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    GSTZ1 glutathione S-transferase zeta 1 [ Homo sapiens (human) ]

    Gene ID: 2954, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GSTZ1provided by HGNC
    Official Full Name
    glutathione S-transferase zeta 1provided by HGNC
    Primary source
    HGNC:HGNC:4643
    See related
    Ensembl:ENSG00000100577 MIM:603758; AllianceGenome:HGNC:4643
    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
    MAI; MAAI; MAAID; GSTZ1-1
    Summary
    This gene is a member of the glutathione S-transferase (GSTs) super-family which encodes multifunctional enzymes important in the detoxification of electrophilic molecules, including carcinogens, mutagens, and several therapeutic drugs, by conjugation with glutathione. This enzyme catalyzes the conversion of maleylacetoacetate to fumarylacetoacatate, which is one of the steps in the phenylalanine/tyrosine degradation pathway. Deficiency of a similar gene in mouse causes oxidative stress. Several transcript variants of this gene encode multiple protein isoforms. [provided by RefSeq, Jul 2015]
    Expression
    Broad expression in liver (RPKM 23.8), testis (RPKM 10.9) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GSTZ1 in Genome Data Viewer
    Location:
    14q24.3
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (77321036..77331597)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (71530399..71540959)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (77787379..77797940)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene microRNA 1260a Neighboring gene neuroglobin Neighboring gene protein O-mannosyltransferase 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5968 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:77769341-77769842 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:77769843-77770342 Neighboring gene Sharpr-MPRA regulatory region 2495 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5969 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5970 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:77787600-77788461 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:77795945-77797144 Neighboring gene transmembrane p24 trafficking protein family member 8 Neighboring gene ATP binding cassette subfamily G member 2 (JR blood group) pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5971 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5972 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8800 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:77846838-77847018 Neighboring gene sterile alpha motif domain containing 15 Neighboring gene HNF1 motif-containing MPRA enhancer 277

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Susceptibility to breast cancer and three polymorphisms of GSTZ1. Saadat I, et al. DNA Cell Biol, 2012 Mar. PMID 21823988
    2. The influence of human GSTZ1 gene haplotype variations on GSTZ1 expression. Langaee TY, et al. Pharmacogenet Genomics, 2015 May. PMID 25738370, Free PMC Article
    3. Haplotype variations in glutathione transferase zeta 1 influence the kinetics and dynamics of chronic dichloroacetate in children. Shroads AL, et al. J Clin Pharmacol, 2015 Jan. PMID 25079374, Free PMC Article
    4. Glutathione S-transferase Z1 (GSTZ1) gene polymorphism in gastric cancer: a preliminary study in a Turkish population. Karakaş-Celik S, et al. Lab Med, 2014 Winter. PMID 24719983
    5. Characterization of catalytic activity and structure of selenocysteine-containing hGSTZ1c-1c based on site-directed mutagenesis and computational analysis. Yu Y, et al. IUBMB Life, 2013 Feb. PMID 23299908

    See all (87) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Clinical physiology and pharmacology of GSTZ1/MAAI.
      Title: Clinical physiology and pharmacology of GSTZ1/MAAI.
    2. Glutathione S-transferase zeta 1 alters the HMGB1/GPX4 axis to drive ferroptosis in bladder cancer cells.
      Title: Glutathione S-transferase zeta 1 alters the HMGB1/GPX4 axis to drive ferroptosis in bladder cancer cells.
    3. GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis.
      Title: GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis.
    4. Age-Related Changes in miRNA Expression Influence GSTZ1 and Other Drug Metabolizing Enzymes.
      Title: Age-Related Changes in miRNA Expression Influence GSTZ1 and Other Drug Metabolizing Enzymes.
    5. GSTZ1-1 downregulates Wnt/beta-catenin signalling in hepatocellular carcinoma cells.
      Title: GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells.
    6. First clinical trial of dichloroacetate (DCA) in multiple myeloma patients revealed that GSTZ1 genotypes are correlated with drug concentrations, tolerability, and disease outcomes. Promoter GSTZ1 polymorphisms may be important determinants of DCA concentrations and neuropathy during chronic treatment.
      Title: GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial.
    7. Study shows that GSTZ1 is markedly downregulated in hepatocellular carcinoma (HCC) thus predicting a poor prognosis. GSTZ1 deficiency induces oxidative stress, thus activating the KEAP1/NRF2 signaling pathway, which promotes HCC progression.
      Title: GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
    8. Results suggested that GSTZ1-1 is downregulated in hepatocellular carcinoma (HCC) and may serve as a prognostic marker. These data indicate an alternative oncogenic action of succinylacetone through activation of the NRF2/IGF1R axis by alkylation of KEAP1.
      Title: GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.
    9. Some properties of cytosolic and mitochondrial GSTZ1 differed.
      Title: Age-Related Changes in Expression and Activity of Human Hepatic Mitochondrial Glutathione Transferase Zeta1.
    10. mild hypersuccinylacetonaemia (MHSA)can be caused by sequence variants in GSTZ1. Such individuals have thus far remained asymptomatic despite receiving no specific treatment.
      Title: Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency.
    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
    Maleylacetoacetate isomerase deficiency
    MedGen: C1291607 OMIM: 617596 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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of glutathione transferase zeta 1 (GSTZ1) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N 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

    • MGC2029

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables glutathione peroxidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables glutathione transferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glutathione transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables maleylacetoacetate isomerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables maleylacetoacetate isomerase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 L-phenylalanine catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in L-phenylalanine catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular detoxification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular oxidant detoxification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glutathione metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutathione metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tyrosine catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    maleylacetoacetate isomerase
    Names
    S-(hydroxyalkyl)glutathione lyase
    glutathione S-alkyltransferase
    glutathione S-aralkyltransferase
    glutathione S-aryltransferase
    glutathione transferase zeta 1
    maleylacetone isomerase
    NP_001299589.1
    NP_001350632.1
    NP_665877.1
    NP_665878.2
    XP_011534973.1
    XP_024305319.1
    XP_024305320.1
    XP_054231880.1
    XP_054231881.1
    XP_054231882.1

    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.

    mRNA and Protein(s)

    1. NM_001312660.2 → NP_001299589.1  maleylacetoacetate isomerase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 3, which lacks a portion of the N-terminus (aa 1-55), and is shorter than isoform 1. This isoform lacks the glutathione-binding site, and hence, is unlikely to retain enzyme activity.
      Source sequence(s)
      AJ001838, AK315154, BC001453
      Consensus CDS
      CCDS9860.1
      UniProtKB/Swiss-Prot
      O43708
      Related
      ENSP00000354959.4, ENST00000361389.8
      Conserved Domains (1) summary
      cl25459
      Location:1 → 156
      GstA; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]

    2. NM_001363703.2 → NP_001350632.1  maleylacetoacetate isomerase isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC007954
      Consensus CDS
      CCDS86416.1
      UniProtKB/Swiss-Prot
      A6NED0, A6NNB8, A8MWD7, B2RCK3, O15308, O43708, O75430, Q6IB17, Q7Z610, Q9BV63
      UniProtKB/TrEMBL
      B2RDN1, G3V4T6
      Related
      ENSP00000451976.1, ENST00000553586.5
      Conserved Domains (1) summary
      TIGR01262
      Location:8 → 212
      maiA; maleylacetoacetate isomerase

    3. NM_145870.3 → NP_665877.1  maleylacetoacetate isomerase isoform 1

      See identical proteins and their annotated locations for NP_665877.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AJ001838, BC001453
      Consensus CDS
      CCDS9858.1
      UniProtKB/Swiss-Prot
      A6NED0, A6NNB8, A8MWD7, B2RCK3, O15308, O43708, O75430, Q6IB17, Q7Z610, Q9BV63
      UniProtKB/TrEMBL
      A0A0C4DFM0, B2RDN1
      Related
      ENSP00000216465.5, ENST00000216465.10
      Conserved Domains (1) summary
      TIGR01262
      Location:7 → 211
      maiA; maleylacetoacetate isomerase

    4. NM_145871.3 → NP_665878.2  maleylacetoacetate isomerase isoform 2

      See identical proteins and their annotated locations for NP_665878.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AJ001838, BC001453
      Consensus CDS
      CCDS9859.1
      UniProtKB/TrEMBL
      A0A0A0MR33, G3V5T0
      Related
      ENSP00000314404.5, ENST00000349555.7
      Conserved Domains (3) summary
      cd03191
      Location:73 → 165
      GST_C_Zeta; C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases
      cd03042
      Location:6 → 72
      GST_N_Zeta; GST_N family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, ...
      TIGR01262
      Location:7 → 169
      maiA; maleylacetoacetate isomerase

    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_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      77321036..77331597
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024449551.2 → XP_024305319.1  maleylacetoacetate isomerase isoform X2

      Related
      ENSP00000377335.1, ENST00000393734.5
      Conserved Domains (1) summary
      cl25459
      Location:1 → 156
      GstA; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]

    2. XM_024449552.2 → XP_024305320.1  maleylacetoacetate isomerase isoform X2

      Conserved Domains (1) summary
      cl25459
      Location:1 → 156
      GstA; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]

    3. XM_011536671.3 → XP_011534973.1  maleylacetoacetate isomerase isoform X1

      UniProtKB/TrEMBL
      B2RDN1
      Conserved Domains (3) summary
      cd03191
      Location:74 → 166
      GST_C_Zeta; C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases
      cd03042
      Location:7 → 73
      GST_N_Zeta; GST_N family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, ...
      TIGR01262
      Location:8 → 170
      maiA; maleylacetoacetate isomerase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      71530399..71540959
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375906.1 → XP_054231881.1  maleylacetoacetate isomerase isoform X2

    2. XM_054375907.1 → XP_054231882.1  maleylacetoacetate isomerase isoform X2

    3. XM_054375905.1 → XP_054231880.1  maleylacetoacetate isomerase isoform X1

      UniProtKB/TrEMBL
      B2RDN1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001513.3: Suppressed sequence

      Description
      NM_001513.3: This RefSeq was removed because currently there is no support for the transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43708.3 GenPept UniProtKB/Swiss-Prot:O43708

    Gene LinkOut

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

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