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

    Gene ID: 53373, updated on 27-Nov-2024

    Summary

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    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

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    See TPCN1 in Genome Data Viewer
    Location:
    12q24.13
    Exon count:
    35
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (113221464..113298585)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (113198077..113275213)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (113659269..113736390)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:113623217-113623866 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113623867-113624517 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113624518-113625167 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113629297-113629950 Neighboring gene Sharpr-MPRA regulatory region 6569 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113639865-113640756 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7064 Neighboring gene RBPJ interacting and tubulin associated 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7065 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7066 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7067 Neighboring gene IQ motif containing D Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7068 Neighboring gene Sharpr-MPRA regulatory region 2606 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24601 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24602 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7069 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7070 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113669293-113669843 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7071 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7072 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113683649-113684312 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113684313-113684976 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113689411-113689911 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7073 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24609 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:113705834-113706026 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24611 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24613 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24616 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113736197-113736894 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113736895-113737590 Neighboring gene Sharpr-MPRA regulatory region 468 Neighboring gene NANOG hESC enhancer GRCh37_chr12:113740736-113741469 Neighboring gene microRNA 6762 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:113744904-113746103 Neighboring gene solute carrier family 8 member B1 Neighboring gene MPRA-validated peak1972 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4893 Neighboring gene uncharacterized LOC105369989 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4894 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4895 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113797151-113797650 Neighboring gene phospholipase B domain containing 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Regulation of a proteinaceous elicitor-induced Ca2+ influx and production of phytoalexins by a putative voltage-gated cation channel, OsTPC1, in cultured rice cells. Hamada H, et al. J Biol Chem, 2012 Mar 23. PMID 22270358, Free PMC Article
    2. Membrane potential regulates nicotinic acid adenine dinucleotide phosphate (NAADP) dependence of the pH- and Ca2+-sensitive organellar two-pore channel TPC1. Rybalchenko V, et al. J Biol Chem, 2012 Jun 8. PMID 22500018, Free PMC Article
    3. Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca2+. Pitt SJ, et al. Sci Signal, 2014 May 20. PMID 24847115, Free PMC Article
    4. NAADP-evoked Ca(2+) signals through two-pore channel-1 require arginine residues in the first S4-S5 linker. Patel S, et al. Cell Calcium, 2017 Dec. PMID 29129203, Free PMC Article
    5. The human two-pore channel 1 is modulated by cytosolic and luminal calcium. Lagostena L, et al. Sci Rep, 2017 Mar 2. PMID 28252105, Free PMC Article

    See all (38) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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

    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

    Homology

    Clone Names

    • FLJ20612, KIAA1169

    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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    NEW Try the new Transcript table

    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)

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      113221464..113298585
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/TrEMBL
      B3KSG7

    2. 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

    3. 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

    4. XM_047429011.1 → XP_047284967.1  two pore channel protein 1 isoform X3

    5. XM_047429016.1 → XP_047284972.1  two pore channel protein 1 isoform X6

    6. XM_047429015.1 → XP_047284971.1  two pore channel protein 1 isoform X5

      UniProtKB/TrEMBL
      B7Z3R2

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

      UniProtKB/TrEMBL
      B7Z3R2

    8. XM_047429012.1 → XP_047284968.1  two pore channel protein 1 isoform X4

    9. XM_047429014.1 → XP_047284970.1  two pore channel protein 1 isoform X5

      UniProtKB/TrEMBL
      B7Z3R2

    RNA

    1. XR_001748766.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      113198077..113275213
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/Swiss-Prot
      A7E258, Q86XS9, Q8NC20, Q9ULQ1

    2. XM_054372299.1 → XP_054228274.1  two pore channel protein 1 isoform X1

    3. XM_054372303.1 → XP_054228278.1  two pore channel protein 1 isoform X5

      UniProtKB/TrEMBL
      B7Z3R2

    4. XM_054372301.1 → XP_054228276.1  two pore channel protein 1 isoform X3

    5. XM_054372306.1 → XP_054228281.1  two pore channel protein 1 isoform X6

    6. XM_054372305.1 → XP_054228280.1  two pore channel protein 1 isoform X5

      UniProtKB/TrEMBL
      B7Z3R2

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

      UniProtKB/TrEMBL
      B7Z3R2

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

    RNA

    1. XR_008488620.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9ULQ1.3 GenPept UniProtKB/Swiss-Prot:Q9ULQ1

    Gene LinkOut

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