CHAC1_MOUSE
ID CHAC1_MOUSE Reviewed; 223 AA.
AC Q8R3J5; A2AV63; Q9D944;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Glutathione-specific gamma-glutamylcyclotransferase 1 {ECO:0000303|PubMed:23070364};
DE Short=Gamma-GCG 1 {ECO:0000303|PubMed:23070364};
DE EC=4.3.2.7 {ECO:0000269|PubMed:23070364};
DE AltName: Full=Blocks Notch protein {ECO:0000303|PubMed:22445366};
DE Short=Botch {ECO:0000303|PubMed:22445366};
DE AltName: Full=Cation transport regulator-like protein 1 {ECO:0000250|UniProtKB:Q9BUX1};
GN Name=Chac1 {ECO:0000250|UniProtKB:Q9BUX1};
GN Synonyms=Botch {ECO:0000303|PubMed:22445366};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP NOTCH1.
RX PubMed=22445366; DOI=10.1016/j.devcel.2012.02.011;
RA Chi Z., Zhang J., Tokunaga A., Harraz M.M., Byrne S.T., Dolinko A., Xu J.,
RA Blackshaw S., Gaiano N., Dawson T.M., Dawson V.L.;
RT "Botch promotes neurogenesis by antagonizing Notch.";
RL Dev. Cell 22:707-720(2012).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLU-116.
RX PubMed=23070364; DOI=10.1038/embor.2012.156;
RA Kumar A., Tikoo S., Maity S., Sengupta S., Sengupta S., Kaur A.,
RA Bachhawat A.K.;
RT "Mammalian proapoptotic factor ChaC1 and its homologues function as gamma-
RT glutamyl cyclotransferases acting specifically on glutathione.";
RL EMBO Rep. 13:1095-1101(2012).
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. Glutathione depletion is an important
CC factor for apoptosis initiation and execution. Acts as a pro-apoptotic
CC component of the unfolded protein response pathway by mediating the
CC pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade (By
CC similarity). Negative regulator of Notch signaling pathway involved in
CC embryonic neurogenesis: acts by inhibiting Notch cleavage by furin,
CC maintaining Notch in an immature inactive form, thereby promoting
CC neurogenesis in embryos (PubMed:22445366).
CC {ECO:0000250|UniProtKB:Q9BUX1, ECO:0000269|PubMed:22445366,
CC ECO:0000269|PubMed:23070364}.
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:23070364};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.13 mM for glutathione {ECO:0000269|PubMed:23070364};
CC Vmax=980 umol/h/mg enzyme {ECO:0000269|PubMed:23070364};
CC -!- SUBUNIT: Interacts with NOTCH1 (via extracellular region).
CC {ECO:0000269|PubMed:22445366}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9BUX1}. Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:22445366}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with high expression in forebrain
CC and anterior spinal cord. Expressed at intermediate level in the dorsal
CC aorta and heart. Present throughout adult brain (at protein level).
CC {ECO:0000269|PubMed:22445366}.
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family. ChaC
CC subfamily. {ECO:0000305}.
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DR EMBL; AK007378; BAB24997.1; -; mRNA.
DR EMBL; AK032218; BAC27764.1; -; mRNA.
DR EMBL; AL929318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025169; AAH25169.1; -; mRNA.
DR CCDS; CCDS16601.1; -.
DR RefSeq; NP_081205.1; NM_026929.4.
DR AlphaFoldDB; Q8R3J5; -.
DR SMR; Q8R3J5; -.
DR STRING; 10090.ENSMUSP00000028780; -.
DR PhosphoSitePlus; Q8R3J5; -.
DR PaxDb; Q8R3J5; -.
DR PRIDE; Q8R3J5; -.
DR ProteomicsDB; 283903; -.
DR ABCD; Q8R3J5; 1 sequenced antibody.
DR Antibodypedia; 23207; 310 antibodies from 28 providers.
DR DNASU; 69065; -.
DR Ensembl; ENSMUST00000028780; ENSMUSP00000028780; ENSMUSG00000027313.
DR GeneID; 69065; -.
DR KEGG; mmu:69065; -.
DR UCSC; uc008lts.3; mouse.
DR CTD; 79094; -.
DR MGI; MGI:1916315; Chac1.
DR VEuPathDB; HostDB:ENSMUSG00000027313; -.
DR eggNOG; KOG3182; Eukaryota.
DR GeneTree; ENSGT00390000003855; -.
DR HOGENOM; CLU_070703_2_2_1; -.
DR InParanoid; Q8R3J5; -.
DR OMA; RPECTAV; -.
DR OrthoDB; 1238273at2759; -.
DR PhylomeDB; Q8R3J5; -.
DR TreeFam; TF313048; -.
DR BRENDA; 4.3.2.7; 3474.
DR Reactome; R-MMU-174403; Glutathione synthesis and recycling.
DR SABIO-RK; Q8R3J5; -.
DR BioGRID-ORCS; 69065; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q8R3J5; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R3J5; protein.
DR Bgee; ENSMUSG00000027313; Expressed in vault of skull and 143 other tissues.
DR Genevisible; Q8R3J5; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
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:0005112; F:Notch binding; IDA:UniProtKB.
DR GO; GO:0006751; P:glutathione catabolic process; IBA:GO_Central.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0010955; P:negative regulation of protein processing; ISS:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IMP:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
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 Apoptosis; Cytoplasm; Golgi apparatus; Lyase; Neurogenesis;
KW Notch signaling pathway; Reference proteome; Unfolded protein response.
FT CHAIN 1..223
FT /note="Glutathione-specific gamma-glutamylcyclotransferase
FT 1"
FT /id="PRO_0000239011"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 116
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O75223"
FT BINDING 36..41
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O75223"
FT MUTAGEN 116
FT /note="E->Q: Loss of catalytic activity against
FT glutathione."
FT /evidence="ECO:0000269|PubMed:23070364"
FT CONFLICT 25
FT /note="S -> F (in Ref. 3; AAH25169)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="R -> H (in Ref. 3; AAH25169)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 223 AA; 24547 MW; 2DF793150C1C3B67 CRC64;
MKQESASQST PPPSLSPAPS SAQPSWGDGD PQALWIFGYG SLVWKPDFAY SDSRVGFVRG
YSRRFWQGDT FHRGSDKMPG RVVTLLEDRE GCTWGVAYQV RGEQVNEALK YLNVREAVLG
GYDTKEVTFY PQDTPDQPLT ALAYVATPQN PGYLGPAPEE VIATQILACR GFSGHNLEYL
LRLADFMQLC GPQAQDEHLE AIVDAVGTLL PCSYLPEQPL ALT
