GGCT_HUMAN
ID GGCT_HUMAN Reviewed; 188 AA.
AC O75223; B2RDN0; B8ZZN4; B8ZZR8; Q9BS37;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Gamma-glutamylcyclotransferase {ECO:0000305};
DE EC=4.3.2.9 {ECO:0000269|PubMed:18515354};
DE AltName: Full=Cytochrome c-releasing factor 21;
GN Name=GGCT {ECO:0000312|HGNC:HGNC:21705}; Synonyms=C7orf24, CRF21;
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 MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, Lung, Skin, and Urinary bladder;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INDUCTION.
RX PubMed=16765912; DOI=10.1016/j.bbrc.2006.05.161;
RA Masuda Y., Maeda S., Watanabe A., Sano Y., Aiuchi T., Nakajo S., Itabe H.,
RA Nakaya K.;
RT "A novel 21-kDa cytochrome c-releasing factor is generated upon treatment
RT of human leukemia U937 cells with geranylgeraniol.";
RL Biochem. Biophys. Res. Commun. 346:454-460(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS), IDENTIFICATION BY MASS
RP SPECTROMETRY, FUNCTION, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF GLY-23;
RP GLU-98; TYR-105 AND TYR-125, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=18515354; DOI=10.1074/jbc.m803623200;
RA Oakley A.J., Yamada T., Liu D., Coggan M., Clark A.G., Board P.G.;
RT "The identification and structural characterization of C7orf24 as gamma-
RT glutamyl cyclotransferase: an essential enzyme in the gamma-glutamyl
RT cycle.";
RL J. Biol. Chem. 283:22031-22042(2008).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 2-188, AND SUBUNIT.
RX PubMed=17932939; DOI=10.1002/prot.21719;
RA Bae E., Bingman C.A., Aceti D.J., Phillips G.N. Jr.;
RT "Crystal structure of Homo sapiens protein LOC79017.";
RL Proteins 70:588-591(2008).
CC -!- FUNCTION: Catalyzes the formation of 5-oxoproline from gamma-glutamyl
CC dipeptides and may play a significant role in glutathione homeostasis
CC (PubMed:18515354). Induces release of cytochrome c from mitochondria
CC with resultant induction of apoptosis (PubMed:16765912).
CC {ECO:0000269|PubMed:16765912, ECO:0000269|PubMed:18515354}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-(gamma-L-glutamyl)-L-amino acid = 5-oxo-L-proline +
CC an L-alpha-amino acid; Xref=Rhea:RHEA:20505, ChEBI:CHEBI:58402,
CC ChEBI:CHEBI:59869, ChEBI:CHEBI:71304; EC=4.3.2.9;
CC Evidence={ECO:0000269|PubMed:18515354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20506;
CC Evidence={ECO:0000305|PubMed:18515354};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.0 mM for gamma-glutamyl-L-alanine {ECO:0000269|PubMed:18515354};
CC Vmax=50.3 umol/min/mg enzyme {ECO:0000269|PubMed:18515354};
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:17932939,
CC ECO:0000305|PubMed:18515354}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O75223-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75223-2; Sequence=VSP_035599, VSP_035600;
CC Name=3;
CC IsoId=O75223-3; Sequence=VSP_046463;
CC Name=4;
CC IsoId=O75223-4; Sequence=VSP_046464;
CC -!- INDUCTION: By geranylgeraniol. {ECO:0000269|PubMed:16765912}.
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family.
CC {ECO:0000305}.
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DR EMBL; AK315608; BAG37977.1; -; mRNA.
DR EMBL; AC005154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471073; EAW93950.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93952.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93953.1; -; Genomic_DNA.
DR EMBL; BC000625; AAH00625.1; -; mRNA.
DR EMBL; BC005356; AAH05356.1; -; mRNA.
DR EMBL; BC013937; AAH13937.1; -; mRNA.
DR EMBL; BC019243; AAH19243.1; -; mRNA.
DR CCDS; CCDS5428.1; -. [O75223-1]
DR CCDS; CCDS56474.1; -. [O75223-3]
DR CCDS; CCDS56475.1; -. [O75223-2]
DR CCDS; CCDS56476.1; -. [O75223-4]
DR RefSeq; NP_001186744.1; NM_001199815.1. [O75223-4]
DR RefSeq; NP_001186745.1; NM_001199816.1. [O75223-2]
DR RefSeq; NP_001186746.1; NM_001199817.1. [O75223-3]
DR RefSeq; NP_076956.1; NM_024051.3. [O75223-1]
DR PDB; 2I5T; X-ray; 2.01 A; A/B=2-188.
DR PDB; 2PN7; X-ray; 2.41 A; A/B=1-188.
DR PDB; 2Q53; X-ray; 2.01 A; A/B=2-188.
DR PDB; 2RBH; X-ray; 2.10 A; A/B=1-188.
DR PDB; 3CRY; X-ray; 1.70 A; A/B=1-188.
DR PDBsum; 2I5T; -.
DR PDBsum; 2PN7; -.
DR PDBsum; 2Q53; -.
DR PDBsum; 2RBH; -.
DR PDBsum; 3CRY; -.
DR AlphaFoldDB; O75223; -.
DR SMR; O75223; -.
DR BioGRID; 122486; 40.
DR IntAct; O75223; 13.
DR MINT; O75223; -.
DR STRING; 9606.ENSP00000275428; -.
DR GuidetoPHARMACOLOGY; 1392; -.
DR GlyGen; O75223; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75223; -.
DR PhosphoSitePlus; O75223; -.
DR BioMuta; GGCT; -.
DR OGP; O75223; -.
DR CPTAC; CPTAC-514; -.
DR CPTAC; CPTAC-515; -.
DR EPD; O75223; -.
DR jPOST; O75223; -.
DR MassIVE; O75223; -.
DR MaxQB; O75223; -.
DR PaxDb; O75223; -.
DR PeptideAtlas; O75223; -.
DR PRIDE; O75223; -.
DR ProteomicsDB; 49871; -. [O75223-1]
DR ProteomicsDB; 49872; -. [O75223-2]
DR ProteomicsDB; 7409; -.
DR ProteomicsDB; 7425; -.
DR Antibodypedia; 12613; 195 antibodies from 31 providers.
DR DNASU; 79017; -.
DR Ensembl; ENST00000005374.10; ENSP00000005374.6; ENSG00000006625.18. [O75223-2]
DR Ensembl; ENST00000275428.9; ENSP00000275428.4; ENSG00000006625.18. [O75223-1]
DR Ensembl; ENST00000409144.5; ENSP00000386610.1; ENSG00000006625.18. [O75223-3]
DR Ensembl; ENST00000409390.5; ENSP00000387235.1; ENSG00000006625.18. [O75223-4]
DR GeneID; 79017; -.
DR KEGG; hsa:79017; -.
DR MANE-Select; ENST00000275428.9; ENSP00000275428.4; NM_024051.4; NP_076956.1.
DR UCSC; uc003tba.4; human. [O75223-1]
DR CTD; 79017; -.
DR DisGeNET; 79017; -.
DR GeneCards; GGCT; -.
DR HGNC; HGNC:21705; GGCT.
DR HPA; ENSG00000006625; Low tissue specificity.
DR MIM; 137170; gene.
DR neXtProt; NX_O75223; -.
DR OpenTargets; ENSG00000006625; -.
DR PharmGKB; PA162389392; -.
DR VEuPathDB; HostDB:ENSG00000006625; -.
DR eggNOG; KOG4059; Eukaryota.
DR GeneTree; ENSGT00500000044921; -.
DR HOGENOM; CLU_048475_2_1_1; -.
DR InParanoid; O75223; -.
DR OMA; APHDYVM; -.
DR PhylomeDB; O75223; -.
DR TreeFam; TF314378; -.
DR BRENDA; 4.3.2.9; 2681.
DR PathwayCommons; O75223; -.
DR Reactome; R-HSA-174403; Glutathione synthesis and recycling.
DR SignaLink; O75223; -.
DR BioGRID-ORCS; 79017; 10 hits in 1045 CRISPR screens.
DR ChiTaRS; GGCT; human.
DR EvolutionaryTrace; O75223; -.
DR GenomeRNAi; 79017; -.
DR Pharos; O75223; Tchem.
DR PRO; PR:O75223; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O75223; protein.
DR Bgee; ENSG00000006625; Expressed in mammalian vulva and 205 other tissues.
DR ExpressionAtlas; O75223; baseline and differential.
DR Genevisible; O75223; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0003839; F:gamma-glutamylcyclotransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:UniProtKB.
DR CDD; cd06661; GGCT_like; 1.
DR InterPro; IPR017939; G-Glutamylcylcotransferase.
DR InterPro; IPR013024; GGCT-like.
DR InterPro; IPR036568; GGCT-like_sf.
DR PANTHER; PTHR12935; PTHR12935; 1.
DR SUPFAM; SSF110857; SSF110857; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Lyase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..188
FT /note="Gamma-glutamylcyclotransferase"
FT /id="PRO_0000089580"
FT ACT_SITE 98
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:18515354"
FT BINDING 19..24
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18515354"
FT BINDING 139
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18515354"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D7X8"
FT VAR_SEQ 48..141
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046463"
FT VAR_SEQ 97..188
FT /note="QEGVKSGMYVVIEVKVATQEGKEITCRSYLMTNYESAPPSPQYKKIICMGAK
FT ENGLPLEYQEKLKAIEPNDYTGKVSEEIEDIIKKGETQTL -> WRKKRHTAFQNQGNH
FT PCKHKTRMWDRDPKIPVQNLSLALCWQAQSGHGTCNRLFAWVQKKMVCRWSIKRS (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_046464"
FT VAR_SEQ 97..114
FT /note="QEGVKSGMYVVIEVKVAT -> LFAWVQKKMVCRWSIKRS (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035599"
FT VAR_SEQ 115..188
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035600"
FT MUTAGEN 23
FT /note="G->A: Marked decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:18515354"
FT MUTAGEN 98
FT /note="E->A,Q: Abolishes activity without altering
FT structure."
FT /evidence="ECO:0000269|PubMed:18515354"
FT MUTAGEN 105
FT /note="Y->F: Marked decrease in catalytic efficiency and
FT specific activity."
FT /evidence="ECO:0000269|PubMed:18515354"
FT MUTAGEN 125
FT /note="Y->F: Little or no change in reaction kinetics."
FT /evidence="ECO:0000269|PubMed:18515354"
FT STRAND 16..21
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 28..34
FT /evidence="ECO:0007829|PDB:3CRY"
FT STRAND 39..56
FT /evidence="ECO:0007829|PDB:3CRY"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:3CRY"
FT STRAND 68..87
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 91..97
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:3CRY"
FT STRAND 106..114
FT /evidence="ECO:0007829|PDB:3CRY"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:3CRY"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 137..149
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:3CRY"
FT HELIX 174..181
FT /evidence="ECO:0007829|PDB:3CRY"
SQ SEQUENCE 188 AA; 21008 MW; 88B5C6F67F31C56C CRC64;
MANSGCKDVT GPDEESFLYF AYGSNLLTER IHLRNPSAAF FCVARLQDFK LDFGNSQGKT
SQTWHGGIAT IFQSPGDEVW GVVWKMNKSN LNSLDEQEGV KSGMYVVIEV KVATQEGKEI
TCRSYLMTNY ESAPPSPQYK KIICMGAKEN GLPLEYQEKL KAIEPNDYTG KVSEEIEDII
KKGETQTL
