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FLASH GENE

Symbol

PNKD

contributors: mct - updated : 03-01-2017

HGNC name	paroxysmal nonkinesiogenic dyskinesia
HGNC id	9153

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DYT8 dystonia 8, paroxysmal dystonic choreoathetosis
Location	2q35      Physical location : 219.135.114 - 219.211.515
Synonym name	likely ortholog of mouse brain protein 17
	trans-activated by hepatitis C virus core protein 2
	myofibrillogenesis regulator 1
Synonym symbol(s)	FKSG19, TAHCCP2, KIAA1184, MGC31943, MR-1, BRP17, PDC, FPD1, KIPP1184, MR1, DYT8, PKND1, TAHCCP2
EC.number	3.1.2.6

DNA

TYPE	functioning gene
STRUCTURE	76.40 kb     10 Exon(s)

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_015488 10 - 3129 42.9 385 specifically in brain, only in the central nervous system (CNS) mitochondrial 2011 21487022 PNKD-L, MR-1 L (variant 1) located to the cell membrane, and remains in late endosomes before trafficking to the cell membrane N-terminus of the wild-type (WT) long PNKD isoform (PNKD-L) undergoing a cleavage event contain the beta-lactamase domain in the C-terminus degraded through the proteasomal, lysosomal and autophagy pathways may be involved in vesicle recycling or membrane protein transport in CNS neurons NM_022572 9 - 3002 NP_072094 40.7 361 widely, localized in the Golgi apparatus, ER and plasma membrane (Ghezzi 2009) 2011 21487022 MR-1M (variant 2) PNKD-M isoforms contain the beta-lactamase domain in the C-terminus exons 3 to 10 and a unique 5'exon encoding 56 AA specifically located in the perinuclear region NM_001077399 3 - 774 - 142 ubiquitous 2011 21487022 MR-1S (variant 3) PNKD-S contains three exons with no homology to any known protein exon 1 and 2 and a unique 3'exon encoding 63 AA before a stop codon located only in the cytoplasm and nucleus, mitochondrial, widely distributed in cells

EXPRESSION

Type

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 Cardiovascular heart         Lymphoid/Immune spleen         Nervous brain       highly   spinal cord         Reproductive female system ovary         male system testis       Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	zinc binding residues
	a transmembrane domain
	MTS (mitochondrial targeting sequence)
	a beta-lactamase domain in the C-terminus

HOMOLOGY

intraspecies	homolog to HAGH
	homolog to murine Brp17

Homologene

FAMILY

beta-lactamase-like family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,nucleus

basic FUNCTION	playing a role in neuronal excitability
	important role in maintaining cellular redox status
	functions likely to modulate striatal neuro-transmitter release in response to stress and other precipitating factors
	functions as a tumor promoter in MCF7 cells by activating the MEK/ERK signaling
	is a novel synaptic protein with a regulatory role in neurotransmitter release

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with MYL9 (Ren 2008)
	interacts with synaptic active zone proteins Rab3-interacting molecule (RIMS1) and RIMS2, localizes to synapses, and modulates neurotransmitter release

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DYT8

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   associated with cancer cell proliferation and migration through MYL9 (Ren 2008) tumoral     --over   in human breast cancer cells and participates in tumor promotion in human breast cancer MCF7 cells by activating the ERK1/2 signaling pathway

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	(Ren 2008)
	System Type Disorder Pubmed cancer     might be a potential cancer therapeutic target

ANIMAL & CELL MODELS

Pnkd-deficient mice have lower brain glutathione levels and impaired motor coordination