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FLASH GENE

Symbol

PDE10A

contributors: mct - updated : 29-04-2016

HGNC name	phosphodiesterase 10A
HGNC id	8772

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	COCBS Childhood-Onset Chorea with Bilateral Striatal Lesions
Location	6q27      Physical location : 165.740.778 - 166.075.584
Synonym name	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Synonym symbol(s)	HSPDE10A, FLJ11894, FLJ25677, PDE10A19
EC.number	3.4.1.17, 3.1.4.35

DNA

TYPE	functioning gene
STRUCTURE	334.81 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (CAAT box)
	cytosine-phosphate-guanine/HTF
text structure	promoter sequence highly GC-rich and did not contain a TATA motif and a CAAT box, suggesting it is a housekeeping gene

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	without/with a phosphorylation site respectively 12 splice variants characterized by unique N- and C-terminal sequences have been described (PMID: 22105073)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001130690 22 splicing 8189 NP_001124162 89.4 789 - 2006 16330539 NM_006661 23 splicing 8317 NP_006652 - 779 - 2001 14604994 N-terminus having a putative phosphorylation site by cAMP-dependent protein kinase (cAK) phosphorylation at Thr16 by PKA caused alteration of subcellular localization of PDE10A2 from the Golgi apparatus to cytosol

EXPRESSION

Type

widely

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   brain basal nuclei putamen     Homo sapiens Nervous brain basal nuclei caudate nucleus     Homo sapiens   brain basal nuclei striatum   predominantly Homo sapiens Reproductive male system testis     highly Homo sapiens mRNA Visual eye retina       Rattus norvegicus

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Visual cone photoreceptor Rattus norvegicus Visual rod photoreceptor Rattus norvegicus

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a single N terminal putative cGMP binding sequence, and a tandem of so-called GAF domains in its N-terminal regulatory regions , and this two N-terminal domains, GAF-A and GAF-B, of which the latter binds to cAMP
	a C terminal catalytic domain

HOMOLOGY

Homologene

FAMILY

cyclic nucleotide phosphodiesterase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
text	cAMP signaling in the Golgi area and the cytosol in neurons is controlled through alteration of subcellular localization of PDE10A brought by activation of PKA in response to intracellular elevations of cAMP
	most often associated with membranes in dendrites and spines

basic FUNCTION	exhibiting unique kinetic properties and inhibitor sensitivity
	playing a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides
	may have a role in the pain pathway of migraine as well as trigeminal neuralgia and trigeminal autonomic cephalalgias
	potential role of PDE10A in the adaptation of cyclic nucleotide signaling to daily changes in light intensity in retinal neurons including photoreceptors
	is potently stimulated by cAMP, and the GAF-mediated stimulation alters the enzymatic parameters such that the enzyme acts as a cAMP-specific phosphodiesterase
	plays a pivotal role in striatal signaling and striatum-mediated salience attribution
	critical role of PDE10A in motor control
	contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein

cell & other

REGULATION

activated by

cAMP, is the only PDE activated by cAMP

inhibited by	by the non-specific PDE inhibitor, IBMX
	by cGMP

Other

phosphorylation of PDE10A has an impact on the interaction with other signaling proteins and adds an additional line of complexity to the role of PDE10A in regulation of synaptic transmission

ASSOCIATED DISORDERS

corresponding disease(s)

COCBS

Susceptibility

to hyperthyrotropinaemia (and possibly hypothyroidism)

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology dystonia   pharmacological manipulation of cAMP levels in striatal medium spiny neurons (MSNs), is a promising therapeutic strategy for the treatment of chorea and other movement disorders

ANIMAL & CELL MODELS