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FLASH GENE

Symbol

ATP2A2

contributors: mct - updated : 22-11-2017

HGNC name	ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
HGNC id	812

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AKV acrokeratosis verruciformis DAR Darier-White disease
Location	12q24.11      Physical location : 110.719.031 - 110.788.895
Synonym name	sarcoplasmic endoplasmic reticulum calcium ATPase2
	Ca2+ transporting sarco/endo-plasmic reticulum pump type 2 isoforms
	endoplasmic reticulum class 1/2 Ca
	calcium pump 2
	cardiac Ca2+ ATPase
	calcium-transporting ATPase sarcoplasmic reticulum type,
	slow twitch skeletal muscle isoform
Synonym symbol(s)	ATP2B, SERCA2, ATA2, DD, MGC45367, ATP2B, FLJ20293, FLJ38063, DKFZp686P0211
EC.number	3.6.3.8

DNA

TYPE	functioning gene
STRUCTURE	69.87 kb     21 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	Sp1 binding site positively transactivates the ATP2A2 promoter in Keratinocytes

MAPPING

cloned

Y

linked

N

status

confirmed

Map

cen - D12S1110 - (D12S1865 - D12S353 - D12S1126 ) - D12S1163E - D12S1127 - D12S84 - D12S1893 - SELPLG - D12S1637 - (D12S1876 - D12S1605 ) - D12S1440 - DAO - D12S105 - D12S1204E - D12S1583 - D12S1645 - D12S1111 - D12S1339 - D12S1324 - D12S1327 - D12S1838 - (D12S2308 ,D12S1332 ) - SCA2 - D12S2307 - D12S2303 - D12S2298 - ALDH2 - (D12S1344 ,D12S1333 ) - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001681 21 - 4359 NP_001672 - 997 . heart, skeletal muscle, slow twitch and cardiac muscle . restricted to a region within 1.5 microm of the nucleus in pulmonary arterial smooth muscle cells (PMID: 20177054) 2009 19541629 also called ATP2A2a (HK2), or SERCA2a NM_170665 20 splicing 8329 NP_733765 - 1042 . ubiquitously : the most abundant isoform in smooth muscle, non muscle tissue, skin (epidermis), liver . primarily found within 1.5 microm of the plasma membrane in pulmonary arterial smooth muscle cells (PMID: 20177054) 2009 19541629 also called SERCA2b alternative splicing of exon 20 four C terminal residues replaced by a sequence of 49aa mutated in Darier disease playing a key role in the biology of the epidermis coexpressed with the related SERCA type 3 (SERCA3) in many tissues maintains high Ca(2+) concentration in the lumen of the endoplasmic reticulum, interacts specifically with the human delta opioid receptor during early steps of receptor biogenesis in human embryonic kidney 293 cells (PMID: 17588601) association with SERCA2b is required for efficient folding and/or membrane integration of G protein-coupled receptors (PMID: 17588601) high apparent Ca2+ affinity resulting from a direct interaction between its unique C terminus and upstream luminal loops (PMID: 19846779) NM_001135765 19 - 8248 NP_001129237 - 1015 . premature monocytes . only detected in a confined area of cardiomyocytes, in close proximity to the sarcolemma 2006 16402920 also called SERCA2C having lower apparent affinity for cytosolic Ca2+ than SERCA2A and a catalytic turnover rate similar to SERCA2B variant D - - - isoform D - 980 skeletal muscle 2005 15972723

EXPRESSION

Type	restricted

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         Digestive liver       highly Homo sapiens Nervous brain

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining epidermis     Muscular smooth     highly Muscular striatum cardiac     Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Reproductive spermatozoa Homo sapiens Skin/Tegument keratinocyte

cell lineage
cell lines
fluid/secretion	sperm

at STAGE

physiological period

embryo

Text	developing heart (8-wk gestation)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ten transmembrane coiled coil helices
	four of which containing Ca2+ binding sites
	a cytoplasmic beta strand between TM2/3
	a phosphorylation and ATP binding globular domains (the latter linked to stalk sector 5) between TM4/5

HOMOLOGY

interspecies

homolog to murine Atp2a2

Homologene

FAMILY	cation transport ATPase (P-type) family
	type IIA subfamily

CATEGORY

enzyme , signaling , transport

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nuclear envelope
text	sarco/endoplasmic membrane X nuclear envelope ATP2A2-b
	sarcoplasmic reticulum (SERCA2A)

basic FUNCTION	membrane protein that catalyzes the ATP-dependent transport of Ca(2+) from the cytosol to the Sarcoplasmic reticulum
	sarco/endoplasmic reticulum Ca2+ pump
	playing a pivotal role in intracellular Ca2+ signaling and in the regulation of contraction/relaxation cycle
	rate determining factor of Ca2+ reuptake into the SR
	playing an important role in epidermal cell adhesion and differentiation
	playing a role in sperm
	with ATP2A3, modulate thrombin-stimulated SOCE (store-operated Ca(2+)entry) probably by direct interaction with the TRPC1 channel inplatelets
	contributes to cellular calcium homeostasis
	low Ca2+-affinity ATP2A3, and the high Ca2+-affinity ATP2A2 enzymes are simultaneously expressed in B cells
	SERCA2B delivers Ca2+ to sarcoplasmic reticulum Ca2+ stores, where Ca2+ is then released via RYR1 to mediate vasodilatation in pulmonary arterial smooth muscle
	SERCA2A delivers Ca2+ to sarcoplasmic reticulum Ca2+ stores, where Ca2+ is then released via RYR3 and RYR2 to initiate vasoconstriction in pulmonary arterial smooth muscle
	Ca2+-transport ATPase, whose only known function is the reuptake of Ca2+ from the cytosol into the ER lumen (

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

locomotion , active transport

text	calcium transporter, slow-twitch muscle

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	interacting with CALR (degraded via a proteasome-dependent pathway following the formation of a complex with CALR under the stress with H(2)O(2))
	interacting with PLN (a weak inhibitor of ATP2A2a, PLN(R9C), which is diminished in its ability to modify the level of ATP2A2a activity, leads to heart failure despite fast sarcoplasmic reticulum Ca(2+) reuptake)
	although TFAM and TFB2M are recognized as mtDNA-specific transcription factors, they also regulate transcription of nuclear DNA, ATP2A2 gene
	binds to SUMO1 and to ubiquitin-conjugating enzyme E2I (UBE2I)
	TMEM64 interacts with sarcoplasmic endoplasmic reticulum Ca(2+) ATPase 2 (ATP2A2) and modulates its activity
	interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia
	AGTRAP enhances the activity of ATP2A2 and, consequently, facilitates ventricular relaxation

cell & other

REGULATION

inhibited by

by phospholamban (PLN) and sarcolipin (SLN)

Other	SUMOylated at lysines 480 and 585 and this SUMOylation is essential for preserving its ATPase activity and stability
	SUMOylation increases the stability of ATP2A2 by preventing 26S-proteasomal degradation of ATP2A2

ASSOCIATED DISORDERS

corresponding disease(s)

DAR , AKV

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       in acantholytic dyskeratotic naevus constitutional     --low   in airway smooth muscle in asthma that contributes to its secretory and hyperproliferative phenotype and which may play a key role in mechanisms of airway remodeling constitutional     --low   loss of SERCA2b function/regulation and a consequent decrease in ER calcium levels in the liver reduce chaperone function and ER folding capacity ( constitutional     --low   of SUMOylated ATP2A2 was significantly reduced in failing hearts compared to normal heart

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   development of therapeutic agents targeted at effectively enhancing SERCA2b activity, which would in turn decrease ER stress, enhance glucose tolerance, and reduce hepatosteatosis

ANIMAL & CELL MODELS

	overexpression of Serca2b in the liver of obese mice significantly reduces the lipogenic gene expression and the triglyceride content in the liver