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Protein

Glutathione-specific gamma-glutamylcyclotransferase 1

Gene

CHAC1

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

Functioni

Catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides (PubMed:27913623). Glutathione depletion is an important factor for apoptosis initiation and execution. Acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade (PubMed:19109178). Negative regulator of Notch signaling pathway involved in embryonic neurogenesis: acts by inhibiting Notch cleavage by furin, maintaining Notch in an immature inactive form, thereby promoting neurogenesis in embryos (PubMed:22445366).3 Publications

Catalytic activityi

Glutathione = L-cysteinylglycine + 5-oxo-L-proline.1 Publication

Kineticsi

kcat is 225.2 min(-1) for glutathione.1 Publication
  1. KM=2.2 mM for glutathione1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei115Proton acceptorBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • glutathione biosynthetic process Source: Reactome
    • glutathione catabolic process Source: GO_Central
    • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
    • negative regulation of Notch signaling pathway Source: UniProtKB
    • negative regulation of protein processing Source: UniProtKB
    • neurogenesis Source: UniProtKB
    • Notch signaling pathway Source: UniProtKB-KW
    • response to unfolded protein Source: UniProtKB-KW

    Keywordsi

    Molecular functionLyase
    Biological processApoptosis, Neurogenesis, Notch signaling pathway, Unfolded protein response

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000128965-MONOMER
    ReactomeiR-HSA-174403 Glutathione synthesis and recycling

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutathione-specific gamma-glutamylcyclotransferase 11 Publication (EC:4.3.2.71 Publication)
    Short name:
    Gamma-GCG 11 Publication
    Alternative name(s):
    Blocks Notch protein1 Publication
    Short name:
    Botch1 Publication
    Cation transport regulator-like protein 11 Publication
    Gene namesi
    Name:CHAC11 PublicationImported
    Synonyms:BOTCH1 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000128965.11
    HGNCiHGNC:28680 CHAC1
    MIMi614587 gene
    neXtProtiNX_Q9BUX1

    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, Golgi apparatus

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi79094
    OpenTargetsiENSG00000128965
    PharmGKBiPA142672119

    Polymorphism and mutation databases

    BioMutaiCHAC1
    DMDMi294862423

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002390101 – 222Glutathione-specific gamma-glutamylcyclotransferase 1Add BLAST222

    Proteomic databases

    EPDiQ9BUX1
    MaxQBiQ9BUX1
    PaxDbiQ9BUX1
    PeptideAtlasiQ9BUX1
    PRIDEiQ9BUX1
    ProteomicsDBi79141
    79142 [Q9BUX1-2]

    PTM databases

    iPTMnetiQ9BUX1
    PhosphoSitePlusiQ9BUX1

    Expressioni

    Inductioni

    Induced by chemical activators of the unfolded protein response (UPR) such as tunicamycin, DTT and thapsigargin.1 Publication

    Gene expression databases

    BgeeiENSG00000128965
    CleanExiHS_CHAC1
    ExpressionAtlasiQ9BUX1 baseline and differential
    GenevisibleiQ9BUX1 HS

    Organism-specific databases

    HPAiHPA042708
    HPA043505

    Interactioni

    Subunit structurei

    Interacts with NOTCH1 (via extracellular region).By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RHOXF2Q9BQY42EBI-751127,EBI-372094

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi122541, 1 interactor
    IntActiQ9BUX1, 1 interactor
    STRINGi9606.ENSP00000398105

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BUX1
    SMRiQ9BUX1
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni35 – 40Substrate bindingBy similarity6

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG3182 Eukaryota
    COG3703 LUCA
    GeneTreeiENSGT00390000003855
    HOGENOMiHOG000264264
    HOVERGENiHBG056733
    InParanoidiQ9BUX1
    KOiK07232
    OMAiTWGVAFE
    OrthoDBiEOG091G0MZM
    PhylomeDBiQ9BUX1
    TreeFamiTF313048

    Family and domain databases

    CDDicd06661 GGCT_like, 1 hit
    InterProiView protein in InterPro
    IPR006840 ChaC
    IPR013024 GGCT-like
    IPR036568 GGCT-like_sf
    PANTHERiPTHR12192 PTHR12192, 1 hit
    PfamiView protein in Pfam
    PF04752 ChaC, 1 hit
    SUPFAMiSSF110857 SSF110857, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9BUX1-1) [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
    MKQESAAPNT PPTSQSPTPS AQFPRNDGDP QALWIFGYGS LVWRPDFAYS
    60 70 80 90 100
    DSRVGFVRGY SRRFWQGDTF HRGSDKMPGR VVTLLEDHEG CTWGVAYQVQ
    110 120 130 140 150
    GEQVSKALKY LNVREAVLGG YDTKEVTFYP QDAPDQPLKA LAYVATPQNP
    160 170 180 190 200
    GYLGPAPEEA IATQILACRG FSGHNLEYLL RLADFMQLCG PQAQDEHLAA
    210 220
    IVDAVGTMLP CFCPTEQALA LV
    Length:222
    Mass (Da):24,418
    Last modified:April 25, 2018 - v3
    Checksum:iDDE5A288BADB079E
    GO
    Isoform 2 (identifier: Q9BUX1-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         104-148: Missing.

    Show »
    Length:177
    Mass (Da):19,466
    Checksum:i1244F5B8187B3218
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti17P → H in AAW23972 (Ref. 1) Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_038960104 – 148Missing in isoform 2. 1 PublicationAdd BLAST45

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY702027 mRNA Translation: AAW23972.1
    AC020661 Genomic DNA No translation available.
    BC001683 mRNA Translation: AAH01683.1
    BC001847 mRNA Translation: AAH01847.1
    BC019625 mRNA Translation: AAH19625.1
    CCDSiCCDS10070.2 [Q9BUX1-1]
    CCDS45233.1 [Q9BUX1-2]
    RefSeqiNP_077016.2, NM_024111.4 [Q9BUX1-1]
    UniGeneiHs.155569

    Genome annotation databases

    EnsembliENST00000617961; ENSP00000481816; ENSG00000128965 [Q9BUX1-1]
    GeneIDi79094
    KEGGihsa:79094
    UCSCiuc001znh.2 human [Q9BUX1-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiCHAC1_HUMAN
    AccessioniPrimary (citable) accession number: Q9BUX1
    Secondary accession number(s): Q0VIA0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
    Last sequence update: April 25, 2018
    Last modified: July 18, 2018
    This is version 127 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

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