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FLASH GENE
Symbol ITPR1 contributors: mct/npt - updated : 25-05-2016
HGNC name inositol 1,4,5-triphosphate receptor, type 1
HGNC id 6180
Corresponding disease
CLA4 cerebellar ataxia 4
GLSPS2 Gillespie syndrome 2
SCA15 spinocerebellar ataxia 15
SCA16 spinocerebellar ataxia 16
Location 3p26.1      Physical location : 4.535.031 - 4.889.522
Synonym name
  • IP3 receptor isoform 1
  • type 1 inositol 1,4,5-trisphosphate receptor
  • Synonym symbol(s) IP3R1, INSP3R1, IP3R, DKFZp313N1434, DKFZp313E1334, ACV, CLA4, INSP3R1, PPP1R94,
    DNA
    TYPE functioning gene
    STRUCTURE 354.49 kb     59 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    CCR2 3p21.31 chemokine (C-C motif) receptor 2 CCR5 3p21.31 chemokine (C-C motif) receptor 5 CCRL2 3p21.32-p21.31 chemokine (C-C motif) receptor-like 2 CHL1 3p26 cell adhesion molecule with homology to L1CAM (close homolog of L1) LOC391503 3 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) CNTN6 3p26-p25 contactin 6 LOC391504 3 similar to 60S ribosomal protein L23a LOC391505 3 similar to 60S ribosomal protein L21 CNTN4 3p26.2 contactin 4 IL5RA 3p26-p25 interleukin 5 receptor, alpha TRNT1 3p25.1 tRNA nucleotidyl transferase, CCA-adding, 1 LOC51185 3p26.2 protein x 0001 LRRN1 3p26.2 leucine rich repeat neuronal 1 SETMAR 3p26.1 SET domain and mariner transposase fusion gene SUMF1 3p26.2 SET domain and mariner transposase fusion gene MRPS10P2 3p26 mitochondrial ribosomal protein S10 pseudogene 2 ITPR1 3p26-p25 inositol 1,4,5-triphosphate receptor, type 1 BHLHB2 3p26.1-p25.3 basic helix-loop-helix domain containing, class B, 2 LOC391506 3 similar to autoantigen NOR-90 FLJ10702 EDEM1 3p26.1 ER degradation enhancer, mannosidase alpha-like 1 MRPS35P1 3p25.3 mitochondrial ribosomal protein S35 pseudogene 1 MRPS36P1 3p25.3 mitochondrial ribosomal protein S36 pseudogene GRM7 3p26.1-p25.2 glutamate receptor, metabotropic 7 LOC389092 3 LOC389092 LMCD1 3p26-p24 LIM and cysteine-rich domains 1 LOH3CR2A 3 loss of heterozygosity, 3, chromosomal region 2, gene A LOC51066 3p25.3 fls485 LOC391507 3 similar to seven transmembrane helix receptor CAV3 3p25 caveolin 3 OXTR 3p25 oxytocin receptor RAD18 3p25-p24 RAD18 homolog (S. cerevisiae)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    59 - 10098 - 2710 - 2016 27108797
    58 - 10053 - 2695 - 2016 27108797
  • lacks exon 12
  • 61 - 10197 - 2743 - 2016 27108797
  • lacks exon 12, uses an alternate in-frame splice site in intron 23, and includes three additional exons between variant 1 exons 39 and 40
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Nervousbrain   predominantly Homo sapiens
    Reproductivemale systemprostate  highly
    Respiratorylung   moderately
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Nervousperipherous  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet
    Nervousneuron Homo sapiens
    NervousPurkinje cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • a N terminal cytoplasmic ligand binding domain linked by a modulatory domain to a channel forming hydrophobic domain made of six membrane-spanning segments near the C terminus (calcium channel)
  • ATP binding sites (GXGXXG sequence)
  • a IRBIT (inositol triphosphate receptor binding protein) domain
  • a central transducing/modulatory domain,
  • a C-terminal channel domain
  • conjugated ubiquitinated
    mono polymer homomer , tetramer
    HOMOLOGY
    Homologene
    FAMILY
  • INSP3 receptor family
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleolus
    text
  • intracellular membranes of platelets
  • coexpressed with RYR3
  • clustered at the node of Ranvier, in a distribution that is similar to the Nav1.6 sodium channels in the sciatic nerve
  • basic FUNCTION
  • inositol 1,4,5-triphosphate receptor, involved in Ca++ mobilization from the endoplastic reticulum
  • major neuronal member in the central nervous system
  • significantly decreases total Ca(2+) signals and terminates Ca(2+) oscillations
  • playing a predominant role in the function of the vascular smooth muscle
  • ITPR1 and ITPR3 may play a redundant role in the development of the second heart field (SHF)
  • ITPR1 localization, via protein EPB41L1, is necessary for Ca(2+) wave formation, which in turn mediates neurite formation
  • role for the HIF2A/ITPR1 axis in regulating Clear cell renal carcinomas cell survival
  • Ca(2+) release mediated by ITPR1 is an essential mechanism during the early steps of myoblast differentiation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text calcium ion transporter
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • constituent of heterotetrameric channel with ITPR2 and ITPR3
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to ITPR2, ITPR3, CABP1 (in the brain)
  • binding to CYCS during apoptosis
  • interacting with RYR1, RYR2, SHANK1, SHANK3 and TRPC4
  • interacting with TXNDC4 in a pH, redox-state and calcium-dependent manner
  • interacting with PKD2 (modulate intracellular Ca2+ signaling)
  • binding CIB1 (White 2006)
  • CABP1 interacting with ITPR1 in the brain through a Ca2+-induced binding of the CABP1 C-domain to the N-terminal region of ITPR1 (residues 1-587)
  • interaction juxtaposing the cytosolic RING domain of RNF170 with the cytosolic regions of activated ITPR1 that become ubiquitinated
  • ITPR1, ITPR2 enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2
  • CA8 is an allosteric inhibitor of ITPR1, which regulates intracellular calcium release fundamental to critical cellular functions including neuronal excitability, neurite outgrowth, neurotransmitter release
  • DISC1 binds ITPR1 mRNA with ZNF385A, thereby regulating its dendritic transport for synaptic plasticity
  • calcium-release channel that is inositol 1,4,5-trisphosphate (IP3) responsive
  • cell & other
    REGULATION
    repressed by downregulated by muscarinic receptor activation
    Other highly sensitive to ATP mediating less regular Ca++ oscillations,in T lymphocyte
    phosphorylated by cAMP kinases
    regulated by TNF-alpha (in a neuronal environment modulates ITPR1 expression and intracellular Ca(2+) homeostasis) (Park 2009)
    RNF170, a E3 ligase, mediates ITPR1 ubiquitination
    ASSOCIATED DISORDERS
    corresponding disease(s) SCA16 , SCA15 , GLSPS2 , CLA4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in neurodegenerative disease (olivopontocerebellar atrophy, cerebellar atrophy of Holmes type, Alzheimers disease, Friedreich's ataxia, cerebellopontine ataxia)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    CA8 and ITPR1 represent new therapeutic targets for chronic pain
    ANIMAL & CELL MODELS
  • mice with complete homozygosity for Itpr1 ablation suffer from severe epilepsy and ataxia and die either in utero or before weaning