KEGG   ENZYME: 3.4.19.9
Entry
EC 3.4.19.9                 Enzyme                                 
Name
folate gamma-glutamyl hydrolase;
GGH (gene name);
conjugase;
folate conjugase;
lysosomal gamma-glutamyl carboxypeptidase;
gamma-Glu-X carboxypeptidase;
pteroyl-poly-gamma-glutamate hydrolase;
carboxypeptidase G;
folic acid conjugase;
poly(gamma-glutamic acid) endohydrolase;
polyglutamate hydrolase;
poly(glutamic acid) hydrolase II;
pteroylpoly-gamma-glutamyl hydrolase;
gamma-glutamyl hydrolase
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Omega peptidases
Sysname
tetrahydropteroyl-poly-gamma-glutamyl gamma-glutamyl hydrolase
Reaction(IUBMB)
tetrahydropteroyl-(gamma-glutamyl)n + (n-1) H2O = 5,6,7,8-tetrahydrofolate + (n-1) L-glutamate [RN:R04242]
Reaction(KEGG)
R04242
Substrate
tetrahydropteroyl-(gamma-glutamyl)n;
(n-1) H2O
Product
5,6,7,8-tetrahydrofolate [CPD:C00101];
(n-1) L-glutamate
Comment
The enzyme, which occurs only in animals and plants, can be either endo- and/or exopeptidase. It acts on tetrahydropteroyl polyglutamates and their modified forms, as well as the polyglutamates of the folate breakdown product N-(4-aminobenzoyl)-L-glutamate (pABA-Glu). The initial cleavage may release either monoglutamate or poly-gamma-glutamate of two or more residues, depending on the specific enzyme. For example, GGH1 from the plant Arabidopsis thaliana cleaves pentaglutamates, mainly to di- and triglutamates, whereas GGH2 from the same organism yields mainly monoglutamates. The enzyme is lysosomal (and secreted) in animals and vacuolar in plants.
History
EC 3.4.19.9 created 1972 as EC 3.4.12.10, transferred 1978 to EC 3.4.22.12, transferred 1992 to EC 3.4.19.9, modified 1997, modified 2018
Pathway
ec00790  Folate biosynthesis
Orthology
K01307  gamma-glutamyl hydrolase
Genes
HSA8836(GGH)
PTR464204(GGH)
PPS100969380(GGH)
GGO101150735(GGH)
PON100435664(GGH)
NLE100595851(GGH)
MCC700747(GGH)
MCF102126049(GGH)
CSAB103236874(GGH)
CATY105585198(GGH)
PANU101017510(GGH)
TGE112630600(GGH)
RRO104660106(GGH)
RBB108543162(GGH)
TFN117079021(GGH)
PTEH111549272(GGH)
CJC100415059(GGH)
SBQ101047923(GGH)
CSYR103271634(GGH)
MMUR105858423(GGH)
OGA100964654(GGH)
MMU14590(Ggh)
MCAL110292984(Ggh)
MPAH110338856(Ggh)
RNO25455(Ggh)
MCOC116088030(Ggh)
MUN110565305(Ggh)
CGE100751581(Ggh)
PLEU114690070(Ggh)
NGI103737737(Ggh)
HGL101724155(Ggh)
CPOC100719750(Ggh)
CCAN109698223(Ggh)
DORD105980440(Ggh)
DSP122095698(Ggh)
OCU100350070(GGH)
OPI101527903(GGH)
TUP102485618(GGH)
CFA100856436(GGH)
VVP112929757(GGH)
VLG121498767(GGH)
AML100482891(GGH)
UMR103677471(GGH)
UAH113268062(GGH)
UAR123786702(GGH)
ELK111155475
LLV125098098
MPUF101684113(GGH)
ORO101373905(GGH)
EJU114213492(GGH)
ZCA113909455(GGH)
MLX118014862(GGH)
FCA101100943(GGH)
PYU121038202(GGH)
PBG122495452(GGH)
PTG102970330(GGH)
PPAD109250251(GGH)
AJU106988829(GGH)
HHV120246941(GGH)
BTA525303(GGH)
BOM102276825(GGH)
BIU109568566(GGH)
BBUB102416206(GGH)
CHX102190334(GGH)
OAS101118706(GGH)
ODA120878613(GGH)
CCAD122451112(GGH)
SSC100154232(GGH)
CFR102507789(GGH)
CBAI105081466(GGH)
CDK105094475(GGH)
VPC102540963(GGH)
BACU103016741(GGH)
LVE103090393(GGH)
OOR101273875(GGH)
DLE111185619(GGH)
PCAD102976253(GGH)
PSIU116742760(GGH)
ECB100052567(GGH)
EPZ103553263(GGH)
EAI106834311(GGH)
MYB102240048(GGH)
MYD102768461(GGH)
MMYO118670881(GGH)
MLF102425869(GGH)
MNA107526439(GGH)
PKL118718304(GGH)
HAI109375951(GGH)
DRO112315497(GGH)
SHON118995507(GGH)
AJM119040494(GGH)
PDIC114514678(GGH)
PHAS123833368(GGH)
MMF118631705(GGH)
RFQ117034021(GGH)
PALE102886790(GGH)
PGIG120607206(GGH)
PVP105295062(GGH)
RAY107521315(GGH)
MJV108385737(GGH)
TOD119241085(GGH)
SARA101544129(GGH) 105943532
LAV100671079(GGH)
TMU101347582
DNM101445199(GGH)
MDO100029624(GGH)
GAS123253406(GGH)
SHR100922531(GGH)
PCW110219063(GGH)
OAA100082379(GGH)
GGA421144(GGH)
PCOC116242169(GGH)
MGP100540892(GGH)
CJO107310260(GGH)
NMEL110394036(GGH)
APLA101790897(GGH)
ACYG106039060(GGH)
AFUL116485718(GGH)
TGU100220150(GGH)
LSR110484740(GGH)
SCAN103816283(GGH)
PMOA120499222(GGH)
OTC121340354(GGH)
PRUF121356883(GGH)
GFR102038404(GGH)
FAB101814012(GGH)
PHI102105349(GGH)
PMAJ107200637(GGH)
CCAE111924794(GGH)
CCW104692925(GGH)
ETL114062627(GGH)
ZAB102074695(GGH)
FPG101919182(GGH)
FCH102055448(GGH)
CLV102087830(GGH)
EGZ104122047(GGH)
NNI104010542(GGH)
ACUN113476136(GGH)
TALA104366116(GGH)
PADL103923701(GGH)
ACHC115340518(GGH)
AAM106494371(GGH)
AROW112960446(GGH)
NPD112944771(GGH)
DNE112986697(GGH)
ASN102387582(GGH)
AMJ102558989(GGH)
CPOO109315539(GGH)
GGN109304918(GGH)
PSS102460960(GGH)
CMY102935783(GGH)
CPIC101933582 101939707(GGH)
TST117871823(GGH) 117873525
CABI116835020(GGH) 116835024
MRV120396693(GGH) 120398947
ACS100563793(ggh)
PVT110088990(GGH)
SUND121929266(GGH)
PBI103066894(GGH)
PMUR107302720(GGH)
TSR106543965(GGH)
PGUT117672835(GGH)
VKO123020532(GGH)
PMUA114600570(GGH)
ZVI118090197(GGH)
GJA107110867(GGH)
XLA444589(ggh.L) 496099(ggh.2.L)
XTR100490929 594986(ggh)
NPR108796604(GGH) 108800416
RTEM120933180 120941032(GGH)
BBUF120986275 121001484(GGH)
BGAR122927317 122938575(GGH)
DRE406624(ggh) 553228 563836
SRX107712179 107718463 107721078 107730126 107731608 107747801
SANH107678461 107698074 107698580 107698674 107702651
SGH107549371 107559845(ggh) 107563161
CCAR109062240 109065404 109113352
CAUA113039422 113040374 113051621 113071001 113080560 113100972 113106321 113106741
IPU108265017 108267579(ggh) 108281015
PHYP113537998 113539783(ggh) 113546028
SMEO124387339(ggh) 124400153 124401930
AMEX103026830 103043942 103044433 111194246
EEE113579324 113583714 113590246
TRU101066803(ggh) 101071237
TNGGSTEN00025459G001 GSTEN00030938G001
LCO104920826 104928764 104929067 104937010
NCC104950284 104961852
CGOB115008906 115012961 115025318 115025756
ELY117252006 117256558 117264276
PLEP121944931 121955898 121960604(ggh)
SLUC116034560 116040061(ggh) 116054359
ECRA117937576(ggh) 117944025 117944298
PFLV114549269 114554356 114555211
GAT120830861 120834571
PPUG119198866(ggh) 119198868 119224715 119230070
MSAM119886844 119892181 119912675(ggh)
CUD121507204 121510147 121527080(ggh)
MZE101473896 101480685 101486490
ONL100692082 100704938
OAU116310507 116313210 116324455(ggh)
OLA101155553 101161409 101175559
OML112145648 112148585 112151516(ggh)
XMA102226146 102227572 102233721
XCO114136300 114136863 114155218
XHE116711215 116711744 116730477
PRET103456931 103464304 103470103
PFOR103140516 103141766 103143243
PLAI106935993 106944947 106957108
PMEI106903532 106924708 106932146
GAF122823937(ggh) 122827478 122834265
CVG107081843(ggh) 107086287 107099038
CTUL119787327(ggh) 119787503 119798569
GMU124856936 124858035(ggh) 124878161
NFU107383077 107384984 107394140
KMR108233685 108234706(ggh) 108243634
ALIM106513681 106515525 106522369
NWH119412899 119413036 119426899(ggh)
AOCE111563821 111564690 111565277 111566848
CSEM103377435 103386516 103397649
POV109637155 109639637 109644647 109644648
SSEN122761983 122767834 122768547 122768554 122769492 122779010 122780799 122780800 122780804
HHIP117754203(ggh) 117761174 117761760 117761761 117761762 117768541
LCF108873658 108882243 108885089
SDU111230814 111231562 111237818
SLAL111645170 111645769(ggh) 111649717 111668504
XGL120783009 120789609(ggh) 120805714
HCQ109510306 109519086 109526524
BPEC110156566 110158323 110158334 110167053 110171015
MALB109956504 109960883 109972403
SASA106566184 106579566(GGH) 106580573(GGH) 106583721 106590426
OTW112221987 112233580 112234052 112262616
OMY110489713(ggh) 110494812 110535297 110536323
OGO123990335 124003921 124035266 124039595
ONE115104551 115130168 115140607 115143531
SALP111953407 111957406 111973442 112074482
SNH120027805 120037226 120051003 120062797
ELS105006271 105014093(rnf122) 105019553
SFM108929602(ggh) 108931250 108940349
PKI111834805 111837171 111857520
AANG118210571 118225428(ggh) 118237315
LOC102684400 102693303(ggh) 102696303
PSPA121298090 121302983 121314299
ARUT117397909 117435332(ggh) 117964043 117966135
LCM102357327
CMK103180721
RTP109918930 109919274(ggh) 109938117
BFO118428959 118428980
BBEL109484058
SPU115923532 582718
APLC110980374
SKO100376948 100377250 100378724 102807920
DMEDmel_CG32155(l(3)72Dp)
DER6544839 6544840
DSE6605895
DSIDsimw501_GD14608(Dsim_GD14608)
DYADyak_GE19534 Dyak_GE19535 Dyak_GE23118 Dyak_GE23119
DSR110190582 110190653 110190654
DPODpse_GA16719 Dpse_GA16720
DPE113566355 6599706
DMN108151283 108151286
DWI6638672 6638673 6642180
DGR6557649
DMODmoj_GI12643 Dmoj_GI12644
DAZ108612709 108614335
DNV108650079 108650081
DHE111600468 111600478
DVI6623638
CCAT101459395
BOD106616995
MDE101892443 101892617
SCAC106081973
LCQ111680034 111680036
AGAAgaP_AGAP006670
ACOZ120950002
AARA120896072
AAG5573776
AALB109402593 109416472
CQUCpipJ_CPIJ006930
CPII120424879
CNS116345762 116349973
BIM100742651
BBIF117214380
BVK117231476
BVAN117166538
BTER100651812
BPYO122572940
OBB114873242
MGEN117227279
NMEA116423959
CGIG122403188
SOC105196643
MPHA105833742
AEC105148388
ACEP105627444
PBAR105430931
VEM105565622
PGC109851946
PCF106793498
TPRE106650503
MDL103569120
CGLO123268800
FAS105267568 105270830
DAM107045077
TCA659635
DPA109537699
SOY115874295 115890232
ATD109605216
CSET123322174
AGB108912203 108912234
LDC111514295
NVL108567519 108567547
PPYR116173930
OTU111414754 111423587
BMOR101736547
BMAN114249578
MSEX115450911
DPLKGM_204888A
BANY112044054 112044916 112055583
PMAC106708714
PPOT106104540
PXU106121066
PRAP110999791 110999805
ZCE119828177 119840852
HAW110370080
TNL113496419
OFU114359872 114359874 114359892
PXY105393491
API100161199 100167343 100571243
DNX107162989 107163018 107163019
AGS114124325 114124338 114124339
RMD113555681 114253640 114253641
BTAB109030105 109040644 109040645 109043775
DCI103506392 103508601 103510655
CLEC106662649 106674278
HHAL106688034 106688705 106690332
NLU111053256 111053436 111058597
PHUPhum_PHUM191920
FOC113202079 113203470
ZNE110829400 110829401 110829402
CSEC111863412 111863454 111863481
FCD110848151
DPXDAPPUDRAFT_302567 DAPPUDRAFT_305752 DAPPUDRAFT_307408 DAPPUDRAFT_315503
DMK116934583
PVM113807057 113828928 113829328
PJA122251136 122254923 122266422
HAME121855122 121861553
PCLA123754008
PTRU123518530
HAZT108675247
EAF111711448 111714885 111715381
RMP119179291 119179292
VDE111251856
VJA111268378
TUT107361416 107368043
DPTE113790317
DFR124495161
CSCU111634942
PTEP107448459
SDM118184332
LGILOTGIDRAFT_229608
PCAN112561388
BGT106066004 106078575 106078642
GAE121378218 121378219
HRF124150840 124150884 124150885 124150887
HRJ124262107 124262108 124262114 124262122
CRG105317584
MYI110442066 110464678
PMAX117315515 117333501
MMER123564971
LAK106166411
NVE116614404 116620875 5499460 5504677 5505604 5516937 5520163 5520215
EPA110238085 110239918 110239960 110240017 110244007 110251763
ATEN116288702 116291157 116302182 116308884
ADF107351159 107351173 107353245 107353247
AMIL114946883 114947371 114947372
PDAM113677037 113680336 113683869
SPIS111320493 111325560 111325581 111329701 111337063 111347046
DGT114518074 114524118 114524495 114537983
XEN124439822 124439823 124439824 124446505 124446517 124447382 124447465
HMG100198228 100203476 100207447 100209771 100209963 100215242
TADTRIADDRAFT_34071
AQU100636296 100636727 105316060
ATHAT1G78660(GGH1) AT1G78670(GGH3) AT1G78680(GGH2)
ALY9298735 9298737 9298738 9323814 9323815 9323816
CRB17895161 17895321 17895703
CSAT104703200 104703201 104714134 104714135 104752295 104752296
EUSEUTSA_v10018738mg EUTSA_v10018776mg
BRP103832344 103832347 103853141
BNA106354680 106354681 106381435 106390062 106397984 106430293 106440334
BOE106300899 106324790
RSZ108823691 108827022 108828095 108841471 108843491
THJ104813997
CPAP110812565
CIT102625054 102625524 102628535 102629472 102629856
CICCICLE_v10020608mg CICLE_v10020872mg CICLE_v10021719mg CICLE_v10024365mg
PVY116115190 116135797 116137046
MINC123209358
TCC18594335
GRA105777093 105777125
GHI107917114 107918036 107934690
GAB108480536
DZI111276559
EGR104448560 104448563 104448584 104451569 108954044
GMX100796947 547881(GH)
GSJ114376495 114376919
PVUPHAVU_005G080600g PHAVU_005G080700g
VRA106778129 106778134 106778138
VAR108333002 108333003
VUN114183153 114183810
CCAJ109811931 109811946
APRC113853566
MTRMTR_2g075760 MTR_2g075770 MTR_2g075780 MTR_2g075790
CAM101490861 101491176
LJALj0g3v0178769.1(Lj0g3v0178769.1) Lj0g3v0338049.1(Lj0g3v0338049.1)
ADU107459833
AIP107613260
AHF112703586 112771592
LANG109334584 109348097
FVE101290933
RCN112168382 112168386 112168389
PPER18779010
PMUM103325967
PAVI110757564
PDUL117624639
MDM103408080 103418191 103448789
PXB103926865 103934880
ZJU107403905
MNT21386200
CSV101203165 101206873 101219276
CMO103501819
BHJ120086372 120086854
MCHA111008276 111008284
CMAX111480987
CMOS111446777
CPEP111789236
RCU8288177
HBR110650012
MESC110602166 110610408
POP112326977 18095447 18103357 7484350
PEU105109679 105139350
PALZ118027469 118038288
JRE109011928
QSU112014043
QLO115955772
TWL119985976
VVI100262251
VRI117908414 117909674
SLY100191133(GGH1) 100191134(GGH3) 100191135(GGH2)
SPEN107024264 107024510 107031819
SOT102581354 102584938 102585261
CANN107845624 107878577
NTA107760660 107783395 107799082 107805981 107828474(GGH2)
NSY104220526 104249293
NTO104100144 104120726
NAU109206503 109206504 109229853
INI109188447(DR15) 109188449
ITR116005822
SIND105176926
OEU111370840
EGT105966772 105970294 105970361 105970363 105970364
SSPL121783415 121784903
HAN110912906
ECAD122592401 122599177
LSV111898963 111913893
CCAV112500606 112506641
DCR108220262
CSIN114263512
BVG104891329
SOE110786247 110795307
CQI110690162 110734036 110737819
NNU104586570 104591286
MING122058769
TSS122652236
PSOM113302144 113328845 113342758 113352792 113356356
NCOL116260413
OSA4339329
DOSAOs05t0517500-01(Os05g0517500)
OBR102700528
BDI100828890
ATS109747252
TDC119287156 119349013
TAES123063295 123140200 123182645
SBI8067519 8082979
ZMA100274493
SITA101782252
SVS117850729
PVIR120644125 120664914 120688409 120698113
PHAI112886673
PDA103708964
EGU105047475
MUS103989604
DCT110094990
PEQ110025254
AOF109848496
ATR18426350
SMOSELMODRAFT_109437 SELMODRAFT_177157 SELMODRAFT_423816
PPP112277717 112287009 112293995 112294850
CRECHLRE_06g275050v5 CHLRE_07g315050v5
VCNVOLCADRAFT_102798 VOLCADRAFT_106317
MNGMNEG_1386 MNEG_14015 MNEG_1646
CSLCOCSUDRAFT_31205 COCSUDRAFT_54091 COCSUDRAFT_64380
CVRCHLNCDRAFT_133025 CHLNCDRAFT_52559
APROF751_0355 F751_6351
MISMICPUN_76094
MBRMONBRDRAFT_29193
SREPTSG_00836 PTSG_07318
DDIDDB_G0286535(gghA) DDB_G0289365(gghB)
DPPDICPUDRAFT_31892 DICPUDRAFT_51633 DICPUDRAFT_73725
DFADFA_01284 DFA_11781(gghA)
ACANACA1_266910 ACA1_267110 ACA1_305550
TETTTHERM_000129409 TTHERM_00030360 TTHERM_000564438 TTHERM_00130000 TTHERM_00321670 TTHERM_00449200 TTHERM_00564450 TTHERM_00819530 TTHERM_01027470 TTHERM_01156850
PTMGSPATT00002255001 GSPATT00005223001 GSPATT00009190001 GSPATT00035342001 GSPATT00036518001 GSPATT00037241001 GSPATT00038899001
SMINv1.2.013270.t1(symbB.v1.2.013270.t1) v1.2.013687.t1(symbB.v1.2.013687.t1) v1.2.023128.t1(symbB.v1.2.023128.t1) v1.2.024246.t1(symbB.v1.2.024246.t1)
PTIPHATR_13333
PIFPITG_07349
PSOJPHYSODRAFT_359609
SPARSPRG_03486 SPRG_08278 SPRG_16945 SPRG_17396
EHXEMIHUDRAFT_68526 EMIHUDRAFT_78425
GTTGUITHDRAFT_72685
NGRNAEGRDRAFT_2938 NAEGRDRAFT_56320 NAEGRDRAFT_60907
 » show all
Reference
1
  Authors
McGuire, J.J. and Coward, J.K.
  Title
Pteroylpolyglutamates: biosynthesis, degradation and function.
  Journal
In: Blakley, R.L. and Benkovic, S.J. (Eds.), Folates and Pterins, John Wiley and Sons, New York, 1984, p. 135-191.
Reference
2  [PMID:8343522]
  Authors
Wang Y, Nimec Z, Ryan TJ, Dias JA, Galivan J.
  Title
The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma cells.
  Journal
Biochim Biophys Acta 1164:227-35 (1993)
DOI:10.1016/0167-4838(93)90253-N
  Sequence
[rno:25455]
Reference
3  [PMID:7565632]
  Authors
Yao R, Rhee MS, Galivan J.
  Title
Effects of gamma-glutamyl hydrolase on folyl and antifolylpolyglutamates in cultured H35 hepatoma cells.
  Journal
Mol Pharmacol 48:505-11 (1995)
Reference
4  [PMID:8816764]
  Authors
Yao R, Schneider E, Ryan TJ, Galivan J.
  Title
Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro.
  Journal
Proc Natl Acad Sci U S A 93:10134-8 (1996)
DOI:10.1073/pnas.93.19.10134
  Sequence
[hsa:8836]
Reference
5  [PMID:8621474]
  Authors
Yao R, Nimec Z, Ryan TJ, Galivan J
  Title
Identification, cloning, and sequencing of a cDNA coding for rat gamma-glutamyl hydrolase.
  Journal
J Biol Chem 271:8525-8 (1996)
DOI:10.1074/jbc.271.15.8525
  Sequence
[rno:25455]
Reference
6  [PMID:15961386]
  Authors
Orsomando G, de la Garza RD, Green BJ, Peng M, Rea PA, Ryan TJ, Gregory JF 3rd, Hanson AD
  Title
Plant gamma-glutamyl hydrolases and folate polyglutamates: characterization, compartmentation, and co-occurrence in vacuoles.
  Journal
J Biol Chem 280:28877-84 (2005)
DOI:10.1074/jbc.M504306200
Reference
7  [PMID:18757550]
  Authors
Akhtar TA, McQuinn RP, Naponelli V, Gregory JF 3rd, Giovannoni JJ, Hanson AD
  Title
Tomato gamma-glutamylhydrolases: expression, characterization, and evidence for heterodimer formation.
  Journal
Plant Physiol 148:775-85 (2008)
DOI:10.1104/pp.108.124479
Other DBs
ExplorEnz - The Enzyme Database: 3.4.19.9
IUBMB Enzyme Nomenclature: 3.4.19.9
ExPASy - ENZYME nomenclature database: 3.4.19.9
BRENDA, the Enzyme Database: 3.4.19.9
CAS: 9074-87-7

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