This is version 139 of the entry and version 2 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 21

Human chromosome 21: entries, gene names and cross-references to MIM