ATP2A1 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATP2A1provided by HGNC
Official Full Name: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1provided by HGNC
Primary source: HGNC:HGNC:811
See related: Ensembl:ENSG00000196296 MIM:108730; AllianceGenome:HGNC:811
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 three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]
Expression: Biased expression in esophagus (RPKM 15.8), prostate (RPKM 13.1) and 1 other tissue See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 16p11.2

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (28878488..28904466)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (29158988..29184960)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (28889809..28915787)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer's Disease on the Pump Activity.
Title: Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer's Disease on the Pump Activity.
Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases.
Title: Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases.
Atomistic Structure and Dynamics of the Ca(2+)-ATPase Bound to Phosphorylated Phospholamban.
Title: Atomistic Structure and Dynamics of the Ca(2+)-ATPase Bound to Phosphorylated Phospholamban.
Study demonstrated that (a) the distribution and the expression levels of total SERCA1 and SERCA2, the activity of SR Ca2+ ATPase, and the oligomerization of SERCA1 are similar in patients with myotonic dystrophy 1, myotonic dystrophy 2, hypothyroid myopathy and control subjects; and (b) SERCA1b is expressed in patients with myotonic dystrophy, mainly in myotonic dystrophy 2 muscles.
Title: Characterization of sarcoplasmic reticulum Ca(2+) ATPase pumps in muscle of patients with myotonic dystrophy and with hypothyroid myopathy.
These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity.
Title: Interactions between small ankyrin 1 and sarcolipin coordinately regulate activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1).
CAPN3 deficiency leads to degradation of SERCA proteins and Ca2+ dysregulation in the skeletal muscle.
Title: Calpain 3 deficiency affects SERCA expression and function in the skeletal muscle.
The sphingolipid sphingosine increases the [Ca(2+)]i by inhibiting the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca(2+) pump.
Title: Sphingosine inhibits the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity.
Thus the human SERCA1b has a different expression pattern from that of rodents and it is associated with DM2.
Title: The neonatal sarcoplasmic reticulum Ca2+-ATPase gives a clue to development and pathology in human muscles.
Formalin evokes calcium transients from the endoplasmatic reticulum via SERCA1-dependent, TRPA1-independent mechanism that may underlie formaldehyde-induced pan-neuronal excitation and subsequent inflammation.
Title: Formalin evokes calcium transients from the endoplasmatic reticulum.
We conclude that PLB C-terminal residues are critical for localization, oligomerization, and regulatory function. In particular, the PLB C terminus is an important determinant of the quaternary structure of the SERCA regulatory complex.
Title: Phospholamban C-terminal residues are critical determinants of the structure and function of the calcium ATPase regulatory complex.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Brody myopathy MedGen: C1832918 OMIM: 601003 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

NoName (e-PCR)
- UniSTS:484683

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

RH48558 (e-PCR)
- UniSTS:92336

SH2B_9440 (e-PCR)
- UniSTS:471756

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	ISS Inferred from Sequence or Structural Similarity more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables P-type calcium transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables P-type calcium transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables P-type calcium transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables P-type calcium transporter activity	TAS Traceable Author Statement more info
enables calcium ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables calcium-dependent ATPase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic mitochondrial changes	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium ion import	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium ion import into sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maintenance of mitochondrion location	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in negative regulation of endoplasmic reticulum calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of striated muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ATPase-coupled calcium transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of calcium ion import into sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cardiac muscle cell contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of endoplasmic reticulum calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fast-twitch skeletal muscle fiber contraction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mitochondrial calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cardiac conduction	TAS Traceable Author Statement more info
involved_in regulation of striated muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in relaxation of skeletal muscle	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in H zone	IDA Inferred from Direct Assay more info	PubMed
located_in I band	IDA Inferred from Direct Assay more info	PubMed
part_of calcium channel complex	IC Inferred by Curator more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum-Golgi intermediate compartment	ISS Inferred from Sequence or Structural Similarity more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in platelet dense tubular network membrane	TAS Traceable Author Statement more info
located_in sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in sarcoplasmic reticulum	NAS Non-traceable Author Statement more info	PubMed
located_in sarcoplasmic reticulum membrane	IC Inferred by Curator more info	PubMed
located_in sarcoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in sarcoplasmic reticulum membrane	TAS Traceable Author Statement more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: sarcoplasmic/endoplasmic reticulum calcium ATPase 1

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

NP_001273004.1

EC 7.2.2.10

NP_004311.1

EC 7.2.2.10

NP_775293.1

EC 7.2.2.10

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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..30979

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001286075.2 → NP_001273004.1 sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform c

See identical proteins and their annotated locations for NP_001273004.1

Status: REVIEWED

Description

Transcript Variant: This variant (c) differs in the 5' UTR and coding sequence compared to variant a. The resulting isoform (c) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

AC133550, AK128456, AL706356, BX537784

Consensus CDS

CCDS66997.1

UniProtKB/TrEMBL

Q7Z675

Related

ENSP00000443101.1, ENST00000536376.5

Conserved Domains (5) summary

TIGR01116
Location:1 → 864

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

pfam00122
Location:3 → 215

E1-E2_ATPase; E1-E2 ATPase

pfam00689
Location:659 → 862

Cation_ATPase_C; Cation transporting ATPase, C-terminus

pfam12710
Location:486 → 587

HAD; haloacid dehalogenase-like hydrolase

pfam13246
Location:294 → 403

Cation_ATPase; Cation transport ATPase (P-type)
NM_004320.6 → NP_004311.1 sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform a

See identical proteins and their annotated locations for NP_004311.1

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/TrEMBL

Q7Z675

Related

ENSP00000378879.5, ENST00000395503.9

Conserved Domains (6) summary

TIGR01116
Location:53 → 989

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

pfam00122
Location:93 → 340

E1-E2_ATPase; E1-E2 ATPase

pfam00689
Location:784 → 987

Cation_ATPase_C; Cation transporting ATPase, C-terminus

pfam00690
Location:4 → 72

Cation_ATPase_N; Cation transporter/ATPase, N-terminus

pfam12710
Location:611 → 712

HAD; haloacid dehalogenase-like hydrolase

pfam13246
Location:419 → 528

Cation_ATPase; Cation transport ATPase (P-type)
NM_173201.5 → NP_775293.1 sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform b

See identical proteins and their annotated locations for NP_775293.1

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

A8K5J9, B3KY17, O14983, O14984

UniProtKB/TrEMBL

Q7Z675

Related

ENSP00000349595.3, ENST00000357084.7

Conserved Domains (6) summary

TIGR01116
Location:53 → 989

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

pfam00122
Location:93 → 340

E1-E2_ATPase; E1-E2 ATPase

pfam00689
Location:784 → 987

Cation_ATPase_C; Cation transporting ATPase, C-terminus

pfam00690
Location:4 → 72

Cation_ATPase_N; Cation transporter/ATPase, N-terminus

pfam12710
Location:611 → 712

HAD; haloacid dehalogenase-like hydrolase

pfam13246
Location:419 → 528

Cation_ATPase; Cation transport ATPase (P-type)