This gene encodes a member of the gamma-glutamylcyclotransferase family of proteins. The encoded protein has been shown to promote neuronal differentiation by deglycination of the Notch receptor, which prevents receptor maturation and inhibits Notch signaling. This protein may also play a role in the unfolded protein response, and in regulation of glutathione levels and oxidati... See more...

Aliases for CHAC1 Gene

Aliases for CHAC1 Gene

  • ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 2 3 5
  • Glutathione-Specific Gamma-Glutamylcyclotransferase 1 3 4
  • Gamma-GCT Acting On Glutathione Homolog 1 2 3
  • Blocks Notch Protein 3 4
  • Gamma-GCG 1 3 4
  • Botch 3 4
  • ChaC, Cation Transport Regulator Homolog 1 (E. Coli) 2
  • ChaC, Cation Transport Regulator Homolog 1 3
  • Cation Transport Regulator-Like Protein 1 4
  • ChaC, Cation Transport Regulator-Like 1 3
  • EC 4.3.2.7 4
  • MGC4504 2
  • CHAC1 5
  • BOTCH 4

External Ids for CHAC1 Gene

Previous GeneCards Identifiers for CHAC1 Gene

  • GC15P039033
  • GC15P041245
  • GC15P018094
  • GC15P040952

Summaries for CHAC1 Gene

Entrez Gene Summary for CHAC1 Gene

  • This gene encodes a member of the gamma-glutamylcyclotransferase family of proteins. The encoded protein has been shown to promote neuronal differentiation by deglycination of the Notch receptor, which prevents receptor maturation and inhibits Notch signaling. This protein may also play a role in the unfolded protein response, and in regulation of glutathione levels and oxidative balance in the cell. Elevated expression of this gene may indicate increased risk of cancer recurrence among breast and ovarian cancer patients. [provided by RefSeq, Sep 2016]

GeneCards Summary for CHAC1 Gene

CHAC1 (ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1) is a Protein Coding gene. Diseases associated with CHAC1 include Locked-In Syndrome. Among its related pathways are Cytochrome P450 - arranged by substrate type and Glutathione metabolism. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring acyl groups and Notch binding. An important paralog of this gene is CHAC2.

UniProtKB/Swiss-Prot Summary for CHAC1 Gene

  • 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).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CHAC1 Gene

Genomics for CHAC1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CHAC1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CHAC1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CHAC1

Top Transcription factor binding sites by QIAGEN in the CHAC1 gene promoter:
  • AREB6
  • C/EBPalpha
  • C/EBPbeta
  • E47
  • FOXD1
  • Hand1
  • Ik-1
  • Nkx2-5
  • p53
  • TBP

Genomic Locations for CHAC1 Gene

Latest Assembly
chr15:40,942,137-40,956,518
(GRCh38/hg38)
Size:
14,382 bases
Orientation:
Plus strand

Previous Assembly
chr15:41,245,669-41,248,710
(GRCh37/hg19 by Entrez Gene)
Size:
3,042 bases
Orientation:
Plus strand

chr15:41,245,160-41,248,710
(GRCh37/hg19 by Ensembl)
Size:
3,551 bases
Orientation:
Plus strand

Genomic View for CHAC1 Gene

Genes around CHAC1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CHAC1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CHAC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CHAC1 Gene

Proteins for CHAC1 Gene

  • Protein details for CHAC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BUX1-CHAC1_HUMAN
    Recommended name:
    Glutathione-specific gamma-glutamylcyclotransferase 1
    Protein Accession:
    Q9BUX1
    Secondary Accessions:
    • Q0VIA0

    Protein attributes for CHAC1 Gene

    Size:
    222 amino acids
    Molecular mass:
    24418 Da
    Quaternary structure:
    • Interacts with NOTCH1 (via extracellular region).

    Alternative splice isoforms for CHAC1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CHAC1 Gene

Post-translational modifications for CHAC1 Gene

  • Ubiquitination at Lys109
  • Modification sites at PhosphoSitePlus

Other Protein References for CHAC1 Gene

No data available for DME Specific Peptides for CHAC1 Gene

Domains & Families for CHAC1 Gene

Gene Families for CHAC1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for CHAC1 Gene

Suggested Antigen Peptide Sequences for CHAC1 Gene

GenScript: Design optimal peptide antigens:
  • Cation transport regulator-like protein 1 (CHAC1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BUX1

UniProtKB/Swiss-Prot:

CHAC1_HUMAN :
  • Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.
Family:
  • Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.
genes like me logo Genes that share domains with CHAC1: view

Function for CHAC1 Gene

Molecular function for CHAC1 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=glutathione = 5-oxo-L-proline + L-cysteinylglycine; Xref=Rhea:RHEA:47724, ChEBI:CHEBI:57925, ChEBI:CHEBI:58402, ChEBI:CHEBI:61694; EC=4.3.2.7; Evidence={ECO:0000269|PubMed:27913623};.
UniProtKB/Swiss-Prot Induction:
Induced by chemical activators of the unfolded protein response (UPR) such as tunicamycin, DTT and thapsigargin.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=2.2 mM for glutathione {ECO:0000269|PubMed:27913623}; Note=kcat is 225.2 min(-1) for glutathione. {ECO:0000269|PubMed:27913623};

Enzyme Numbers (IUBMB) for CHAC1 Gene

Phenotypes From GWAS Catalog for CHAC1 Gene

Gene Ontology (GO) - Molecular Function for CHAC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003839 gamma-glutamylcyclotransferase activity IBA 21873635
GO:0005112 Notch binding IEA,ISS --
GO:0005515 protein binding IPI 16189514
GO:0016829 lyase activity IEA --
GO:0061928 glutathione specific gamma-glutamylcyclotransferase activity IEA --
genes like me logo Genes that share ontologies with CHAC1: view
genes like me logo Genes that share phenotypes with CHAC1: view

miRNA for CHAC1 Gene

miRTarBase miRNAs that target CHAC1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CHAC1

Clone products for research

  • Addgene plasmids for CHAC1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CHAC1 Gene

Localization for CHAC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CHAC1 Gene

Cytoplasm, cytosol. Golgi apparatus, trans-Golgi network.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CHAC1 gene
Compartment Confidence
cytosol 5
golgi apparatus 4
mitochondrion 3
extracellular 2
nucleus 2
endoplasmic reticulum 2
plasma membrane 1
cytoskeleton 1
endosome 1
lysosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CHAC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005794 Golgi apparatus IEA --
GO:0005802 trans-Golgi network IEA,ISS --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with CHAC1: view

Pathways & Interactions for CHAC1 Gene

genes like me logo Genes that share pathways with CHAC1: view

Pathways by source for CHAC1 Gene

Interacting Proteins for CHAC1 Gene

Gene Ontology (GO) - Biological Process for CHAC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006750 glutathione biosynthetic process TAS --
GO:0006751 glutathione catabolic process IBA 21873635
GO:0006915 apoptotic process IEA --
GO:0006986 response to unfolded protein IEA --
GO:0007219 Notch signaling pathway IEA --
genes like me logo Genes that share ontologies with CHAC1: view

No data available for SIGNOR curated interactions for CHAC1 Gene

Drugs & Compounds for CHAC1 Gene

No Compound Related Data Available

Transcripts for CHAC1 Gene

mRNA/cDNA for CHAC1 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CHAC1

Clone products for research

  • Addgene plasmids for CHAC1

Alternative Splicing Database (ASD) splice patterns (SP) for CHAC1 Gene

No ASD Table

Relevant External Links for CHAC1 Gene

GeneLoc Exon Structure for
CHAC1

Expression for CHAC1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CHAC1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CHAC1 Gene

This gene is overexpressed in Muscle - Skeletal (x13.8).

Protein differential expression in normal tissues from HIPED for CHAC1 Gene

This gene is overexpressed in Hair follicle (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CHAC1 Gene



Protein tissue co-expression partners for CHAC1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CHAC1

SOURCE GeneReport for Unigene cluster for CHAC1 Gene:

Hs.155569

Evidence on tissue expression from TISSUES for CHAC1 Gene

  • Liver(4.3)
  • Muscle(4.3)
  • Pancreas(2.1)
genes like me logo Genes that share expression patterns with CHAC1: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CHAC1 Gene

Orthologs for CHAC1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CHAC1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CHAC1 29 30
  • 99.75 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CHAC1 30
  • 92 (a)
OneToOne
LOC487504 29
  • 89.1 (n)
Cow
(Bos Taurus)
Mammalia CHAC1 29 30
  • 88.28 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Chac1 29
  • 86.04 (n)
Mouse
(Mus musculus)
Mammalia Chac1 29 16 30
  • 83.93 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CHAC1 30
  • 83 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CHAC1 29 30
  • 69 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CHAC1 30
  • 54 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia chac1 29
  • 66.32 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.12642 29
Zebrafish
(Danio rerio)
Actinopterygii chac1 29 30
  • 63.43 (n)
OneToOne
Dr.24239 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG10365 30
  • 32 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea F22F7.7 29 30
  • 50.26 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 30
  • 27 (a)
OneToMany
Wheat
(Triticum aestivum)
Liliopsida Ta.9452 29
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.3881 30
  • 31 (a)
OneToOne
Species where no ortholog for CHAC1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for CHAC1 Gene

ENSEMBL:
Gene Tree for CHAC1 (if available)
TreeFam:
Gene Tree for CHAC1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CHAC1: view image
Alliance of Genome Resources:
Additional Orthologs for CHAC1

Paralogs for CHAC1 Gene

Paralogs for CHAC1 Gene

(1) SIMAP similar genes for CHAC1 Gene using alignment to 2 proteins:

  • CHAC1_HUMAN
  • H0YK90_HUMAN
genes like me logo Genes that share paralogs with CHAC1: view

Variants for CHAC1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CHAC1 Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
916423 Likely Benign: not provided 40,953,754(+) G/A
NM_024111.6(CHAC1):c.171G>A (p.Val57=)
SYNONYMOUS
rs193920914 Uncertain Significance: Malignant tumor of prostate 40,955,384(+) G/A
NM_024111.6(CHAC1):c.279G>A (p.Trp93Ter)
NONSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CHAC1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CHAC1 Gene

Variant ID Type Subtype PubMed ID
nsv1504 CNV insertion 18451855

Variation tolerance for CHAC1 Gene

Residual Variation Intolerance Score: 77.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.44; 54.73% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CHAC1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CHAC1
Leiden Open Variation Database (LOVD)
CHAC1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CHAC1 Gene

Disorders for CHAC1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for CHAC1 Gene - From: COP

Disorder Aliases PubMed IDs
locked-in syndrome
  • locked in syndrome
- elite association - COSMIC cancer census association via MalaCards
Search CHAC1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CHAC1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CHAC1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CHAC1 Gene

Publications for CHAC1 Gene

  1. CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. (PMID: 19109178) Mungrue IN … Lusis AJ (Journal of immunology (Baltimore, Md. : 1950) 2009) 3 4 22
  2. Botch promotes neurogenesis by antagonizing Notch. (PMID: 22445366) Chi Z … Dawson VL (Developmental cell 2012) 3 4
  3. Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione. (PMID: 23070364) Kumar A … Bachhawat AK (EMBO reports 2012) 2 3
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi. (PMID: 31111570) Ogawa T … Eishi Y (Helicobacter 2019) 3

Products for CHAC1 Gene

Sources for CHAC1 Gene