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1.A.4.5.5
ADP-ribose/NAD/pyrimidine nucleotide-gated Ca2+ permeable, cation nonselective, long transient receptor potential channel-2, LTRPC2; Melastatin 2; TRPM2 (ATP inhibitable). The 3-D structure resembles a swollen bell shaped structure (Maruyama et al., 2007). Can be converted to an anion selective channel by introducing a lysyl residue in TMS 6 (Kuhn et al., 2007). Transports Ca2+ and Mg2+ with equal facility (Xia et al., 2008).  Four Ca2+ ions activate TRPM2 channels by binding in deep crevices near the pore but intracellularly of the gate (Csanády and Törocsik, 2009). Protons also regulate activity (Starkus et al., 2010). Present in the plasma membrane and lysosomes; plays a role in ROS-induced inflammatory processes and cell death. Melastatin is required for innate immunity against Listeria monocytogenes (Knowles et al., 2011). Functions in pathogen-evoked phagocyte activation, postischemic neuronal apoptosis, and glucose-evoked insulin secretion, by linking these cellular responses to oxidative stress (Tóth and Csanády, 2012).  Pore collapse upon prolonged stimulation underlies irreversible inactivation (Tóth and Csanády 2012).  TRPM2 is preferentially expressed in cells of the myeloid lineage and modulates signaling pathways converging into NF-kB but does not seem to play a major role in myeloid leukemogenesis. Its loss does not augment the cytotoxicity of standard AML chemotherapeutic agents (Haladyna et al. 2016).  TrpM2, expressed in hypothalamic neurons in the brain is a thermosensitive, redox-sensitive channel, required for thermoregulation.  It regulates body temperature, limiting fever and driving hypothermia (Song et al. 2016). 

Accession Number:O94759
Protein Name:LTRPC2 aka TRPM2 aka TRPC7 aka KNP3
Length:1503
Molecular Weight:171198.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:8
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Ca2+

Cross database links:

Genevestigator: O94759
eggNOG: prNOG13332
RefSeq: NP_003298.1   
Entrez Gene ID: 7226   
Pfam: PF00520   
OMIM: 603749  gene
KEGG: hsa:7226   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0047631 F:ADP-ribose diphosphatase activity
GO:0005262 F:calcium channel activity
GO:0005272 F:sodium channel activity
GO:0006816 P:calcium ion transport
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport

References (9)

[1] “Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain.”  Nagamine K.et.al.   9806837
[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.et.al.   11960981
[3] “A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death.”  Zhang W.et.al.   12594222
[4] “Characterization of human and mouse TRPM2 genes: identification of a novel N-terminal truncated protein specifically expressed in human striatum.”  Uemura T.et.al.   15708008
[5] “The DNA sequence of human chromosome 21.”  Hattori M.et.al.   10830953
[6] “ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology.”  Perraud A.-L.et.al.   11385575
[7] “Immunocyte Ca2+ influx system mediated by LTRPC2.”  Sano Y.et.al.   11509734
[8] “LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death.”  Hara Y.et.al.   11804595
[9] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MEPSALRKAG SEQEEGFEGL PRRVTDLGMV SNLRRSNSSL FKSWRLQCPF GNNDKQESLS 
61:	SWIPENIKKK ECVYFVESSK LSDAGKVVCQ CGYTHEQHLE EATKPHTFQG TQWDPKKHVQ 
121:	EMPTDAFGDI VFTGLSQKVK KYVRVSQDTP SSVIYHLMTQ HWGLDVPNLL ISVTGGAKNF 
181:	NMKPRLKSIF RRGLVKVAQT TGAWIITGGS HTGVMKQVGE AVRDFSLSSS YKEGELITIG 
241:	VATWGTVHRR EGLIHPTGSF PAEYILDEDG QGNLTCLDSN HSHFILVDDG THGQYGVEIP 
301:	LRTRLEKFIS EQTKERGGVA IKIPIVCVVL EGGPGTLHTI DNATTNGTPC VVVEGSGRVA 
361:	DVIAQVANLP VSDITISLIQ QKLSVFFQEM FETFTESRIV EWTKKIQDIV RRRQLLTVFR 
421:	EGKDGQQDVD VAILQALLKA SRSQDHFGHE NWDHQLKLAV AWNRVDIARS EIFMDEWQWK 
481:	PSDLHPTMTA ALISNKPEFV KLFLENGVQL KEFVTWDTLL YLYENLDPSC LFHSKLQKVL 
541:	VEDPERPACA PAAPRLQMHH VAQVLRELLG DFTQPLYPRP RHNDRLRLLL PVPHVKLNVQ 
601:	GVSLRSLYKR SSGHVTFTMD PIRDLLIWAI VQNRRELAGI IWAQSQDCIA AALACSKILK 
661:	ELSKEEEDTD SSEEMLALAE EYEHRAIGVF TECYRKDEER AQKLLTRVSE AWGKTTCLQL 
721:	ALEAKDMKFV SHGGIQAFLT KVWWGQLSVD NGLWRVTLCM LAFPLLLTGL ISFREKRLQD 
781:	VGTPAARARA FFTAPVVVFH LNILSYFAFL CLFAYVLMVD FQPVPSWCEC AIYLWLFSLV 
841:	CEEMRQLFYD PDECGLMKKA ALYFSDFWNK LDVGAILLFV AGLTCRLIPA TLYPGRVILS 
901:	LDFILFCLRL MHIFTISKTL GPKIIIVKRM MKDVFFFLFL LAVWVVSFGV AKQAILIHNE 
961:	RRVDWLFRGA VYHSYLTIFG QIPGYIDGVN FNPEHCSPNG TDPYKPKCPE SDATQQRPAF 
1021:	PEWLTVLLLC LYLLFTNILL LNLLIAMFNY TFQQVQEHTD QIWKFQRHDL IEEYHGRPAA 
1081:	PPPFILLSHL QLFIKRVVLK TPAKRHKQLK NKLEKNEEAA LLSWEIYLKE NYLQNRQFQQ 
1141:	KQRPEQKIED ISNKVDAMVD LLDLDPLKRS GSMEQRLASL EEQVAQTAQA LHWIVRTLRA 
1201:	SGFSSEADVP TLASQKAAEE PDAEPGGRKK TEEPGDSYHV NARHLLYPNC PVTRFPVPNE 
1261:	KVPWETEFLI YDPPFYTAER KDAAAMDPMG DTLEPLSTIQ YNVVDGLRDR RSFHGPYTVQ 
1321:	AGLPLNPMGR TGLRGRGSLS CFGPNHTLYP MVTRWRRNED GAICRKSIKK MLEVLVVKLP 
1381:	LSEHWALPGG SREPGEMLPR KLKRILRQEH WPSFENLLKC GMEVYKGYMD DPRNTDNAWI 
1441:	ETVAVSVHFQ DQNDVELNRL NSNLHACDSG ASIRWQVVDR RIPLYANHKT LLQKAAAEFG 
1501:	AHY