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
HSA: 8836(GGH)
PTR: 464204(GGH)
PPS: 100969380(GGH)
GGO: 101150735(GGH)
PON: 100435664(GGH)
NLE: 100595851(GGH)
MCC: 700747(GGH)
MCF: 102126049(GGH)
CSAB: 103236874(GGH)
CATY: 105585198(GGH)
PANU: 101017510(GGH)
RRO: 104660106(GGH)
RBB: 108543162(GGH)
TFN: 117079021(GGH)
PTEH: 111549272(GGH)
CJC: 100415059(GGH)
SBQ: 101047923(GGH)
MMUR: 105858423(GGH)
MMU: 14590(Ggh)
MCAL: 110292984(Ggh)
MPAH: 110338856(Ggh)
RNO: 25455(Ggh)
MCOC: 116088030(Ggh)
MUN: 110565305(Ggh)
CGE: 100751581(Ggh)
PLEU: 114690070(Ggh)
NGI: 103737737(Ggh)
HGL: 101724155(Ggh)
CPOC: 100719750(Ggh)
CCAN: 109698223(Ggh)
OCU: 100350070(GGH)
OPI: 101527903(GGH)
TUP: 102485618(GGH)
CFA: 100856436(GGH)
VVP: 112929757(GGH)
VLG: 121498767(GGH)
AML: 100482891(GGH)
UMR: 103677471(GGH)
UAH: 113268062(GGH)
ORO: 101373905(GGH)
ELK: 111155475
MPUF: 101684113(GGH)
EJU: 114213492(GGH)
MLX: 118014862(GGH)
FCA: 101100943(GGH)
PYU: 121038202(GGH)
PBG: 122495452(GGH)
PTG: 102970330(GGH)
PPAD: 109250251(GGH)
AJU: 106988829(GGH)
HHV: 120246941(GGH)
BTA: 525303(GGH)
BOM: 102276825(GGH)
BIU: 109568566(GGH)
BBUB: 102416206(GGH)
CHX: 102190334(GGH)
OAS: 101118706(GGH)
ODA: 120878613(GGH)
CCAD: 122451112(GGH)
SSC: 100154232(GGH)
CFR: 102507789(GGH)
CBAI: 105081466(GGH)
CDK: 105094475(GGH)
BACU: 103016741(GGH)
LVE: 103090393(GGH)
OOR: 101273875(GGH)
DLE: 111185619(GGH)
PCAD: 102976253(GGH)
PSIU: 116742760(GGH)
ECB: 100052567(GGH)
EPZ: 103553263(GGH)
EAI: 106834311(GGH)
MYB: 102240048(GGH)
MYD: 102768461(GGH)
MMYO: 118670881(GGH)
MLF: 102425869(GGH)
MNA: 107526439(GGH)
PKL: 118718304(GGH)
HAI: 109375951(GGH)
DRO: 112315497(GGH)
SHON: 118995507(GGH)
AJM: 119040494(GGH)
PDIC: 114514678(GGH)
MMF: 118631705(GGH)
RFQ: 117034021(GGH)
PALE: 102886790(GGH)
PGIG: 120607206(GGH)
RAY: 107521315(GGH)
MJV: 108385737(GGH)
TOD: 119241085(GGH)
LAV: 100671079(GGH)
TMU: 101347582
MDO: 100029624(GGH)
GAS: 123253406(GGH)
SHR: 100922531(GGH)
PCW: 110219063(GGH)
OAA: 100082379(GGH)
GGA: 421144(GGH)
PCOC: 116242169(GGH)
MGP: 100540892(GGH)
CJO: 107310260(GGH)
NMEL: 110394036(GGH)
APLA: 101790897(GGH)
ACYG: 106039060(GGH)
TGU: 100220150(GGH)
LSR: 110484740(GGH)
SCAN: 103816283(GGH)
PMOA: 120499222(GGH)
OTC: 121340354(GGH)
PRUF: 121356883(GGH)
GFR: 102038404(GGH)
FAB: 101814012(GGH)
PHI: 102105349(GGH)
PMAJ: 107200637(GGH)
CCAE: 111924794(GGH)
CCW: 104692925(GGH)
ETL: 114062627(GGH)
FPG: 101919182(GGH)
FCH: 102055448(GGH)
CLV: 102087830(GGH)
EGZ: 104122047(GGH)
NNI: 104010542(GGH)
ACUN: 113476136(GGH)
PADL: 103923701(GGH)
AAM: 106494371(GGH)
AROW: 112960446(GGH)
NPD: 112944771(GGH)
DNE: 112986697(GGH)
ASN: 102387582(GGH)
AMJ: 102558989(GGH)
CPOO: 109315539(GGH)
GGN: 109304918(GGH)
PSS: 102460960(GGH)
CMY: 102935783(GGH)
CPIC: 101933582 101939707(GGH)
TST: 117871823(GGH) 117873525
CABI: 116835020(GGH) 116835024
MRV: 120396693(GGH) 120398947
ACS: 100563793(ggh)
PVT: 110088990(GGH)
SUND: 121929266(GGH)
PBI: 103066894(GGH)
PMUR: 107302720(GGH)
TSR: 106543965(GGH)
PGUT: 117672835(GGH)
VKO: 123020532(GGH)
PMUA: 114600570(GGH)
ZVI: 118090197(GGH)
GJA: 107110867(GGH)
XLA: 444589(ggh.L) 496099(ggh.2.L)
XTR: 100490929 594986(ggh)
NPR: 108796604(GGH) 108800416
DRE: 406624(ggh) 553228 563836
IPU: 108265017 108267579(GGH) 108281015(Ggh)
TRU: 101066803(ggh) 101071237
LCM: 102357327
CMK: 103180721
BBEL: 109484058
APLC: 110980374
DME: Dmel_CG32155(l(3)72Dp)
DSE: 6605895
DSI: Dsimw501_GD14608(Dsim_GD14608)
DGR: 6557649
DVI: 6623638
CCAT: 101459395
BOD: 106616995
SCAC: 106081973
ACOZ: 120950002
AARA: 120896072
AAG: 5573776
CPII: 120424879
BIM: 100742651
BBIF: 117214380
BVK: 117231476
BVAN: 117166538
BTER: 100651812
BPYO: 122572940
OBB: 114873242
MGEN: 117227279
NMEA: 116423959
CGIG: 122403188
SOC: 105196643
MPHA: 105833742
AEC: 105148388
ACEP: 105627444
PBAR: 105430931
VEM: 105565622
PGC: 109851946
PCF: 106793498
TPRE: 106650503
MDL: 103569120
CGLO: 123268800
DAM: 107045077
TCA: 659635
DPA: 109537699
ATD: 109605216
LDC: 111514295
PPYR: 116173930
BMOR: 101736547
BMAN: 114249578
MSEX: 115450911
PMAC: 106708714
PPOT: 106104540
PXU: 106121066
HAW: 110370080
TNL: 113496419
PXY: 105393491
FCD: 110848151
HAZT: 108675247
VDE: 111251856
VJA: 111268378
DPTE: 113790317
CSCU: 111634942
PTEP: 107448459
SDM: 118184332
PCAN: 112561388
CRG: 105317584
LAK: 106166411
ATH: AT1G78660(GGH1) AT1G78670(GGH3) AT1G78680(GGH2)
THJ: 104813997
CPAP: 110812565
MINC: 123209358
TCC: 18594335
GAB: 108480536
DZI: 111276559
GMX: 100796947 547881(GH)
APRC: 113853566
LJA: Lj0g3v0178769.1(Lj0g3v0178769.1) Lj0g3v0338049.1(Lj0g3v0338049.1)
ADU: 107459833
AIP: 107613260
FVE: 101290933
PPER: 18779010
PMUM: 103325967
PAVI: 110757564
PDUL: 117624639
ZJU: 107403905
MNT: 21386200
CMO: 103501819
CMAX: 111480987
CMOS: 111446777
CPEP: 111789236
RCU: 8288177
HBR: 110650012
JRE: 109011928
QSU: 112014043
QLO: 115955772
TWL: 119985976
VVI: 100262251
SLY: 100191133(GGH1) 100191134(GGH3) 100191135(GGH2)
INI: 109188447(DR15) 109188449
ITR: 116005822
SIND: 105176926
OEU: 111370840
HAN: 110912906
DCR: 108220262
CSIN: 114263512
BVG: 104891329
MING: 122058769
NCOL: 116260413
OSA: 4339329
DOSA: Os05t0517500-01(Os05g0517500)
OBR: 102700528
BDI: 100828890
ATS: 109747252
ZMA: 100274493
SITA: 101782252
PHAI: 112886673
PDA: 103708964
EGU: 105047475
MUS: 103989604
DCT: 110094990
PEQ: 110025254
AOF: 109848496
ATR: 18426350
DDI: DDB_G0286535(gghA) DDB_G0289365(gghB)
DFA: DFA_01284 DFA_11781(gghA)
SMIN: v1.2.013270.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)
 » 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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