Human Gene ITPR1 (ENST00000456211.8)
  Description: Homo sapiens inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), transcript variant 2, mRNA. (from RefSeq NM_002222)
RefSeq Summary (NM_002222): This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009].
Gencode Transcript: ENST00000456211.8
Gencode Gene: ENSG00000150995.20
Transcript (Including UTRs)
   Position: hg38 chr3:4,493,452-4,847,397 Size: 353,946 Total Exon Count: 58 Strand: +
Coding Region
   Position: hg38 chr3:4,516,492-4,846,225 Size: 329,734 Coding Exon Count: 56 

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

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:4,493,452-4,847,397)mRNA (may differ from genome)Protein (2695 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGImyGene2neXtProtOMIM
PubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ITPR1_HUMAN
DESCRIPTION: RecName: Full=Inositol 1,4,5-trisphosphate receptor type 1; AltName: Full=IP3 receptor isoform 1; Short=IP3R 1; Short=InsP3R1; AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor; Short=Type 1 InsP3 receptor;
FUNCTION: Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways (By similarity).
SUBUNIT: Homotetramer. Interacts with TRPC4. The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium- dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with AHCYL1 (By similarity). Interacts with MRVI1 and CABP1 (via N-terminus).
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Widely expressed.
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: Phosphorylated by cAMP kinase. Phosphorylation prevents the ligand-induced opening of the calcium channels (By similarity).
PTM: Phosphorylated on tyrosine residues.
PTM: Ubiquitination at multiple lysines targets ITPR1 for proteasomal degradation. Approximately 40% of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'-linked (By similarity).
DISEASE: Defects in ITPR1 are the cause of spinocerebellar ataxia type 15 (SCA15) [MIM:606658]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar ataxia (ADCA). It is very slow progressing form with a wide range of onset, ranging from childhood to adult. Most patients remain ambulatory.
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.
CAUTION: Alternative splice sites (AA 1053-1054) represent a non- canonical GA-AG donor-acceptor pair, but are well-supported by all available human transcripts, and by homologous transcripts in mouse, rat and cow.

-  MalaCards Disease Associations
  MalaCards Gene Search: ITPR1
Diseases sorted by gene-association score: spinocerebellar ataxia 29, congenital nonprogressive* (1668), gillespie syndrome* (1589), spinocerebellar ataxia 15* (1269), spinocerebellar ataxia type15* (100), spinocerebellar ataxia type 16 (25), ataxia (16), cerebral palsy, ataxic, autosomal recessive (12), iris hypoplasia (7), autosomal dominant cerebellar ataxia (6), cerebellar ataxia (5), mental retardation and microcephaly with pontine and cerebellar hypoplasia (5), cerebellar disease (4), huntington disease (3)
* = 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: 33.72 RPKM in Brain - Cerebellum
Total median expression: 455.91 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 -90.30246-0.367 Picture PostScript Text
3' UTR -256.501172-0.219 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 Q14643
FrontTopSide
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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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
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:0005515 protein binding
GO:0015085 calcium ion transmembrane transporter activity
GO:0015278 calcium-release channel activity
GO:0019855 calcium channel inhibitor activity
GO:0035091 phosphatidylinositol binding
GO:0070679 inositol 1,4,5 trisphosphate binding

Biological Process:
GO:0001666 response to hypoxia
GO:0006811 ion transport
GO:0006816 calcium ion transport
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0009791 post-embryonic development
GO:0010506 regulation of autophagy
GO:0030168 platelet activation
GO:0032469 endoplasmic reticulum calcium ion homeostasis
GO:0042045 epithelial fluid transport
GO:0048016 inositol phosphate-mediated signaling
GO:0050796 regulation of insulin secretion
GO:0050849 negative regulation of calcium-mediated signaling
GO:0050882 voluntary musculoskeletal movement
GO:0051209 release of sequestered calcium ion into cytosol
GO:0055085 transmembrane transport
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070588 calcium ion transmembrane transport
GO:1903779 regulation of cardiac conduction

Cellular Component:
GO:0005635 nuclear envelope
GO:0005637 nuclear inner membrane
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0005955 calcineurin complex
GO:0014069 postsynaptic density
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016529 sarcoplasmic reticulum
GO:0030658 transport vesicle membrane
GO:0031088 platelet dense granule membrane
GO:0031094 platelet dense tubular network
GO:0031095 platelet dense tubular network membrane
GO:0031410 cytoplasmic vesicle
GO:0032991 macromolecular complex
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  LF207325 - JP 2014500723-A/14828: Polycomb-Associated Non-Coding RNAs.
MA442902 - JP 2018138019-A/14828: Polycomb-Associated Non-Coding RNAs.
AK311008 - Homo sapiens cDNA, FLJ18050.
D26070 - Homo sapiens mRNA for type 1 inositol 1,4,5-trisphosphate receptor, complete cds.
L38019 - Homo sapiens inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) mRNA, complete cds.
BC144563 - Homo sapiens inositol 1,4,5-triphosphate receptor, type 1, mRNA (cDNA clone IMAGE:9053091), complete cds.
U23850 - Homo sapiens inositol 1,4,5 trisphosphate receptor type 1-like mRNA, partial sequence.
AB208868 - Homo sapiens mRNA for Inositol 1,4,5-trisphosphate receptor type 1 variant protein.
S82269 - inositol 1,4,5 trisphosphate receptor [human, Epstein Barr Virus-transformed lymphoblastoid cells, mRNA Partial, 527 nt].
JD356762 - Sequence 337786 from Patent EP1572962.
JD407845 - Sequence 388869 from Patent EP1572962.
JD390704 - Sequence 371728 from Patent EP1572962.
JD132735 - Sequence 113759 from Patent EP1572962.
LF364792 - JP 2014500723-A/172295: Polycomb-Associated Non-Coding RNAs.
MA600369 - JP 2018138019-A/172295: Polycomb-Associated Non-Coding RNAs.
AK293752 - Homo sapiens cDNA FLJ51757 partial cds, highly similar to Inositol 1,4,5-trisphosphate receptor type 1.
LF364813 - JP 2014500723-A/172316: Polycomb-Associated Non-Coding RNAs.
MA600390 - JP 2018138019-A/172316: Polycomb-Associated Non-Coding RNAs.
LF364814 - JP 2014500723-A/172317: Polycomb-Associated Non-Coding RNAs.
MA600391 - JP 2018138019-A/172317: Polycomb-Associated Non-Coding RNAs.
LF364815 - JP 2014500723-A/172318: Polycomb-Associated Non-Coding RNAs.
MA600392 - JP 2018138019-A/172318: Polycomb-Associated Non-Coding RNAs.
LF364818 - JP 2014500723-A/172321: Polycomb-Associated Non-Coding RNAs.
MA600395 - JP 2018138019-A/172321: Polycomb-Associated Non-Coding RNAs.
LF364821 - JP 2014500723-A/172324: Polycomb-Associated Non-Coding RNAs.
MA600398 - JP 2018138019-A/172324: Polycomb-Associated Non-Coding RNAs.
LF364824 - JP 2014500723-A/172327: Polycomb-Associated Non-Coding RNAs.
MA600401 - JP 2018138019-A/172327: Polycomb-Associated Non-Coding RNAs.
LF364863 - JP 2014500723-A/172366: Polycomb-Associated Non-Coding RNAs.
MA600440 - JP 2018138019-A/172366: Polycomb-Associated Non-Coding RNAs.
LF364864 - JP 2014500723-A/172367: Polycomb-Associated Non-Coding RNAs.
MA600441 - JP 2018138019-A/172367: Polycomb-Associated Non-Coding RNAs.
AK309981 - Homo sapiens cDNA, FLJ17023.
AK294594 - Homo sapiens cDNA FLJ54348 complete cds, highly similar to Inositol 1,4,5-trisphosphate receptor type 1.
AK296235 - Homo sapiens cDNA FLJ50742 complete cds, highly similar to Inositol 1,4,5-trisphosphate receptor type 1.
LF364878 - JP 2014500723-A/172381: Polycomb-Associated Non-Coding RNAs.
MA600455 - JP 2018138019-A/172381: Polycomb-Associated Non-Coding RNAs.
LF364879 - JP 2014500723-A/172382: Polycomb-Associated Non-Coding RNAs.
MA600456 - JP 2018138019-A/172382: Polycomb-Associated Non-Coding RNAs.
LF207327 - JP 2014500723-A/14830: Polycomb-Associated Non-Coding RNAs.
MA442904 - JP 2018138019-A/14830: Polycomb-Associated Non-Coding RNAs.
JD281252 - Sequence 262276 from Patent EP1572962.
JD438757 - Sequence 419781 from Patent EP1572962.
JD503171 - Sequence 484195 from Patent EP1572962.
JD357229 - Sequence 338253 from Patent EP1572962.
LF364887 - JP 2014500723-A/172390: Polycomb-Associated Non-Coding RNAs.
MA600464 - JP 2018138019-A/172390: Polycomb-Associated Non-Coding RNAs.
JD466061 - Sequence 447085 from Patent EP1572962.
JD159099 - Sequence 140123 from Patent EP1572962.
JD428440 - Sequence 409464 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
hsa05016 - Huntington's disease

Reactome (by CSHL, EBI, and GO)

Protein Q14643 (Reactome details) participates in the following event(s):

R-HSA-418442 PKG1 phosphorylates IRAG:IP3R1 inhibiting IP3-stimulated Ca2+ release
R-HSA-169680 IP3 binds to the IP3 receptor, opening the endoplasmic reticulum Ca2+ channel
R-HSA-139941 Binding of IP3 to IP3 receptor
R-HSA-5226904 AHCYL1:NAD+ binds ITPR1:I(1,3,5)P3 tetramer, inhibiting it
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-139854 IP3R tetramer:I(1,4,5)P3:4xCa2+ transports Ca2+ from platelet dense tubular system to cytosol
R-HSA-418457 cGMP effects
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-392154 Nitric oxide stimulates guanylate cyclase
R-HSA-114508 Effects of PIP2 hydrolysis
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-418346 Platelet homeostasis
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-416476 G alpha (q) signalling events
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-109582 Hemostasis
R-HSA-139853 Elevation of cytosolic Ca2+ levels
R-HSA-388396 GPCR downstream signalling
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-418360 Platelet calcium homeostasis
R-HSA-372790 Signaling by GPCR

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000456211.1, ENST00000456211.2, ENST00000456211.3, ENST00000456211.4, ENST00000456211.5, ENST00000456211.6, ENST00000456211.7, INSP3R1, ITPR1_HUMAN, NM_002222, Q14643, Q14660, Q99897, uc021wsj.1, uc021wsj.2, uc021wsj.3, uc021wsj.4
UCSC ID: ENST00000456211.8
RefSeq Accession: NM_002222
Protein: Q14643 (aka ITPR1_HUMAN or IP3R_HUMAN)
CCDS: CCDS46740.2, CCDS54550.1, CCDS54551.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ITPR1:
sca15 (Spinocerebellar Ataxia Type 15)
ataxias (Hereditary Ataxia Overview)

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