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1.A.1.11.19
The phosphoinositide (PI(3,5)P2)-activated Na+ two pore channel-2, TPC2, in endosomes and lysosomes (Wang et al. 2012). Previously thought, incorectly, according to Wang et al. 2012, to be a nicotinic acid adenine dinucleotide phosphate (NAADP)-dependent two pore Ca2+ channel.  TPC2, like TPC1, has a 12 TMS topology (two channel units) (Hooper et al., 2011). The two domains of human TPCs can insert into the membrane independently (Churamani et al., 2012).  Cang et al. (2013), showed that TPC1 and TPC2 together form an ATP-sensitive two-pore Na+ channel that senses the metabolic state of the cell.  The channel complex detects nutrient status, becomes constitutively open upon nutrient removal, and controls the lysosome's membrane potential, pH stability, and amino acid homeostasis.  Essential for Ebola virus (EBOV) host entry. Several inhibitors of TPC2 that act in the nM (tetrandrine) or μM (verapamil; Ned19) range block channel activity, prevent Ebola Virus from escaping cell vesicles and may be used to treat the disease (Sakurai et al. 2015).  TPC2 may transport both Na+ and Ca2+ (Sakurai et al. 2015).

Accession Number:Q8NHX9
Protein Name:Two pore calcium channel protein 2
Length:752
Molecular Weight:85243.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Lysosome membrane1 / Multi-pass membrane protein2
Substrate Na+

Cross database links:

Genevestigator: Q8NHX9
HEGENOM: HBG358288
Entrez Gene ID: 219931   
Pfam: PF00520   
KEGG: hsa:219931   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005765 C:lysosomal membrane
GO:0005262 F:calcium channel activity
GO:0005244 F:voltage-gated ion channel activity

References (6)

[1] “NAADP mobilizes calcium from acidic organelles through two-pore channels.”  Calcraft P.J.et.al.   19387438
[2] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[5] “Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling.”  Brailoiu E.et.al.   19620632
[6] “Two newly identified genetic determinants of pigmentation in Europeans.”  Sulem P.et.al.   18488028

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAEPQAESEP LLGGARGGGG DWPAGLTTYR SIQVGPGAAA RWDLCIDQAV VFIEDAIQYR 
61:	SINHRVDASS MWLYRRYYSN VCQRTLSFTI FLILFLAFIE TPSSLTSTAD VRYRAAPWEP 
121:	PCGLTESVEV LCLLVFAADL SVKGYLFGWA HFQKNLWLLG YLVVLVVSLV DWTVSLSLVC 
181:	HEPLRIRRLL RPFFLLQNSS MMKKTLKCIR WSLPEMASVG LLLAIHLCLF TMFGMLLFAG 
241:	GKQDDGQDRE RLTYFQNLPE SLTSLLVLLT TANNPDVMIP AYSKNRAYAI FFIVFTVIGS 
301:	LFLMNLLTAI IYSQFRGYLM KSLQTSLFRR RLGTRAAFEV LSSMVGEGGA FPQAVGVKPQ 
361:	NLLQVLQKVQ LDSSHKQAMM EKVRSYGSVL LSAEEFQKLF NELDRSVVKE HPPRPEYQSP 
421:	FLQSAQFLFG HYYFDYLGNL IALANLVSIC VFLVLDADVL PAERDDFILG ILNCVFIVYY 
481:	LLEMLLKVFA LGLRGYLSYP SNVFDGLLTV VLLVLEISTL AVYRLPHPGW RPEMVGLLSL 
541:	WDMTRMLNML IVFRFLRIIP SMKLMAVVAS TVLGLVQNMR AFGGILVVVY YVFAIIGINL 
601:	FRGVIVALPG NSSLAPANGS APCGSFEQLE YWANNFDDFA AALVTLWNLM VVNNWQVFLD 
661:	AYRRYSGPWS KIYFVLWWLV SSVIWVNLFL ALILENFLHK WDPRSHLQPL AGTPEATYQM 
721:	TVELLFRDIL EEPGEDELTE RLSQHPHLWL CR