TPCN1 two pore segment channel 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TPCN1provided by HGNC
Official Full Name: two pore segment channel 1provided by HGNC
Primary source: HGNC:HGNC:18182
See related: Ensembl:ENSG00000186815 MIM:609666; AllianceGenome:HGNC:18182
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TPC1
Summary: Voltage-gated Ca(2+) and Na+ channels have 4 homologous domains, each containing 6 transmembrane segments, S1 to S6. TPCN1 is similar to these channels, but it has only 2 domains containing S1 to S6 (Ishibashi et al., 2000 [PubMed 10753632]).[supplied by OMIM, Mar 2008]
Expression: Ubiquitous expression in kidney (RPKM 17.8), heart (RPKM 16.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.13

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (113221464..113298585)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (113198077..113275213)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (113659269..113736390)

Chromosome 12 - NC_000012.12 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: 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?

TPC1 is involved in the norepinephrine (NE)-stimulated [Ca(2+)]i rise in Smooth muscle cells. Inhibition of TPC1 activity by NED 19 could be the reason for partial inhibition of aortic rings contraction in response to NE.
Title: The Role of Two-Pore Channels in Norepinephrine-Induced [Ca(2+)](i) Rise in Rat Aortic Smooth Muscle Cells and Aorta Contraction.
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.
These data point to a process in which Ca(2+) permeation in human TPC1 has a positive feedback on channel activity while Na(+) acts as a negative regulator.
Title: The human two-pore channel 1 is modulated by cytosolic and luminal calcium.
a cluster of arginine residues in the first domain required for selective voltage-gating of TPC1 map not to the voltage-sensing fourth transmembrane region (S4) but to a cytosolic downstream region (S4-S5 linker).
Title: NAADP-evoked Ca(2+) signals through two-pore channel-1 require arginine residues in the first S4-S5 linker.
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.
Studies suggest that both two-pore channels TPC1 and TPC2 as nicotinic acid adenine dinucleotide phosphate (NAADP) targets.
Title: Function and dysfunction of two-pore channels.
The TPC1 was shown to interact with citron kinase, with TPC1 overexpression affecting RhoA activity and myosin light chain phosphorylation levels in cytokinesis.
Title: Two-pore channel 1 interacts with citron kinase, regulating completion of cytokinesis.
NAADP induced marked Ca(2+) transients in HEK293 cells that stably coexpressed hTPC2 with hTPC1 or cTPC3, but failed to evoke any such response in cells that coexpressed interacting hTPC2 and rTPC3 subunits
Title: Organelle-specific subunit interactions of the vertebrate two-pore channel family.
TPC2, but not TPC1, caused a proliferation of endolysosomal structures, dysregulating intracellular trafficking, and cellular pigmentation.
Title: The Two-pore channel (TPC) interactome unmasks isoform-specific roles for TPCs in endolysosomal morphology and cell pigmentation.
TPC1 and TPC2 proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy.
Title: Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment.

Submit: New GeneRIF Correction See all GeneRIFs (15)

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

EBI GWAS Catalog

Description
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network. 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

G16004 (e-PCR)
- UniSTS:48911

D12S1195E (e-PCR)
- UniSTS:4133

A004Q10 (e-PCR)
- UniSTS:41019

STS-AA001615 (e-PCR)
- UniSTS:24394

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

TPCN1 (e-PCR)
- UniSTS:504205

RH79706 (e-PCR)
- UniSTS:84622

D12S1973 (e-PCR)
- UniSTS:12944

RH103133 (e-PCR)
- UniSTS:97467

RH44581 (e-PCR)
- UniSTS:54981

SHGC-148490 (e-PCR)
- UniSTS:173018

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 identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3,5-bisphosphate binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables syntaxin binding	IEA Inferred from Electronic Annotation more info
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

Process	Evidence Code	Pubs
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling	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 monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in positive regulation of autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in early endosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in endolysosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	TAS Traceable Author Statement more info	PubMed
is_active_in endosome membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
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	TAS Traceable Author Statement more info	PubMed
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in recycling endosome membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: two pore channel protein 1

Names: two pore calcium channel protein 1; two-pore channel 1, homolog; 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_001143819.3 → NP_001137291.1 two pore channel protein 1 isoform 1

See identical proteins and their annotated locations for NP_001137291.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK057414, AK093490, BC150203

Consensus CDS

CCDS44985.1

UniProtKB/TrEMBL

B3KSG7

Related

ENSP00000448083.1, ENST00000550785.5

Conserved Domains (1) summary

pfam00520
Location:214 → 402

Ion_trans; Ion transport protein
NM_001301214.2 → NP_001288143.1 two pore channel protein 1 isoform 3

See identical proteins and their annotated locations for NP_001288143.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1. Variants 3, 4, and 5 all encode the same isoform (3).

Source sequence(s)

AK296268, BC150203

Consensus CDS

CCDS76605.1

UniProtKB/TrEMBL

B3KSG7, B7Z3R2

Related

ENSP00000376350.4, ENST00000392569.8

Conserved Domains (1) summary

pfam00520
Location:372 → 623

Ion_trans; Ion transport protein
NM_001351346.2 → NP_001338275.1 two pore channel protein 1 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (4), as well as variants 3 and 5, encodes isoform 3.

Source sequence(s)

AC010178, AC089999

Consensus CDS

CCDS76605.1

UniProtKB/TrEMBL

B3KSG7, B7Z3R2

Conserved Domains (1) summary

pfam00520
Location:372 → 623

Ion_trans; Ion transport protein
NM_001351347.1 → NP_001338276.1 two pore channel protein 1 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (5), as well as variants 3 and 4, encodes isoform 3.

Source sequence(s)

AC010178, AC089999

Consensus CDS

CCDS76605.1

UniProtKB/TrEMBL

B3KSG7, B7Z3R2

Conserved Domains (1) summary

pfam00520
Location:372 → 623

Ion_trans; Ion transport protein
NM_017901.6 → NP_060371.2 two pore channel protein 1 isoform 2

See identical proteins and their annotated locations for NP_060371.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AK093490, BC150203

Consensus CDS

CCDS31908.1

UniProtKB/Swiss-Prot

A7E258, Q86XS9, Q8NC20, Q9ULQ1

UniProtKB/TrEMBL

B3KSG7

Related

ENSP00000335300.6, ENST00000335509.11

Conserved Domains (1) summary

pfam00520
Location:440 → 690

Ion_trans; Ion transport protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

113221464..113298585

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017019480.3 → XP_016874969.1 two pore channel protein 1 isoform X1

UniProtKB/TrEMBL

B3KSG7
XM_011538493.3 → XP_011536795.1 two pore channel protein 1 isoform X5

See identical proteins and their annotated locations for XP_011536795.1

UniProtKB/TrEMBL

B3KSG7, B7Z3R2

Conserved Domains (1) summary

pfam00520
Location:372 → 623

Ion_trans; Ion transport protein
XM_011538492.3 → XP_011536794.1 two pore channel protein 1 isoform X2

See identical proteins and their annotated locations for XP_011536794.1

UniProtKB/Swiss-Prot

A7E258, Q86XS9, Q8NC20, Q9ULQ1

UniProtKB/TrEMBL

B3KSG7

Conserved Domains (1) summary

pfam00520
Location:440 → 690

Ion_trans; Ion transport protein
XM_047429011.1 → XP_047284967.1 two pore channel protein 1 isoform X3
XM_047429016.1 → XP_047284972.1 two pore channel protein 1 isoform X6
XM_047429015.1 → XP_047284971.1 two pore channel protein 1 isoform X5

UniProtKB/TrEMBL

B7Z3R2
XM_047429013.1 → XP_047284969.1 two pore channel protein 1 isoform X5

UniProtKB/TrEMBL

B7Z3R2
XM_047429012.1 → XP_047284968.1 two pore channel protein 1 isoform X4
XM_047429014.1 → XP_047284970.1 two pore channel protein 1 isoform X5

UniProtKB/TrEMBL

B7Z3R2

RNA

XR_001748766.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

113198077..113275213

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054372300.1 → XP_054228275.1 two pore channel protein 1 isoform X2

UniProtKB/Swiss-Prot

A7E258, Q86XS9, Q8NC20, Q9ULQ1
XM_054372299.1 → XP_054228274.1 two pore channel protein 1 isoform X1
XM_054372303.1 → XP_054228278.1 two pore channel protein 1 isoform X5

UniProtKB/TrEMBL

B7Z3R2
XM_054372301.1 → XP_054228276.1 two pore channel protein 1 isoform X3
XM_054372306.1 → XP_054228281.1 two pore channel protein 1 isoform X6
XM_054372305.1 → XP_054228280.1 two pore channel protein 1 isoform X5

UniProtKB/TrEMBL

B7Z3R2
XM_054372304.1 → XP_054228279.1 two pore channel protein 1 isoform X5

UniProtKB/TrEMBL

B7Z3R2
XM_054372302.1 → XP_054228277.1 two pore channel protein 1 isoform X4