Full text data of GGCT
GGCT
(C7orf24, CRF21)
[Confidence: low (only semi-automatic identification from reviews)]
Gamma-glutamylcyclotransferase; 2.3.2.4 (Cytochrome c-releasing factor 21)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Gamma-glutamylcyclotransferase; 2.3.2.4 (Cytochrome c-releasing factor 21)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O75223
ID GGCT_HUMAN Reviewed; 188 AA.
AC O75223; B2RDN0; B8ZZN4; B8ZZR8; Q9BS37;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 99.
DE RecName: Full=Gamma-glutamylcyclotransferase;
DE EC=2.3.2.4;
DE AltName: Full=Cytochrome c-releasing factor 21;
GN Name=GGCT; Synonyms=C7orf24, CRF21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Itabe H., Nakaya K.;
RT "A novel 21-kDa cytochrome c-releasing factor is generated upon
RT treatment 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.,
RA Buerckstuemmer T., 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, AND MUTAGENESIS OF
RP GLY-23; GLU-98; TYR-105 AND TYR-125.
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
RT gamma-glutamyl cyclotransferase: an essential enzyme in the gamma-
RT glutamyl 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-
CC glutamyl dipeptides and may play a significant role in glutathione
CC homeostasis. Induces release of cytochrome c from mitochondria
CC with resultant induction of apoptosis.
CC -!- CATALYTIC ACTIVITY: (Gamma-L-glutamyl)-L-amino acid = 5-oxoproline
CC + L-amino acid.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.0 mM for gamma-glutamyl-L-alanine;
CC Vmax=50.3 umol/min/mg enzyme;
CC -!- SUBUNIT: Homodimer (Probable).
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=O75223-3; Sequence=VSP_046463;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data;
CC Name=4;
CC IsoId=O75223-4; Sequence=VSP_046464;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data;
CC -!- INDUCTION: By geranylgeraniol.
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family.
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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 RefSeq; NP_001186744.1; NM_001199815.1.
DR RefSeq; NP_001186745.1; NM_001199816.1.
DR RefSeq; NP_001186746.1; NM_001199817.1.
DR RefSeq; NP_076956.1; NM_024051.3.
DR UniGene; Hs.530024; -.
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 ProteinModelPortal; O75223; -.
DR SMR; O75223; 15-183.
DR IntAct; O75223; 1.
DR STRING; 9606.ENSP00000275428; -.
DR PhosphoSite; O75223; -.
DR OGP; O75223; -.
DR PaxDb; O75223; -.
DR PeptideAtlas; O75223; -.
DR PRIDE; O75223; -.
DR DNASU; 79017; -.
DR Ensembl; ENST00000005374; ENSP00000005374; ENSG00000006625.
DR Ensembl; ENST00000275428; ENSP00000275428; ENSG00000006625.
DR Ensembl; ENST00000409144; ENSP00000386610; ENSG00000006625.
DR Ensembl; ENST00000409390; ENSP00000387235; ENSG00000006625.
DR GeneID; 79017; -.
DR KEGG; hsa:79017; -.
DR UCSC; uc022abf.1; human.
DR CTD; 79017; -.
DR GeneCards; GC07M030536; -.
DR HGNC; HGNC:21705; GGCT.
DR HPA; HPA020735; -.
DR HPA; HPA029914; -.
DR MIM; 137170; gene.
DR neXtProt; NX_O75223; -.
DR PharmGKB; PA162389392; -.
DR eggNOG; NOG87076; -.
DR HOGENOM; HOG000008049; -.
DR HOVERGEN; HBG050922; -.
DR InParanoid; O75223; -.
DR KO; K00682; -.
DR OMA; AFCCVAR; -.
DR OrthoDB; EOG7H1JNT; -.
DR PhylomeDB; O75223; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; GGCT; human.
DR EvolutionaryTrace; O75223; -.
DR GenomeRNAi; 79017; -.
DR NextBio; 67678; -.
DR PRO; PR:O75223; -.
DR ArrayExpress; O75223; -.
DR Bgee; O75223; -.
DR CleanEx; HS_GGCT; -.
DR Genevestigator; O75223; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0003839; F:gamma-glutamylcyclotransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; TAS:Reactome.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.10.490.10; -; 1.
DR InterPro; IPR013024; Butirosin_synth_BtrG-like.
DR InterPro; IPR017939; G-Glutamylcylcotransferase.
DR PANTHER; PTHR12935; PTHR12935; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing;
KW Complete proteome; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1 188 Gamma-glutamylcyclotransferase.
FT /FTId=PRO_0000089580.
FT REGION 19 22 Substrate binding (By similarity).
FT ACT_SITE 98 98 Proton acceptor (By similarity).
FT MOD_RES 173 173 Phosphoserine (By similarity).
FT VAR_SEQ 48 141 Missing (in isoform 3).
FT /FTId=VSP_046463.
FT VAR_SEQ 97 188 QEGVKSGMYVVIEVKVATQEGKEITCRSYLMTNYESAPPSP
FT QYKKIICMGAKENGLPLEYQEKLKAIEPNDYTGKVSEEIED
FT IIKKGETQTL -> WRKKRHTAFQNQGNHPCKHKTRMWDRD
FT PKIPVQNLSLALCWQAQSGHGTCNRLFAWVQKKMVCRWSIK
FT RS (in isoform 4).
FT /FTId=VSP_046464.
FT VAR_SEQ 97 114 QEGVKSGMYVVIEVKVAT -> LFAWVQKKMVCRWSIKRS
FT (in isoform 2).
FT /FTId=VSP_035599.
FT VAR_SEQ 115 188 Missing (in isoform 2).
FT /FTId=VSP_035600.
FT MUTAGEN 23 23 G->A: Marked decrease in catalytic
FT efficiency.
FT MUTAGEN 98 98 E->A,Q: Abolishes activity without
FT altering structure.
FT MUTAGEN 105 105 Y->F: Marked decrease in catalytic
FT efficiency and specific activity.
FT MUTAGEN 125 125 Y->F: Little or no change in reaction
FT kinetics.
FT STRAND 16 21
FT HELIX 24 26
FT HELIX 28 34
FT STRAND 39 56
FT TURN 62 64
FT STRAND 68 87
FT HELIX 88 90
FT HELIX 91 97
FT HELIX 100 102
FT STRAND 106 114
FT STRAND 119 126
FT STRAND 128 132
FT HELIX 137 149
FT HELIX 154 161
FT HELIX 174 181
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
//
ID GGCT_HUMAN Reviewed; 188 AA.
AC O75223; B2RDN0; B8ZZN4; B8ZZR8; Q9BS37;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 99.
DE RecName: Full=Gamma-glutamylcyclotransferase;
DE EC=2.3.2.4;
DE AltName: Full=Cytochrome c-releasing factor 21;
GN Name=GGCT; Synonyms=C7orf24, CRF21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Itabe H., Nakaya K.;
RT "A novel 21-kDa cytochrome c-releasing factor is generated upon
RT treatment 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.,
RA Buerckstuemmer T., 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, AND MUTAGENESIS OF
RP GLY-23; GLU-98; TYR-105 AND TYR-125.
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
RT gamma-glutamyl cyclotransferase: an essential enzyme in the gamma-
RT glutamyl 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-
CC glutamyl dipeptides and may play a significant role in glutathione
CC homeostasis. Induces release of cytochrome c from mitochondria
CC with resultant induction of apoptosis.
CC -!- CATALYTIC ACTIVITY: (Gamma-L-glutamyl)-L-amino acid = 5-oxoproline
CC + L-amino acid.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.0 mM for gamma-glutamyl-L-alanine;
CC Vmax=50.3 umol/min/mg enzyme;
CC -!- SUBUNIT: Homodimer (Probable).
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=O75223-3; Sequence=VSP_046463;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data;
CC Name=4;
CC IsoId=O75223-4; Sequence=VSP_046464;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data;
CC -!- INDUCTION: By geranylgeraniol.
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family.
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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 RefSeq; NP_001186744.1; NM_001199815.1.
DR RefSeq; NP_001186745.1; NM_001199816.1.
DR RefSeq; NP_001186746.1; NM_001199817.1.
DR RefSeq; NP_076956.1; NM_024051.3.
DR UniGene; Hs.530024; -.
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 ProteinModelPortal; O75223; -.
DR SMR; O75223; 15-183.
DR IntAct; O75223; 1.
DR STRING; 9606.ENSP00000275428; -.
DR PhosphoSite; O75223; -.
DR OGP; O75223; -.
DR PaxDb; O75223; -.
DR PeptideAtlas; O75223; -.
DR PRIDE; O75223; -.
DR DNASU; 79017; -.
DR Ensembl; ENST00000005374; ENSP00000005374; ENSG00000006625.
DR Ensembl; ENST00000275428; ENSP00000275428; ENSG00000006625.
DR Ensembl; ENST00000409144; ENSP00000386610; ENSG00000006625.
DR Ensembl; ENST00000409390; ENSP00000387235; ENSG00000006625.
DR GeneID; 79017; -.
DR KEGG; hsa:79017; -.
DR UCSC; uc022abf.1; human.
DR CTD; 79017; -.
DR GeneCards; GC07M030536; -.
DR HGNC; HGNC:21705; GGCT.
DR HPA; HPA020735; -.
DR HPA; HPA029914; -.
DR MIM; 137170; gene.
DR neXtProt; NX_O75223; -.
DR PharmGKB; PA162389392; -.
DR eggNOG; NOG87076; -.
DR HOGENOM; HOG000008049; -.
DR HOVERGEN; HBG050922; -.
DR InParanoid; O75223; -.
DR KO; K00682; -.
DR OMA; AFCCVAR; -.
DR OrthoDB; EOG7H1JNT; -.
DR PhylomeDB; O75223; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; GGCT; human.
DR EvolutionaryTrace; O75223; -.
DR GenomeRNAi; 79017; -.
DR NextBio; 67678; -.
DR PRO; PR:O75223; -.
DR ArrayExpress; O75223; -.
DR Bgee; O75223; -.
DR CleanEx; HS_GGCT; -.
DR Genevestigator; O75223; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0003839; F:gamma-glutamylcyclotransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; TAS:Reactome.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.10.490.10; -; 1.
DR InterPro; IPR013024; Butirosin_synth_BtrG-like.
DR InterPro; IPR017939; G-Glutamylcylcotransferase.
DR PANTHER; PTHR12935; PTHR12935; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing;
KW Complete proteome; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1 188 Gamma-glutamylcyclotransferase.
FT /FTId=PRO_0000089580.
FT REGION 19 22 Substrate binding (By similarity).
FT ACT_SITE 98 98 Proton acceptor (By similarity).
FT MOD_RES 173 173 Phosphoserine (By similarity).
FT VAR_SEQ 48 141 Missing (in isoform 3).
FT /FTId=VSP_046463.
FT VAR_SEQ 97 188 QEGVKSGMYVVIEVKVATQEGKEITCRSYLMTNYESAPPSP
FT QYKKIICMGAKENGLPLEYQEKLKAIEPNDYTGKVSEEIED
FT IIKKGETQTL -> WRKKRHTAFQNQGNHPCKHKTRMWDRD
FT PKIPVQNLSLALCWQAQSGHGTCNRLFAWVQKKMVCRWSIK
FT RS (in isoform 4).
FT /FTId=VSP_046464.
FT VAR_SEQ 97 114 QEGVKSGMYVVIEVKVAT -> LFAWVQKKMVCRWSIKRS
FT (in isoform 2).
FT /FTId=VSP_035599.
FT VAR_SEQ 115 188 Missing (in isoform 2).
FT /FTId=VSP_035600.
FT MUTAGEN 23 23 G->A: Marked decrease in catalytic
FT efficiency.
FT MUTAGEN 98 98 E->A,Q: Abolishes activity without
FT altering structure.
FT MUTAGEN 105 105 Y->F: Marked decrease in catalytic
FT efficiency and specific activity.
FT MUTAGEN 125 125 Y->F: Little or no change in reaction
FT kinetics.
FT STRAND 16 21
FT HELIX 24 26
FT HELIX 28 34
FT STRAND 39 56
FT TURN 62 64
FT STRAND 68 87
FT HELIX 88 90
FT HELIX 91 97
FT HELIX 100 102
FT STRAND 106 114
FT STRAND 119 126
FT STRAND 128 132
FT HELIX 137 149
FT HELIX 154 161
FT HELIX 174 181
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
//
MIM
137170
*RECORD*
*FIELD* NO
137170
*FIELD* TI
*137170 GAMMA-GLUTAMYL CYCLOTRANSFERASE; GGCT
;;GLUTAMYLCYCLOTRANSFERASE, GAMMA; GCTG;;
read moreCHROMOSOME 7 OPEN READING FRAME 24; C7ORF24;;
CYTOCHROME c-RELEASING FACTOR, 21-KD; CRF21
*FIELD* TX
DESCRIPTION
GGCT (EC 2.3.2.4) catalyzes the formation of 5-oxoproline (pyroglutamic
acid) from gamma-glutamyl dipeptides and may play a significant role in
glutathione homeostasis (Oakley et al., 2008).
CLONING
By mass spectrometric analysis of peptides obtained from an
apoptosis-inducing protein, followed by database analysis and RT-PCR of
total RNA from a human leukemia cell line, Masuda et al. (2006) cloned
GGCT, which they called CRF21. SDS-PAGE detected purified CRF21 at an
apparent molecular mass of 21 kD.
Using tryptic peptides obtained from GGCT partially purified from
expired human red blood cells for database analysis, Oakley et al.
(2008) obtained a full-length GGCT cDNA. The deduced 188-amino acid
protein has a calculated molecular mass of 21 kD. EST database analysis
revealed moderate GGCT expression in a wide range of human tissues, with
highest levels in bladder and salivary gland. Database analysis
identified GGCT orthologs in a range of species from C. elegans to
mammals, but not in plants.
GENE FUNCTION
Geranylgeraniol (GGO) induces apoptosis in human tumor cell lines
through a mitochondria-dependent pathway that includes cytochrome c
release. Masuda et al. (2006) found that GGO was unable to induce
cytochrome c release from isolated human mitochondria directly, and they
identified CRF21 as a cytosolic cytochrome c-releasing factor involved
in GGO-induced apoptosis. Overexpression of CRF21 in HeLa cells induced
cytochrome c release and apoptosis. Masuda et al. (2006) noted that
GGO-induced apoptosis was inhibited by a dominant-negative mutation of
JNK (MAPK8; 601158) that impeded JNK signaling, suggesting involvement
of JNK and CRF21 in GGO-induced apoptosis.
Oakley et al. (2008) confirmed that recombinant human GGCT used
gamma-glutamyl-L-alanine as its substrate. The enzymatic kinetics were
similar to those of GGCT purified from human erythrocytes.
BIOCHEMICAL FEATURES
- Crystal Structure
Oakley et al. (2008) determined the crystal structure of recombinant
human GGCT to 2.4-angstrom resolution. GGCT adopted a mixed alpha/beta
topology with 6 beta stands, 5 alpha helices, and 4 short 3(10) helices,
and it assumed a unique structural fold that the authors termed a GGCT
fold. GGCT formed dimers, and each monomer featured an invagination that
Oakley et al. (2008) proposed was the active site. The site was lined
with hydrophilic and amphipathic residues, including a conserved glu98
that appeared to function as a general acid/base in the reaction.
Mutation of glu98 to ala or gln did not alter the structural fold, but
it completely inactivated the enzyme. Mutation analysis showed that
gly23 and tyr105 also contributed to substrate binding interactions.
GENE STRUCTURE
Oakley et al. (2008) determined that the GGCT gene contains 5 exons and
spans 8 kb.
MAPPING
Bissbort et al. (1984) assigned the GGCT gene to chromosome 7pter-p14 by
somatic cell hybrid studies.
By genomic sequence analysis, Oakley et al. (2008) mapped the GGCT gene
to chromosome 7p15-p14. They identified putative GGCT pseudogenes on
chromosomes 5 and 20. Oakley et al. (2008) noted that the mouse Ggct
gene maps to a region of chromosome 6 that shares homology of synteny
with human chromosome 7p15-p14.
*FIELD* RF
1. Bissbort, S.; Bender, K.; Grzeschik, K. H.: Assignment of the
human gene for gamma-glutamyl-cyclo-transferase (GCTG) to chromosome
7p. (Abstract) Cytogenet. Cell Genet. 37: 442 only, 1984.
2. Masuda, Y.; Maeda, S.; Watanabe, A.; Sano, Y.; Aiuchi, T.; Nakajo,
S.; Itabe, H.; Nakaya, K.: A novel 21-kDa cytochrome c-releasing
factor is generated upon treatment of human leukemia U937 cells with
geranylgeraniol. Biochem. Biophys. Res. Commun. 346: 454-460, 2006.
3. Oakley, A. J.; Yamada, T.; Liu, D.; Coggan, M.; Clark, A. G.; Board,
P. G.: The identification and structural characterization of C7orf24
as gamma-glutamyl cyclotransferase: an essential enzyme in the gamma-glutamyl
cycle. J. Biol. Chem. 283: 22031-22042, 2008. Note: Erratum: J.
Biol. Chem. 283: 32152 only, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 12/8/2008
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 08/09/2012
joanna: 12/24/2008
mgross: 12/9/2008
terry: 12/8/2008
mgross: 9/19/2008
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988
reenie: 6/4/1986
*RECORD*
*FIELD* NO
137170
*FIELD* TI
*137170 GAMMA-GLUTAMYL CYCLOTRANSFERASE; GGCT
;;GLUTAMYLCYCLOTRANSFERASE, GAMMA; GCTG;;
read moreCHROMOSOME 7 OPEN READING FRAME 24; C7ORF24;;
CYTOCHROME c-RELEASING FACTOR, 21-KD; CRF21
*FIELD* TX
DESCRIPTION
GGCT (EC 2.3.2.4) catalyzes the formation of 5-oxoproline (pyroglutamic
acid) from gamma-glutamyl dipeptides and may play a significant role in
glutathione homeostasis (Oakley et al., 2008).
CLONING
By mass spectrometric analysis of peptides obtained from an
apoptosis-inducing protein, followed by database analysis and RT-PCR of
total RNA from a human leukemia cell line, Masuda et al. (2006) cloned
GGCT, which they called CRF21. SDS-PAGE detected purified CRF21 at an
apparent molecular mass of 21 kD.
Using tryptic peptides obtained from GGCT partially purified from
expired human red blood cells for database analysis, Oakley et al.
(2008) obtained a full-length GGCT cDNA. The deduced 188-amino acid
protein has a calculated molecular mass of 21 kD. EST database analysis
revealed moderate GGCT expression in a wide range of human tissues, with
highest levels in bladder and salivary gland. Database analysis
identified GGCT orthologs in a range of species from C. elegans to
mammals, but not in plants.
GENE FUNCTION
Geranylgeraniol (GGO) induces apoptosis in human tumor cell lines
through a mitochondria-dependent pathway that includes cytochrome c
release. Masuda et al. (2006) found that GGO was unable to induce
cytochrome c release from isolated human mitochondria directly, and they
identified CRF21 as a cytosolic cytochrome c-releasing factor involved
in GGO-induced apoptosis. Overexpression of CRF21 in HeLa cells induced
cytochrome c release and apoptosis. Masuda et al. (2006) noted that
GGO-induced apoptosis was inhibited by a dominant-negative mutation of
JNK (MAPK8; 601158) that impeded JNK signaling, suggesting involvement
of JNK and CRF21 in GGO-induced apoptosis.
Oakley et al. (2008) confirmed that recombinant human GGCT used
gamma-glutamyl-L-alanine as its substrate. The enzymatic kinetics were
similar to those of GGCT purified from human erythrocytes.
BIOCHEMICAL FEATURES
- Crystal Structure
Oakley et al. (2008) determined the crystal structure of recombinant
human GGCT to 2.4-angstrom resolution. GGCT adopted a mixed alpha/beta
topology with 6 beta stands, 5 alpha helices, and 4 short 3(10) helices,
and it assumed a unique structural fold that the authors termed a GGCT
fold. GGCT formed dimers, and each monomer featured an invagination that
Oakley et al. (2008) proposed was the active site. The site was lined
with hydrophilic and amphipathic residues, including a conserved glu98
that appeared to function as a general acid/base in the reaction.
Mutation of glu98 to ala or gln did not alter the structural fold, but
it completely inactivated the enzyme. Mutation analysis showed that
gly23 and tyr105 also contributed to substrate binding interactions.
GENE STRUCTURE
Oakley et al. (2008) determined that the GGCT gene contains 5 exons and
spans 8 kb.
MAPPING
Bissbort et al. (1984) assigned the GGCT gene to chromosome 7pter-p14 by
somatic cell hybrid studies.
By genomic sequence analysis, Oakley et al. (2008) mapped the GGCT gene
to chromosome 7p15-p14. They identified putative GGCT pseudogenes on
chromosomes 5 and 20. Oakley et al. (2008) noted that the mouse Ggct
gene maps to a region of chromosome 6 that shares homology of synteny
with human chromosome 7p15-p14.
*FIELD* RF
1. Bissbort, S.; Bender, K.; Grzeschik, K. H.: Assignment of the
human gene for gamma-glutamyl-cyclo-transferase (GCTG) to chromosome
7p. (Abstract) Cytogenet. Cell Genet. 37: 442 only, 1984.
2. Masuda, Y.; Maeda, S.; Watanabe, A.; Sano, Y.; Aiuchi, T.; Nakajo,
S.; Itabe, H.; Nakaya, K.: A novel 21-kDa cytochrome c-releasing
factor is generated upon treatment of human leukemia U937 cells with
geranylgeraniol. Biochem. Biophys. Res. Commun. 346: 454-460, 2006.
3. Oakley, A. J.; Yamada, T.; Liu, D.; Coggan, M.; Clark, A. G.; Board,
P. G.: The identification and structural characterization of C7orf24
as gamma-glutamyl cyclotransferase: an essential enzyme in the gamma-glutamyl
cycle. J. Biol. Chem. 283: 22031-22042, 2008. Note: Erratum: J.
Biol. Chem. 283: 32152 only, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 12/8/2008
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 08/09/2012
joanna: 12/24/2008
mgross: 12/9/2008
terry: 12/8/2008
mgross: 9/19/2008
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988
reenie: 6/4/1986