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FLASH GENE

Symbol

ITPR2

contributors: mct/npt - updated : 25-05-2016

HGNC name	inositol 1,4,5-triphosphate receptor, type 2
HGNC id	6181

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	497.85 kb     57 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002223 57 - 12568 NP_002214 308 2701 - 2015 25499268

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive         predominantly Homo sapiens   liver       highly Reproductive female system uterus     highly   female system breast mammary gland   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Muscular striatum skeletal     Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES		Hydrophobic
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
	five MIR domains
	a central transducing/modulatory domain,
	a C-terminal channel domain

HOMOLOGY

Homologene

FAMILY

INSP3 receptor family

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	coexpressed with RYR3
	concentrated in the vicinity of the node, and the outer Schwann cell cytoplasm similar to the Kv1.5 potassium channel
	located on the endoplasmic reticulum (ER)

basic FUNCTION	inositol 1,4,5-triphosphate receptor, involved in Ca2+ mobilization from the endoplastic reticulum
	required for long lasting, regular Ca++ oscillations
	calcium signaling
	phosphoregulation of ITPR2 results in subtype-specific effects and may play a role in the specificity of calcium signals by 'shaping' the spatio-temporal profile of the response (Yule 2003)
	its apical concentration is essential for the formation of Ca(2+) waves in hepatocytes (Hernandez 2007)
	pericanalicular calcium signaling mediated by ITPR2 plays an important role in maintaining bile salt secretion through posttranslational regulation of ABCB11, suggesting that loss or redistribution of ITPR2 may contribute to the pathophysiology of intrahepatic cholestasis
	modulates apical acinar cell Ca(2+) signals and pancreatic enzyme secretion
	functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria
	ITPR2, ITPR3 are essential for tear secretion in both parasympathetic and sympathetic pathways
	key regulator for the activity of calcium ion transmembrane transportation, which plays a critical role in cell cycle and proliferation
	leaky RYR2, but not ITPR2, channels cause mitochondrial Ca2+ overload and dysfunction in heart failure

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

constituent of heterotetrameric channel with ITPR1 and ITPR3

INTERACTION

DNA

RNA

small molecule

protein	ITPR1
	ITPR3
	ITPR1, ITPR2 enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2

cell & other

REGULATION

Other	transcriptionally regulated during myelopoiesis target of EVI-1 and EVI1-VP16 fusion gene
	highly sensitive to IP3 oscillations

ASSOCIATED DISORDERS

corresponding disease(s)

IANHI

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   expression was greater in the peripheral blood of ALS patients (van Es 2007) constitutional       loss of function loss of ITPR2-mediated Ca2+ release causes isolated anhidrosis in humans constitutional       loss of function known to mediate endoplasmic reticulum (ER) calcium release, as well as loss of MCU, necessary for mitochondrial calcium uptake, enable escape from oncogene-induced senescence (OIS)

Susceptibility

to amyotrophic lateral sclerosis

Variant & Polymorphism	variant increasing the risk of ALS (Dupre 2009)

Candidate gene
Marker	is a novel biomarker for worse prognosis in cytogenetically normal acute myeloid leukemia
Therapy target
	System Type Disorder Pubmed dermatology skin   specific ITPR2 inhibitors have the potential to reduce sweat production in hyperhidrosis

ANIMAL & CELL MODELS

Itpr2-/- mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2-/- animals revealed a decrease in Ca2+ response compared with controls