Human Disease Model Report: cardiac arrhythmia (postulated), ATP2A-related

General Information

Name

cardiac arrhythmia (postulated), ATP2A-related

FlyBase ID

FBhh0000728

Disease Ontology Term

heart conduction disease

Parent Disease

cardiac arrhythmias

OMIM

Overview

Abnormalities in the amount or structure of SERCA Ca(2+)-ATPase proteins have been linked to cardiac malfunction in mammals. There are three SERCA Ca(2+)-ATPase genes in human, ATP2A1, ATP2A2, and ATP2A3, more completely described as encoding ATPase sarcoplasmic/endoplasmic reticulum Ca[2+] transporting proteins. ATP2A1 and ATP2A2 are implicated in human diseases (see Brody myopathy, MIM:601003, and the OMIM report for ATP2A2, MIM:108740), as are several related genes (see 'neurological disorders, ATPα-related' FBhh0000547, and 'migraine, familial hemiplegic 2' FBhh0000548). There is a single orthologous gene in Drosophila, Dmel\SERCA, for which classical loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

None of the ATP2A human genes has been introduced into flies.

Dmel\SERCA protein is observed at high levels in the larval heart. Animals homozygous for temperature-sensitive loss-of-function mutations exhibit serious defects in muscle action potential generation in flight muscles; the phenotype is more severe at elevated temperatures. Heart beat, monitored at the white prepupal stage, shows a decrease in frequency and abnormal rhythmicity in mutant animals at elevated temperatures. Genetic and many physical interactions have been described for Dmel\SERCA; see below and in the SERCA gene report.

See also 'neuromuscular disease, ATP2A-related' (FBhh0000729).

[updated Feb. 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: cardiac arrhythmias

Symptoms and phenotype

The term "arrhythmia" refers to any change from the normal sequence of electrical impulses in the heart, such as atrial fibrillation, bradycardia (slow heartbeat), tachycardia (rapid heart rate), conduction disorders, rhythm disorders, ventricular fibrillation, premature contractions. Arrhythmias may be completely harmless or life-threatening. (http://www.heart.org/HEARTORG/Conditions/Arrhythmia/AboutArrhythmia/About-Arrhythmia_UCM_002010_Article.jsp)

(FlyBase Curators, 2013-)

Specific Disease Summary: cardiac arrhythmia (postulated), ATP2A-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

ATP2A1, ATP2A2, ATP2A3 encode SERCA Ca(2+)-ATPases, intracellular pumps located in the sarcoplasmic or endoplasmic reticulum of muscle cells. These enzymes catalyze the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen; some are involved in calcium sequestration associated with muscular excitation and contraction. [Gene Cards, ATP2A1, ATP2A2, ATP2A3; 2018.02.15]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): ATP2A1
Gene2Function (human gene): ATP2A2
Gene2Function (human gene): ATP2A3
Gene Cards: ATP2A1
Gene Cards: ATP2A2
Gene Cards: ATP2A3
MedlinePlus (gene): ATP2A3
MedlinePlus (gene): ATP2A2
MedlinePlus (gene): ATP2A1
MARRVEL (human gene): ATP2A1
MARRVEL (human gene): ATP2A2
MARRVEL (human gene): ATP2A3
NCBI (Entrez) gene: ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1
NCBI (Entrez) gene: ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2
NCBI (Entrez) gene: ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3

Disease synonyms

cardiac dysrhythmia

heart arrhythmia

Search term: calcium channelopathy

Search term: P-type ATPase-related disease

Related Diseases

Related human health report(s)

cardiac arrhythmias

neurological disorders, ATPα-related

neuromuscular disease, ATP2A-related

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3

D. melanogaster ortholog (based on DIOPT)

Dmel\SERCA

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 3 human to 1 Drosophila. The human genes are ATP2A1, ATP2A2, and ATP2A3.

Human gene (HGNC)

Symbol / Name

ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1

D. melanogaster ortholog (based on DIOPT)

Dmel\SERCA

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 3 human to 1 Drosophila. The human genes are ATP2A1, ATP2A2, and ATP2A3.

Human gene (HGNC)

Symbol / Name

ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2

D. melanogaster ortholog (based on DIOPT)

Dmel\SERCA

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 3 human to 1 Drosophila. The human genes are ATP2A1, ATP2A2, and ATP2A3.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\SERCA

Gene Snapshot

Sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) encodes an endoplasmic reticulum (ER) calcium pump with roles in ER calcium homeostasis and lipid storage. [Date last reviewed: 2019-09-26]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

ATPIIA

Comments on ortholog(s)

High-scoring ortholog of human ATP2A1, ATP2A2, and ATP2A3 (1 Drosophila to 3 human); Dmel\SERCA shares 68-72% identity and 80-85% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (107 groups)

SERCA

protein-protein

Interacting group

Assay

References

SERCA - Agpat3

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Akt

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

SERCA - Arf1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Arl8

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Atpα

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - ATPsynβ

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - ATPsynγ

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - blw

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - cathD

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CCT3

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CCT6

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Cdc50

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG1416

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG2065

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG2070

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG3164

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG5854

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG6550

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG13220

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG15098

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG30344

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG31729

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CG33303

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Chc

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Cnx99A

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - CtsL1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Cyp12d1-p

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Desat1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Diap1

anti bait coimmunoprecipitation, western blot

(Maurya and Tapadia, 2023)

SERCA - Dredd

anti tag coimmunoprecipitation, peptide massfingerprinting

(Fukuyama et al., 2012)

SERCA - Droj2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - ds

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

SERCA - Dsor1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

SERCA - egg

two hybrid

(Stabell et al., 2006)

SERCA - eIF4E1

two hybrid

(Santalla et al., 2022)

SERCA - eIF4E4

two hybrid

(Santalla et al., 2022)

SERCA - FASN1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Fatp1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - fax

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - fj

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

SERCA - GCS2β

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Gfat2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Gp93

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Gp210

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Hel25E

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - hpo

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

SERCA - Hsp83

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Idh3a

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Ipo9

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - jagn

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Karyβ3

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - KdelR

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Kdsr

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - kkv

ubiquitin reconstruction, pull down, western blot, tandem affinity purification, Identification by mass spectrometry, bimolecular fluorescence complementation, fluorescence microscopy, anti bait coimmunoprecipitation

(Zhu et al., 2022)

SERCA - Kr-h2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - ksr

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

SERCA - Ldh

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - mats

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

SERCA - Mcad

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Mec2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Mhc

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Mpcp2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - MRP

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - mt:CoII

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Nep4

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Schiemann et al., 2022)

SERCA - Nfs1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Ost48

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - OstΔ

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - ox

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Pcb

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Pdk1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

SERCA - Pi3K68D

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - porin

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Pp2A-29B

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Prm

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rab1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rab2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rab5

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rab6

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Raf

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

SERCA - Rap1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rdh1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rer1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - RpS10b

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Rpt1

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - SclA

anti tag coimmunoprecipitation, western blot

(Magny et al., 2013)

SERCA - SclB

anti tag coimmunoprecipitation, western blot

(Magny et al., 2013)

SERCA - ScsβA

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - ScsβG

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Sec61α

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Seipin

anti tag coimmunoprecipitation, western blot, peptide massfingerprinting

(Bi et al., 2014)

SERCA - sima

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

SERCA - spidey

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Spindly

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - SsRβ

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - sstn

anti tag coimmunoprecipitation, peptide massfingerprinting

(Liu et al., 2015)

SERCA - Surf4

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Tapδ

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Tecr

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - THADA

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot

(Moraru et al., 2017)

SERCA - Tm2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Tspo

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - UQCR-C2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - Vha68-2

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - wal

experimental knowledge based

(Guruharsha et al., 2011)

SERCA - wts

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

SERCA - ZnT63C

experimental knowledge based

(Guruharsha et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)

SERCA

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

SERCA^JF01948

model of heart disease

CEA

(Kuo et al., 2014)

model of Brody myopathy

CEA

(Bruels et al., 2019)

SERCA^HMS02878

model of Brody myopathy

CEA

(Bruels et al., 2019)

Modifiers Based on Experimental Evidence ( 6 )

Allele

Disease

Interaction

References

SERCA^UAS.Tag:MYC

ameliorates neurodegenerative disease

modeled by trp^P365

(Huang et al., 2016)

SERCA^KK107371

ameliorates amyotrophic lateral sclerosis type 10

modeled by TBPH^{UAS.Tag:FLAG.Tag:HA}

(Park et al., 2020)

ameliorates frontotemporal dementia and/or amyotrophic lateral sclerosis 1

modeled by Zzzz\poly-PR^PO-100.UAS

(Park et al., 2020)

modeled by Zzzz\poly-GR^PO-100.UAS

(Park et al., 2020)

SERCA^JF01948

ameliorates Huntington's disease

modeled by Hsap\HTT^Q128.UAS

(Martin et al., 2021)

SERCA^wt.tinC

ameliorates dilated cardiomyopathy

modeled by wupA^hdp-2

(Abraham and Wolf, 2013)

SERCA^HMS02878

ameliorates Huntington's disease

modeled by Hsap\HTT^Q128.UAS

(Martin et al., 2021)

SERCA^UAS.cFa

ameliorates neurodegenerative disease

modeled by sws¹

(Sunderhaus et al., 2019)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

P-type ATPase disorders

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

SERCA^{RNAi.13xlexAop.cZa}

P{13xlexAop-SERCA.RNAi.Z}

y¹ v¹; P{TRiP.JF01948}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS02878}attP2

SERCA^VDRC.cUa

P{VDRC.SERCA.U}

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

SERCA^rev4

loss of function allele

w¹¹¹⁸; SERCA^rev4/CyO; l(3)*^*/MKRS

SERCA^UAS.cFa

w¹¹¹⁸; P{UAS-SERCA.F}8

References (6)

Report Sections

Open Close