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

Summary

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

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_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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?

Clinical physiology and pharmacology of GSTZ1/MAAI.
Title: Clinical physiology and pharmacology of GSTZ1/MAAI.
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.
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.
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.
GSTZ1-1 downregulates Wnt/beta-catenin signalling in hepatocellular carcinoma cells.
Title: GSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells.
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.
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.
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.
Some properties of cytosolic and mitochondrial GSTZ1 differed.
Title: Age-Related Changes in Expression and Activity of Human Hepatic Mitochondrial Glutathione Transferase Zeta1.
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

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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

D11S2921 (e-PCR)
- UniSTS:152074

PMC64834P1 (e-PCR)
- UniSTS:273421

G66716 (e-PCR)
- UniSTS:166952

G66717 (e-PCR)
- UniSTS:166953

G66718 (e-PCR)
- UniSTS:166954

PMC156606P1 (e-PCR)
- UniSTS:271408

L18426 (e-PCR)
- UniSTS:34648

D14S641E (e-PCR)
- UniSTS:32389

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 more info	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

EC 2.5.1.18

EC 5.2.1.2

NP_001350632.1

EC 2.5.1.18

EC 5.2.1.2

NP_665877.1

EC 2.5.1.18

EC 5.2.1.2

NP_665878.2

EC 2.5.1.18

EC 5.2.1.2

XP_011534973.1

EC 2.5.1.18

EC 5.2.1.2

XP_024305319.1

EC 2.5.1.18

EC 5.2.1.2

XP_024305320.1

EC 2.5.1.18

EC 5.2.1.2

XP_054231880.1

EC 2.5.1.18

EC 5.2.1.2

XP_054231881.1

EC 2.5.1.18

EC 5.2.1.2

XP_054231882.1

EC 2.5.1.18

EC 5.2.1.2

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)

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]
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
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
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

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

77321036..77331597

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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