TPCN1 Membrane Protein Introduction

Introduction of TPCN1

TPCN1 (two-pore calcium channel protein 1) is a human protein encoded by the TPCN1 gene. TPCN1 only has two domains, each containing 6 transmembrane segments compared with other calcium and sodium channels. Belonging to ancient members of the voltage-gated ion channel superfamily, TPCN1 is calcium-permeable ion channel localized in the membranes of endolysosomal calcium stores. It might be a predecessor of the conventional four repeat voltage-gated Ca²⁺ and Na⁺ channels. TPCN1 has been found to be permeable to both Ca²⁺ and monovalent cations and its permeability to protons is the highest.

Basic Information of SV2C
Protein Name	Two pore calcium channel protein 1
Gene Name	TPCN1
Aliases	Two Pore Segment Channel 1, Voltage-Dependent Calcium Channel Protein TPC1
Organism	Homo sapiens (Human)
UniProt ID	Q9ULQ1
Transmembrane Times	14
Length (aa)	816
Sequence	MAVSLDDDVPLILTLDEGGSAPLAPSNGLGQEELPSKNGGSYAIHDSQAPSLSSGGESSPSSPAHNWEMNYQEAAIYLQEGENNDKFFTHPKDAKALAAYLFAHNHLFYLMELATALLLLLLSLCEAPAVPALRLGIYVHATLELFALMVVVFELCMKLRWLGLHTFIRHKRTMVKTSVLVVQFVEAIVVLVRQMSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLLLFFMIIFAILGFYLFSPNPSDPYFSTLENSIVSLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVVFDTFNDIEKRKFKSLLLHKRTAIQHAYRLLISQRRPAGISYRQFEGLMRFYKPRMSARERYLTFKALNQNNTPLLSLKDFYDIYEVAALKWKAKKNREHWFDELPRTALLIFKGINILVKSKAFQYFMYLVVAVNGVWILVETFMLKGGNFFSKHVPWSYLVFLTIYGVELFLKVAGLGPVEYLSSGWNLFDFSVTVFAFLGLLALALNMEPFYFIVVLRPLQLLRLFKLKERYRNVLDTMFELLPRMASLGLTLLIFYYSFAIVGMEFFCGIVFPNCCNTSTVADAYRWRNHTVGNRTVVEEGYYYLNNFDNILNSFVTLFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKNQDSEVDGGITLEKEISKEELVAVLELYREARGASSDVTRLLETLSQMERYQQHSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQRQLSSSAAPAAQQPPGSRQRSQTVT

Function of TPCN1 Membrane Protein

Both TPCN1 and TPCN2 are ion channels that contribute to nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca²⁺ release from acidic intracellular endolysosomal stores. Increasing researches reported TPC-mediated intracellular signaling in various pathologies, such as Ebola infection, cancer, Parkinson's disease and so on. TPCs exerted their physiological effects via releasing Ca²⁺ from acidic organelles in response to cues such as the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). The Ca²⁺-releasing ability of TPC1 depended on the ionic composition of the acidic stores and could be influenced by other regulators affecting TPC1 ion permeation.

Fig.1 Secondary structure of TPCN1.

Application of TPCN1 Membrane Protein in Literature

Dardou D., et al. A role for Sv2c in basal ganglia functions. Brain Research. 2013, 1507(17): 61-73. PubMed ID: 23458503

This article revealed different mechanisms of TPC1 and TPC2 in gating regulation and ion conducting properties. And different properties suggested that TPC1 and TPC2 might play complementary physiological roles as Ca²⁺-release channels of the endolysosomal system.
Patel S. and Kilpatrick B.S. Two-pore channels and disease. Biochimica et Biophysica Acta. 2018, 1865(11 Pt B): 1678-1686. PubMed ID: 29746898

This article mainly reviewed TPC1 and TPC2 played a role via mediating Ca²⁺ changes in the pathological process of some diseases such as Parkinson's disease, non-alcoholic fatty liver disease, Ebola infection, cancer, cardiac dysfunction, and diabetes.
Jahidin A.H., et al. Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells. Biochemical & Biophysical Research Communications. 2016, 477(4): 731-736. PubMed ID: 27353380

This article assessed the relationship between TCPs and non-tumorigenic and tumorigenic breast cell lines, and the results showed that TPC1 and TPC2 might have regulation of signaling processes in breast cancer cells.
Brailoiu E., et al. Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. The Journal of Cell Biology. 2017, 186(2): 201-209. PubMed ID: 19620632.

This article reported that overexpression of TPC1 enhanced NAADP-mediated calcium signals, while TPC1-knockdown attenuated the signals. It was indicated that TPC1 was important to NAADP action.
Pitt S.J., et al. Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca²⁺. Science Signaling. 2014, 7(326): ra46. PubMed ID: 24847115

This article discovered that TPC1 was permeable to both Ca²⁺ and monovalent cations, and its permeability to protons was the highest. Both TPC1 and TPC2 could be stimulated by NAADP, but they differed in ion selectivity and modulation by Ca²⁺ and pH.

TPCN1 Preparation Options

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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