GGACT_HUMAN
ID GGACT_HUMAN Reviewed; 153 AA.
AC Q9BVM4; B3KTN1; Q9BT41;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Gamma-glutamylaminecyclotransferase;
DE Short=GGACT;
DE EC=4.3.2.8 {ECO:0000269|PubMed:20110353};
DE AltName: Full=AIG2-like domain-containing protein 1;
DE AltName: Full=Gamma-glutamylamine cyclotransferase;
GN Name=GGACT; Synonyms=A2LD1;
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].
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=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
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].
RC TISSUE=Lung;
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 X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) IN COMPLEX WITH 5-OXOPROLINE AND
RP NITRATE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ACTIVE SITE, AND
RP MUTAGENESIS OF GLU-82.
RX PubMed=20110353; DOI=10.1074/jbc.m109.082099;
RA Oakley A.J., Coggan M., Board P.G.;
RT "Identification and characterization of gamma-glutamylamine
RT cyclotransferase, an enzyme responsible for gamma-glutamyl-epsilon-lysine
RT catabolism.";
RL J. Biol. Chem. 285:9642-9648(2010).
CC -!- FUNCTION: Contributes to degradation of proteins cross-linked by
CC transglutaminases by degrading the cross-link between a lysine and a
CC glutamic acid residue. Catalyzes the formation of 5-oxo-L-proline from
CC L-gamma-glutamyl-L-epsilon-lysine. Inactive with L-gamma-glutamyl-
CC alpha-amino acid substrates such as L-gamma-glutamyl-L-alpha-cysteine
CC and L-gamma-glutamyl-L-alpha-alanine. {ECO:0000269|PubMed:20110353}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=epsilon-(gamma-L-glutamyl)-L-lysine = 5-oxo-L-proline + L-
CC lysine; Xref=Rhea:RHEA:16961, ChEBI:CHEBI:32551, ChEBI:CHEBI:58402,
CC ChEBI:CHEBI:133752; EC=4.3.2.8;
CC Evidence={ECO:0000269|PubMed:20110353};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20110353}.
CC -!- INTERACTION:
CC Q9BVM4; O43679: LDB2; NbExp=3; IntAct=EBI-10299852, EBI-2865580;
CC Q9BVM4; Q96KN8-3: PLAAT5; NbExp=8; IntAct=EBI-10299852, EBI-10290304;
CC Q9BVM4; O96006: ZBED1; NbExp=3; IntAct=EBI-10299852, EBI-740037;
CC -!- SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH04360.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK095850; BAG53143.1; -; mRNA.
DR EMBL; AL136526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471085; EAX09037.1; -; Genomic_DNA.
DR EMBL; BC001077; AAH01077.2; -; mRNA.
DR EMBL; BC004360; AAH04360.1; ALT_INIT; mRNA.
DR CCDS; CCDS45066.1; -.
DR RefSeq; NP_001182016.1; NM_001195087.1.
DR RefSeq; NP_149101.1; NM_033110.2.
DR RefSeq; XP_005254140.1; XM_005254083.2.
DR RefSeq; XP_011519431.1; XM_011521129.2.
DR RefSeq; XP_016876293.1; XM_017020804.1.
DR PDB; 3JUB; X-ray; 1.20 A; A=1-153.
DR PDB; 3JUC; X-ray; 1.20 A; A=1-153.
DR PDB; 3JUD; X-ray; 0.98 A; A=1-153.
DR PDBsum; 3JUB; -.
DR PDBsum; 3JUC; -.
DR PDBsum; 3JUD; -.
DR AlphaFoldDB; Q9BVM4; -.
DR SMR; Q9BVM4; -.
DR BioGRID; 124581; 10.
DR IntAct; Q9BVM4; 4.
DR STRING; 9606.ENSP00000365426; -.
DR DrugBank; DB01942; Formic acid.
DR BioMuta; GGACT; -.
DR DMDM; 74752384; -.
DR EPD; Q9BVM4; -.
DR jPOST; Q9BVM4; -.
DR MassIVE; Q9BVM4; -.
DR MaxQB; Q9BVM4; -.
DR PaxDb; Q9BVM4; -.
DR PeptideAtlas; Q9BVM4; -.
DR PRIDE; Q9BVM4; -.
DR ProteomicsDB; 79220; -.
DR Antibodypedia; 57333; 83 antibodies from 16 providers.
DR DNASU; 87769; -.
DR Ensembl; ENST00000376250.6; ENSP00000365426.1; ENSG00000134864.11.
DR Ensembl; ENST00000455100.2; ENSP00000410449.1; ENSG00000134864.11.
DR Ensembl; ENST00000683975.1; ENSP00000508020.1; ENSG00000134864.11.
DR GeneID; 87769; -.
DR KEGG; hsa:87769; -.
DR MANE-Select; ENST00000683975.1; ENSP00000508020.1; NM_001195087.2; NP_001182016.1.
DR UCSC; uc001voq.2; human.
DR CTD; 87769; -.
DR DisGeNET; 87769; -.
DR GeneCards; GGACT; -.
DR HGNC; HGNC:25100; GGACT.
DR HPA; ENSG00000134864; Tissue enriched (kidney).
DR MIM; 613378; gene.
DR neXtProt; NX_Q9BVM4; -.
DR OpenTargets; ENSG00000134864; -.
DR PharmGKB; PA164714645; -.
DR VEuPathDB; HostDB:ENSG00000134864; -.
DR eggNOG; KOG4450; Eukaryota.
DR GeneTree; ENSGT00390000010543; -.
DR HOGENOM; CLU_083466_1_0_1; -.
DR InParanoid; Q9BVM4; -.
DR OMA; YQRTALR; -.
DR OrthoDB; 1389682at2759; -.
DR PhylomeDB; Q9BVM4; -.
DR TreeFam; TF323258; -.
DR BRENDA; 4.3.2.8; 2681.
DR BRENDA; 4.3.2.9; 2681.
DR PathwayCommons; Q9BVM4; -.
DR SignaLink; Q9BVM4; -.
DR BioGRID-ORCS; 87769; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; GGACT; human.
DR EvolutionaryTrace; Q9BVM4; -.
DR GenomeRNAi; 87769; -.
DR Pharos; Q9BVM4; Tbio.
DR PRO; PR:Q9BVM4; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9BVM4; protein.
DR Bgee; ENSG00000134864; Expressed in secondary oocyte and 108 other tissues.
DR ExpressionAtlas; Q9BVM4; baseline and differential.
DR Genevisible; Q9BVM4; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0061929; F:gamma-glutamylaminecyclotransferase activity; IDA:UniProtKB.
DR GO; GO:0042219; P:cellular modified amino acid catabolic process; IDA:UniProtKB.
DR CDD; cd06661; GGCT_like; 1.
DR InterPro; IPR009288; AIG2-like_dom.
DR InterPro; IPR039126; GGACT.
DR InterPro; IPR013024; GGCT-like.
DR InterPro; IPR036568; GGCT-like_sf.
DR PANTHER; PTHR12510; PTHR12510; 1.
DR Pfam; PF06094; GGACT; 1.
DR SUPFAM; SSF110857; SSF110857; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Lyase; Reference proteome.
FT CHAIN 1..153
FT /note="Gamma-glutamylaminecyclotransferase"
FT /id="PRO_0000320203"
FT REGION 130..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 82
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:20110353"
FT BINDING 7..10
FT /ligand="substrate"
FT MUTAGEN 82
FT /note="E->A,Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:20110353"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:3JUD"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:3JUD"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 28..38
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:3JUD"
FT TURN 46..49
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:3JUD"
FT HELIX 72..81
FT /evidence="ECO:0007829|PDB:3JUD"
FT TURN 82..86
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 89..98
FT /evidence="ECO:0007829|PDB:3JUD"
FT STRAND 113..121
FT /evidence="ECO:0007829|PDB:3JUD"
FT HELIX 126..130
FT /evidence="ECO:0007829|PDB:3JUD"
SQ SEQUENCE 153 AA; 17329 MW; 1A01F350F761D208 CRC64;
MALVFVYGTL KRGQPNHRVL RDGAHGSAAF RARGRTLEPY PLVIAGEHNI PWLLHLPGSG
RLVEGEVYAV DERMLRFLDD FESCPALYQR TVLRVQLLED RAPGAEEPPA PTAVQCFVYS
RATFPPEWAQ LPHHDSYDSE GPHGLRYNPR ENR
