O43708 (MAAI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Maleylacetoacetate isomerase
Short name=MAAI
EC=5.2.1.2

Alternative name(s):
GSTZ1-1
Glutathione S-transferase zeta 1
EC=2.5.1.18

Gene names

Name:	GSTZ1
Synonyms:	MAAI

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	216 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.14
Catalytic activity	4-maleylacetoacetate = 4-fumarylacetoacetate. Ref.14 RX + glutathione = HX + R-S-glutathione. Ref.14
Cofactor	Glutathione. Required for the MAAI activity.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 5/6.
Subunit structure	Homodimer. Ref.15
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Mostly expressed in liver followed by kidney, skeletal muscle and brain. Also expressed in melanocytes, synovium, placenta, breast and fetal liver and heart.
Sequence similarities	Belongs to the GST superfamily. Zeta family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.

Ontologies

Keywords
Biological process	Phenylalanine catabolism Tyrosine catabolism
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Isomerase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	L-phenylalanine catabolic process Traceable author statement. Source: Reactome glutathione metabolic process Inferred from direct assay Ref.14. Source: UniProtKB tyrosine catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	glutathione peroxidase activity Traceable author statement Ref.2. Source: ProtInc glutathione transferase activity Inferred from direct assay Ref.14. Source: UniProtKB maleylacetoacetate isomerase activity Inferred from direct assay Ref.14. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-748043,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43708-1)

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.

Isoform 2 (identifier: O43708-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 216

216

Maleylacetoacetate isomerase

PRO_0000186022

Regions

Domain

4 – 87

84

GST N-terminal

Domain

92 – 212

121

GST C-terminal

Region

14 – 19

6

Glutathione binding

Region

71 – 72

2

Glutathione binding

Region

115 – 117

3

Glutathione binding

Sites

Binding site

45

1

Glutathione

Binding site

59

1

Glutathione; via amide nitrogen and carbonyl oxygen

Binding site

111

1

Glutathione

Amino acid modifications

Modified residue

32

1

N6-acetyllysine Ref.12

Natural variations

Alternative sequence

1 – 55

55

Missing in isoform 2.

VSP_039862

Natural variant

32

1

K → E in allele GSTZ1*C. Ref.3 Ref.7 Ref.8 Ref.10 Ref.14
Corresponds to variant rs7975 [ dbSNP | Ensembl ].

VAR_009705

Natural variant

42

1

R → G in allele GSTZ1*B and allele GSTZ1*C. Ref.1 Ref.3 Ref.4 Ref.6 Ref.7 Ref.8 Ref.10 Ref.14
Corresponds to variant rs7972 [ dbSNP | Ensembl ].

VAR_009706

Natural variant

82

1

M → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Corresponds to variant rs1046428 [ dbSNP | Ensembl ].

VAR_009707

Natural variant

133

1

N → H. Ref.7
Corresponds to variant rs2234955 [ dbSNP | Ensembl ].

VAR_014505

Secondary structure

1

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216

Helix Strand Turn

Details...

Beta strand

7 – 10

4

Helix

15 – 26

12

Beta strand

32 – 35

4

Helix

44 – 46

3

Helix

48 – 53

6

Beta strand

61 – 64

4

Beta strand

67 – 71

5

Helix

72 – 82

11

Helix

93 – 109

17

Helix

111 – 114

4

Helix

116 – 122

7

Helix

124 – 149

26

Beta strand

150 – 156

7

Helix

161 – 175

15

Helix

184 – 194

11

Helix

197 – 199

3

Turn

200 – 202

3

Helix

204 – 206

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 3. Checksum: 2B3112B8AE6B55E0	FASTA	216	24,212
	10 20 30 40 50 60 MQAGKPILYS YFRSSCSWRV RIALALKGID YKTVPINLIK DRGQQFSKDF QALNPMKQVP 70 80 90 100 110 120 TLKIDGITIH QSLAIIEYLE EMRPTPRLLP QDPKKRASVR MISDLIAGGI QPLQNLSVLK 130 140 150 160 170 180 QVGEEMQLTW AQNAITCGFN ALEQILQSTA GIYCVGDEVT MADLCLVPQV ANAERFKVDL 190 200 210 TPYPTISSIN KRLLVLEAFQ VSHPCRQPDT PTELRA
	Isoform 2 [UniParc]. Checksum: 8EF7E58223F1C0E3	FASTA	161	17,896
	10 20 30 40 50 60 MKQVPTLKID GITIHQSLAI IEYLEEMRPT PRLLPQDPKK RASVRMISDL IAGGIQPLQN 70 80 90 100 110 120 LSVLKQVGEE MQLTWAQNAI TCGFNALEQI LQSTAGIYCV GDEVTMADLC LVPQVANAER 130 140 150 160 FKVDLTPYPT ISSINKRLLV LEAFQVSHPC RQPDTPTELR A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a fungal maleylacetoacetate isomerase gene and identification of its human homologue." Fernandez-Canon J.M., Penalva M.A. J. Biol. Chem. 273:329-337(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, VARIANTS GLY-42 AND THR-82.
[2]	"Zeta, a novel class of glutathione transferases in a range of species from plants to humans." Board P.G., Baker R.T., Chelvanayagam G., Jermiin L.S. Biochem. J. 328:929-935(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT THR-82, CHARACTERIZATION.
[3]	"Characterization and chromosome location of the gene GSTZ1 encoding the human zeta class glutathione transferase and maleylacetoacetate isomerase." Blackburn A.C., Woollatt E., Sutherland G.R., Board P.G. Cytogenet. Cell Genet. 83:109-114(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS GLU-32; GLY-42 AND THR-82.
[4]	"Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase." Fernandez-Canon J.M., Hejna J., Reifsteck C., Olson S., Grompe M. Genomics 58:263-269(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS GLY-42 AND THR-82.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT THR-82. Tissue: Skeletal muscle.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLY-42 AND THR-82.
[7]	NIEHS SNPs program Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-32; GLY-42; THR-82 AND HIS-133.
[8]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS GLU-32 AND GLY-42.
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLU-32 AND GLY-42. Tissue: Placenta.
[11]	"Glutathione transferase zeta catalyses the oxygenation of the carcinogen dichloroacetic acid to glyoxylic acid." Tong Z., Board P.G., Anders M.W. Biochem. J. 331:371-374(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32, MASS SPECTROMETRY.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Discovery of a functional polymorphism in human glutathione transferase zeta by expressed sequence tag database analysis." Blackburn A.C., Tzeng H.F., Anders M.W., Board P.G. Pharmacogenetics 10:49-57(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLU-32 AND GLY-42, FUNCTION, CATALYTIC ACTIVITY.
[15]	"Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity." Polekhina G., Board P.G., Blackburn A.C., Parker M.W. Biochemistry 40:1567-1576(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, SUBUNIT.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
BC001453 mRNA. Translation: AAH01453.1.

IPI

IPI00013809.
IPI00472241.

RefSeq

NP_001504.2. NM_001513.3.
NP_665877.1. NM_145870.2.
NP_665878.2. NM_145871.2.

UniGene

Hs.655292.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FW1	X-ray	1.90	A	1-216	[»]

ProteinModelPortal

O43708.

SMR

O43708. Positions 5-212.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43708. 5 interactions.

MINT

MINT-1444642.

STRING

9606.ENSP00000216465.

PTM databases

PhosphoSite

O43708.

Proteomic databases

PaxDb

O43708.

PRIDE

O43708.

Protocols and materials databases

DNASU

2954.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216465; ENSP00000216465; ENSG00000100577.
ENST00000361389; ENSP00000354959; ENSG00000100577.
ENST00000393734; ENSP00000377335; ENSG00000100577.
ENST00000557639; ENSP00000451927; ENSG00000100577.

GeneID

2954.

KEGG

hsa:2954.

UCSC

uc001xtj.3. human.

Organism-specific databases

CTD

2954.

GeneCards

GC14P077787.

HGNC

HGNC:4643. GSTZ1.

HPA

HPA004701.

MIM

603758. gene.

neXtProt

NX_O43708.

PharmGKB

PA29031.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0625.

HOVERGEN

HBG001501.

KO

K01800.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02114-MONOMER.

BRENDA

5.2.1.2. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00139; UER00340.

Gene expression databases

ArrayExpress

O43708.

Bgee

O43708.

CleanEx

HS_GSTZ1.

Genevestigator

O43708.

GermOnline

ENSG00000100577. Homo sapiens.

Family and domain databases

Gene3D

1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR004046. GST_C.
IPR005955. Mal_ac_isom.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Pfam

PF00043. GST_C. 1 hit.
[Graphical view]

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

TIGRFAMs

TIGR01262. maiA. 1 hit.

PROSITE

PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL4949.

ChiTaRS

GSTZ1. human.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

O43708.

GenomeRNAi

2954.

NextBio

11706.

SOURCE

Search...

Entry information

Entry name

MAAI_HUMAN

Accession

Primary (citable) accession number: O43708
Secondary accession number(s): A6NNB8 , A8MWD7, B2RCK3, O15308, O75430, Q6IB17, Q7Z610, Q9BV63

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 145 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.