CHAC2_HUMAN
ID CHAC2_HUMAN Reviewed; 184 AA.
AC Q8WUX2; Q8WVI8;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Glutathione-specific gamma-glutamylcyclotransferase 2 {ECO:0000303|PubMed:27913623};
DE Short=Gamma-GCG 2 {ECO:0000305};
DE EC=4.3.2.7 {ECO:0000269|PubMed:27913623};
DE AltName: Full=Cation transport regulator-like protein 2 {ECO:0000250|UniProtKB:Q9BUX1};
GN Name=CHAC2 {ECO:0000312|HGNC:HGNC:32363};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-82.
RC TISSUE=Brain, Kidney, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=27913623; DOI=10.1074/jbc.m116.727479;
RA Kaur A., Gautam R., Srivastava R., Chandel A., Kumar A., Karthikeyan S.,
RA Bachhawat A.K.;
RT "ChaC2, an enzyme for slow turnover of cytosolic glutathione.";
RL J. Biol. Chem. 292:638-651(2017).
CC -!- FUNCTION: Catalyzes the cleavage of glutathione into 5-oxo-L-proline
CC and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on
CC other gamma-glutamyl peptides. {ECO:0000269|PubMed:27913623}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione = 5-oxo-L-proline + L-cysteinylglycine;
CC Xref=Rhea:RHEA:47724, ChEBI:CHEBI:57925, ChEBI:CHEBI:58402,
CC ChEBI:CHEBI:61694; EC=4.3.2.7;
CC Evidence={ECO:0000269|PubMed:27913623};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.7 mM for glutathione {ECO:0000269|PubMed:27913623};
CC Note=kcat is 15.9 min(-1) for glutathione.
CC {ECO:0000269|PubMed:27913623};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:27913623}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:27913623}.
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family. ChaC
CC subfamily. {ECO:0000305}.
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DR EMBL; AC007883; AAY24351.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00172.1; -; Genomic_DNA.
DR EMBL; BC017941; AAH17941.1; -; mRNA.
DR EMBL; BC019239; AAH19239.1; -; mRNA.
DR EMBL; BC025376; AAH25376.1; -; mRNA.
DR EMBL; BC053896; AAH53896.1; -; mRNA.
DR CCDS; CCDS33196.1; -.
DR RefSeq; NP_001008708.1; NM_001008708.3.
DR RefSeq; NP_001333056.1; NM_001346127.1.
DR PDB; 6K95; X-ray; 2.29 A; A/B/C=1-184.
DR PDB; 6KY0; X-ray; 2.06 A; A/B/C=1-174.
DR PDB; 6KY1; X-ray; 2.04 A; A/B/C=1-175.
DR PDBsum; 6K95; -.
DR PDBsum; 6KY0; -.
DR PDBsum; 6KY1; -.
DR AlphaFoldDB; Q8WUX2; -.
DR SMR; Q8WUX2; -.
DR BioGRID; 138943; 22.
DR IntAct; Q8WUX2; 3.
DR STRING; 9606.ENSP00000295304; -.
DR GlyGen; Q8WUX2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WUX2; -.
DR PhosphoSitePlus; Q8WUX2; -.
DR BioMuta; CHAC2; -.
DR DMDM; 74730779; -.
DR EPD; Q8WUX2; -.
DR jPOST; Q8WUX2; -.
DR MassIVE; Q8WUX2; -.
DR MaxQB; Q8WUX2; -.
DR PaxDb; Q8WUX2; -.
DR PeptideAtlas; Q8WUX2; -.
DR PRIDE; Q8WUX2; -.
DR ProteomicsDB; 74718; -.
DR Antibodypedia; 30211; 113 antibodies from 20 providers.
DR DNASU; 494143; -.
DR Ensembl; ENST00000295304.5; ENSP00000295304.4; ENSG00000143942.5.
DR GeneID; 494143; -.
DR KEGG; hsa:494143; -.
DR MANE-Select; ENST00000295304.5; ENSP00000295304.4; NM_001008708.4; NP_001008708.1.
DR UCSC; uc002rxk.2; human.
DR CTD; 494143; -.
DR DisGeNET; 494143; -.
DR GeneCards; CHAC2; -.
DR HGNC; HGNC:32363; CHAC2.
DR HPA; ENSG00000143942; Low tissue specificity.
DR MIM; 617446; gene.
DR neXtProt; NX_Q8WUX2; -.
DR OpenTargets; ENSG00000143942; -.
DR PharmGKB; PA142672120; -.
DR VEuPathDB; HostDB:ENSG00000143942; -.
DR eggNOG; KOG3182; Eukaryota.
DR GeneTree; ENSGT00390000003855; -.
DR HOGENOM; CLU_070703_2_2_1; -.
DR InParanoid; Q8WUX2; -.
DR OMA; LLWYTDF; -.
DR OrthoDB; 1238273at2759; -.
DR PhylomeDB; Q8WUX2; -.
DR TreeFam; TF313048; -.
DR BioCyc; MetaCyc:ENSG00000143942-MON; -.
DR BRENDA; 4.3.2.7; 2681.
DR PathwayCommons; Q8WUX2; -.
DR Reactome; R-HSA-174403; Glutathione synthesis and recycling.
DR SignaLink; Q8WUX2; -.
DR BioGRID-ORCS; 494143; 17 hits in 1073 CRISPR screens.
DR GenomeRNAi; 494143; -.
DR Pharos; Q8WUX2; Tbio.
DR PRO; PR:Q8WUX2; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8WUX2; protein.
DR Bgee; ENSG00000143942; Expressed in trabecular bone tissue and 135 other tissues.
DR Genevisible; Q8WUX2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0003839; F:gamma-glutamylcyclotransferase activity; IBA:GO_Central.
DR GO; GO:0061928; F:glutathione specific gamma-glutamylcyclotransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006750; P:glutathione biosynthetic process; TAS:Reactome.
DR GO; GO:0006751; P:glutathione catabolic process; IBA:GO_Central.
DR CDD; cd06661; GGCT_like; 1.
DR InterPro; IPR006840; ChaC.
DR InterPro; IPR013024; GGCT-like.
DR InterPro; IPR036568; GGCT-like_sf.
DR PANTHER; PTHR12192; PTHR12192; 1.
DR Pfam; PF04752; ChaC; 1.
DR SUPFAM; SSF110857; SSF110857; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Lyase; Reference proteome.
FT CHAIN 1..184
FT /note="Glutathione-specific gamma-glutamylcyclotransferase
FT 2"
FT /id="PRO_0000314912"
FT ACT_SITE 83
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O75223"
FT BINDING 3..8
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O75223"
FT VARIANT 82
FT /note="R -> G (in dbSNP:rs17851583)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038123"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:6KY1"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:6KY1"
FT STRAND 18..42
FT /evidence="ECO:0007829|PDB:6KY1"
FT STRAND 47..66
FT /evidence="ECO:0007829|PDB:6KY1"
FT HELIX 72..80
FT /evidence="ECO:0007829|PDB:6KY1"
FT STRAND 87..101
FT /evidence="ECO:0007829|PDB:6KY1"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:6KY1"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:6KY1"
FT HELIX 124..133
FT /evidence="ECO:0007829|PDB:6KY1"
FT HELIX 141..155
FT /evidence="ECO:0007829|PDB:6KY1"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:6KY1"
FT HELIX 162..171
FT /evidence="ECO:0007829|PDB:6KY1"
SQ SEQUENCE 184 AA; 20875 MW; E0F10C446A105E22 CRC64;
MWVFGYGSLI WKVDFPYQDK LVGYITNYSR RFWQGSTDHR GVPGKPGRVV TLVEDPAGCV
WGVAYRLPVG KEEEVKAYLD FREKGGYRTT TVIFYPKDPT TKPFSVLLYI GTCDNPDYLG
PAPLEDIAEQ IFNAAGPSGR NTEYLFELAN SIRNLVPEEA DEHLFALEKL VKERLEGKQN
LNCI
