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Protein

Gamma-glutamylcyclotransferase

Gene

GGCT

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

Functioni

Catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis. Induces release of cytochrome c from mitochondria with resultant induction of apoptosis.2 Publications

Catalytic activityi

(Gamma-L-glutamyl)-L-amino acid = 5-oxoproline + L-amino acid.

Kineticsi

  1. KM=2.0 mM for gamma-glutamyl-L-alanine
  1. Vmax=50.3 µmol/min/mg enzyme

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei98 – 981Proton acceptor1 Publication
Binding sitei139 – 1391Substrate1 Publication

GO - Molecular functioni

  • gamma-glutamylcyclotransferase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.3.2.4. 2681.
ReactomeiREACT_6960. Glutathione synthesis and recycling.

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-glutamylcyclotransferase (EC:2.3.2.4)
Alternative name(s):
Cytochrome c-releasing factor 21
Gene namesi
Name:GGCT
Synonyms:C7orf24, CRF21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:21705. GGCT.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi23 – 231G → A: Marked decrease in catalytic efficiency. 1 Publication
Mutagenesisi98 – 981E → A or Q: Abolishes activity without altering structure. 1 Publication
Mutagenesisi105 – 1051Y → F: Marked decrease in catalytic efficiency and specific activity. 1 Publication
Mutagenesisi125 – 1251Y → F: Little or no change in reaction kinetics. 1 Publication

Organism-specific databases

PharmGKBiPA162389392.

Polymorphism and mutation databases

BioMutaiGGCT.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 188188Gamma-glutamylcyclotransferasePRO_0000089580Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei173 – 1731PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO75223.
PaxDbiO75223.
PeptideAtlasiO75223.
PRIDEiO75223.

2D gel databases

OGPiO75223.

PTM databases

PhosphoSiteiO75223.

Expressioni

Inductioni

By geranylgeraniol.1 Publication

Gene expression databases

BgeeiO75223.
CleanExiHS_GGCT.
ExpressionAtlasiO75223. baseline and differential.
GenevisibleiO75223. HS.

Organism-specific databases

HPAiHPA020735.
HPA029914.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi122486. 2 interactions.
IntActiO75223. 5 interactions.
STRINGi9606.ENSP00000275428.

Structurei

Secondary structure

1
188
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi16 – 216Combined sources
Helixi24 – 263Combined sources
Helixi28 – 347Combined sources
Beta strandi39 – 5618Combined sources
Turni62 – 643Combined sources
Beta strandi68 – 8720Combined sources
Helixi88 – 903Combined sources
Helixi91 – 977Combined sources
Helixi100 – 1023Combined sources
Beta strandi106 – 1149Combined sources
Beta strandi119 – 1268Combined sources
Beta strandi128 – 1325Combined sources
Helixi137 – 14913Combined sources
Helixi154 – 1618Combined sources
Helixi174 – 1818Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I5TX-ray2.01A/B2-188[»]
2PN7X-ray2.41A/B1-188[»]
2Q53X-ray2.01A/B2-188[»]
2RBHX-ray2.10A/B1-188[»]
3CRYX-ray1.70A/B1-188[»]
ProteinModelPortaliO75223.
SMRiO75223. Positions 15-183.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75223.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni19 – 246Substrate binding1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG87076.
GeneTreeiENSGT00500000044921.
HOGENOMiHOG000008049.
HOVERGENiHBG050922.
InParanoidiO75223.
KOiK00682.
OMAiRCPHSPM.
OrthoDBiEOG7H1JNT.
PhylomeDBiO75223.
TreeFamiTF314378.

Family and domain databases

Gene3Di3.10.490.10. 1 hit.
InterProiIPR013024. Butirosin_synth_BtrG-like.
IPR017939. G-Glutamylcylcotransferase.
[Graphical view]
PANTHERiPTHR12935. PTHR12935. 1 hit.
SUPFAMiSSF110857. SSF110857. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75223-1) [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
MANSGCKDVT GPDEESFLYF AYGSNLLTER IHLRNPSAAF FCVARLQDFK
60 70 80 90 100
LDFGNSQGKT SQTWHGGIAT IFQSPGDEVW GVVWKMNKSN LNSLDEQEGV
110 120 130 140 150
KSGMYVVIEV KVATQEGKEI TCRSYLMTNY ESAPPSPQYK KIICMGAKEN
160 170 180
GLPLEYQEKL KAIEPNDYTG KVSEEIEDII KKGETQTL
Length:188
Mass (Da):21,008
Last modified:November 1, 1998 - v1
Checksum:i88B5C6F67F31C56C
GO
Isoform 2 (identifier: O75223-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     97-114: QEGVKSGMYVVIEVKVAT → LFAWVQKKMVCRWSIKRS
     115-188: Missing.

Note: No experimental confirmation available.
Show »
Length:114
Mass (Da):12,943
Checksum:i45207EF9348A6A72
GO
Isoform 3 (identifier: O75223-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-141: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:94
Mass (Da):10,504
Checksum:i8E15402CE6521BCC
GO
Isoform 4 (identifier: O75223-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     97-188: QEGVKSGMYV...IIKKGETQTL → WRKKRHTAFQ...MVCRWSIKRS

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:166
Mass (Da):19,092
Checksum:iD0D2773376F33287
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei48 – 14194Missing in isoform 3. CuratedVSP_046463Add
BLAST
Alternative sequencei97 – 18892QEGVK…ETQTL → WRKKRHTAFQNQGNHPCKHK TRMWDRDPKIPVQNLSLALC WQAQSGHGTCNRLFAWVQKK MVCRWSIKRS in isoform 4. CuratedVSP_046464Add
BLAST
Alternative sequencei97 – 11418QEGVK…VKVAT → LFAWVQKKMVCRWSIKRS in isoform 2. 1 PublicationVSP_035599Add
BLAST
Alternative sequencei115 – 18874Missing in isoform 2. 1 PublicationVSP_035600Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK315608 mRNA. Translation: BAG37977.1.
AC005154 Genomic DNA. No translation available.
CH471073 Genomic DNA. Translation: EAW93950.1.
CH471073 Genomic DNA. Translation: EAW93952.1.
CH471073 Genomic DNA. Translation: EAW93953.1.
BC000625 mRNA. Translation: AAH00625.1.
BC005356 mRNA. Translation: AAH05356.1.
BC013937 mRNA. Translation: AAH13937.1.
BC019243 mRNA. Translation: AAH19243.1.
CCDSiCCDS5428.1. [O75223-1]
CCDS56474.1. [O75223-3]
CCDS56475.1. [O75223-2]
CCDS56476.1. [O75223-4]
RefSeqiNP_001186744.1. NM_001199815.1. [O75223-4]
NP_001186745.1. NM_001199816.1. [O75223-2]
NP_001186746.1. NM_001199817.1. [O75223-3]
NP_076956.1. NM_024051.3. [O75223-1]
UniGeneiHs.530024.

Genome annotation databases

EnsembliENST00000005374; ENSP00000005374; ENSG00000006625. [O75223-2]
ENST00000275428; ENSP00000275428; ENSG00000006625.
ENST00000409144; ENSP00000386610; ENSG00000006625. [O75223-3]
ENST00000409390; ENSP00000387235; ENSG00000006625. [O75223-4]
GeneIDi79017.
KEGGihsa:79017.
UCSCiuc003tba.3. human. [O75223-1]
uc003tbb.3. human. [O75223-2]
uc022abe.1. human.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK315608 mRNA. Translation: BAG37977.1.
AC005154 Genomic DNA. No translation available.
CH471073 Genomic DNA. Translation: EAW93950.1.
CH471073 Genomic DNA. Translation: EAW93952.1.
CH471073 Genomic DNA. Translation: EAW93953.1.
BC000625 mRNA. Translation: AAH00625.1.
BC005356 mRNA. Translation: AAH05356.1.
BC013937 mRNA. Translation: AAH13937.1.
BC019243 mRNA. Translation: AAH19243.1.
CCDSiCCDS5428.1. [O75223-1]
CCDS56474.1. [O75223-3]
CCDS56475.1. [O75223-2]
CCDS56476.1. [O75223-4]
RefSeqiNP_001186744.1. NM_001199815.1. [O75223-4]
NP_001186745.1. NM_001199816.1. [O75223-2]
NP_001186746.1. NM_001199817.1. [O75223-3]
NP_076956.1. NM_024051.3. [O75223-1]
UniGeneiHs.530024.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I5TX-ray2.01A/B2-188[»]
2PN7X-ray2.41A/B1-188[»]
2Q53X-ray2.01A/B2-188[»]
2RBHX-ray2.10A/B1-188[»]
3CRYX-ray1.70A/B1-188[»]
ProteinModelPortaliO75223.
SMRiO75223. Positions 15-183.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122486. 2 interactions.
IntActiO75223. 5 interactions.
STRINGi9606.ENSP00000275428.

PTM databases

PhosphoSiteiO75223.

Polymorphism and mutation databases

BioMutaiGGCT.

2D gel databases

OGPiO75223.

Proteomic databases

MaxQBiO75223.
PaxDbiO75223.
PeptideAtlasiO75223.
PRIDEiO75223.

Protocols and materials databases

DNASUi79017.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000005374; ENSP00000005374; ENSG00000006625. [O75223-2]
ENST00000275428; ENSP00000275428; ENSG00000006625.
ENST00000409144; ENSP00000386610; ENSG00000006625. [O75223-3]
ENST00000409390; ENSP00000387235; ENSG00000006625. [O75223-4]
GeneIDi79017.
KEGGihsa:79017.
UCSCiuc003tba.3. human. [O75223-1]
uc003tbb.3. human. [O75223-2]
uc022abe.1. human.

Organism-specific databases

CTDi79017.
GeneCardsiGC07M030536.
HGNCiHGNC:21705. GGCT.
HPAiHPA020735.
HPA029914.
MIMi137170. gene.
neXtProtiNX_O75223.
PharmGKBiPA162389392.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG87076.
GeneTreeiENSGT00500000044921.
HOGENOMiHOG000008049.
HOVERGENiHBG050922.
InParanoidiO75223.
KOiK00682.
OMAiRCPHSPM.
OrthoDBiEOG7H1JNT.
PhylomeDBiO75223.
TreeFamiTF314378.

Enzyme and pathway databases

BRENDAi2.3.2.4. 2681.
ReactomeiREACT_6960. Glutathione synthesis and recycling.

Miscellaneous databases

ChiTaRSiGGCT. human.
EvolutionaryTraceiO75223.
GenomeRNAii79017.
NextBioi67678.
PROiO75223.
SOURCEiSearch...

Gene expression databases

BgeeiO75223.
CleanExiHS_GGCT.
ExpressionAtlasiO75223. baseline and differential.
GenevisibleiO75223. HS.

Family and domain databases

Gene3Di3.10.490.10. 1 hit.
InterProiIPR013024. Butirosin_synth_BtrG-like.
IPR017939. G-Glutamylcylcotransferase.
[Graphical view]
PANTHERiPTHR12935. PTHR12935. 1 hit.
SUPFAMiSSF110857. SSF110857. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Skeletal muscle.
  2. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORMS 1 AND 2).
    Tissue: Kidney, Lung, Skin and Urinary bladder.
  5. "A novel 21-kDa cytochrome c-releasing factor is generated upon treatment of human leukemia U937 cells with geranylgeraniol."
    Masuda Y., Maeda S., Watanabe A., Sano Y., Aiuchi T., Nakajo S., Itabe H., Nakaya K.
    Biochem. Biophys. Res. Commun. 346:454-460(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INDUCTION.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  8. "The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase: an essential enzyme in the gamma-glutamyl cycle."
    Oakley A.J., Yamada T., Liu D., Coggan M., Clark A.G., Board P.G.
    J. Biol. Chem. 283:22031-22042(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS), IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF GLY-23; GLU-98; TYR-105 AND TYR-125.
  9. "Crystal structure of Homo sapiens protein LOC79017."
    Bae E., Bingman C.A., Aceti D.J., Phillips G.N. Jr.
    Proteins 70:588-591(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 2-188, SUBUNIT.

Entry informationi

Entry nameiGGCT_HUMAN
AccessioniPrimary (citable) accession number: O75223
Secondary accession number(s): B2RDN0
, B8ZZN4, B8ZZR8, Q9BS37
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 22, 2003
Last sequence update: November 1, 1998
Last modified: July 22, 2015
This is version 115 of the entry and version 1 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.