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Protein

Maleylacetoacetate isomerase

Gene

GSTZ1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • identical protein binding Source: IntAct
  • maleylacetoacetate isomerase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIsomerase, 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-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.

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.
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. 9 interactors.
MINTiMINT-1444642.
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: November 22, 2017
This is version 187 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, Multifunctional enzyme, 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