Human Gene ITPR2 (ENST00000381340.8)
  Description: Homo sapiens inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), mRNA. (from RefSeq NM_002223)
RefSeq Summary (NM_002223): The protein encoded by this gene belongs to the inositol 1,4,5-triphosphate receptor family, whose members are second messenger intracellular calcium release channels. These proteins mediate a rise in cytoplasmic calcium in response to receptor activated production of inositol triphosphate. Inositol triphosphate receptor-mediated signaling is involved in many processes including cell migration, cell division, smooth muscle contraction, and neuronal signaling. This protein is a type 2 receptor that consists of a cytoplasmic amino-terminus that binds inositol triphosphate, six membrane-spanning helices that contribute to the ion pore, and a short cytoplasmic carboxy-terminus. A mutation in this gene has been associated with anhidrosis, suggesting that intracellular calcium release mediated by this protein is required for eccrine sweat production. [provided by RefSeq, Apr 2015]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Gencode Transcript: ENST00000381340.8
Gencode Gene: ENSG00000123104.12
Transcript (Including UTRs)
   Position: hg38 chr12:26,335,352-26,833,194 Size: 497,843 Total Exon Count: 57 Strand: -
Coding Region
   Position: hg38 chr12:26,339,397-26,832,781 Size: 493,385 Coding Exon Count: 57 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:26,335,352-26,833,194)mRNA (may differ from genome)Protein (2701 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGImyGene2neXtProtOMIM
PubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ITPR2_HUMAN
DESCRIPTION: RecName: Full=Inositol 1,4,5-trisphosphate receptor type 2; AltName: Full=IP3 receptor isoform 2; Short=IP3R 2; Short=InsP3R2; AltName: Full=Type 2 inositol 1,4,5-trisphosphate receptor; Short=Type 2 InsP3 receptor;
FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA (By similarity).
SUBUNIT: Homotetramer (By similarity). Interacts with CABP1.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Isoform Short is found in skeletal muscle and heart.
DOMAIN: The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand- binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.
PTM: Phosphorylation by cAMP-dependent PKA on Ser-937 increases calcium release (By similarity).
MISCELLANEOUS: Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium- binding protein which then inhibits the receptor.
SIMILARITY: Belongs to the InsP3 receptor family.
SIMILARITY: Contains 5 MIR domains.

-  MalaCards Disease Associations
  MalaCards Gene Search: ITPR2
Diseases sorted by gene-association score: anhidrosis, isolated, with normal sweat glands* (1630), anhidrosis (30)
* = Manually curated disease association

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

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.60 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 152.65 RPKM



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

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -207.50413-0.502 Picture PostScript Text
3' UTR -996.904045-0.246 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
IPR000699 - Ca-rel_channel
IPR014821 - Ins145_P3_rcpt
IPR000493 - InsP3_rcpt-bd
IPR005821 - Ion_trans_dom
IPR016093 - MIR_motif
IPR013662 - RIH_assoc-dom
IPR015925 - Ryanodine_recept-rel

Pfam Domains:
PF08709 - Inositol 1,4,5-trisphosphate/ryanodine receptor
PF00520 - Ion transport protein
PF02815 - MIR domain
PF08454 - RyR and IP3R Homology associated
PF01365 - RIH domain

ModBase Predicted Comparative 3D Structure on Q14571
FrontTopSide
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
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI     
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005216 ion channel activity
GO:0005220 inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity
GO:0005262 calcium channel activity
GO:0005509 calcium ion binding
GO:0015085 calcium ion transmembrane transporter activity
GO:0015278 calcium-release channel activity
GO:0035091 phosphatidylinositol binding
GO:0070679 inositol 1,4,5 trisphosphate binding
GO:0097110 scaffold protein binding

Biological Process:
GO:0001666 response to hypoxia
GO:0006811 ion transport
GO:0006816 calcium ion transport
GO:0007165 signal transduction
GO:0030168 platelet activation
GO:0048016 inositol phosphate-mediated signaling
GO:0050796 regulation of insulin secretion
GO:0051209 release of sequestered calcium ion into cytosol
GO:0055085 transmembrane transport
GO:0070588 calcium ion transmembrane transport
GO:0071320 cellular response to cAMP
GO:0071361 cellular response to ethanol
GO:1903779 regulation of cardiac conduction

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0005938 cell cortex
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016529 sarcoplasmic reticulum
GO:0031095 platelet dense tubular network membrane
GO:0033017 sarcoplasmic reticulum membrane
GO:0043235 receptor complex


-  Descriptions from all associated GenBank mRNAs
  D26350 - Homo sapiens mRNA for type 2 inositol 1,4,5-trisphosphate receptor, complete cds.
BC172383 - Synthetic construct Homo sapiens clone IMAGE:100069077, MGC:199088 inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) mRNA, encodes complete protein.
AK307686 - Homo sapiens cDNA, FLJ97634.
AK307712 - Homo sapiens cDNA, FLJ97660.
AK310504 - Homo sapiens cDNA, FLJ17546.
AY429550 - Homo sapiens ITPR2v_3 mRNA sequence; alternatively spliced.
AB012610 - Homo sapiens TIPR mRNA for inositol 1,4,5-trisphosphate receptor type 2, complete cds.
JD502187 - Sequence 483211 from Patent EP1572962.
JD490525 - Sequence 471549 from Patent EP1572962.
JD546875 - Sequence 527899 from Patent EP1572962.
JD075066 - Sequence 56090 from Patent EP1572962.
JD067509 - Sequence 48533 from Patent EP1572962.
JD291963 - Sequence 272987 from Patent EP1572962.
JD564766 - Sequence 545790 from Patent EP1572962.
JD352318 - Sequence 333342 from Patent EP1572962.
JD045905 - Sequence 26929 from Patent EP1572962.
JD558012 - Sequence 539036 from Patent EP1572962.
JD539452 - Sequence 520476 from Patent EP1572962.
JD050737 - Sequence 31761 from Patent EP1572962.
JD296016 - Sequence 277040 from Patent EP1572962.
JD052844 - Sequence 33868 from Patent EP1572962.
JD350429 - Sequence 331453 from Patent EP1572962.
JD038434 - Sequence 19458 from Patent EP1572962.
JD042673 - Sequence 23697 from Patent EP1572962.
JD176715 - Sequence 157739 from Patent EP1572962.
JD371622 - Sequence 352646 from Patent EP1572962.
JD087599 - Sequence 68623 from Patent EP1572962.
JD503495 - Sequence 484519 from Patent EP1572962.
JD556897 - Sequence 537921 from Patent EP1572962.
JD563914 - Sequence 544938 from Patent EP1572962.
JD267126 - Sequence 248150 from Patent EP1572962.
JD408804 - Sequence 389828 from Patent EP1572962.
JD341959 - Sequence 322983 from Patent EP1572962.
JD201598 - Sequence 182622 from Patent EP1572962.
JD213842 - Sequence 194866 from Patent EP1572962.
JD538661 - Sequence 519685 from Patent EP1572962.
JD297286 - Sequence 278310 from Patent EP1572962.
JD248955 - Sequence 229979 from Patent EP1572962.
MP330168 - Sequence 133 from Patent WO2019180153.
JD370858 - Sequence 351882 from Patent EP1572962.
JD445755 - Sequence 426779 from Patent EP1572962.
JD124916 - Sequence 105940 from Patent EP1572962.
JD194462 - Sequence 175486 from Patent EP1572962.
JD462670 - Sequence 443694 from Patent EP1572962.
JD340094 - Sequence 321118 from Patent EP1572962.
JD468990 - Sequence 450014 from Patent EP1572962.
JD214634 - Sequence 195658 from Patent EP1572962.
JD445377 - Sequence 426401 from Patent EP1572962.
JD066017 - Sequence 47041 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04020 - Calcium signaling pathway
hsa04070 - Phosphatidylinositol signaling system
hsa04114 - Oocyte meiosis
hsa04270 - Vascular smooth muscle contraction
hsa04540 - Gap junction
hsa04720 - Long-term potentiation
hsa04730 - Long-term depression
hsa04912 - GnRH signaling pathway
hsa05010 - Alzheimer's disease

Reactome (by CSHL, EBI, and GO)

Protein Q14571 (Reactome details) participates in the following event(s):

R-HSA-139941 Binding of IP3 to IP3 receptor
R-HSA-169680 IP3 binds to the IP3 receptor, opening the endoplasmic reticulum Ca2+ channel
R-HSA-5226904 AHCYL1:NAD+ binds ITPR1:I(1,3,5)P3 tetramer, inhibiting it
R-HSA-139854 IP3R tetramer:I(1,4,5)P3:4xCa2+ transports Ca2+ from platelet dense tubular system to cytosol
R-HSA-169683 IP3R:I(1,4,5)P3 tetramer transports Ca2+ from ER lumen to cytosol
R-HSA-1168376 STIM1 oligomerizes
R-HSA-4420052 Decreasing cGMP concentration promotes intracellular Ca2+ release in response to WNT
R-HSA-114508 Effects of PIP2 hydrolysis
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-112043 PLC beta mediated events
R-HSA-422356 Regulation of insulin secretion
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-1489509 DAG and IP3 signaling
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-4086398 Ca2+ pathway
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-416476 G alpha (q) signalling events
R-HSA-5578775 Ion homeostasis
R-HSA-112040 G-protein mediated events
R-HSA-163685 Energy Metabolism
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-3858494 Beta-catenin independent WNT signaling
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-139853 Elevation of cytosolic Ca2+ levels
R-HSA-109582 Hemostasis
R-HSA-388396 GPCR downstream signalling
R-HSA-5576891 Cardiac conduction
R-HSA-111885 Opioid Signalling
R-HSA-1430728 Metabolism
R-HSA-1280218 Adaptive Immune System
R-HSA-162582 Signal Transduction
R-HSA-168249 Innate Immune System
R-HSA-195721 Signaling by WNT
R-HSA-194138 Signaling by VEGF
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-418360 Platelet calcium homeostasis
R-HSA-372790 Signaling by GPCR
R-HSA-397014 Muscle contraction
R-HSA-418594 G alpha (i) signalling events
R-HSA-168256 Immune System
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-418346 Platelet homeostasis

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000381340.1, ENST00000381340.2, ENST00000381340.3, ENST00000381340.4, ENST00000381340.5, ENST00000381340.6, ENST00000381340.7, ITPR2_HUMAN, NM_002223, O94773, Q14571, uc001rhg.1, uc001rhg.2, uc001rhg.3, uc001rhg.4, uc001rhg.5
UCSC ID: ENST00000381340.8
RefSeq Accession: NM_002223
Protein: Q14571 (aka ITPR2_HUMAN or IP3S_HUMAN)
CCDS: CCDS41764.1

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