Reviewed,
UniProtKB/Swiss-Prot O94759 (TRPM2_HUMAN)
Last modified
July 7, 2009.
Version 91.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Transient receptor potential cation channel subfamily M member 2 EC=3.6.1.13 Alternative name(s): Long transient receptor potential channel 2 Short name=LTrpC-2 Short name=LTrpC2 Transient receptor potential channel 7 Short name=TrpC7 Estrogen-responsive element-associated gene 1 protein | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1503 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence 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.11 |
| Catalytic activity | ADP-ribose + H2O = AMP + D-ribose 5-phosphate. Ref.9 |
| 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 | |
| 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.9 Ref.10 |
| Induction | NAD+. |
| Sequence similarities | Belongs to the transient receptor family. LTrpC subfamily. 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. |
Ontologies
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1503 | 1503 | Transient receptor potential cation channel subfamily M member 2 | PRO_0000215326 | |||||
Regions | |||||||||
| Topological domain | 1 – 752 | 752 | Cytoplasmic Potential | ||||||
| Transmembrane | 753 – 773 | 21 | Potential | ||||||
| Topological domain | 774 – 795 | 22 | Extracellular Potential | ||||||
| Transmembrane | 796 – 816 | 21 | Potential | ||||||
| Topological domain | 817 – 872 | 56 | Cytoplasmic Potential | ||||||
| Transmembrane | 873 – 893 | 21 | Potential | ||||||
| Topological domain | 894 – 896 | 3 | Extracellular Potential | ||||||
| Transmembrane | 897 – 917 | 21 | Potential | ||||||
| Topological domain | 918 – 936 | 19 | Cytoplasmic Potential | ||||||
| Transmembrane | 937 – 957 | 21 | Potential | ||||||
| Topological domain | 958 – 1025 | 68 | Extracellular Potential | ||||||
| Transmembrane | 1026 – 1046 | 21 | Potential | ||||||
| Topological domain | 1047 – 1503 | 457 | Cytoplasmic Potential | ||||||
| Domain | 1197 – 1503 | 307 | Nudix hydrolase | ||||||
| Nucleotide binding | 1390 – 1412 | 23 | NAD | ||||||
Natural variations | |||||||||
| Alternative sequence | 538 – 557 | 20 | Missing in isoform 2. | VSP_006574 | |||||
| Alternative sequence | 847 – 1503 | 657 | Missing in isoform 3. | VSP_013018 | |||||
| Alternative sequence | 1291 – 1325 | 35 | DTLEP…AGLPL → E in isoform 2. | VSP_006575 | |||||
| Natural variant | 52 | 1 | N → K Ref.6 | VAR_025216 | |||||
| Natural variant | 166 | 1 | V → I: dbSNP rs45544142. | VAR_025217 | |||||
| Natural variant | 385 | 1 | V → M: dbSNP rs45485992. | VAR_025218 | |||||
| Natural variant | 543 | 1 | D → E: dbSNP rs1556314. Ref.6 | VAR_020032 | |||||
| Natural variant | 780 | 1 | D → E: dbSNP rs9974927. | VAR_025219 | |||||
| Natural variant | 1189 | 1 | Q → R: dbSNP rs9978351. | VAR_025220 | |||||
| Natural variant | 1199 | 1 | R → W: dbSNP rs45611537. | VAR_025221 | |||||
| Natural variant | 1201 | 1 | S → G Ref.6 | VAR_025222 | |||||
| Natural variant | 1249 | 1 | N → S Ref.6 | VAR_025223 | |||||
| Natural variant | 1347 | 1 | T → M Ref.6 | VAR_025224 | |||||
| Natural variant | 1359 | 1 | E → K: dbSNP rs45570639. | VAR_025225 | |||||
| Natural variant | 1368 | 1 | I → M: dbSNP rs45613636. | VAR_025226 | |||||
| Natural variant | 1438 | 1 | A → S Ref.6 | VAR_025227 | |||||
Experimental info | |||||||||
| Mutagenesis | 1397 | 1 | M → I: Only slight effect on activity. Ref.11 | ||||||
| Sequence conflict | 1088 | 1 | S → N in CAD01139. Ref.2 | ||||||
Sequences
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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: 9806837] [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: 11960981] [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: 12594222] [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: 15708008] [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. Yaspo M.-L.Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | "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. |
| [9] | "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: 11385575] [Abstract] Cited for: CATALYTIC ACTIVITY, REGULATION BY ADP-RIBOSE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. |
| [10] | "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: 11509734] [Abstract] Cited for: REGULATION BY PYRIMIDINE NUCLEOTIDES, TISSUE SPECIFICITY. |
| [11] | "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: 11804595] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF MET-1397. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| 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. AB017549 mRNA. Translation: BAB64300.1. Frameshift. | |
| IPI | IPI00014911. IPI00412399. IPI00480087. |
| RefSeq | NP_003298.1. |
| UniGene | Hs.369759 |
3D structure databases | |
| ModBase | Search... |
Protein family/group databases | |
| TCDB | 1.A.4.5.5. transient receptor potential Ca2+ channel (TRP-CC) family. |
PTM databases | |
| PhosphoSite | O94759. |
Proteomic databases | |
| PRIDE | O94759. |
Genome annotation databases | |
| Ensembl | ENSG00000142185. Homo sapiens. [Contig view] |
| GeneID | 7226. |
| KEGG | hsa:7226. |
| NMPDR | fig|9606.3.peg.21072. |
| UCSC | uc002zet.1. human. |
Organism-specific databases | |
| GeneCards | GC21P044597. |
| H-InvDB | HIX0040835. |
| HGNC | HGNC:12339. TRPM2. |
| MIM | 603749. gene. |
| PharmGKB | PA37012. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | O94759. |
| HOVERGEN | O94759. |
Enzyme and pathway databases | |
| BRENDA | 3.6.1.13. 247. |
Gene expression databases | |
| ArrayExpress | O94759. |
| Bgee | O94759. |
| CleanEx | HS_TRPC7. HS_TRPM2. |
| GermOnline | ENSG00000142185. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR005821. Ion_trans. IPR000086. NUDIX_hydrolase_core. [Graphical view] |
| Pfam | PF00520. Ion_trans. 1 hit. [Graphical view] |
| PROSITE | PS00893. NUDIX. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 28299. |
| SOURCE | Search... |
Entry information
| Entry name | TRPM2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O94759 Secondary accession number(s): Q5KTC2 Q96Q93 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 21 Human chromosome 21: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


