Tpcn1 two pore channel 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tpcn1provided by MGI
Official Full Name: two pore channel 1provided by MGI
Primary source: MGI:MGI:2182472
See related: Ensembl:ENSMUSG00000032741 AllianceGenome:MGI:2182472
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Tpc1; mKIAA1169; 5730403B01Rik
Summary: Enables several functions, including cation channel activity; phosphatidylinositol-3,5-bisphosphate binding activity; and protein homodimerization activity. Involved in endocytosis involved in viral entry into host cell and sodium ion transmembrane transport. Located in early endosome membrane; endolysosome; and recycling endosome membrane. Is integral component of membrane. Is expressed in several structures, including alimentary system; brain; cardiovascular system; genitourinary system; and immune system. Orthologous to human TPCN1 (two pore segment channel 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in kidney adult (RPKM 55.6), colon adult (RPKM 48.2) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 F; 5 60.63 cM

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (120672222..120726731, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (120534157..120588678, complement)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Two-pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling.
Title: Two-pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling.
Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory.
Title: Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory.
TPC1 directly interacts with syntaxins and regulates protein processing through early and recycling endosomes.
Title: The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes.
electron cryo-microscopy structures of mouse TPC1 (MmTPC1)-a voltage-dependent, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)-activated Na(+)-selective channel-in both the apo closed state and ligand-bound open state
Title: Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.
TPC1 and TPC2 were found to be essential for appropriate basal and induced autophagic flux in cardiomyocytes.
Title: Endolysosomal two-pore channels regulate autophagy in cardiomyocytes.
The results confirmed the altered expression of HFABP, a key fatty acid transport protein, and of enolase and PGK1, the key enzymes in the glycolytic process
Title: Metabolic alterations derived from absence of Two-Pore Channel 1 at cardiac level.
Mice lacking the endo-lysosomal TPC1 were protected from myocardial ischemia reperfusion injury.
Title: Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore.
Genetic ablation of endolysosomal TPC1 or TPC2 channels attenuates glucose- and sulfonylurea-induced membrane currents, depolarization, cytoplasmic Ca2+ signals, and insulin secretion in pancreatic beta cells.
Title: Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Endolysosomal Two-pore Channels Modulate Membrane Excitability and Stimulus-Secretion Coupling in Mouse Pancreatic β Cells.
It was concluded that Tpcn1/2(-/-) mice show mature-onset obesity due to reduced lipid availability and use, and a defect in beta-adrenergic receptor signaling, leading to impaired thermogenic activity, in brown adipose tissue.
Title: Absence of intracellular ion channels TPC1 and TPC2 leads to mature-onset obesity in male mice, due to impaired lipid availability for thermogenesis in brown adipose tissue.
Results report the existence of a novel, alternative variant isoform of Tpcn1, termed Tpcn1B, resulting from an alternative promoter and giving rise to a TPC1B protein with an N-terminal truncation relative to the sequence of the TPC1A.
Title: TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (2)
Targeted (5) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Tpcn1 (e-PCR), detects polymorphism
- UniSTS:536691

Tpcn1 (e-PCR), detects polymorphism
- UniSTS:536692

Tpcn1 (e-PCR), detects polymorphism
- UniSTS:536693

TPCN1 (e-PCR)
- UniSTS:504205

D5Mit159 (e-PCR), detects polymorphism
- UniSTS:130285

D5Mit159.1 (e-PCR), detects polymorphism
- UniSTS:130286

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
NOT enables NAADP-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium channel activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity	IDA Inferred from Direct Assay more info	PubMed
enables intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity	ISO Inferred from Sequence Orthology more info
enables ligand-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables ligand-gated sodium channel activity	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3,5-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables syntaxin binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated sodium channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in endocytosis involved in viral entry into host cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endocytosis involved in viral entry into host cell	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endolysosome	IDA Inferred from Direct Assay more info	PubMed
located_in endolysosome	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation more info
is_active_in endosome membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome membrane	ISO Inferred from Sequence Orthology more info
is_active_in lysosomal membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	ISO Inferred from Sequence Orthology more info
located_in lysosome	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in recycling endosome membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: two pore calcium channel protein 1

Names: voltage-dependent calcium channel protein TPC1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001418256.1 → NP_001405185.1 two pore calcium channel protein 1 isoform a

Status: VALIDATED

Source sequence(s)

AC125183

UniProtKB/Swiss-Prot

Q3V2Z6, Q6ZPW5, Q9EQJ0
NM_001418258.1 → NP_001405187.1 two pore calcium channel protein 1 isoform b

Status: VALIDATED

Source sequence(s)

AC125183
NM_001418259.1 → NP_001405188.1 two pore calcium channel protein 1 isoform c

Status: VALIDATED

Source sequence(s)

AC125183
NM_001418260.1 → NP_001405189.1 two pore calcium channel protein 1 isoform d

Status: VALIDATED

Source sequence(s)

AC125183
NM_001418261.1 → NP_001405190.1 two pore calcium channel protein 1 isoform e

Status: VALIDATED

Source sequence(s)

AC125183
NM_001418262.1 → NP_001405191.1 two pore calcium channel protein 1 isoform f

Status: VALIDATED

Source sequence(s)

AC125183
NM_145853.3 → NP_665852.1 two pore calcium channel protein 1 isoform a

See identical proteins and their annotated locations for NP_665852.1

Status: VALIDATED

Source sequence(s)

AC125183

Consensus CDS

CCDS39239.1

UniProtKB/Swiss-Prot

Q3V2Z6, Q6ZPW5, Q9EQJ0

UniProtKB/TrEMBL

Q3UV38

Related

ENSMUSP00000042188.9, ENSMUST00000046426.10

Conserved Domains (1) summary

pfam00520
Location:441 → 691

Ion_trans; Ion transport protein

RNA

NR_184702.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC125183

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000071.7 Reference GRCm39 C57BL/6J

Range

120672222..120726731 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030254513.1 → XP_030110373.1 two pore calcium channel protein 1 isoform X1

UniProtKB/Swiss-Prot

Q3V2Z6, Q6ZPW5, Q9EQJ0

UniProtKB/TrEMBL

Q3UV38

Conserved Domains (1) summary

pfam00520
Location:441 → 691

Ion_trans; Ion transport protein
XM_030254514.1 → XP_030110374.1 two pore calcium channel protein 1 isoform X2

UniProtKB/TrEMBL

Q3UV38

Conserved Domains (1) summary

pfam00520
Location:425 → 675

Ion_trans; Ion transport protein