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Protein

Glutathione-specific gamma-glutamylcyclotransferase 1

Gene

CHAC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the cleavage glutathione into 5-oxoproline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides. Glutathione depletion is an important factor for apoptosis initiation and execution (PubMed:23070364). 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 = 5-oxoproline + cysteinylglycine.1 Publication

Kineticsi

  1. KM=3.13 mM for glutathione1 Publication
  1. Vmax=980 µmol/h/mg enzyme1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei157 – 1571Proton acceptorBy similarity

GO - Molecular functioni

GO - Biological processi

  • 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
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Apoptosis, Neurogenesis, Notch signaling pathway, Unfolded protein response

Names & Taxonomyi

Protein namesi
Recommended name:
Glutathione-specific gamma-glutamylcyclotransferase 11 Publication (EC:2.3.2.-1 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
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:28680. CHAC1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi157 – 1571E → Q: Loss of catalytic activity against glutathione. 1 Publication

Organism-specific databases

PharmGKBiPA142672119.

Polymorphism and mutation databases

BioMutaiCHAC1.
DMDMi294862423.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 264264Glutathione-specific gamma-glutamylcyclotransferase 1PRO_0000239010Add
BLAST

Proteomic databases

MaxQBiQ9BUX1.
PaxDbiQ9BUX1.
PRIDEiQ9BUX1.

PTM databases

PhosphoSiteiQ9BUX1.

Expressioni

Inductioni

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

Gene expression databases

BgeeiQ9BUX1.
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

Protein-protein interaction databases

BioGridi122541. 1 interaction.
IntActiQ9BUX1. 1 interaction.
MINTiMINT-1451921.
STRINGi9606.ENSP00000398105.

Structurei

3D structure databases

ProteinModelPortaliQ9BUX1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni77 – 826Substrate bindingBy similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG3703.
GeneTreeiENSGT00390000003855.
HOGENOMiHOG000264264.
HOVERGENiHBG056733.
InParanoidiQ9BUX1.
KOiK07232.
OMAiGTMKQES.
OrthoDBiEOG7F7W9F.
PhylomeDBiQ9BUX1.
TreeFamiTF313048.

Family and domain databases

Gene3Di3.10.490.10. 1 hit.
InterProiIPR013024. Butirosin_synth_BtrG-like.
IPR006840. ChaC.
[Graphical view]
PANTHERiPTHR12192. PTHR12192. 1 hit.
PfamiPF04752. ChaC. 1 hit.
[Graphical view]
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
MGGAQLELPS GARPGVCVRR SFRAHAGDQP RRPPGPIPVP GTMKQESAAP
60 70 80 90 100
NTPPTSQSPT PSAQFPRNDG DPQALWIFGY GSLVWRPDFA YSDSRVGFVR
110 120 130 140 150
GYSRRFWQGD TFHRGSDKMP GRVVTLLEDH EGCTWGVAYQ VQGEQVSKAL
160 170 180 190 200
KYLNVREAVL GGYDTKEVTF YPQDAPDQPL KALAYVATPQ NPGYLGPAPE
210 220 230 240 250
EAIATQILAC RGFSGHNLEY LLRLADFMQL CGPQAQDEHL AAIVDAVGTM
260
LPCFCPTEQA LALV
Length:264
Mass (Da):28,747
Last modified:April 20, 2010 - v2
Checksum:i746047C1AD03D375
GO
Isoform 2 (identifier: Q9BUX1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-190: Missing.

Show »
Length:219
Mass (Da):23,795
Checksum:iA7EC06A98FB979EA
GO

Sequence cautioni

The sequence AAH01683.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAH01847.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAH19625.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence AAW23972.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 123SGA → ARG in AAH01683 (PubMed:15489334).Curated
Sequence conflicti59 – 591P → H in AAW23972 (Ref. 3) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei146 – 19045Missing in isoform 2. 1 PublicationVSP_038960Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC020661 Genomic DNA. No translation available.
BC001683 mRNA. Translation: AAH01683.1. Different initiation.
BC001847 mRNA. Translation: AAH01847.1. Different initiation.
BC019625 mRNA. Translation: AAH19625.1. Different initiation.
AY702027 mRNA. Translation: AAW23972.1. Different initiation.
CCDSiCCDS10070.2. [Q9BUX1-1]
CCDS45233.1. [Q9BUX1-2]
RefSeqiNP_001136248.1. NM_001142776.1. [Q9BUX1-2]
NP_077016.2. NM_024111.3. [Q9BUX1-1]
UniGeneiHs.155569.

Genome annotation databases

EnsembliENST00000444189; ENSP00000395466; ENSG00000128965. [Q9BUX1-2]
ENST00000446533; ENSP00000398105; ENSG00000128965.
ENST00000617768; ENSP00000484644; ENSG00000128965.
GeneIDi79094.
KEGGihsa:79094.
UCSCiuc001znh.2. human. [Q9BUX1-1]
uc010uct.1. human. [Q9BUX1-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC020661 Genomic DNA. No translation available.
BC001683 mRNA. Translation: AAH01683.1. Different initiation.
BC001847 mRNA. Translation: AAH01847.1. Different initiation.
BC019625 mRNA. Translation: AAH19625.1. Different initiation.
AY702027 mRNA. Translation: AAW23972.1. Different initiation.
CCDSiCCDS10070.2. [Q9BUX1-1]
CCDS45233.1. [Q9BUX1-2]
RefSeqiNP_001136248.1. NM_001142776.1. [Q9BUX1-2]
NP_077016.2. NM_024111.3. [Q9BUX1-1]
UniGeneiHs.155569.

3D structure databases

ProteinModelPortaliQ9BUX1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122541. 1 interaction.
IntActiQ9BUX1. 1 interaction.
MINTiMINT-1451921.
STRINGi9606.ENSP00000398105.

PTM databases

PhosphoSiteiQ9BUX1.

Polymorphism and mutation databases

BioMutaiCHAC1.
DMDMi294862423.

Proteomic databases

MaxQBiQ9BUX1.
PaxDbiQ9BUX1.
PRIDEiQ9BUX1.

Protocols and materials databases

DNASUi79094.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000444189; ENSP00000395466; ENSG00000128965. [Q9BUX1-2]
ENST00000446533; ENSP00000398105; ENSG00000128965.
ENST00000617768; ENSP00000484644; ENSG00000128965.
GeneIDi79094.
KEGGihsa:79094.
UCSCiuc001znh.2. human. [Q9BUX1-1]
uc010uct.1. human. [Q9BUX1-2]

Organism-specific databases

CTDi79094.
GeneCardsiGC15P041245.
H-InvDBHIX0012144.
HGNCiHGNC:28680. CHAC1.
HPAiHPA042708.
HPA043505.
MIMi614587. gene.
neXtProtiNX_Q9BUX1.
PharmGKBiPA142672119.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG3703.
GeneTreeiENSGT00390000003855.
HOGENOMiHOG000264264.
HOVERGENiHBG056733.
InParanoidiQ9BUX1.
KOiK07232.
OMAiGTMKQES.
OrthoDBiEOG7F7W9F.
PhylomeDBiQ9BUX1.
TreeFamiTF313048.

Miscellaneous databases

ChiTaRSiCHAC1. human.
GenomeRNAii79094.
NextBioi67939.
PROiQ9BUX1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BUX1.
CleanExiHS_CHAC1.
ExpressionAtlasiQ9BUX1. baseline and differential.
GenevisibleiQ9BUX1. HS.

Family and domain databases

Gene3Di3.10.490.10. 1 hit.
InterProiIPR013024. Butirosin_synth_BtrG-like.
IPR006840. ChaC.
[Graphical view]
PANTHERiPTHR12192. PTHR12192. 1 hit.
PfamiPF04752. ChaC. 1 hit.
[Graphical view]
SUPFAMiSSF110857. SSF110857. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "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] OF 9-264 (ISOFORM 1).
    Tissue: Liver and Muscle.
  3. "Cloning and analyzing of a new chaC like cDNA from human kidney."
    Zheng J.M., Liu Z.H., Li L.S.
    Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-264 (ISOFORM 2).
  4. "CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade."
    Mungrue I.N., Pagnon J., Kohannim O., Gargalovic P.S., Lusis A.J.
    J. Immunol. 182:466-476(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
  5. Cited for: FUNCTION.
  6. "Mammalian proapoptotic factor ChaC1 and its homologues function as gamma-glutamyl cyclotransferases acting specifically on glutathione."
    Kumar A., Tikoo S., Maity S., Sengupta S., Sengupta S., Kaur A., Bachhawat A.K.
    EMBO Rep. 13:1095-1101(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-157.

Entry informationi

Entry nameiCHAC1_HUMAN
AccessioniPrimary (citable) accession number: Q9BUX1
Secondary accession number(s): Q0VIA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: April 20, 2010
Last modified: July 22, 2015
This is version 102 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

Caution

It is uncertain whether Met-1 or Met-43 is the initiator. Met-1 is not conserved in orthologs.Curated

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.