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    MICU1 mitochondrial calcium uptake 1 [ Homo sapiens (human) ]

    Gene ID: 10367, updated on 2-Nov-2024

    Summary

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    Official Symbol
    MICU1provided by HGNC
    Official Full Name
    mitochondrial calcium uptake 1provided by HGNC
    Primary source
    HGNC:HGNC:1530
    See related
    Ensembl:ENSG00000107745 MIM:605084; AllianceGenome:HGNC:1530
    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
    CALC; EFHA3; MPXPS; CBARA1; ara CALC
    Summary
    This gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2013]
    Expression
    Ubiquitous expression in kidney (RPKM 30.5), adrenal (RPKM 20.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MICU1 in Genome Data Viewer
    Location:
    10q22.1
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (72367340..72626079, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (73238332..73497425, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (74127098..74385837, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3536 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:74035325-74035848 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:74046277-74046777 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3537 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2471 Neighboring gene Sharpr-MPRA regulatory region 1217 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3538 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2472 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:74057879-74058535 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:74069939-74070924 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3540 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2473 Neighboring gene Sharpr-MPRA regulatory region 14427 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr10:74081426-74082625 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:74084563-74085524 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3543 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2474 Neighboring gene DNA damage inducible transcript 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3544 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3545 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3546 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3547 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3548 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3549 Neighboring gene DnaJ heat shock protein family (Hsp40) member B12 Neighboring gene RNA, U6 small nuclear 805, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:74182311-74183044 Neighboring gene sorting nexin 19 pseudogene 4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2475 Neighboring gene COX7C pseudogene 4 Neighboring gene RNA, 7SL, cytoplasmic 840, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:74385604-74386141 Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 34 Neighboring gene Sharpr-MPRA regulatory region 12193 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3551 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2476 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2477 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2478 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3552 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2479 Neighboring gene microRNA 4676 Neighboring gene mitochondrial calcium uniporter

    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. Probing novel roles of the mitochondrial uniporter in ovarian cancer cells using nanoparticles. Arvizo RR, et al. J Biol Chem, 2013 Jun 14. PMID 23615904, Free PMC Article
    2. MICU1 motifs define mitochondrial calcium uniporter binding and activity. Hoffman NE, et al. Cell Rep, 2013 Dec 26. PMID 24332854, Free PMC Article
    3. MICU1 occludes the mitochondrial calcium uniporter in divalent-free conditions. Rodríguez-Prados M, et al. Proc Natl Acad Sci U S A, 2023 May 9. PMID 37126688, Free PMC Article
    4. Molecular pathophysiology of human MICU1 deficiency. Kohlschmidt N, et al. Neuropathol Appl Neurobiol, 2021 Oct. PMID 33428302
    5. Evidence supporting the MICU1 occlusion mechanism and against the potentiation model in the mitochondrial calcium uniporter complex. Tsai CW, et al. Proc Natl Acad Sci U S A, 2023 Apr 18. PMID 37036971, Free PMC Article

    See all (102) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MICU1 and MICU2 control mitochondrial calcium signaling in the mammalian heart.
      Title: MICU1 and MICU2 control mitochondrial calcium signaling in the mammalian heart.
    2. Mechanisms and significance of tissue-specific MICU regulation of the mitochondrial calcium uniporter complex.
      Title: Mechanisms and significance of tissue-specific MICU regulation of the mitochondrial calcium uniporter complex.
    3. The Splicing of the Mitochondrial Calcium Uniporter Genuine Activator MICU1 Is Driven by RBFOX2 Splicing Factor during Myogenic Differentiation.
      Title: The Splicing of the Mitochondrial Calcium Uniporter Genuine Activator MICU1 Is Driven by RBFOX2 Splicing Factor during Myogenic Differentiation.
    4. Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients.
      Title: Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients.
    5. Molecular pathophysiology of human MICU1 deficiency.
      Title: Molecular pathophysiology of human MICU1 deficiency.
    6. 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.
    7. Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity.
      Title: Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity.
    8. 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.
    9. 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.
    10. Dysregulation of Mitochondrial Ca(2+) Uptake and Sarcolemma Repair Underlie Muscle Weakness and Wasting in Patients and Mice Lacking MICU1.
      Title: Dysregulation of Mitochondrial Ca(2+) Uptake and Sarcolemma Repair Underlie Muscle Weakness and Wasting in Patients and Mice Lacking MICU1.
    Submit: New GeneRIF Correction See all GeneRIFs (39)

    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
    Proximal myopathy with extrapyramidal signs
    MedGen: C3810285 OMIM: 615673 GeneReviews: Not available
    		Compare labs

    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

    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

    • FLJ12684, DKFZp564C246

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium channel inhibitor 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 binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables calcium ion sensor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium ion sensor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in calcium import into the mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in calcium ion import IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to calcium ion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to calcium ion starvation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in defense response TAS
    Traceable Author Statement
    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 mitochondrial calcium ion transmembrane transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cristae formation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of mitochondrial calcium ion concentration 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 protein homooligomerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cellular hyperosmotic salinity response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of calcium channel complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in mitochondrial crista junction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 IMP
    Inferred from Mutant Phenotype
    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 mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in mitochondrion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    part_of uniplex complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    calcium uptake protein 1, mitochondrial
    Names
    atopy-related autoantigen CALC
    calcium-binding atopy-related autoantigen 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_033179.1 RefSeqGene

      Range
      5113..263852
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001195518.2 → NP_001182447.1  calcium uptake protein 1, mitochondrial isoform 2

      See identical proteins and their annotated locations for NP_001182447.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded protein (isoform 2) is shorter compared to isoform 1.
      Source sequence(s)
      AC091769, AK023318, AL513185
      Consensus CDS
      CCDS55715.1
      UniProtKB/Swiss-Prot
      A0A0U1RRK1, A8MV96, B3KN20, B4DJH9, B4DPI1, B5MBY3, D3YTJ3, O75785, Q9BPX6, Q9H9N6, Q9UFX0
      Related
      ENSP00000354415.5, ENST00000361114.10
      Conserved Domains (1) summary
      cd16173
      Location:222 → 441
      EFh_MICU1; EF-hand, calcium binding motif, found in calcium uptake protein 1, mitochondrial (MICU1) and similar proteins

    2. NM_001195519.2 → NP_001182448.1  calcium uptake protein 1, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001182448.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation to occur at a downstream start codon compared to variant 1. The encoded protein (isoform 3) is shorter and has a distinct N-terminus compared to isoform 1. In the absence of experimental data indicating otherwise, isoform 3 is presumed to be localized to the mitochondria, similarly to isoforms 1 and 2.
      Source sequence(s)
      AK296086, AL513185, BU627477
      Consensus CDS
      CCDS55714.1
      UniProtKB/Swiss-Prot
      Q9BPX6
      Related
      ENSP00000402470.2, ENST00000418483.6
      Conserved Domains (2) summary
      pfam13202
      Location:25 → 48
      EF-hand_5; EF hand
      pfam13499
      Location:14 → 47
      EF-hand_7; EF-hand domain pair

    3. NM_001363513.2 → NP_001350442.1  calcium uptake protein 1, mitochondrial isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC091769, AL513185
      Consensus CDS
      CCDS86101.1
      UniProtKB/TrEMBL
      A0A286YF11
      Related
      ENSP00000493232.1, ENST00000642044.1
      Conserved Domains (1) summary
      cd16173
      Location:228 → 447
      EFh_MICU1; EF-hand, calcium binding motif, found in calcium uptake protein 1, mitochondrial (MICU1) and similar proteins

    4. NM_006077.4 → NP_006068.2  calcium uptake protein 1, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_006068.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1).
      Source sequence(s)
      AC091769, AL117423, AL513185
      Conserved Domains (1) summary
      pfam13202
      Location:225 → 248
      EF-hand_5; EF hand

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      72367340..72626079 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011539119.2 → XP_011537421.1  calcium uptake protein 1, mitochondrial isoform X1

      Conserved Domains (1) summary
      pfam13202
      Location:279 → 302
      EF-hand_5; EF hand

    2. XM_047424441.1 → XP_047280397.1  calcium uptake protein 1, mitochondrial isoform X3

    3. XM_047424440.1 → XP_047280396.1  calcium uptake protein 1, mitochondrial isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      73238332..73497425 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054364482.1 → XP_054220457.1  calcium uptake protein 1, mitochondrial isoform X1

    2. XM_054364483.1 → XP_054220458.1  calcium uptake protein 1, mitochondrial isoform X2

    3. XM_054364484.1 → XP_054220459.1  calcium uptake protein 1, mitochondrial isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BPX6.1 GenPept UniProtKB/Swiss-Prot:Q9BPX6

    Gene LinkOut

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

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