TPCN2 two pore segment channel 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TPCN2provided by HGNC
Official Full Name: two pore segment channel 2provided by HGNC
Primary source: HGNC:HGNC:20820
See related: Ensembl:ENSG00000162341 MIM:612163; AllianceGenome:HGNC:20820
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TPC2; SHEP10
Summary: This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]
Expression: Ubiquitous expression in skin (RPKM 3.4), endometrium (RPKM 3.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.3

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (69048932..69090597)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (69059173..69101661)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (68816400..68858065)

Chromosome 11 - NC_000011.10 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2.
Title: Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2.
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.
cryo-EM structure of human TPC2 provides insights into the mechanism of PI(3,5)P2-regulated gating of TPC2, which is distinct from that of TPC1
Title: Structural mechanisms of phospholipid activation of the human TPC2 channel.
support a role of TPC2 in autophagy progression and extracellular vesicle trafficking in cancer cells
Title: TPC2 mediates autophagy progression and extracellular vesicle secretion in cancer cells.
PI(3,5)P2-binding site in hTPC2 identified at positively charged amino acids (K203, K204, and K207) in the linker between transmembrane helices S4 and S5 and by S322 in the cytosolic extension of S6 and protein-lipid interface upon mutations of residues within the lipid-binding pocket had neither an effect on the binding behavior nor on the channel's lipid sensitivity.
Title: Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2.
TPC2 polymorphisms are associated with a hair pigmentation.
Title: TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms.
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.
the divergent pore regions from human TPC2, a two-domain channel that holds a key intermediate position in the evolution of voltage-gated ion channels, were characterized.
Title: Isolated pores dissected from human two-pore channel 2 are functional.
The ion selectivity of Arabidopsis thaliana TPC1 was compared with the selectivity of human TPC2. HsTPC2 was confirmed as a Na(+)-selective channel activated by phosphatidylinositol 3,5-bisphosphate. The ion permeability ratios of HsTPC2 and its mutants were calculated.
Title: Tuning the ion selectivity of two-pore channels.
These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
Title: Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Skin/hair/eye pigmentation, variation in, 10 MedGen: C2677088 OMIM: 612267 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Two newly identified genetic determinants of pigmentation in Europeans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Web-based, participant-driven studies yield novel genetic associations for common traits. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-146387 (e-PCR)
- UniSTS:175192

G35510 (e-PCR)
- UniSTS:44150

G65699 (e-PCR)
- UniSTS:225493

SGC31049 (e-PCR)
- UniSTS:69108

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT enables NAADP-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
enables NAADP-sensitive calcium-release channel activity	IDA Inferred from Direct Assay more info	PubMed
enables NAADP-sensitive calcium-release channel activity	TAS Traceable Author Statement more info
enables calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
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 phosphatidylinositol-3,5-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables voltage-gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated calcium channel activity	ISS Inferred from Sequence or Structural Similarity more info
NOT enables voltage-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium-mediated signaling	IGI Inferred from Genetic Interaction more info	PubMed
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 endosome to lysosome transport of low-density lipoprotein particle	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular calcium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular pH reduction	IDA Inferred from Direct Assay more info	PubMed
involved_in lysosome organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in negative regulation of developmental pigmentation	IDA Inferred from Direct Assay more info	PubMed
involved_in receptor-mediated endocytosis of virus by host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of autophagy	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of exocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in release of sequestered calcium ion into cytosol	IEA Inferred from Electronic Annotation more info
involved_in response to vitamin D	IEA Inferred from Electronic Annotation more info
involved_in smooth muscle contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in endolysosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	IEA Inferred from Electronic Annotation 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	TAS Traceable Author Statement more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome membrane	IDA Inferred from Direct Assay more info	PubMed
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.