Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 1.5.1.6 - formyltetrahydrofolate dehydrogenase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC1.5.1.6
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
aldh1l1, 10-formyltetrahydrofolate dehydrogenase, aldh1l2, 10-fthfdh, formyltetrahydrofolate dehydrogenase, mtfdh, 10-fdh, 10-formyl-h4folate dehydrogenase, 10-fthf dehydrogenase, n10-formyltetrahydrofolate dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10-FDH
-
-
-
-
10-formyl tetrahydrofolate:NADP oxidoreductase
-
-
-
-
10-formyl-H2PtGlu:NADP oxidoreductase
-
-
-
-
10-formyl-H4folate dehydrogenase
-
-
-
-
10-formyltetrahydrofolate dehydrogenase
10-fTHF dehydrogenase
-
-
10-FTHFDH
-
-
-
-
ALDH1L2
dehydrogenase, formyltetrahydrofolate
-
-
-
-
FBP-CI
-
-
-
-
FBP-CI proteins
-
-
-
-
folate-binding proteins, cytosol I
-
-
-
-
mtFDH
-
mitochondrial isoform
N10-formyltetrahydrofolate dehydrogenase
-
-
-
-
proteins, folate-binding, cytosol I
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
10-formyltetrahydrofolate:NADP+ oxidoreductase
-
CAS REGISTRY NUMBER
COMMENTARY hide
37256-25-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
10-formyltetrahydrofolate + NADP+ + H2O
tetrahydrofolate + CO2 + NADPH + H+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
10-formyltetrahydrofolate
-
10-formyltetrahydrofolate
tetrahydrofolate
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4'-phosphopantetheinyl transferase
-
4'-phosphopantetheinyl transferase activates dehydrogenase catalysis of ALDH1L2 by modifying Ser375
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0114 - 0.05
10-formyltetrahydrofolate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
assay at room temperature
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
transformed embryonic kidney cell line HEK-293A
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
much lower levels than in liver, preferentially localized in Müller cells, FDH levels in human retina are higher than in rat retina, folate levels in human retina are 14% of those in rat retina
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
-
moderate FDH mRNA level
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
FDH induces apoptosis in PC-3 prostate cells through simultaneous activation of the c-Jun-NH2-kinase JNK and extracellular signal-regulated kinase ERK pathways with JNK phosphorylating c-Jun and ERK1/2 phosphorylating Elk-1. The JNK1/2 inhibitor SP600125 or ERK1/2 inhibitor PD98059 prevents phosphorylation of c-Jun and Elk-1, correspondingly and partially protects PC-3 cells from FDH-induced cytotoxicity. Combination of the two inhibitors produces an additive effect. The FDH-induced apoptosis in p53-proficient A-549 cells also proceeds through activation of JNK1/2, but the down-stream target for JNK2 is p53 instead of c-Jun. In A-549 cells, FDH activates caspase 9, whereas in PC-3 cells, it activates caspase 8
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
AL1L1_HUMAN
902
0
98829
Swiss-Prot
other Location (Reliability: 2)
AL1L2_HUMAN
923
0
101746
Swiss-Prot
Mitochondrion (Reliability: 2)
B4DTU7_HUMAN
923
0
101716
TrEMBL
Mitochondrion (Reliability: 2)
Q53H87_HUMAN
902
0
98857
TrEMBL
other Location (Reliability: 2)
Q59G10_HUMAN
954
0
104099
TrEMBL
Mitochondrion (Reliability: 4)
Q53HP5_HUMAN
902
0
98803
TrEMBL
other Location (Reliability: 2)
A0A0S2Z586_HUMAN
505
0
55394
TrEMBL
other Location (Reliability: 2)
Q6ZV71_HUMAN
470
0
50830
TrEMBL
Mitochondrion (Reliability: 3)
A0A0S2Z527_HUMAN
555
0
61148
TrEMBL
other Location (Reliability: 2)
A0A494C1M4_HUMAN
932
0
102850
TrEMBL
Mitochondrion (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
-
full-length enzyme, gel filtration
130000
x * 130000, green fluorescent protein fusion construct, SDS-PAGE
14500
-
4 * 14500, C-terminal domain, SDS-PAGE
58000
-
C-terminal domain, gel filtration
96000
-
x * 96000, SDS-PAGE
98700
-
x * 98700, protein with 902 amino acids, calculated from cDNA
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
-
4 * 14500, C-terminal domain, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospholipoprotein
-
the broad specificity human 4-phosphopantetheinyl transferase phosphopantetheinylates apo-FDH to holoenzyme and thus activates FDH catalysis. Silencing 4-phosphopantetheinyl transferase by small interfering RNA in A-549 cells prevents FDH modification
proteolytic modification
sequence contains a 22 amino acid N-terminal mitochondrial translocation signal
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C707A
-
catalytically inactive mutant
S374A
-
the mutant is activated by 4'-phosphopantetheinyl transferase
S374A/S375A
-
the mutant is not activated by 4'-phosphopantetheinyl transferase
S375A
-
the mutant is not activated by 4'-phosphopantetheinyl transferase
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in general activity is labile
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
free of 10-formyltetrahydrofolate hydrolase activity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning and sequencing of the cDNA encoding FDH from fetal liver
-
cloning of the cDNA encoding FDH, cells from several tumor cell lines are transfected with FDH cDNA cloned into pcDNA 3.1+ vector using LipofectAMINE, expression of FDH inhibits the proliferation of the cell lines as a result of its enzymatic activity
-
expressed in Escherichia coli BL21(DE3) Codon Plus cells
-
expression in Escherichia coli
-
transfection of COS-7 and A-549 cells, and expression with green fluorescent protein fusion construct
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Johlin, F.C.; Swain, E.; Smith, C.; Tephly, T.R.
Studies on the mechanism of methanol poisoning: purification and comparison of rat and human liver 10-formyltetrahydrofolate dehydrogenase
Mol. Pharmacol.
35
745-750
1989
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Hong, M.; Lee, Y.; Kim, J.W.; Lim, J.S.; Chang, S.Y.; Lee, K.S.; Paik, S.G.; Choe, I.S.
Isolation and characterization of cDNA clone for human liver 10-formyltetrahydrofolate dehydrogenase
Biochem. Mol. Biol. Int.
47
407-415
1999
Homo sapiens
Manually annotated by BRENDA team
Krupenko, S.A.; Oleinik, N.V.
10-Formyltetrahydrofolate dehydrogenase, one of the major folate enzymes, is down-regulated in tumor tissues and possesses suppressor effects on cancer cells
Cell Growth Differ.
13
227-236
2002
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Martinasevic, M.K.; Green, M.D.; Baron, J.; Tephly, T.R.
Folate and 10-formyltetrahydrofolate dehydrogenase in human and rat retina: Relation to methanol toxicity
Toxicol. Appl. Pharmacol.
141
373-381
1996
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Oleinik, N.V.; Krupenko, S.A.
Ectopic expression of 10-formyltetrahydrofolate dehydrogenase in A549 cells induces G1 cell cycle arrest and apoptosis
Mol. Cancer Res.
1
577-588
2003
Homo sapiens
Manually annotated by BRENDA team
Oleinik, N.V.; Krupenko, N.I.; Priest, D.G.; Krupenko, S.A.
Cancer cells activate p53 in response to 10-formyltetrahydrofolate dehydrogenase expression
Biochem. J.
391
503-511
2005
Homo sapiens
Manually annotated by BRENDA team
Strickland, K.C.; Hoeferlin, L.A.; Oleinik, N.V.; Krupenko, N.I.; Krupenko, S.A.
Acyl carrier protein-specific 4-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase
J. Biol. Chem.
285
1627-1633
2010
Homo sapiens
Manually annotated by BRENDA team
Krupenko, N.I.; Dubard, M.E.; Strickland, K.C.; Moxley, K.M.; Oleinik, N.V.; Krupenko, S.A.
ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase
J. Biol. Chem.
285
23056-23063
2010
Homo sapiens (O75891), Homo sapiens (Q3SY69), Homo sapiens
Manually annotated by BRENDA team
Ghose, S.; Oleinik, N.V.; Krupenko, N.I.; Krupenko, S.A.
10-formyltetrahydrofolate dehydrogenase-induced c-Jun-NH2-kinase pathways diverge at the c-Jun-NH2-kinase substrate level in cells with different p53 status
Mol. Cancer Res.
7
99-107
2009
Homo sapiens
Manually annotated by BRENDA team
Strickland, K.C.; Krupenko, N.I.; Dubard, M.E.; Hu, C.J.; Tsybovsky, Y.; Krupenko, S.A.
Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase
Chem. Biol. Interact.
191
129-136
2011
Homo sapiens
Manually annotated by BRENDA team