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    ATP2A2 ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [ Homo sapiens (human) ]

    Gene ID: 488, updated on 3-Nov-2024

    Summary

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    Official Symbol
    ATP2A2provided by HGNC
    Official Full Name
    ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2provided by HGNC
    Primary source
    HGNC:HGNC:812
    See related
    Ensembl:ENSG00000174437 MIM:108740; AllianceGenome:HGNC:812
    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
    DD; DAR; ATP2B; SERCA2
    Summary
    This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]
    Expression
    Broad expression in heart (RPKM 220.5), esophagus (RPKM 62.0) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ATP2A2 in Genome Data Viewer
    Location:
    12q24.11
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (110280616..110351093)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (110258258..110328744)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (110718421..110788898)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369976 Neighboring gene Sharpr-MPRA regulatory region 13461 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110546777-110547368 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110547369-110547960 Neighboring gene CRISPRi-validated cis-regulatory element chr12.3595 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4853 Neighboring gene intraflagellar transport 81 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:110610112-110610892 Neighboring gene MPRA-validated peak1945 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:110661551-110662051 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110695091-110695683 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110706905-110707507 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4854 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:110719747-110720501 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6999 Neighboring gene Sharpr-MPRA regulatory region 3729 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7000 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:110778306-110779505 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:110782389-110783588 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110786998-110787545 Neighboring gene MPRA-validated peak1946 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110803582-110804450 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:110804451-110805318 Neighboring gene uncharacterized LOC124903014 Neighboring gene RNA, 7SL, cytoplasmic 769, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Two novel frame-shift mutations of ATP2A2 gene in Chinese patients with Darier's disease. Quan C, et al. J Eur Acad Dermatol Venereol, 2008 Jun. PMID 18482030
    2. Involvement of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) in mPRα (PAQR7)-mediated progesterone induction of vascular smooth muscle relaxation. Pang Y, et al. Am J Physiol Endocrinol Metab, 2021 Mar 1. PMID 33427050
    3. Clioquinol inhibits cell growth in a SERCA2-dependent manner. Lv X, et al. J Biochem Mol Toxicol, 2021 May. PMID 33511738
    4. A novel splice acceptor site mutation in the ATP2A2 gene in a family with Darier disease. Chiavetta V, et al. G Ital Dermatol Venereol, 2016 Oct. PMID 27595213
    5. [Analysis of ATP2A2 gene mutations in a pedigree and a sporadic case with Darier disease]. Zhao X, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2016 Oct. PMID 27577212

    See all (430) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Persistent Cutaneous Lesions of Darier Disease and Second-Hit Somatic Variants in ATP2A2 Gene.
      Title: Persistent Cutaneous Lesions of Darier Disease and Second-Hit Somatic Variants in ATP2A2 Gene.
    2. IL-37 Modulates Myocardial Calcium Handling via the p-STAT3/SERCA2a Axis in HF-Related Engineered Human Heart Tissue.
      Title: IL-37 Modulates Myocardial Calcium Handling via the p-STAT3/SERCA2a Axis in HF-Related Engineered Human Heart Tissue.
    3. Familial comedonal Darier's disease: a new ATP2A2 mutation with intra-family clinical heterogeneity.
      Title: Familial comedonal Darier's disease: a new ATP2A2 mutation with intra-family clinical heterogeneity.
    4. SERCA2 phosphorylation at the heart of the disease.
      Title: SERCA2 phosphorylation at the heart of the disease.
    5. Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8[+] T cell metabolic fitness and function in tumors.
      Title: Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8(+) T cell metabolic fitness and function in tumors.
    6. Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure.
      Title: Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure.
    7. Association of Somatic ATP2A2 Damaging Variants With Grover Disease.
      Title: Association of Somatic ATP2A2 Damaging Variants With Grover Disease.
    8. SERCA2 phosphorylation at serine 663 is a key regulator of Ca[2+] homeostasis in heart diseases.
      Title: SERCA2 phosphorylation at serine 663 is a key regulator of Ca(2+) homeostasis in heart diseases.
    9. Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a.
      Title: Identification and Characterization of p300-Mediated Lysine Residues in Cardiac SERCA2a.
    10. A motor neuron disease-associated mutation produces non-glycosylated Seipin that induces ER stress and apoptosis by inactivating SERCA2b.
      Title: A motor neuron disease-associated mutation produces non-glycosylated Seipin that induces ER stress and apoptosis by inactivating SERCA2b.
    Submit: New GeneRIF Correction See all GeneRIFs (175)

    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

    Associated conditions

    Description Tests
    Acrokeratosis verruciformis of Hopf
    MedGen: C0265971 OMIM: 101900 GeneReviews: Not available
    		Compare labs
    Keratosis follicularis
    MedGen: C0022595 OMIM: 124200 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies protein quantitative trait loci (pQTLs).
    EBI GWAS Catalog
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 Env is identified to have a physical interaction with ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Rev rev HIV-1 Rev interacting protein, Ca++ dependent-ATPase 2 (ATP2A2), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa. The interaction of Rev with ATP2A2 is increased by RRE PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20293, FLJ38063, MGC45367, DKFZp686P0211

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IEA
    Inferred from Electronic Annotation
    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
    		 PubMed 
    enables P-type calcium transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables P-type calcium transporter activity involved in regulation of cardiac muscle cell membrane potential IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables S100 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables lncRNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane transporter binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ER-nucleus signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in T-tubule organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in autophagosome assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in autophagosome assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in autophagosome membrane docking IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium ion import into sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium ion transport from cytosol to endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cardiac muscle hypertrophy in response to stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell adhesion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to oxidative stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in endoplasmic reticulum calcium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in epidermis development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in intracellular calcium ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular calcium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intracellular calcium ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrion-endoplasmic reticulum membrane tethering IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in monoatomic ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in negative regulation of heart contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of receptor binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neuron cellular homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in organelle localization by membrane tethering IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cardiac muscle cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of endoplasmic reticulum calcium ion concentration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of heart rate TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of calcium ion-dependent exocytosis of neurotransmitter IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of cardiac conduction TAS
    Traceable Author Statement
    more info
    		  
    involved_in regulation of cardiac muscle cell action potential involved in regulation of contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of cardiac muscle cell membrane potential IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cardiac muscle cell membrane potential ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of cardiac muscle cell membrane potential TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of cardiac muscle contraction by calcium ion signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of cardiac muscle contraction by calcium ion signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of the force of heart contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in relaxation of cardiac muscle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to endoplasmic reticulum stress ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sarcoplasmic reticulum calcium ion transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in transition between fast and slow fiber IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of calcium ion-transporting ATPase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    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
    		  
    colocalizes_with intercalated disc IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in longitudinal sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in platelet dense tubular network membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in ribbon synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in sarcoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in sarcoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sarcoplasmic/endoplasmic reticulum calcium ATPase 2
    Names
    ATPase Ca++ transporting cardiac muscle slow twitch 2
    ATPase, Ca++ dependent, slow-twitch, cardiac muscle-2
    SR Ca(2+)-ATPase 2
    calcium pump 2
    cardiac Ca2+ ATPase
    endoplasmic reticulum class 1/2 Ca(2+) ATPase
    NP_001399942.1
    NP_001399943.1
    NP_001399944.1
    NP_001672.1
    NP_733765.1
    XP_011536704.1
    XP_054228098.1

    NCBI Reference Sequences (RefSeq)

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    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

    1. NG_007097.2 RefSeqGene

      Range
      4621..74467
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001413013.1 → NP_001399942.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform c

      Status: REVIEWED

      Source sequence(s)
      AC006088

    2. NM_001413014.1 → NP_001399943.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform d

      Status: REVIEWED

      Source sequence(s)
      AC006088

    3. NM_001413015.1 → NP_001399944.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform e

      Status: REVIEWED

      Source sequence(s)
      AC006088
      Related
      ENSP00000449454.2, ENST00000548169.2

    4. NM_001681.4 → NP_001672.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform a

      See identical proteins and their annotated locations for NP_001672.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) differs in the 3' coding region and 3' UTR, resulting in an alternate termination codon, compared to variant 1. The encoded isoform (a, also known as SERCA2a, S2a or HK2) has a shorter and distinct C-terminus, compared to isoform b.
      Source sequence(s)
      AK000300, BG773489, BI553880, M23115
      Consensus CDS
      CCDS9143.1
      UniProtKB/TrEMBL
      H7C5W9
      Related
      ENSP00000311186.6, ENST00000308664.10
      Conserved Domains (1) summary
      cd02083
      Location:5 → 988
      P-type_ATPase_SERCA; sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), similar to mammalian ATP2A1-3/SERCA1-3

    5. NM_170665.4 → NP_733765.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b

      See identical proteins and their annotated locations for NP_733765.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) represents the longest transcript and encodes the longest isoform (b, also known as SERCA2b, S2b or HK1).
      Source sequence(s)
      AK000300, BC035588, BG773489, BI553880, BX648282
      Consensus CDS
      CCDS9144.1
      UniProtKB/Swiss-Prot
      A6NDN7, B4DF05, P16614, P16615, Q86VJ2
      UniProtKB/TrEMBL
      A0A0S2Z3L2, H7C5W9
      Related
      ENSP00000440045.2, ENST00000539276.7
      Conserved Domains (1) summary
      cd02083
      Location:5 → 988
      P-type_ATPase_SERCA; sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), similar to mammalian ATP2A1-3/SERCA1-3

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      110280616..110351093
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538402.4 → XP_011536704.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1

      See identical proteins and their annotated locations for XP_011536704.1

      UniProtKB/TrEMBL
      H7C5W9
      Conserved Domains (6) summary
      TIGR01116
      Location:53 → 988
      ATPase-IIA1_Ca; sarco/endoplasmic reticulum calcium-translocating P-type ATPase
      pfam00122
      Location:93 → 340
      E1-E2_ATPase; E1-E2 ATPase
      pfam00689
      Location:783 → 986
      Cation_ATPase_C; Cation transporting ATPase, C-terminus
      pfam00690
      Location:4 → 72
      Cation_ATPase_N; Cation transporter/ATPase, N-terminus
      pfam12710
      Location:605 → 711
      HAD; haloacid dehalogenase-like hydrolase
      pfam13246
      Location:419 → 527
      Cation_ATPase; Cation transport ATPase (P-type)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      110258258..110328744
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054372123.1 → XP_054228098.1  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001135765.1: Suppressed sequence

      Description
      NM_001135765.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P16615.1 GenPept UniProtKB/Swiss-Prot:P16615

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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