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P19440

- GGT1_HUMAN

UniProt

P19440 - GGT1_HUMAN

Protein

Gamma-glutamyltranspeptidase 1

Gene

GGT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 167 (01 Oct 2014)
      Sequence version 2 (07 Mar 2006)
      Previous versions | rss
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    Functioni

    Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide, cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive.6 Publications

    Catalytic activityi

    A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.
    Glutathione + H2O = L-cysteinylglycine + L-glutamate.
    Leukotriene C4 + H2O = leukotriene D4 + L-glutamate.

    Enzyme regulationi

    Activated by autocatalytic cleavage.1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei107 – 1071Glutamate1 Publication
    Active sitei381 – 3811Nucleophile1 Publication
    Binding sitei399 – 3991Glutamate1 Publication
    Binding sitei420 – 4201Glutamate1 Publication

    GO - Molecular functioni

    1. gamma-glutamyltransferase activity Source: UniProtKB
    2. glutathione hydrolase activity Source: UniProtKB
    3. protein binding Source: UniProtKB

    GO - Biological processi

    1. arachidonic acid metabolic process Source: Reactome
    2. cellular amino acid metabolic process Source: ProtInc
    3. cysteine biosynthetic process Source: UniProtKB
    4. glutamate metabolic process Source: UniProtKB
    5. glutathione biosynthetic process Source: UniProtKB
    6. glutathione catabolic process Source: UniProtKB
    7. glutathione derivative biosynthetic process Source: Reactome
    8. glutathione metabolic process Source: UniProtKB
    9. leukotriene biosynthetic process Source: UniProtKB
    10. leukotriene metabolic process Source: Reactome
    11. regulation of immune system process Source: UniProtKB
    12. regulation of inflammatory response Source: UniProtKB
    13. small molecule metabolic process Source: Reactome
    14. spermatogenesis Source: UniProtKB
    15. xenobiotic metabolic process Source: Reactome
    16. zymogen activation Source: UniProtKB

    Keywords - Molecular functioni

    Acyltransferase, Hydrolase, Protease, Transferase

    Keywords - Biological processi

    Glutathione biosynthesis

    Keywords - Ligandi

    Sialic acid

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01957-MONOMER.
    BRENDAi2.3.2.2. 2681.
    ReactomeiREACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_6960. Glutathione synthesis and recycling.
    SABIO-RKP19440.
    UniPathwayiUPA00204.

    Protein family/group databases

    MEROPSiT03.006.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Gamma-glutamyltranspeptidase 1 (EC:2.3.2.2)
    Short name:
    GGT 1
    Alternative name(s):
    Gamma-glutamyltransferase 1
    Glutathione hydrolase 1 (EC:3.4.19.13)
    Leukotriene-C4 hydrolase (EC:3.4.19.14)
    CD_antigen: CD224
    Cleaved into the following 2 chains:
    Gene namesi
    Name:GGT1
    Synonyms:GGT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:4250. GGT1.

    Subcellular locationi

    Cell membrane 2 Publications; Single-pass type II membrane protein 2 Publications

    GO - Cellular componenti

    1. anchored component of external side of plasma membrane Source: UniProtKB
    2. extracellular space Source: UniProt
    3. extracellular vesicular exosome Source: UniProt
    4. integral component of membrane Source: UniProtKB-KW
    5. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Glutathionuria (GLUTH) [MIM:231950]: Autosomal recessive disease.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi100 – 1001K → N: No effect on activity. 1 Publication
    Mutagenesisi102 – 1021E → Q: No effect on activity. 1 Publication
    Mutagenesisi107 – 1071R → K: Reduces enzyme activity by 99%. 1 Publication
    Mutagenesisi107 – 1071R → Q or H: Abolishes enzyme activity. 1 Publication
    Mutagenesisi108 – 1081E → Q: Reduces enzyme activity by 98%. 1 Publication
    Mutagenesisi112 – 1121R → Q: No effect on activity. 1 Publication
    Mutagenesisi139 – 1391R → Q: No effect on activity. 1 Publication
    Mutagenesisi147 – 1471R → Q: No effect on activity. 1 Publication
    Mutagenesisi150 – 1501R → Q: No effect on activity. 1 Publication
    Mutagenesisi192 – 1921C → W: Loss of autocatalytic cleavage, cell membrane localization and decrease in catalytic activity; when associated with Y-193. 1 Publication
    Mutagenesisi193 – 1931E → Y: Loss of autocatalytic cleavage, cell membrane localization and decrease in catalytic activity; when associated with W-192. 1 Publication
    Mutagenesisi383 – 3831H → A: Reduces enzyme activity by 66%. 1 Publication
    Mutagenesisi385 – 3851S → A: No effect on activity. 1 Publication
    Mutagenesisi413 – 4131S → A: No effect on activity. 1 Publication
    Mutagenesisi422 – 4221D → A: Reduces enzyme activity by 90%. 1 Publication
    Mutagenesisi423 – 4231D → A: Abolishes enzyme activity. Increases KM by over 1000-fold. 1 Publication
    Mutagenesisi425 – 4251S → A: No effect on activity. 1 Publication
    Mutagenesisi451 – 4511S → A: Reduces enzyme activity by 99%. Abolishes activity; when associated with A-452. 1 Publication
    Mutagenesisi452 – 4521S → A: Reduces enzyme activity by 99%. Abolishes activity; when associated with A-451. 1 Publication
    Mutagenesisi454 – 4541C → A: No effect on activity. 1 Publication
    Mutagenesisi505 – 5051H → A: Reduces enzyme activity by 90%. 1 Publication
    Mutagenesisi545 – 5451Q → K: Reduces enzyme activity by 97%. 1 Publication

    Organism-specific databases

    MIMi231950. phenotype.
    Orphaneti33573. Gamma-glutamyl transpeptidase deficiency.
    PharmGKBiPA28662.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 380380Gamma-glutamyltranspeptidase 1 heavy chainPRO_0000011058Add
    BLAST
    Chaini381 – 569189Gamma-glutamyltranspeptidase 1 light chainPRO_0000011059Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi50 ↔ 741 Publication
    Glycosylationi95 – 951N-linked (GlcNAc...)2 Publications
    Glycosylationi120 – 1201N-linked (GlcNAc...)5 Publications
    Disulfide bondi192 ↔ 1961 Publication
    Glycosylationi230 – 2301N-linked (GlcNAc...)3 Publications
    Glycosylationi266 – 2661N-linked (GlcNAc...)3 Publications
    Glycosylationi297 – 2971N-linked (GlcNAc...)1 Publication
    Glycosylationi344 – 3441N-linked (GlcNAc...)3 Publications
    Glycosylationi511 – 5111N-linked (GlcNAc...)5 Publications

    Post-translational modificationi

    N-glycosylated on both chains. Contains hexoses, hexosamines and sialic acid residues. Glycosylation profiles tested in kidney and liver tissues reveal the presence of tissue-specific and site-specific glycan composition, despite the overlap in composition among the N-glycans. A total of 36 glycan compositions, with 40 unique structures are observed. Up to 15 different glycans are observed at a single site, with site-specific variation in glycan composition. The difference in glycosylation profiles in the 2 tissues do not affect the enzyme activity.9 Publications
    Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    MaxQBiP19440.
    PaxDbiP19440.
    PRIDEiP19440.

    PTM databases

    PhosphoSiteiP19440.

    Expressioni

    Tissue specificityi

    Detected in fetal and adult kidney and liver, adult pancreas, stomach, intestine, placenta and lung. Isoform 3 is lung-specific. There are several other tissue-specific forms that arise from alternative promoter usage but that produce the same protein.

    Gene expression databases

    BgeeiP19440.
    CleanExiHS_GGT1.
    GenevestigatoriP19440.

    Organism-specific databases

    HPAiHPA045635.

    Interactioni

    Subunit structurei

    Heterodimer composed of the light and heavy chains. The active site is located in the light chain.2 Publications

    Protein-protein interaction databases

    BioGridi108946. 5 interactions.
    IntActiP19440. 2 interactions.
    MINTiMINT-2801579.
    STRINGi9606.ENSP00000248923.

    Structurei

    Secondary structure

    1
    569
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi36 – 405
    Beta strandi42 – 443
    Helixi48 – 5912
    Helixi64 – 7815
    Turni79 – 824
    Beta strandi87 – 959
    Turni96 – 994
    Beta strandi100 – 1067
    Helixi122 – 1265
    Helixi129 – 1313
    Helixi137 – 14812
    Helixi153 – 16614
    Helixi172 – 1809
    Helixi182 – 1876
    Helixi189 – 1957
    Beta strandi206 – 2083
    Helixi211 – 22313
    Helixi226 – 2294
    Helixi234 – 24310
    Helixi250 – 2556
    Beta strandi259 – 2635
    Beta strandi265 – 2695
    Beta strandi272 – 2765
    Helixi283 – 29412
    Helixi300 – 3034
    Helixi306 – 32722
    Turni333 – 3353
    Helixi339 – 3457
    Helixi348 – 3558
    Helixi366 – 3694
    Beta strandi382 – 3876
    Beta strandi393 – 3997
    Turni403 – 4064
    Turni411 – 4133
    Helixi420 – 4234
    Helixi439 – 4413
    Beta strandi456 – 4605
    Beta strandi465 – 47612
    Helixi477 – 48913
    Helixi495 – 5006
    Beta strandi508 – 5114
    Beta strandi513 – 5153
    Helixi521 – 5299
    Beta strandi534 – 5363
    Beta strandi543 – 5508
    Beta strandi553 – 5575
    Turni560 – 5623

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4GDXX-ray1.67A2-374[»]
    B375-569[»]
    4GG2X-ray2.21A28-380[»]
    B381-569[»]
    ProteinModelPortaliP19440.
    SMRiP19440. Positions 33-375, 381-569.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 44CytoplasmicSequence Analysis
    Topological domaini27 – 569543ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei5 – 2622Helical; Signal-anchor for type II membrane proteinCuratedAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni451 – 4522Glutamate binding

    Sequence similaritiesi

    Belongs to the gamma-glutamyltransferase family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0405.
    HOGENOMiHOG000175620.
    HOVERGENiHBG005835.
    InParanoidiP19440.
    KOiK00681.
    OMAiTINAREM.
    OrthoDBiEOG7V7665.
    PhylomeDBiP19440.
    TreeFamiTF313608.

    Family and domain databases

    InterProiIPR000101. GGT_peptidase.
    IPR029055. Ntn_hydrolases_N.
    [Graphical view]
    PANTHERiPTHR11686. PTHR11686. 1 hit.
    PfamiPF01019. G_glu_transpept. 1 hit.
    [Graphical view]
    PRINTSiPR01210. GGTRANSPTASE.
    SUPFAMiSSF56235. SSF56235. 1 hit.
    TIGRFAMsiTIGR00066. g_glut_trans. 1 hit.
    PROSITEiPS00462. G_GLU_TRANSPEPTIDASE. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative promoter usage and alternative splicing. Align

    Isoform 1 (identifier: P19440-1) [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

    MKKKLVVLGL LAVVLVLVIV GLCLWLPSAS KEPDNHVYTR AAVAADAKQC    50
    SKIGRDALRD GGSAVDAAIA ALLCVGLMNA HSMGIGGGLF LTIYNSTTRK 100
    AEVINAREVA PRLAFATMFN SSEQSQKGGL SVAVPGEIRG YELAHQRHGR 150
    LPWARLFQPS IQLARQGFPV GKGLAAALEN KRTVIEQQPV LCEVFCRDRK 200
    VLREGERLTL PQLADTYETL AIEGAQAFYN GSLTAQIVKD IQAAGGIVTA 250
    EDLNNYRAEL IEHPLNISLG DVVLYMPSAP LSGPVLALIL NILKGYNFSR 300
    ESVESPEQKG LTYHRIVEAF RFAYAKRTLL GDPKFVDVTE VVRNMTSEFF 350
    AAQLRAQISD DTTHPISYYK PEFYTPDDGG TAHLSVVAED GSAVSATSTI 400
    NLYFGSKVRS PVSGILFNNE MDDFSSPSIT NEFGVPPSPA NFIQPGKQPL 450
    SSMCPTIMVG QDGQVRMVVG AAGGTQITTA TALAIIYNLW FGYDVKRAVE 500
    EPRLHNQLLP NVTTVERNID QAVTAALETR HHHTQIASTF IAVVQAIVRT 550
    AGGWAAASDS RKGGEPAGY 569

    Note: Produced by alternative promoter usage.

    Length:569
    Mass (Da):61,410
    Last modified:March 7, 2006 - v2
    Checksum:i71AE12485239A69F
    GO
    Isoform 2 (identifier: P19440-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         341-366: VVRNMTSEFFAAQLRAQISDDTTHPI → ASSGVSAGGPQHDLRVLRCPAPGPDL
         367-569: Missing.

    Note: Produced by alternative splicing of isoform 1.

    Show »
    Length:366
    Mass (Da):39,420
    Checksum:i726B492DEFA85BE2
    GO
    Isoform 3 (identifier: P19440-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-344: Missing.

    Note: Produced by alternative promoter usage.

    Show »
    Length:225
    Mass (Da):24,080
    Checksum:i46765CED537C40C3
    GO

    Sequence cautioni

    The sequence AAA35899.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti30 – 312SK → KS AA sequence (PubMed:2896486)Curated
    Sequence conflicti47 – 471A → K AA sequence (PubMed:2896486)Curated
    Sequence conflicti139 – 1391R → E in AAA35889. (PubMed:1968061)Curated
    Sequence conflicti356 – 3561A → S in AAI28240. (PubMed:15489334)Curated
    Sequence conflicti361 – 3611D → H in AAI28240. (PubMed:15489334)Curated
    Sequence conflicti372 – 3721E → D in AAA02886. (PubMed:7689219)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti51 – 511S → L.
    Corresponds to variant rs2330837 [ dbSNP | Ensembl ].
    VAR_025545
    Natural varianti52 – 521K → E.
    Corresponds to variant rs2330838 [ dbSNP | Ensembl ].
    VAR_018373
    Natural varianti177 – 1771A → V.
    Corresponds to variant rs3895576 [ dbSNP | Ensembl ].
    VAR_018374
    Natural varianti272 – 2721V → A.6 Publications
    Corresponds to variant rs4049829 [ dbSNP | Ensembl ].
    VAR_018372
    Natural varianti419 – 4191N → D.
    Corresponds to variant rs17004876 [ dbSNP | Ensembl ].
    VAR_025546
    Natural varianti435 – 4351V → A.
    Corresponds to variant rs16986465 [ dbSNP | Ensembl ].
    VAR_049181

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 344344Missing in isoform 3. 2 PublicationsVSP_008132Add
    BLAST
    Alternative sequencei341 – 36626VVRNM…TTHPI → ASSGVSAGGPQHDLRVLRCP APGPDL in isoform 2. 1 PublicationVSP_001746Add
    BLAST
    Alternative sequencei367 – 569203Missing in isoform 2. 1 PublicationVSP_001747Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04131 mRNA. Translation: AAA52547.1.
    M24087 mRNA. Translation: AAA35899.1. Different initiation.
    M24903 mRNA. Translation: AAA52546.1.
    J05235 mRNA. Translation: AAA35889.1.
    X60069 mRNA. Translation: CAA42674.1.
    L20490 mRNA. Translation: AAA02884.1.
    L20493 mRNA. Translation: AAA02886.1.
    CR456494 mRNA. Translation: CAG30380.1.
    AP000356 Genomic DNA. No translation available.
    BC025927 mRNA. Translation: AAH25927.1.
    BC069473 mRNA. Translation: AAH69473.1.
    BC069504 mRNA. Translation: AAH69504.1.
    BC128238 mRNA. Translation: AAI28239.1.
    BC128239 mRNA. Translation: AAI28240.1.
    CCDSiCCDS42992.1. [P19440-1]
    PIRiA31253. EKHUEX.
    A48987.
    A60439.
    JS0067.
    PS0312.
    RefSeqiNP_001275762.1. NM_001288833.1. [P19440-1]
    NP_038265.2. NM_013421.2. [P19440-1]
    NP_038347.2. NM_013430.2. [P19440-1]
    UniGeneiHs.595809.
    Hs.645535.

    Genome annotation databases

    EnsembliENST00000248923; ENSP00000248923; ENSG00000100031. [P19440-1]
    ENST00000400380; ENSP00000383231; ENSG00000100031. [P19440-1]
    ENST00000400382; ENSP00000383232; ENSG00000100031. [P19440-1]
    ENST00000401885; ENSP00000384381; ENSG00000100031. [P19440-3]
    ENST00000403838; ENSP00000384820; ENSG00000100031. [P19440-3]
    ENST00000404532; ENSP00000385445; ENSG00000100031. [P19440-3]
    ENST00000425895; ENSP00000387499; ENSG00000100031. [P19440-2]
    GeneIDi2678.
    KEGGihsa:2678.
    UCSCiuc003aan.1. human. [P19440-1]
    uc003aay.1. human. [P19440-3]

    Polymorphism databases

    DMDMi93140064.

    Keywords - Coding sequence diversityi

    Alternative promoter usage, Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Gamma-glutamyl transpeptidase entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04131 mRNA. Translation: AAA52547.1 .
    M24087 mRNA. Translation: AAA35899.1 . Different initiation.
    M24903 mRNA. Translation: AAA52546.1 .
    J05235 mRNA. Translation: AAA35889.1 .
    X60069 mRNA. Translation: CAA42674.1 .
    L20490 mRNA. Translation: AAA02884.1 .
    L20493 mRNA. Translation: AAA02886.1 .
    CR456494 mRNA. Translation: CAG30380.1 .
    AP000356 Genomic DNA. No translation available.
    BC025927 mRNA. Translation: AAH25927.1 .
    BC069473 mRNA. Translation: AAH69473.1 .
    BC069504 mRNA. Translation: AAH69504.1 .
    BC128238 mRNA. Translation: AAI28239.1 .
    BC128239 mRNA. Translation: AAI28240.1 .
    CCDSi CCDS42992.1. [P19440-1 ]
    PIRi A31253. EKHUEX.
    A48987.
    A60439.
    JS0067.
    PS0312.
    RefSeqi NP_001275762.1. NM_001288833.1. [P19440-1 ]
    NP_038265.2. NM_013421.2. [P19440-1 ]
    NP_038347.2. NM_013430.2. [P19440-1 ]
    UniGenei Hs.595809.
    Hs.645535.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4GDX X-ray 1.67 A 2-374 [» ]
    B 375-569 [» ]
    4GG2 X-ray 2.21 A 28-380 [» ]
    B 381-569 [» ]
    ProteinModelPortali P19440.
    SMRi P19440. Positions 33-375, 381-569.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108946. 5 interactions.
    IntActi P19440. 2 interactions.
    MINTi MINT-2801579.
    STRINGi 9606.ENSP00000248923.

    Chemistry

    BindingDBi P19440.
    ChEMBLi CHEMBL5696.
    DrugBanki DB00143. Glutathione.

    Protein family/group databases

    MEROPSi T03.006.

    PTM databases

    PhosphoSitei P19440.

    Polymorphism databases

    DMDMi 93140064.

    Proteomic databases

    MaxQBi P19440.
    PaxDbi P19440.
    PRIDEi P19440.

    Protocols and materials databases

    DNASUi 2678.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000248923 ; ENSP00000248923 ; ENSG00000100031 . [P19440-1 ]
    ENST00000400380 ; ENSP00000383231 ; ENSG00000100031 . [P19440-1 ]
    ENST00000400382 ; ENSP00000383232 ; ENSG00000100031 . [P19440-1 ]
    ENST00000401885 ; ENSP00000384381 ; ENSG00000100031 . [P19440-3 ]
    ENST00000403838 ; ENSP00000384820 ; ENSG00000100031 . [P19440-3 ]
    ENST00000404532 ; ENSP00000385445 ; ENSG00000100031 . [P19440-3 ]
    ENST00000425895 ; ENSP00000387499 ; ENSG00000100031 . [P19440-2 ]
    GeneIDi 2678.
    KEGGi hsa:2678.
    UCSCi uc003aan.1. human. [P19440-1 ]
    uc003aay.1. human. [P19440-3 ]

    Organism-specific databases

    CTDi 2678.
    GeneCardsi GC22P024980.
    H-InvDB HIX0016314.
    HGNCi HGNC:4250. GGT1.
    HPAi HPA045635.
    MIMi 231950. phenotype.
    612346. gene.
    neXtProti NX_P19440.
    Orphaneti 33573. Gamma-glutamyl transpeptidase deficiency.
    PharmGKBi PA28662.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0405.
    HOGENOMi HOG000175620.
    HOVERGENi HBG005835.
    InParanoidi P19440.
    KOi K00681.
    OMAi TINAREM.
    OrthoDBi EOG7V7665.
    PhylomeDBi P19440.
    TreeFami TF313608.

    Enzyme and pathway databases

    UniPathwayi UPA00204 .
    BioCyci MetaCyc:HS01957-MONOMER.
    BRENDAi 2.3.2.2. 2681.
    Reactomei REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_6960. Glutathione synthesis and recycling.
    SABIO-RK P19440.

    Miscellaneous databases

    ChiTaRSi GGT1. human.
    GeneWikii GGT1.
    GenomeRNAii 2678.
    NextBioi 10574.
    PROi P19440.
    SOURCEi Search...

    Gene expression databases

    Bgeei P19440.
    CleanExi HS_GGT1.
    Genevestigatori P19440.

    Family and domain databases

    InterProi IPR000101. GGT_peptidase.
    IPR029055. Ntn_hydrolases_N.
    [Graphical view ]
    PANTHERi PTHR11686. PTHR11686. 1 hit.
    Pfami PF01019. G_glu_transpept. 1 hit.
    [Graphical view ]
    PRINTSi PR01210. GGTRANSPTASE.
    SUPFAMi SSF56235. SSF56235. 1 hit.
    TIGRFAMsi TIGR00066. g_glut_trans. 1 hit.
    PROSITEi PS00462. G_GLU_TRANSPEPTIDASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase."
      Rajpert-De Meyts E., Heisterkamp N., Groffen J.
      Proc. Natl. Acad. Sci. U.S.A. 85:8840-8844(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-272.
      Tissue: Placenta.
    2. "The primary structure of human gamma-glutamyl transpeptidase."
      Sakamuro D., Yamazoe M., Matsuda Y., Kangawa K., Taniguchi N., Matsuo H., Yoshikawa H., Ogasawara N.
      Gene 73:1-9(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 30-58 AND 381-408, VARIANT ALA-272.
      Tissue: Kidney and Liver.
    3. "Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis."
      Pitot H.C., Goodspeed D.C., Dunn T.J., Hendrich S., Maronpot R.R., Moran S.
      Toxicol. Appl. Pharmacol. 97:23-34(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-272.
    4. "Human gamma-glutamyl transpeptidase cDNA: comparison of hepatoma and kidney mRNA in the human and rat."
      Goodspeed D.C., Dunn T.J., Miller C.D., Pitot H.C.
      Gene 76:1-9(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-272.
      Tissue: Hepatoblastoma.
    5. "An alternatively processed mRNA specific for gamma-glutamyl transpeptidase in human tissues."
      Pawlak A., Cohen E.H., Octave J.-N., Schweickhardt R., Wu S.-J., Bulle F., Chikhi N., Baik J.-H., Siegrist S., Guellaen G.
      J. Biol. Chem. 265:3256-3262(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ALA-272.
      Tissue: Liver.
    6. "Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues."
      Courtay C., Oster T., Michelet F., Visvikis A., Diederich M., Wellman M., Siest G.
      Biochem. Pharmacol. 43:2527-2533(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-272.
      Tissue: Pancreas.
    7. "Human lung expresses unique gamma-glutamyl transpeptidase transcripts."
      Wetmore L.A., Gerard C., Drazen J.M.
      Proc. Natl. Acad. Sci. U.S.A. 90:7461-7465(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), LACK OF FUNCTION OF ISOFORM 3.
      Tissue: Lung.
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    9. "The DNA sequence of human chromosome 22."
      Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
      , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
      Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
      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] (ISOFORMS 1 AND 3).
      Tissue: Lung.
    11. "Renal gamma-glutamyl transpeptidases: structural and immunological studies."
      Tate S.S., Khadse V., Wellner D.
      Arch. Biochem. Biophys. 262:397-408(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 30-48 AND 381-403.
      Tissue: Kidney.
    12. "Gamma-glutamyl transpeptidase gene organization and expression: a comparative analysis in rat, mouse, pig and human species."
      Chikhi N., Holic N., Guellaen G., Laperche Y.
      Comp. Biochem. Physiol. 122B:367-380(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING, ALTERNATIVE PROMOTER USAGE.
    13. "Human kidney gamma-glutamyl transpeptidase. Catalytic properties, subunit structure, and localization of the gamma-glutamyl binding site on the light subunit."
      Tate S.S., Ross M.E.
      J. Biol. Chem. 252:6042-6045(1977) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION, SIALIC ACID CONTENT.
      Tissue: Kidney.
    14. "In vitro translation and processing of human hepatoma cell (Hep G2) gamma-glutamyl transpeptidase."
      Tate S.S., Galbraith R.A.
      Biochem. Biophys. Res. Commun. 154:1167-1173(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION.
    15. "Significance of Arg-107 and Glu-108 in the catalytic mechanism of human gamma-glutamyl transpeptidase. Identification by site-directed mutagenesis."
      Ikeda Y., Fujii J., Taniguchi N.
      J. Biol. Chem. 268:3980-3985(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, AUTOCATALYTIC CLEAVAGE, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-100; GLU-102; ARG-107; GLU-108; ARG-112; ARG-139; ARG-147 AND ARG-150.
    16. "Human gamma-glutamyl transpeptidase mutants involving conserved aspartate residues and the unique cysteine residue of the light subunit."
      Ikeda Y., Fujii J., Taniguchi N., Meister A.
      J. Biol. Chem. 270:12471-12475(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-422; ASP-423 AND CYS-454.
    17. "Involvement of Ser-451 and Ser-452 in the catalysis of human gamma-glutamyl transpeptidase."
      Ikeda Y., Fujii J., Anderson M.E., Taniguchi N., Meister A.
      J. Biol. Chem. 270:22223-22228(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF SER-385; SER-413; SER-425; SER-451 AND SER-452.
    18. "Effects of substitutions of the conserved histidine residues in human gamma-glutamyl transpeptidase."
      Ikeda Y., Fujii J., Taniguchi N.
      J. Biochem. 119:1166-1170(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-383 AND HIS-505.
    19. Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-511.
      Tissue: Bile.
    20. "Kinetic characterization and identification of the acylation and glycosylation sites of recombinant human gamma-glutamyltranspeptidase."
      Castonguay R., Halim D., Morin M., Furtos A., Lherbet C., Bonneil E., Thibault P., Keillor J.W.
      Biochemistry 46:12253-12262(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, ACTIVE SITE, GLYCOSYLATION AT ASN-120; ASN-266; ASN-344 AND ASN-511, IDENTIFICATION BY MASS SPECTROMETRY.
    21. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-120; ASN-230 AND ASN-511.
      Tissue: Liver.
    22. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
      Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
      Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-120.
      Tissue: Leukemic T-cell.
    23. "Analysis of site-specific glycosylation of renal and hepatic gamma-glutamyl transpeptidase from normal human tissue."
      West M.B., Segu Z.M., Feasley C.L., Kang P., Klouckova I., Li C., Novotny M.V., West C.M., Mechref Y., Hanigan M.H.
      J. Biol. Chem. 285:29511-29524(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-95; ASN-120; ASN-230; ASN-266; ASN-297; ASN-344 AND ASN-511.
    24. "Human GGT2 does not autocleave into a functional enzyme: a cautionary tale for interpretation of microarray data on redox signaling."
      West M.B., Wickham S., Parks E.E., Sherry D.M., Hanigan M.H.
      Antioxid. Redox Signal. 19:1877-1888(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, AUTOCATALYTIC CLEAVAGE, ENZYME REGULATION, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF CYS-192 AND GLU-193.
    25. "Novel insights into eukaryotic gamma-glutamyl transpeptidase 1 from the crystal structure of the glutamate-bound human enzyme."
      West M.B., Chen Y., Wickham S., Heroux A., Cahill K., Hanigan M.H., Mooers B.H.
      J. Biol. Chem. 288:31902-31913(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) IN COMPLEX WITH GLUTAMATE AND CHLORIDE IONS, FUNCTION, CATALYTIC ACTIVITY, AUTOCATALYTIC CLEAVAGE, SUBUNIT, MUTAGENESIS OF GLN-545, DISULFIDE BONDS, GLYCOSYLATION AT ASN-95; ASN-120; ASN-230; ASN-266; ASN-344 AND ASN-511.

    Entry informationi

    Entry nameiGGT1_HUMAN
    AccessioniPrimary (citable) accession number: P19440
    Secondary accession number(s): Q08247
    , Q14404, Q8TBS1, Q9UMK1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1991
    Last sequence update: March 7, 2006
    Last modified: October 1, 2014
    This is version 167 of the entry and version 2 of the sequence. [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

    Miscellaneous

    Cys-454 was thought to bind the gamma-glutamyl moiety, but mutagenesis of this residue had no effect on activity.
    Chloride ions bound in the active site cavity may contribute to stabilize the protein fold.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 22
      Human chromosome 22: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    7. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3