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   04-NOV-2026, entry version 163.
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 IN COMPLEX WITH 5-OXOPROLINE AND NITRATE, FUNCTION,
RP   CATALYTIC ACTIVITY, SUBUNIT, ACTIVE SITE, AND 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_001195087.2.
DR   RefSeq; NP_149101.1; NM_033110.3.
DR   RefSeq; XP_011519431.1; XM_011521129.4.
DR   RefSeq; XP_047286664.1; XM_047430708.1.
DR   RefSeq; XP_054231054.1; XM_054375079.1.
DR   RefSeq; XP_054231055.1; XM_054375080.1.
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   AlphaFoldDB; Q9BVM4; -.
DR   SMR; Q9BVM4; -.
DR   BioGRID; 124581; 10.
DR   FunCoup; Q9BVM4; 148.
DR   IntAct; Q9BVM4; 10.
DR   STRING; 9606.ENSP00000365426; -.
DR   DrugBank; DB01942; Formic acid.
DR   GlyGen; Q9BVM4; 1 site.
DR   BioMuta; GGACT; -.
DR   DMDM; 74752384; -.
DR   jPOST; Q9BVM4; -.
DR   MassIVE; Q9BVM4; -.
DR   PaxDb; 9606-ENSP00000365426; -.
DR   PeptideAtlas; Q9BVM4; -.
DR   ProteomicsDB; 79220; -.
DR   Pumba; Q9BVM4; -.
DR   Antibodypedia; 57333; 89 antibodies from 17 providers.
DR   DNASU; 87769; -.
DR   Ensembl; ENST00000376250.6; ENSP00000365426.1; ENSG00000134864.12.
DR   Ensembl; ENST00000455100.2; ENSP00000410449.1; ENSG00000134864.12.
DR   Ensembl; ENST00000683975.1; ENSP00000508020.1; ENSG00000134864.12.
DR   Ensembl; ENST00000881872.1; ENSP00000551931.1; ENSG00000134864.12.
DR   Ensembl; ENST00000881873.1; ENSP00000551932.1; ENSG00000134864.12.
DR   Ensembl; ENST00000881874.1; ENSP00000551933.1; ENSG00000134864.12.
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   AGR; HGNC:25100; -.
DR   ClinPGx; PA164714645; -.
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   OpenTargets; ENSG00000134864; -.
DR   VEuPathDB; HostDB:ENSG00000134864; -.
DR   eggNOG; KOG4450; Eukaryota.
DR   GeneTree; ENSGT00390000010543; -.
DR   HOGENOM; CLU_083466_1_0_1; -.
DR   InParanoid; Q9BVM4; -.
DR   OMA; AAMTHWV; -.
DR   OrthoDB; 113620at2759; -.
DR   PAN-GO; Q9BVM4; 1 GO annotation based on evolutionary models.
DR   PhylomeDB; Q9BVM4; -.
DR   BRENDA; 4.3.2.8; 2681.
DR   BRENDA; 4.3.2.9; 2681.
DR   PathwayCommons; Q9BVM4; -.
DR   SignaLink; Q9BVM4; -.
DR   Agora; ENSG00000134864; -.
DR   BioGRID-ORCS; 87769; 9 hits in 1144 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 110 other cell types or tissues.
DR   ExpressionAtlas; Q9BVM4; baseline and differential.
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:modified amino acid catabolic process; IDA:UniProtKB.
DR   CDD; cd06661; GGCT_like; 1.
DR   FunFam; 3.10.490.10:FF:000008; Gamma-glutamylaminecyclotransferase A; 1.
DR   Gene3D; 3.10.490.10; Gamma-glutamyl cyclotransferase-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:SF4; GAMMA-GLUTAMYLAMINECYCLOTRANSFERASE; 1.
DR   PANTHER; PTHR12510; TROPONIN C-AKIN-1 PROTEIN; 1.
DR   Pfam; PF06094; GGACT; 1.
DR   SUPFAM; SSF110857; Gamma-glutamyl cyclotransferase-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Lyase; Proteomics identification; 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        132..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
//