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

Gene ID: 2954, updated on 2-Nov-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: 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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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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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
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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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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

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

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