TPCN1

Protein-coding gene in the species Homo sapiens

TPCN1

Identifiers

Aliases

TPCN1, TPC1, two pore segment channel 1

External IDs

OMIM: 609666 MGI: 2182472 HomoloGene: 9905 GeneCards: TPCN1

Gene location (Human)

Chr.	Chromosome 12 (human)^[1]

Band	12q24.13	Start	113,221,050 bp^[1]
Band	12q24.13	End	113,298,585 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 5 (mouse)^[2]

Band	5\|5 F	Start	120,672,218 bp^[2]
Band	5\|5 F	End	120,726,738 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

right lobe of thyroid gland

left lobe of thyroid gland

gastric mucosa

right adrenal gland

body of pancreas

right uterine tube

minor salivary glands

right coronary artery

sural nerve

pituitary gland

Top expressed in

lacrimal gland

saccule

yolk sac

aortic valve

ankle

intestinal villus

molar

ascending aorta

submandibular gland

interventricular septum

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	calcium channel activity voltage-gated ion channel activity ion channel activity protein binding identical protein binding NAADP-sensitive calcium-release channel activity voltage-gated calcium channel activity calcium activated cation channel activity
Cellular component	integral component of membrane endosome membrane plasma membrane lysosomal membrane lysosome endosome membrane CatSper complex
Biological process	membrane depolarization during action potential positive regulation of autophagy regulation of ion transmembrane transport ion transport ion transmembrane transport calcium ion transmembrane transport calcium ion transport transmembrane transport release of sequestered calcium ion into cytosol flagellated sperm motility
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


53373


252972

Ensembl


ENSG00000186815


ENSMUSG00000032741

UniProt


Q9ULQ1


Q9EQJ0

RefSeq (mRNA)


NM_001143819 NM_001301214 NM_017901 NM_001351346 NM_001351347


NM_145853

RefSeq (protein)


NP_001137291 NP_001288143 NP_060371 NP_001338275 NP_001338276


NP_665852

Location (UCSC)

Chr 12: 113.22 – 113.3 Mb

Chr 5: 120.67 – 120.73 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Two pore segment channel 1 (TPC1) is a human protein encoded by the TPCN1 gene.^[5] The protein encoded by this gene is an ion channel. In contrast to other calcium and sodium channels which have four homologous domains, each containing six transmembrane segments (S1 to S6), TPCN1 only contains two domains (each containing segments S1 to S6).^[6]^[7]^[8]

Structure

The structure of a TPC1 ortholog from Arabidopsis thaliana has been solved by two laboratories.^[9]^[10] The structures were solved using X-ray crystallography and contained the fold of a voltage-gated ion channel and EF hands. Only a single voltage sensor domain appears to responsible for voltage sensing.

Filoviral infections

Genetic knockout and pharmacological inhibition experiments demonstrate that the two-pore channels, TPC1 and TPC2, are required for infection by Filoviruses Ebola and Marburg in mice.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000186815 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032741 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: two pore segment channel 1".
^ Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (October 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
^ Ishibashi K, Suzuki M, Imai M (April 2000). "Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels". Biochemical and Biophysical Research Communications. 270 (2): 370–6. doi:10.1006/bbrc.2000.2435. PMID 10753632.
^ Clapham DE, Garbers DL (December 2005). "International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels". Pharmacological Reviews. 57 (4): 451–4. doi:10.1124/pr.57.4.7. PMID 16382101. S2CID 35096827.
^ Guo J, Zeng W, Chen Q, Lee C, Chen L, Yang Y, Cang C, Ren D, Jiang Y (March 2016). "Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana". Nature. 531 (7593): 196–201. Bibcode:2016Natur.531..196G. doi:10.1038/nature16446. PMC 4841471. PMID 26689363.
^ Kintzer AF, Stroud RM (March 2016). "Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana". Nature. 531 (7593): 258–62. Bibcode:2016Natur.531..258K. doi:10.1038/nature17194. PMC 4863712. PMID 26961658.
^ Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA (February 2015). "Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment". Science. 347 (6225): 995–8. doi:10.1126/science.1258758. PMC 4550587. PMID 25722412.

External links

TPCN1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin