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    MICU2 mitochondrial calcium uptake 2 [ Homo sapiens (human) ]

    Gene ID: 221154, updated on 27-Nov-2024

    Summary

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    Official Symbol
    MICU2provided by HGNC
    Official Full Name
    mitochondrial calcium uptake 2provided by HGNC
    Primary source
    HGNC:HGNC:31830
    See related
    Ensembl:ENSG00000165487 MIM:610632; AllianceGenome:HGNC:31830
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EFHA1; hMICU3; 1110008L20Rik
    Summary
    Enables calcium ion binding activity; calcium ion sensor activity; and protein heterodimerization activity. Involved in calcium import into the mitochondrion; cellular response to calcium ion; and negative regulation of mitochondrial calcium ion concentration. Located in mitochondrial intermembrane space. Part of uniplex complex. Is active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in kidney (RPKM 25.3), adrenal (RPKM 19.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MICU2 in Genome Data Viewer
    Location:
    13q12.11
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (21492691..21604170, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (20687026..20798493, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (22066830..22178309, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903131 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5161 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5162 Neighboring gene H2B histone pseudogene 6 Neighboring gene small nucleolar RNA U13 Neighboring gene farnesyltransferase, CAAX box, alpha pseudogene 2 Neighboring gene RNA, U6 small nuclear 59, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5163 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7436 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7438 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:22177403-22178022 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:22178023-22178641 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7440 Neighboring gene ribosomal protein S7 pseudogene 10 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5165 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5166 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5167 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5168 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5169 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5170 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7441 Neighboring gene fibroblast growth factor 9

    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
    • 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. A null mutation in MICU2 causes abnormal mitochondrial calcium homeostasis and a severe neurodevelopmental disorder. Shamseldin HE, et al. Brain, 2017 Nov 1. PMID 29053821
    2. The crystal structure of MICU2 provides insight into Ca(2+) binding and MICU1-MICU2 heterodimer formation. Wu W, et al. EMBO Rep, 2019 Sep. PMID 31397067, Free PMC Article
    3. Structure of the MICU1-MICU2 heterodimer provides insights into the gatekeeping threshold shift. Park J, et al. IUCrJ, 2020 Mar 1. PMID 32148862, Free PMC Article
    4. The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter. Wu W, et al. EMBO J, 2020 Oct 1. PMID 32790952, Free PMC Article
    5. MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter. Kamer KJ, et al. EMBO Rep, 2014 Mar. PMID 24503055, Free PMC Article

    See all (63) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion.
      Title: Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion.
    2. Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex.
      Title: Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex.
    3. The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter.
      Title: The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter.
    4. Structures reveal gatekeeping of the mitochondrial Ca(2+) uniporter by MICU1-MICU2.
      Title: Structures reveal gatekeeping of the mitochondrial Ca(2+) uniporter by MICU1-MICU2.
    5. multiple crystal structures of MICU2 and MICU3 from Homo sapiens, were determined.
      Title: Dimerization of MICU Proteins Controls Ca(2+) Influx through the Mitochondrial Ca(2+) Uniporter.
    6. MICU2 restricts spatial crosstalk between InsP3R and MCU channels by regulating threshold and gain of MICU1-mediated inhibition and activation of MCU.
      Title: MICU2 Restricts Spatial Crosstalk between InsP(3)R and MCU Channels by Regulating Threshold and Gain of MICU1-Mediated Inhibition and Activation of MCU.
    7. MICU2 expression in the heart tissues from patients with ventricular hypertrophy.
      Title: Cardiovascular homeostasis dependence on MICU2, a regulatory subunit of the mitochondrial calcium uniporter.
    8. study concludes that cooperative, high-affinity interaction of the MICU1-MICU2 complex with Ca(2+) serves as an on-off switch, leading to a tightly controlled channel, capable of responding directly to cytosolic Ca(2+) signals
      Title: High-affinity cooperative Ca(2+) binding by MICU1-MICU2 serves as an on-off switch for the uniporter.
    9. This is the first demonstration of MICU2 deficiency in humans, which we suggest causes a distinct neurodevelopmental phenotype secondary to impaired mitochondrial calcium uniporter-mediated regulation of intracellular calcium homeostasis.
      Title: A null mutation in MICU2 causes abnormal mitochondrial calcium homeostasis and a severe neurodevelopmental disorder.
    10. Expression of MICU2 mutants lacking functional Ca2+-binding sites leads to a striking loss of Ca2+ uptake in HEK293 cells.
      Title: MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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

    EBI GWAS Catalog

    Description
    Genetic determinants of P wave duration and PR segment.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ25016, FLJ34588

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium channel regulator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium ion sensor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in calcium import into the mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in calcium import into the mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium import into the mitochondrion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in calcium import into the mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to calcium ion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial calcium ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial calcium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial calcium ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrial calcium ion homeostasis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in mitochondrial calcium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of mitochondrial calcium ion concentration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of mitochondrial calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of calcium channel complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial intermembrane space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    part_of uniplex complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of uniplex complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of uniplex complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of uniplex complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    calcium uptake protein 2, mitochondrial
    Names
    EF hand domain family A1
    EF hand domain family, member A1
    EF-hand domain-containing family member A1
    Smhs2 homolog

    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.

    mRNA and Protein(s)

    1. NM_152726.3 → NP_689939.1  calcium uptake protein 2, mitochondrial

      See identical proteins and their annotated locations for NP_689939.1

      Status: VALIDATED

      Source sequence(s)
      AL138680, BC031089, BQ438851
      Consensus CDS
      CCDS9297.1
      UniProtKB/Swiss-Prot
      Q8IYU8, Q8N0T6, Q8NAX8
      UniProtKB/TrEMBL
      A0A0S2Z6V5
      Related
      ENSP00000371811.4, ENST00000382374.9
      Conserved Domains (1) summary
      cd16174
      Location:176 → 395
      EFh_MICU2; EF-hand, calcium binding motif, found in calcium uptake protein 2, mitochondrial (MICU2) and similar proteins

    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_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      21492691..21604170 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047430142.1 → XP_047286098.1  calcium uptake protein 2, mitochondrial isoform X2

    2. XM_017020433.2 → XP_016875922.1  calcium uptake protein 2, mitochondrial isoform X4

    3. XM_047430143.1 → XP_047286099.1  calcium uptake protein 2, mitochondrial isoform X3

    4. XM_047430141.1 → XP_047286097.1  calcium uptake protein 2, mitochondrial isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      20687026..20798493 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054374209.1 → XP_054230184.1  calcium uptake protein 2, mitochondrial isoform X2

    2. XM_054374211.1 → XP_054230186.1  calcium uptake protein 2, mitochondrial isoform X4

    3. XM_054374210.1 → XP_054230185.1  calcium uptake protein 2, mitochondrial isoform X3

    4. XM_054374208.1 → XP_054230183.1  calcium uptake protein 2, mitochondrial isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IYU8.2 GenPept UniProtKB/Swiss-Prot:Q8IYU8

    Gene LinkOut

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

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