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    CS citrate synthase [ Homo sapiens (human) ]

    Gene ID: 1431, updated on 5-May-2024

    Summary

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    Official Symbol
    CSprovided by HGNC
    Official Full Name
    citrate synthaseprovided by HGNC
    Primary source
    HGNC:HGNC:2422
    See related
    Ensembl:ENSG00000062485 MIM:118950; AllianceGenome:HGNC:2422
    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
    Summary
    The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in heart (RPKM 124.5), fat (RPKM 107.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    12q13.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (56271699..56300330, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (56239343..56267970, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (56665483..56694114, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 39 member 5 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29670 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29671 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29672 Neighboring gene ankyrin repeat domain 52 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56650178-56651170 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6483 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6484 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4552 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4553 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4554 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29674 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29675 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6485 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:56660797-56661296 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6486 Neighboring gene Sharpr-MPRA regulatory region 15563 Neighboring gene coenzyme Q10A Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29678 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56693295-56693812 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4556 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4557 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29680 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6488 Neighboring gene MPRA-validated peak1741 silencer Neighboring gene CNPY2 antisense RNA 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56709757-56710345 Neighboring gene canopy FGF signaling regulator 2 Neighboring gene MPRA-validated peak1742 silencer Neighboring gene poly(A) specific ribonuclease subunit PAN2 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_29684

    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. Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase. Schlachter CR, et al. Biol Chem, 2019 Nov 26. PMID 31141475
    2. Reduced expression of citrate synthase leads to excessive superoxide formation and cell apoptosis. Cai Q, et al. Biochem Biophys Res Commun, 2017 Apr 1. PMID 28216161
    3. Loss of the respiratory enzyme citrate synthase directly links the Warburg effect to tumor malignancy. Lin CC, et al. Sci Rep, 2012. PMID 23139858, Free PMC Article
    4. Identification and characterization of the mitochondrial targeting sequence and mechanism in human citrate synthase. Cheng TL, et al. J Cell Biochem, 2009 Aug 1. PMID 19479947
    5. Enhanced citrate synthase activity in human pancreatic cancer. Schlichtholz B, et al. Pancreas, 2005 Mar. PMID 15714131

    See all (116) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Citrate synthase lysine K215 hypoacetylation contributes to microglial citrate accumulation and pro-inflammatory functions after traumatic brain injury.
      Title: Citrate synthase lysine K215 hypoacetylation contributes to microglial citrate accumulation and pro-inflammatory functions after traumatic brain injury.
    2. The left-lateralisation of citrate synthase activity in the anterior cingulate cortex of male violent suicide victims.
      Title: The left-lateralisation of citrate synthase activity in the anterior cingulate cortex of male violent suicide victims.
    3. The Novel Role of Mitochondrial Citrate Synthase and Citrate in the Pathophysiology of Alzheimer's Disease.
      Title: The Novel Role of Mitochondrial Citrate Synthase and Citrate in the Pathophysiology of Alzheimer's Disease.
    4. Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material.
      Title: Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material.
    5. The active sites of the citrate synthase is almost identical, the differences in reactions catalyzed by citrate synthase are caused by residues that are in the vicinity of the active site and influence conformational changes of the citrate synthase.
      Title: Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase.
    6. citrate synthase and ACSS1 have tumorigenic functions in hepatocellular carcinoma
      Title: Gene network analysis reveals a novel 22-gene signature of carbon metabolism in hepatocellular carcinoma.
    7. Citrate synthase activity was lower in patients with heart failure with preserved ejection fraction compared to controls.
      Title: Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance.
    8. mir-122 and its targets G6PC3, ALDOA and CS play roles in the hypoxia responses that regulate glucose and energy metabolism and can serve as hypoxia biomarkers.
      Title: G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers.
    9. METTL12 methylates CS on Lys-395, which is localized in the CS active site. Interestingly, the METTL12-mediated methylation inhibited CS activity and was blocked by the CS substrate oxaloacetate.
      Title: Uncovering human METTL12 as a mitochondrial methyltransferase that modulates citrate synthase activity through metabolite-sensitive lysine methylation.
    10. Data suggest that METTL12, localized in mitochondrial matrix, modifies/methylates Lys368 of citrate synthase in external surface region close to its catalytic site; addition/removal of methylation has no effect on citrate synthase activity; Lys368 occurs in highly conserved sequence of amino acid residues of citrate synthase. (METTL12 = methyltransferase-like protein 12)
      Title: Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase.
    Submit: New GeneRIF Correction See all GeneRIFs (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

    EBI GWAS Catalog

    Description
    Genome-wide association study in Han Chinese identifies three novel loci for human height.
    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

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables citrate (Si)-synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables citrate (Si)-synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in carbohydrate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in carbohydrate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in citrate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tricarboxylic acid cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tricarboxylic acid cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular exosome HDA PubMed 
    is_active_in mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HDA PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus HDA PubMed 

    General protein information

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    Preferred Names
    citrate synthase, mitochondrial
    Names
    citrate (Si)-synthase
    NP_004068.2

    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_004077.3 → NP_004068.2  citrate synthase, mitochondrial precursor

      See identical proteins and their annotated locations for NP_004068.2

      Status: REVIEWED

      Source sequence(s)
      AK074956, BC000105, CB990178
      Consensus CDS
      CCDS8913.1
      UniProtKB/Swiss-Prot
      O75390, Q71UT9, Q7KZH0, Q96FZ8, Q9BWN8
      UniProtKB/TrEMBL
      B4DJV2
      Related
      ENSP00000342056.3, ENST00000351328.8
      Conserved Domains (1) summary
      cd06105
      Location:33 → 459
      ScCit1-2_like; Saccharomyces cerevisiae (Sc) citrate synthases Cit1-2_like. Citrate synthases (CS) catalyzes the condensation of acetyl coenzyme A (AcCoA) with oxaloacetate (OAA) to form citrate and coenzyme A (CoA), the first step in the citric acid cycle (TCA or ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    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
      56271699..56300330 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      56239343..56267970 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_198324.1: Suppressed sequence

      Description
      NM_198324.1: This RefSeq was permanently suppressed because if the correct translation start site is used, it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75390.2 GenPept UniProtKB/Swiss-Prot:O75390

    Gene LinkOut

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

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