Tpcn2 two pore segment channel 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tpcn2provided by MGI
Official Full Name: two pore segment channel 2provided by MGI
Primary source: MGI:MGI:2385297
See related: Ensembl:ENSMUSG00000048677 AllianceGenome:MGI:2385297
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: Gm35086; D830047E22Rik
Summary: Enables NAADP-sensitive calcium-release channel activity and voltage-gated calcium channel activity. Involved in several processes, including endocytosis involved in viral entry into host cell; endosome to lysosome transport of low-density lipoprotein particle; and release of sequestered calcium ion into cytosol. Located in lysosomal membrane. Is expressed in several structures, including alimentary system; brain; cardiovascular system; genitourinary system; and hemolymphoid system gland. Human ortholog(s) of this gene implicated in pigmentation disease. Orthologous to human TPCN2 (two pore segment channel 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in limb E14.5 (RPKM 3.8), ovary adult (RPKM 3.7) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7; 7 F5

Exon count:: 38

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (144735370..144837743, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (145181633..145284011, complement)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

Rac1 and Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneurons.
Title: Rac1 and Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneurons.
A gain-of-function TPC2 variant R210C increases affinity to PI(3,5)P2 and causes lysosome acidification and hypopigmentation.
Title: A gain-of-function TPC2 variant R210C increases affinity to PI(3,5)P(2) and causes lysosome acidification and hypopigmentation.
TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.
Title: TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.
Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect.
Title: Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect.
Data indicate that knockout of two pore calcium channel protein 2 (Tpcn2) may increase insulin action in male, but not female, mice.
Title: Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain.
Under normal Mg(2+) conditions, TPC2 promotes osteoclastogenesis. Under low-Mg(2+) conditions, TPC2 inhibited, rather than promoted, the osteoclast differentiation, and the phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) signaling pathway played a role in the TPC2 activation under low-Mg(2+) conditions.
Title: Role of lysosomal channel protein TPC2 in osteoclast differentiation and bone remodeling under normal and low-magnesium conditions.
Data (including data from studies using tissue from knockout mice) suggest that beta-adrenergic stimulation of pancreas leads to glucagon secretion by hierarchy of calcium signaling in glucagon-secreting cell; such signaling is initiated by cAMP-induced Tpc2-dependent calcium release from acidic stores and is further amplified by calcium release from endoplasmic reticulum.
Title: Adrenaline Stimulates Glucagon Secretion by Tpc2-Dependent Ca(2+) Mobilization From Acidic Stores in Pancreatic α-Cells.
Study identifies two-pore channel 2 (TPC2) as the first reported melanosomal cation conductance by directly patch-clamping skin and eye melanosomes. TPC2 is shown to function as a negative regulator of pigmentation by increasing melanosome membrane potential and melanosome acidity.
Title: A melanosomal two-pore sodium channel regulates pigmentation.
High TPC2 expression is associated with lung metastasis in breast cancer.
Title: Two-Pore Channel Function Is Crucial for the Migration of Invasive Cancer Cells.
Electron micrographs of hearts from TPC1/TPC2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes compared to wild-type mice.
Title: Endolysosomal two-pore channels regulate autophagy in cardiomyocytes.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Variation

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Alleles

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

Gene trapped (1) 1 citation
Targeted (8) 1 citation
Endonuclease-mediated (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:235819

Tpcn2 (e-PCR), detects polymorphism
- UniSTS:536694

Tpcn2 (e-PCR), detects polymorphism
- UniSTS:536695

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables NAADP-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
enables NAADP-sensitive calcium-release channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables calcium channel activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity	ISO Inferred from Sequence Orthology more info
enables ligand-gated sodium channel activity	IBA Inferred from Biological aspect of Ancestor 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	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables voltage-gated calcium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables voltage-gated channel activity	IEA Inferred from Electronic Annotation 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 calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium-mediated signaling	ISO Inferred from Sequence Orthology more info
involved_in endocytosis involved in viral entry into host cell	IBA Inferred from Biological aspect of Ancestor 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
involved_in endosome to lysosome transport of low-density lipoprotein particle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular calcium ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in intracellular pH reduction	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular pH reduction	ISO Inferred from Sequence Orthology more info
involved_in lysosome organization	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 negative regulation of developmental pigmentation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of developmental pigmentation	ISO Inferred from Sequence Orthology more info
involved_in receptor-mediated endocytosis of virus by host cell	ISO Inferred from Sequence Orthology more info
involved_in regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in regulation of exocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in release of sequestered calcium ion into cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smooth muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in endolysosome membrane	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation 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	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	ISO Inferred from Sequence Orthology more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in melanosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: two pore channel protein 2

Names: two pore calcium channel protein 2; voltage-dependent calcium channel protein TPC2

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_146206.6 → NP_666318.2 two pore channel protein 2

See identical proteins and their annotated locations for NP_666318.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the protein.

Source sequence(s)

AC132081

Consensus CDS

CCDS40203.1

UniProtKB/Swiss-Prot

Q6NSV0, Q8BTJ7, Q8BWC0, Q8R396

UniProtKB/TrEMBL

B2RUK7

Related

ENSMUSP00000061308.5, ENSMUST00000058022.6

Conserved Domains (1) summary

pfam00520
Location:103 → 299

Ion_trans; Ion transport protein

RNA

NR_132642.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate exon and uses an alternate splice site in the 3' region compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC132081

Related

ENSMUST00000208841.2
NR_132643.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks six exons and contains four alternate exons in the 3' region compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC132081, AC151715
NR_132644.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks two exons and contains two alternate exons in the 3' region compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC132081, AC151715

Related

ENSMUST00000209047.2

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_000073.7 Reference GRCm39 C57BL/6J

Range

144735370..144837743 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036153027.1 → XP_036008920.1 two pore channel protein 2 isoform X4

UniProtKB/TrEMBL

B2RUK7

Conserved Domains (1) summary

pfam00520
Location:453 → 690

Ion_trans; Ion transport protein
XM_006508614.4 → XP_006508677.1 two pore channel protein 2 isoform X3

UniProtKB/TrEMBL

B2RUK7

Conserved Domains (1) summary

pfam00520
Location:414 → 679

Ion_trans; Ion transport protein
XM_006508613.4 → XP_006508676.1 two pore channel protein 2 isoform X1

UniProtKB/TrEMBL

B2RUK7

Conserved Domains (1) summary

pfam00520
Location:453 → 718

Ion_trans; Ion transport protein
XM_017322226.2 → XP_017177715.1 two pore channel protein 2 isoform X5

UniProtKB/TrEMBL

Q80UQ1

Conserved Domains (1) summary

pfam00520
Location:284 → 549

Ion_trans; Ion transport protein
XM_030242540.1 → XP_030098400.1 two pore channel protein 2 isoform X7

Conserved Domains (1) summary

pfam00520
Location:192 → 457

Ion_trans; Ion transport protein
XM_006508618.4 → XP_006508681.1 two pore channel protein 2 isoform X10

Conserved Domains (1) summary

pfam00520
Location:41 → 306

Ion_trans; Ion transport protein
XM_036153026.1 → XP_036008919.1 two pore channel protein 2 isoform X2

UniProtKB/TrEMBL

B2RUK7

Conserved Domains (1) summary

pfam00520
Location:453 → 716

Ion_trans; Ion transport protein
XM_036153030.1 → XP_036008923.1 two pore channel protein 2 isoform X6

UniProtKB/TrEMBL

Q8BLY6

Related

ENSMUSP00000147178.2, ENSMUST00000208328.2

Conserved Domains (1) summary

pfam00520
Location:68 → 299

Ion_trans; Ion transport protein
XM_036153028.1 → XP_036008921.1 two pore channel protein 2 isoform X6

UniProtKB/TrEMBL

Q8BLY6

Conserved Domains (1) summary

pfam00520
Location:68 → 299

Ion_trans; Ion transport protein
XM_036153029.1 → XP_036008922.1 two pore channel protein 2 isoform X6

UniProtKB/TrEMBL

Q8BLY6

Conserved Domains (1) summary

pfam00520
Location:68 → 299

Ion_trans; Ion transport protein
XM_011241998.2 → XP_011240300.1 two pore channel protein 2 isoform X8

Conserved Domains (1) summary

pfam00520
Location:68 → 299

Ion_trans; Ion transport protein
XM_006508617.2 → XP_006508680.1 two pore channel protein 2 isoform X9

Conserved Domains (1) summary

pfam00520
Location:68 → 299

Ion_trans; Ion transport protein