Human Gene TPCN2 (uc001oos.2)
  Description: Homo sapiens two pore segment channel 2 (TPCN2), mRNA.
RefSeq Summary (NM_139075): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data because no single transcript was available for the full length of the gene. The extent of this transcript is supported by transcript alignments.
Transcript (Including UTRs)
   Position: hg19 chr11:68,816,350-68,858,072 Size: 41,723 Total Exon Count: 25 Strand: +
Coding Region
   Position: hg19 chr11:68,816,466-68,855,421 Size: 38,956 Coding Exon Count: 25 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr11:68,816,350-68,858,072)mRNA (may differ from genome)Protein (752 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Two pore calcium channel protein 2; AltName: Full=Voltage-dependent calcium channel protein TPC2;
FUNCTION: Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal membrane. May be involved in smooth muscle contraction.
SUBUNIT: Homodimer (By similarity). Interacts with LRRK2.
INTERACTION: Self; NbExp=4; IntAct=EBI-5239949, EBI-5239949; Q9ULQ1:TPCN1; NbExp=9; IntAct=EBI-5239949, EBI-5239895;
SUBCELLULAR LOCATION: Lysosome membrane; Multi-pass membrane protein (By similarity). Note=Only the acidic lysosomal fraction is sensitive to NAADP (By similarity).
TISSUE SPECIFICITY: Widely expressed. Expressed at high level in liver and kidney.
DOMAIN: Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity).
PTM: N-glycosylated (By similarity).
POLYMORPHISM: Genetic variants in TPCN2 define the skin/hair/eye pigmentation variation locus 10 (SHEP10) [MIM:612267]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TPCN2
CDC HuGE Published Literature: TPCN2
Positive Disease Associations: Blond vs brown hair color , Cholesterol , Hair Color , Prostatic Neoplasms
Related Studies:
  1. Blond vs brown hair color
    Sulem ,et al. 2008, Two newly identified genetic determinants of pigmentation in Europeans, Nature genetics 2008 40- 7 : 835-7. [PubMed 18488028]
  2. Cholesterol
    , , . [PubMed 0]
  3. Hair Color
    Patrick Sulem et al. Nature genetics 2008, Two newly identified genetic determinants of pigmentation in Europeans., Nature genetics. [PubMed 18488028]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TPCN2
Diseases sorted by gene-association score: deafness, autosomal recessive 63 (12), deafness, autosomal recessive 7 (7), prostate cancer susceptibility (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.23 RPKM in Esophagus - Gastroesophageal Junction
Total median expression: 306.99 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -52.40116-0.452 Picture PostScript Text
3' UTR -1019.102651-0.384 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR005821 - Ion_trans_dom

Pfam Domains:
PF00520 - Ion transport protein

SCOP Domains:
81324 - Voltage-gated potassium channels

ModBase Predicted Comparative 3D Structure on Q8NHX9
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Protein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005216 ion channel activity
GO:0005244 voltage-gated ion channel activity
GO:0005245 voltage-gated calcium channel activity
GO:0005262 calcium channel activity
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0042802 identical protein binding
GO:0072345 NAADP-sensitive calcium-release channel activity

Biological Process:
GO:0006811 ion transport
GO:0006816 calcium ion transport
GO:0006874 cellular calcium ion homeostasis
GO:0006939 smooth muscle contraction
GO:0007040 lysosome organization
GO:0010506 regulation of autophagy
GO:0019722 calcium-mediated signaling
GO:0033280 response to vitamin D
GO:0034220 ion transmembrane transport
GO:0034765 regulation of ion transmembrane transport
GO:0051209 release of sequestered calcium ion into cytosol
GO:0055085 transmembrane transport
GO:0070588 calcium ion transmembrane transport
GO:0086010 membrane depolarization during action potential

Cellular Component:
GO:0005764 lysosome
GO:0005765 lysosomal membrane
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane

-  Descriptions from all associated GenBank mRNAs
  AK023366 - Homo sapiens cDNA FLJ13304 fis, clone OVARC1001391, highly similar to Homo sapiens two pore segment channel 2 (TPCN2), mRNA.
AY029200 - Homo sapiens two-pore calcium channel protein 2 mRNA, complete cds.
AK123089 - Homo sapiens cDNA FLJ41094 fis, clone ASTRO2014923.
BC063008 - Homo sapiens two pore segment channel 2, mRNA (cDNA clone MGC:70581 IMAGE:5214862), complete cds.
AK298919 - Homo sapiens cDNA FLJ58483 complete cds, highly similar to Homo sapiens two pore segment channel 2 (TPCN2), mRNA.
KJ900457 - Synthetic construct Homo sapiens clone ccsbBroadEn_09851 TPCN2 gene, encodes complete protein.
AB209253 - Homo sapiens mRNA for two pore segment channel 2 variant protein.
AL137479 - Homo sapiens mRNA; cDNA DKFZp434M0223 (from clone DKFZp434M0223); partial cds.
DQ587449 - Homo sapiens piRNA piR-54561, complete sequence.
JD493643 - Sequence 474667 from Patent EP1572962.
JD222054 - Sequence 203078 from Patent EP1572962.
JD143094 - Sequence 124118 from Patent EP1572962.
JD073704 - Sequence 54728 from Patent EP1572962.
JD470330 - Sequence 451354 from Patent EP1572962.
JD276047 - Sequence 257071 from Patent EP1572962.
JD161292 - Sequence 142316 from Patent EP1572962.
JD547211 - Sequence 528235 from Patent EP1572962.
JD294533 - Sequence 275557 from Patent EP1572962.
JD213953 - Sequence 194977 from Patent EP1572962.
JD232880 - Sequence 213904 from Patent EP1572962.
BC064339 - Homo sapiens cDNA clone IMAGE:4369783, partial cds.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q8NHX9 (Reactome details) participates in the following event(s):

R-HSA-2685505 TPCN1/2 transport lysosomal Ca2+ to cytosol
R-HSA-2672351 Stimuli-sensing channels
R-HSA-983712 Ion channel transport
R-HSA-382551 Transport of small molecules

-  Other Names for This Gene
  Alternate Gene Symbols: NM_139075, NP_620714, Q8NHX9, Q9NT82, TPC2, TPC2_HUMAN
UCSC ID: uc001oos.2
RefSeq Accession: NM_139075
Protein: Q8NHX9 (aka TPC2_HUMAN)
CCDS: CCDS8189.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_139075.3
exon count: 25CDS single in 3' UTR: no RNA size: 5026
ORF size: 2259CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 4718.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.