ATP2A1 ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: ATP2A1provided by HGNC
Official Full Name: ATPase, Ca++ transporting, cardiac muscle, fast twitch 1provided by HGNC
Primary source: HGNC:811
See related: Ensembl:ENSG00000196296; HPRD:00157; MIM:108730; Vega:OTTHUMG00000131760
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ATP2A; SERCA1
Summary: This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 16p12.1

Sequence :: Chromosome: 16; NC_000016.9 (28889809..28915830)

See ATP2A1 in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

These results indicate that PKC signaling is involved in the splicing of SERCA1 and provide new evidence for a link between alternative splicing and PKC signaling.
Title: Regulation of the alternative splicing of sarcoplasmic reticulum Ca²⁺-ATPase1 (SERCA1) by phorbol 12-myristate 13-acetate (PMA) via a PKC pathway.
both topology and function of PLN are shaped by the interactions with lipids, which fine-tune the regulation of SERCA
Title: Structural topology of phospholamban pentamer in lipid bilayers by a hybrid solution and solid-state NMR method.
Differential SERCA1a S-nitrosylation and SERCA1a/2a co-expression in subsets of slow myofibers should be considered as signs of an altered cytosolic Ca(2+) homeostasis following chronic muscle disuse
Title: Atypical fast SERCA1a protein expression in slow myofibers and differential S-nitrosylation prevented by exercise during long term bed rest.
the increase in mechanical efficiency of cycling occurring during first weeks of endurance training may be due to down-regulation of SERCA pumps
Title: Training induced decrease in oxygen cost of cycling is accompanied by down-regulation of SERCA expression in human vastus lateralis muscle.
The truncated variant of the sarcoendoplasmic reticulum Ca(2+)-ATPase 1 (S1T) amplifies endoplasmic reticulum stress through the PERK-eIF2alpha-ATF4-CHOP pathway.
Title: Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress.
Ca (2+) binding to Site I of SERCA1a in fact slightly reduces Trp fluorescence, and consequently that the rise in this fluorescence generally observed when two Ca (2+) ions bind to WT SERCA1a mainly reflects Ca (2+) binding at Site II of SERCA1a.
Title: Use of glycerol-containing media to study the intrinsic fluorescence properties of detergent-solubilized native or expressed SERCA1a.
Overexpression of the CUG repeat expansion of DMPK mRNA resulted in exclusion of exon 22 of SERCA1.
Title: Molecular mechanisms responsible for aberrant splicing of SERCA1 in myotonic dystrophy type 1.
Despite similar total calcium contents, lower SERCA and PMCA activities were found in sacs associated with hydrocele compared to those associated with undescended testis suggest a difference among the levels of cytosolic calcium.
Title: Sarco(endo)plasmic reticulum and plasmalemmal Ca(2+)-ATPase activities in cremaster muscles and sacs differ according to the associated inguinal pathology.
a functional abnormality in SERCA1 may have a role in inferior oblique overaction, an ocular motor disorder
Title: Calcium uptake and release through sarcoplasmic reticulum in the inferior oblique muscles of patients with inferior oblique overaction.
We suggest that aberrant splicing of SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle
Title: Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1.

Submit: New GeneRIF Correction See all (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
O14983	P35568	IRS1	HPRD	PubMed
O14983	Q9Y4H2	IRS2	HPRD	PubMed
O14983	P26678	PLN	HPRD	PubMed
O14983	O00631	SLN	HPRD	PubMed
BioGRID:106977	BioGRID:107506	CFTR	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106977	BioGRID:114030	CUL3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106977	BioGRID:109915	ITPR3	BioGRID	PubMed	Co-fractionation
BioGRID:106977	BioGRID:111136	PCK1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106977	BioGRID:111365	PLN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106977	BioGRID:112474	SLN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106977	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Alzheimer's disease, organism-specific biosystem (from KEGG)
Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
Alzheimer's disease, conserved biosystem (from KEGG)
Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
Alzheimers Disease, organism-specific biosystem (from WikiPathways)
Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
Calcium signaling pathway, organism-specific biosystem (from KEGG)
Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
Calcium signaling pathway, conserved biosystem (from KEGG)
Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Ion channel transport, organism-specific biosystem (from REACTOME)
Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
Ion transport by P-type ATPases, organism-specific biosystem (from REACTOME)
Ion transport by P-type ATPases, organism-specific biosystemThe P-type ATPases (E1-E2 ATPases) are a large group of evolutionarily related ion pumps that are found in bacteria, archaea and eukaryotes. They are referred to as P-type ATPases because they catal...
Pancreatic secretion, organism-specific biosystem (from KEGG)
Pancreatic secretion, organism-specific biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
Pancreatic secretion, conserved biosystem (from KEGG)
Pancreatic secretion, conserved biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
Platelet calcium homeostasis, organism-specific biosystem (from REACTOME)
Platelet calcium homeostasis, organism-specific biosystemCa2+ homeostasis is controlled by processes that elevate or counter the elevation of cytosolic Ca2+. During steady state conditions, cytoplasmic Ca2+ is reduced by the accumulation of Ca2+ in intrac...
Platelet homeostasis, organism-specific biosystem (from REACTOME)
Platelet homeostasis, organism-specific biosystemUnder normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in charact...
Pre-NOTCH Expression and Processing, organism-specific biosystem (from REACTOME)
Pre-NOTCH Expression and Processing, organism-specific biosystemIn humans and other mammals the NOTCH gene family has four members, NOTCH1, NOTCH2, NOTCH3 and NOTCH4, encoded on four different chromosomes. Their transcription is developmentally regulated and tiss...
Pre-NOTCH Processing in Golgi, organism-specific biosystem (from REACTOME)
Pre-NOTCH Processing in Golgi, organism-specific biosystemNOTCH undergoes final posttranslational processing in the Golgi apparatus (Lardelli et al. 1994, Blaumueller et al. 1997, Weinmaster et al. 1991, Weinmaster et al. 1992, Uyttendaele et al. 1996). Mov...
Reduction of cytosolic Ca++ levels, organism-specific biosystem (from REACTOME)
Reduction of cytosolic Ca++ levels, organism-specific biosystemDuring steady state conditions, cytoplasmic [Ca2+] is reduced by the accumulation of Ca2+ in intracellular stores and Ca2+ extrusion.
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by NOTCH, organism-specific biosystem (from REACTOME)
Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules
calcium transport I, organism-specific biosystem (from BIOCYC)
calcium transport I, organism-specific biosystem
calcium transport I

General gene information

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Markers

NoName (e-PCR)
- UniSTS:484683

SHGC-61052 (e-PCR)
- UniSTS:87425

RH48558 (e-PCR)
- UniSTS:92336

SH2B_9440 (e-PCR)
- UniSTS:471756

Genotypes

See ATP2A1 SNP Geneview Report
See ATP2A1 SNP Genotype Report
See ATP2A1 SNP Variation Viewer Report

Homology

Homologs of the ATP2A1 gene: The ATP2A1 gene is conserved in chimpanzee, dog, cow, mouse, zebrafish, fruit fly, mosquito, C.elegans, M.oryzae, N.crassa, A.thaliana, and rice.
Map Viewer (Mouse)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
ATP binding	ISS Inferred from Sequence or Structural Similarity more info
calcium ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
calcium-transporting ATPase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
ATP catabolic process	ISS Inferred from Sequence or Structural Similarity more info
apoptotic mitochondrial changes	IMP Inferred from Mutant Phenotype more info	PubMed
blood coagulation	TAS Traceable Author Statement more info
calcium ion import	IMP Inferred from Mutant Phenotype more info	PubMed
calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
elevation of endoplasmic reticulum calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
elevation of mitochondrial calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
ion transmembrane transport	TAS Traceable Author Statement more info
maintenance of mitochondrion location	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of striated muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of fast-twitch skeletal muscle fiber contraction	IDA Inferred from Direct Assay more info	PubMed
reduction of endoplasmic reticulum calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of striated muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
relaxation of skeletal muscle	IDA Inferred from Direct Assay more info	PubMed
response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
transmembrane transport	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
H zone	IDA Inferred from Direct Assay more info	PubMed
I band	IDA Inferred from Direct Assay more info	PubMed
calcium channel complex	IC Inferred by Curator more info	PubMed
endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
endoplasmic reticulum-Golgi intermediate compartment	ISS Inferred from Sequence or Structural Similarity more info
integral to membrane	NAS Non-traceable Author Statement more info	PubMed
membrane	ISS Inferred from Sequence or Structural Similarity more info
perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
platelet dense tubular network membrane	TAS Traceable Author Statement more info
sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
sarcoplasmic reticulum	NAS Non-traceable Author Statement more info	PubMed
sarcoplasmic reticulum membrane	IC Inferred by Curator more info	PubMed
sarcoplasmic reticulum membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: sarcoplasmic/endoplasmic reticulum calcium ATPase 1

Names: sarcoplasmic/endoplasmic reticulum calcium ATPase 1; calcium pump 1; SR Ca(2+)-ATPase 1; endoplasmic reticulum class 1/2 Ca(2+) ATPase; calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform

NP_004311.1

EC 3.6.3.8

NP_775293.1

EC 3.6.3.8

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023327.1 RefSeqGene

Range

5001..31022

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004320.4 → NP_004311.1 sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (a) represents the longer transcript but encodes the shorter isoform (a).

Source sequence(s)

AK291314, BX537784, BX647367

Consensus CDS

CCDS42139.1

UniProtKB/Swiss-Prot

O14983

UniProtKB/TrEMBL

Q7Z675

Related

ENSP00000378879, OTTHUMP00000162562, ENST00000395503, OTTHUMT00000254687

Conserved Domains (6) summary

TIGR01116
Location:53 – 989
Blast Score: 4080

ATPase-IIA1_Ca; sarco/endoplasmic reticulum calcium-translocating P-type ATPase

pfam00122
Location:101 – 341
Blast Score: 526

E1-E2_ATPase; E1-E2 ATPase

pfam00689
Location:784 – 987
Blast Score: 383

Cation_ATPase_C; Cation transporting ATPase, C-terminus

pfam00690
Location:4 – 72
Blast Score: 222

Cation_ATPase_N; Cation transporter/ATPase, N-terminus

pfam12710
Location:598 – 712
Blast Score: 104

HAD; haloacid dehalogenase-like hydrolase

pfam13246
Location:418 – 528
Blast Score: 208

Hydrolase_like2; Putative hydrolase of sodium-potassium ATPase alpha subunit
NM_173201.3 → NP_775293.1 sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (b) lacks an exon in the 3' coding region resulting in a frameshift and use of a downstream termination codon, compared to variant a. Isoform b has a longer and distinct C-terminus, compared to isoform a. Isoform b is also referred to as the neonatal isoform.

Source sequence(s)

AK291314, BX537784, BX647367

Consensus CDS

CCDS10643.1

UniProtKB/Swiss-Prot

O14983

UniProtKB/TrEMBL

Q7Z675

Related

ENSP00000349595, OTTHUMP00000162561, ENST00000357084, OTTHUMT00000254686

Conserved Domains (6) summary

TIGR01116
Location:53 – 989
Blast Score: 4083

ATPase-IIA1_Ca; sarco/endoplasmic reticulum calcium-translocating P-type ATPase

pfam00122
Location:101 – 341
Blast Score: 527

E1-E2_ATPase; E1-E2 ATPase

pfam00689
Location:784 – 987
Blast Score: 385

Cation_ATPase_C; Cation transporting ATPase, C-terminus

pfam00690
Location:4 – 72
Blast Score: 222

Cation_ATPase_N; Cation transporter/ATPase, N-terminus

pfam12710
Location:598 – 712
Blast Score: 104

HAD; haloacid dehalogenase-like hydrolase

pfam13246
Location:418 – 528
Blast Score: 208

Hydrolase_like2; Putative hydrolase of sodium-potassium ATPase alpha subunit

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p10 Primary Assembly

Range

28889809..28915830

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

26757144..26783172

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018927.1 Alternate CHM1_1.0

Range

29785812..29811832

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01045684.1 (10779..24373)	None
genomic	ABBA01045685.1	None
genomic	AC109460.3 (20395..37061)	None
genomic	AC133550.2	None
genomic	AMYH01007478.1 (55056..81076)	None
genomic	CH471267.1	EAW52006.1
genomic	HB975088.1	CBG22289.1
genomic	HD032498.1	CBV35450.1
genomic	U96773.1	AAB53112.1
		AAB53113.1
genomic	U96781.1	AAB53112.1
		AAB53113.1
mRNA	AK092691.1	BAG52597.1
mRNA	AK128456.1	BAG54679.1
mRNA	AK291314.1	BAF84003.1
mRNA	BC037354.1	AAH37354.1
mRNA	BC104452.2	None
mRNA	BC104453.2	None
mRNA	BU737186.1	None
mRNA	BX537389.1	CAD97631.1
mRNA	BX537784.1	CAD97841.1
mRNA	BX647365.1	None
mRNA	BX647366.1	None
mRNA	BX647367.1	None
mRNA	BX647368.1	None
mRNA	BX648544.1	None
mRNA	BX649072.1	None
other-genetic	BC148653.1	AAI48654.1