Human Gene TPCN2 (uc001oos.2) Description and Page Index
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
ID:TPC2_HUMAN 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
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.
ModBase Predicted Comparative 3D Structure on Q8NHX9
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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.