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Protein

Maleylacetoacetate isomerase

Gene

GSTZ1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Bifunctional enzyme showing minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with T-butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid.1 Publication

Catalytic activityi

4-maleylacetoacetate = 4-fumarylacetoacetate.1 Publication
RX + glutathione = HX + R-S-glutathione.1 Publication

Cofactori

glutathioneNote: Glutathione is required for the MAAI activity.

Pathwayi: L-phenylalanine degradation

This protein is involved in step 5 of the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine.
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Phenylalanine-4-hydroxylase (PAH)
  2. Tyrosine aminotransferase (TAT)
  3. 4-hydroxyphenylpyruvate dioxygenase (HPD)
  4. Homogentisate 1,2-dioxygenase (HGD)
  5. Maleylacetoacetate isomerase (GSTZ1)
  6. Fumarylacetoacetase (FAH)
This subpathway is part of the pathway L-phenylalanine degradation, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine, the pathway L-phenylalanine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei45Glutathione1 Publication1
Binding sitei59Glutathione; via amide nitrogen and carbonyl oxygen1 Publication1
Binding sitei111Glutathione1 Publication1

GO - Molecular functioni

  • glutathione peroxidase activity Source: ProtInc
  • glutathione transferase activity Source: UniProtKB
  • hydrolase activity, acting on acid halide bonds, in C-halide compounds Source: Reactome
  • identical protein binding Source: IntAct
  • maleylacetoacetate isomerase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIsomerase, Multifunctional enzyme, Transferase
Biological processPhenylalanine catabolism, Tyrosine catabolism

Enzyme and pathway databases

BioCyciMetaCyc:HS02114-MONOMER
BRENDAi2.5.1.18 2681
5.2.1.2 2681
ReactomeiR-HSA-156590 Glutathione conjugation
R-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex
R-HSA-71182 Phenylalanine and tyrosine catabolism
UniPathwayiUPA00139; UER00340

Names & Taxonomyi

Protein namesi
Recommended name:
Maleylacetoacetate isomerase (EC:5.2.1.2)
Short name:
MAAI
Alternative name(s):
GSTZ1-1
Glutathione S-transferase zeta 1 (EC:2.5.1.18)
Gene namesi
Name:GSTZ1
Synonyms:MAAI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100577.18
HGNCiHGNC:4643 GSTZ1
MIMi603758 gene
neXtProtiNX_O43708

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Maleylacetoacetate isomerase deficiency (MAAID)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive inborn error of metabolism characterized by mild elevations in succinylacetone in blood and urine, usually identified by newborn screening. Liver function and coagulation are normal. MAAID is a benign disorder.
See also OMIM:617596
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07925987 – 216Missing in MAAID. 1 PublicationAdd BLAST130
Natural variantiVAR_07926099V → M in MAAID; decreased maleylacetoacetate isomerase activity. 1 Publication1
Natural variantiVAR_079261150A → V in MAAID; decreased maleylacetoacetate isomerase activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2954
MalaCardsiGSTZ1
MIMi617596 phenotype
OpenTargetsiENSG00000100577
PharmGKBiPA29031

Chemistry databases

ChEMBLiCHEMBL4949
DrugBankiDB00143 Glutathione

Polymorphism and mutation databases

BioMutaiGSTZ1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860221 – 216Maleylacetoacetate isomeraseAdd BLAST216

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei32N6-acetyllysineCombined sources1
Modified residuei57N6-succinyllysineBy similarity1
Modified residuei136PhosphothreonineBy similarity1
Modified residuei177N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO43708
MaxQBiO43708
PaxDbiO43708
PeptideAtlasiO43708
PRIDEiO43708

PTM databases

iPTMnetiO43708
PhosphoSitePlusiO43708

Expressioni

Tissue specificityi

Mostly expressed in liver followed by kidney, skeletal muscle and brain. Also expressed in melanocytes, synovium, placenta, breast and fetal liver and heart.

Gene expression databases

BgeeiENSG00000100577
CleanExiHS_GSTZ1
ExpressionAtlasiO43708 baseline and differential
GenevisibleiO43708 HS

Organism-specific databases

HPAiHPA004701

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi109209, 8 interactors
IntActiO43708, 11 interactors
STRINGi9606.ENSP00000216465

Structurei

Secondary structure

1216
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 10Combined sources4
Helixi15 – 26Combined sources12
Beta strandi32 – 35Combined sources4
Helixi44 – 46Combined sources3
Helixi48 – 53Combined sources6
Beta strandi61 – 64Combined sources4
Beta strandi67 – 71Combined sources5
Helixi72 – 82Combined sources11
Helixi93 – 109Combined sources17
Helixi111 – 114Combined sources4
Helixi116 – 122Combined sources7
Helixi124 – 149Combined sources26
Beta strandi150 – 156Combined sources7
Helixi161 – 175Combined sources15
Helixi184 – 194Combined sources11
Helixi197 – 199Combined sources3
Turni200 – 202Combined sources3
Helixi204 – 206Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FW1X-ray1.90A1-216[»]
ProteinModelPortaliO43708
SMRiO43708
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43708

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 87GST N-terminalAdd BLAST84
Domaini92 – 212GST C-terminalAdd BLAST121

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 19Glutathione binding6
Regioni71 – 72Glutathione binding2
Regioni115 – 117Glutathione binding3

Sequence similaritiesi

Belongs to the GST superfamily. Zeta family.Curated

Phylogenomic databases

eggNOGiKOG0868 Eukaryota
COG0625 LUCA
GeneTreeiENSGT00390000006580
HOGENOMiHOG000125758
HOVERGENiHBG001501
InParanoidiO43708
KOiK01800
PhylomeDBiO43708
TreeFamiTF105324

Family and domain databases

CDDicd03191 GST_C_Zeta, 1 hit
cd03042 GST_N_Zeta, 1 hit
InterProiView protein in InterPro
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR004045 Glutathione_S-Trfase_N
IPR004046 GST_C
IPR005955 GST_Zeta
IPR034330 GST_Zeta_C
IPR034333 GST_Zeta_N
IPR036249 Thioredoxin-like_sf
PfamiView protein in Pfam
PF14497 GST_C_3, 1 hit
PF13417 GST_N_3, 1 hit
SUPFAMiSSF47616 SSF47616, 1 hit
SSF52833 SSF52833, 1 hit
TIGRFAMsiTIGR01262 maiA, 1 hit
PROSITEiView protein in PROSITE
PS50405 GST_CTER, 1 hit
PS50404 GST_NTER, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43708-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQAGKPILYS YFRSSCSWRV RIALALKGID YKTVPINLIK DRGQQFSKDF
60 70 80 90 100
QALNPMKQVP TLKIDGITIH QSLAIIEYLE EMRPTPRLLP QDPKKRASVR
110 120 130 140 150
MISDLIAGGI QPLQNLSVLK QVGEEMQLTW AQNAITCGFN ALEQILQSTA
160 170 180 190 200
GIYCVGDEVT MADLCLVPQV ANAERFKVDL TPYPTISSIN KRLLVLEAFQ
210
VSHPCRQPDT PTELRA
Length:216
Mass (Da):24,212
Last modified:November 24, 2009 - v3
Checksum:i2B3112B8AE6B55E0
GO
Isoform 2 (identifier: O43708-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.

Show »
Length:161
Mass (Da):17,896
Checksum:i8EF7E58223F1C0E3
GO
Isoform 3 (identifier: O43708-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     73-114: Missing.

Note: Gene prediction based on EST data.
Show »
Length:174
Mass (Da):19,472
Checksum:i9C4636C87F67ADED
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00970532K → E in allele GSTZ1*C. 6 PublicationsCorresponds to variant dbSNP:rs7975Ensembl.1
Natural variantiVAR_00970642R → G in allele GSTZ1*B and allele GSTZ1*C. 9 PublicationsCorresponds to variant dbSNP:rs7972Ensembl.1
Natural variantiVAR_00970782M → T7 PublicationsCorresponds to variant dbSNP:rs1046428Ensembl.1
Natural variantiVAR_07925987 – 216Missing in MAAID. 1 PublicationAdd BLAST130
Natural variantiVAR_07926099V → M in MAAID; decreased maleylacetoacetate isomerase activity. 1 Publication1
Natural variantiVAR_014505133N → H1 PublicationCorresponds to variant dbSNP:rs2234955Ensembl.1
Natural variantiVAR_079261150A → V in MAAID; decreased maleylacetoacetate isomerase activity. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0398621 – 55Missing in isoform 2. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_04739273 – 114Missing in isoform 3. CuratedAdd BLAST42

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001838 mRNA Translation: CAA05045.1
U86529 mRNA Translation: AAB96392.1
AF053545
, AF053539, AF053540, AF053541, AF053542, AF053543, AF053544 Genomic DNA Translation: AAC33591.1
AF098318
, AF095582, AF098311, AF098312, AF098313, AF098314, AF098315, AF098316, AF098317 Genomic DNA Translation: AAD43007.1
AK315154 mRNA Translation: BAG37600.1
CR456987 mRNA Translation: CAG33268.1
AY316305 Genomic DNA Translation: AAP69526.1
AC007954 Genomic DNA Translation: AAF62559.1
CH471061 Genomic DNA Translation: EAW81278.1
CH471061 Genomic DNA Translation: EAW81279.1
BC001453 mRNA Translation: AAH01453.1
CCDSiCCDS9858.1 [O43708-1]
CCDS9859.1 [O43708-3]
CCDS9860.1 [O43708-2]
RefSeqiNP_001299589.1, NM_001312660.1 [O43708-2]
NP_665877.1, NM_145870.2
NP_665878.2, NM_145871.2
UniGeneiHs.655292

Genome annotation databases

EnsembliENST00000361389; ENSP00000354959; ENSG00000100577 [O43708-2]
ENST00000393734; ENSP00000377335; ENSG00000100577 [O43708-2]
ENST00000557639; ENSP00000451927; ENSG00000100577 [O43708-2]
GeneIDi2954
KEGGihsa:2954
UCSCiuc001xtj.4 human [O43708-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMAAI_HUMAN
AccessioniPrimary (citable) accession number: O43708
Secondary accession number(s): A6NED0
, A6NNB8, A8MWD7, B2RCK3, O15308, O75430, Q6IB17, Q7Z610, Q9BV63
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 24, 2009
Last modified: May 23, 2018
This is version 190 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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