O75223 (GGCT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-glutamylcyclotransferase
EC=2.3.2.4

Alternative name(s):
Cytochrome c-releasing factor 21

Gene names

Name:	GGCT
Synonyms:	C7orf24, CRF21

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	188 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4 Ref.6
Catalytic activity	(Gamma-L-glutamyl)-L-amino acid = 5-oxoproline + L-amino acid.
Subunit structure	Homodimer Probable. Ref.6 Ref.7
Induction	By geranylgeraniol. Ref.4
Sequence similarities	Belongs to the gamma-glutamylcyclotransferase family.
Biophysicochemical properties	Kinetic parameters: KM=2.0 mM for gamma-glutamyl-L-alanine Vmax=50.3 µmol/min/mg enzyme

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	glutathione biosynthetic process Traceable author statement. Source: Reactome release of cytochrome c from mitochondria Inferred from mutant phenotype Ref.4. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Inferred from direct assay Ref.4. Source: UniProtKB
Molecular function	gamma-glutamylcyclotransferase activity Inferred from direct assay Ref.6. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.7Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75223-1)

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.

Isoform 2 (identifier: O75223-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 188

188

Gamma-glutamylcyclotransferase

PRO_0000089580

Regions

Region

19 – 22

4

Substrate binding By similarity

Sites

Active site

98

1

Proton acceptor By similarity

Natural variations

Alternative sequence

97 – 114

18

QEGVK…VKVAT → LFAWVQKKMVCRWSIKRS in isoform 2.

VSP_035599

Alternative sequence

115 – 188

74

Missing in isoform 2.

VSP_035600

Experimental info

Mutagenesis

23

1

G → A: Marked decrease in catalytic efficiency. Ref.6

Mutagenesis

98

1

E → A or Q: Abolishes activity without altering structure. Ref.6

Mutagenesis

105

1

Y → F: Marked decrease in catalytic efficiency and specific activity. Ref.6

Mutagenesis

125

1

Y → F: Little or no change in reaction kinetics. Ref.6

Secondary structure

1

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188

Helix Strand Turn

Details...

Beta strand

16 – 21

6

Helix

24 – 26

3

Helix

28 – 32

5

Beta strand

39 – 56

18

Turn

62 – 64

3

Beta strand

68 – 87

20

Helix

88 – 90

3

Helix

91 – 97

7

Turn

98 – 103

6

Beta strand

106 – 113

8

Beta strand

119 – 126

8

Beta strand

128 – 132

5

Helix

137 – 149

13

Helix

154 – 161

8

Helix

174 – 181

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 88B5C6F67F31C56C	FASTA	188	21,008
	10 20 30 40 50 60 MANSGCKDVT GPDEESFLYF AYGSNLLTER IHLRNPSAAF FCVARLQDFK LDFGNSQGKT 70 80 90 100 110 120 SQTWHGGIAT IFQSPGDEVW GVVWKMNKSN LNSLDEQEGV KSGMYVVIEV KVATQEGKEI 130 140 150 160 170 180 TCRSYLMTNY ESAPPSPQYK KIICMGAKEN GLPLEYQEKL KAIEPNDYTG KVSEEIEDII KKGETQTL
	Isoform 2 [UniParc]. Checksum: 45207EF9348A6A72	FASTA	114	12,943
	10 20 30 40 50 60 MANSGCKDVT GPDEESFLYF AYGSNLLTER IHLRNPSAAF FCVARLQDFK LDFGNSQGKT 70 80 90 100 110 SQTWHGGIAT IFQSPGDEVW GVVWKMNKSN LNSLDELFAW VQKKMVCRWS IKRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skeletal muscle.
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Kidney, Lung, Skin and Urinary bladder.
[4]	"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: 16765912] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INDUCTION.
[5]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"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: 18515354] [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.
[7]	"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: 17932939] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 2-188, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK315608 mRNA. Translation: BAG37977.1.
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.

IPI

IPI00020301.
IPI00031564.

RefSeq

NP_001186744.1. NM_001199815.1.
NP_001186745.1. NM_001199816.1.
NP_001186746.1. NM_001199817.1.
NP_076956.1. NM_024051.3.

UniGene

Hs.530024.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I5T	X-ray	2.01	A/B	2-188	[»]
2PN7	X-ray	2.41	A/B	1-188	[»]
2Q53	X-ray	2.01	A/B	2-188	[»]
2RBH	X-ray	2.10	A/B	1-188	[»]
3CRY	X-ray	1.70	A/B	1-188	[»]

ProteinModelPortal

O75223.

SMR

O75223. Positions 15-183.

ModBase

Search...

Protein-protein interaction databases

STRING

O75223.

PTM databases

PhosphoSite

O75223.

2D gel databases

OGP

O75223.

Proteomic databases

PeptideAtlas

O75223.

PRIDE

O75223.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000275428; ENSP00000275428; ENSG00000006625.

GeneID

79017.

KEGG

hsa:79017.

UCSC

uc003tba.1. human.

Organism-specific databases

CTD

79017.

GeneCards

GC07M030536.

HGNC

HGNC:21705. GGCT.

HPA

HPA020735.
HPA029914.

MIM

137170. gene.

neXtProt

NX_O75223.

PharmGKB

PA134968801.
PA162389392.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05413.

GeneTree

ENSGT00500000044921.

HOGENOM

HBG542988.

HOVERGEN

HBG050922.

InParanoid

O75223.

OMA

EGWRLTF.

OrthoDB

EOG4907B2.

PhylomeDB

O75223.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

O75223.

CleanEx

HS_GGCT.

Genevestigator

O75223.

GermOnline

ENSG00000006625. Homo sapiens.

Family and domain databases

InterPro

IPR009288. AIG2-like.
IPR013024. Butirosin_synth_BtrG-like.
IPR017939. G-Glutamylcylcotransferase.
[Graphical view]

Gene3D

G3DSA:3.10.490.10. Butirosin_synth_BtrG-like. 1 hit.

KO

K00682.

PANTHER

PTHR12935. G-Glutamylcylcotransferase. 1 hit.

Pfam

PF06094. AIG2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

67678.

SOURCE

Search...

Entry information

Entry name

GGCT_HUMAN

Accession

Primary (citable) accession number: O75223
Secondary accession number(s): B2RDN0, Q9BS37

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 22, 2003
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.