Any feedback?
Information on EC 1.8.3.7 - formylglycine-generating enzyme and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC1.8.3.7Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.8.3.7 formylglycine-generating enzymeIUBMB Comments
Requires a copper cofactor and Ca2+. The enzyme, which is found in both prokaryotes and eukaryotes, catalyses a modification of a conserved L-cysteine residue in the active site of sulfatases, generating a unique 3-oxo-L-alanine residue that is essential for sulfatase activity. The exact nature of the thiol involved is still not clear - dithiothreitol and cysteamine are the most efficiently used thiols in vitro. Glutathione alo acts in vitro, but it is not known whether it is used in vivo.
Specify your search results
Word Map
- 1.8.3.7
-
sulfatases
-
metachromatic
- mucopolysaccharidosis
- leukodystrophy
-
ichthyosis
-
antibody-drug
-
ultra-rare
- morquio
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
a [sulfatase]-L-cysteine
+
+
2
=
a [sulfatase]-3-oxo-L-alanine
+
+
+
Synonyms
sumf1, formylglycine-generating enzyme, formylglycine generating enzyme, sulfatase-modifying factor 1, fgly-generating enzyme, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Calpha-formylglycine-generating enzyme 1
-
-
-
-
FGE
sulfatase-modifying factor 1
SUMF1
FGE
-
sulfatase-modifying factor 1
-
-
-
-
SUMF1
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
[sulfatase]-L-cysteine:oxygen oxidoreductase (3-oxo-L-alanine-forming)
Requires a copper cofactor and Ca2+. The enzyme, which is found in both prokaryotes and eukaryotes, catalyses a modification of a conserved L-cysteine residue in the active site of sulfatases, generating a unique 3-oxo-L-alanine residue that is essential for sulfatase activity. The exact nature of the thiol involved is still not clear - dithiothreitol and cysteamine are the most efficiently used thiols in vitro. Glutathione alo acts in vitro, but it is not known whether it is used in vivo.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a [sulfatase]-L-cysteine + O(2) + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
a [sulfatase]-L-cysteine + O2 + 2 a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
preference of the enzyme for CXPXR-type motifs
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
Ac-AL-3-oxo-L-Ala-TPSRGSLFTGR-NH2 + hydrogen sulfide + oxidized dithiothreitol + H2O
?
-
-
-
?
Ac-EQSCTAGRAAFITGQGLCTPSRAG-NH2 + O2 + reduced dithiothreitol
? + hydrogen sulfide + oxidized dithiothreitol + H2O
accepts the sequence CTPSR. The human enzyme strictly converts proline-containing aldehyde tags, either in vivo or in vitro, whereas in the presence of copper, the enzyme fom Streptomyces coelicolor and Mycobacterium tuberculosis tolerate proline-to-alanine substitutions in the core motif
-
-
?
a [sulfatase]-L-cysteine + O(2) + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O(2) + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a [sulfatase]-L-cysteine + O(2) + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
a [sulfatase]-L-cysteine + O(2) + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O(2) + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
-
?
a [sulfatase]-L-cysteine + O2 + a thiol
a [sulfatase]-3-oxo-L-alanine + hydrogen sulfide + a disulfide + H2O
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cu2+
the enzyme contains a copper cofactor. The purified enzyme requires preactivation with copper
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Cu2+
the substrate specificity for the cysteine motifs CTPS is not changed upon addition of the cofactor copper
additional information
proprotein convertases like furin, PACE4, and PC5a process and thereby inactivate formylglycine-generating enzyme
-
additional information
-
proprotein convertases like furin, PACE4, and PC5a process and thereby inactivate formylglycine-generating enzyme
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
O2
for maximal activity the enzyme requires an O2 concentration of 9% (0.105 mM)
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
malfunction
-
enzyme dysfunction causes a lysosomal storage disorder known as multiple sulfatase deficiency, where all sulfatases either lack or suffer from a severely reduced, catalytic activity caused by incomplete generation of formylglycine
malfunction
enzyme inactivity results in multiple sulfatase deficiency, a fatal autosomal recessive syndrome
malfunction
multiple sulfatase deficiency is caused by mutations in the SUMF1 gene encoding the formylglycine-generating enzyme
malfunction
-
structural distortions due to missense mutations in human formylglycine-generating enzyme lead to multiple sulfatase deficiency
metabolism
enzyme overexpression stimulates the generation of catalytically active sulfatases
metabolism
the enzyme posttranslationally activates sulfatases by generating formylglycine in their catalytic sites
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SUMF1_HUMAN
374
0
40556
Swiss-Prot
Secretory Pathway (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with bromide and iodide ions, using 20-25% (w/v) PEG 4000, 0.1 M Tris-HCl pH 8.0-9.0, 0.2-0.3 M CaCl2
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A177P
A279V
A348P
C218Y
C336R
C336S
E130D
N259I
P266L
R224W
R345C
R349Q
R349W
S155P
W179S
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
HisTrap Excel resin column chromatography and Sephadex G-25 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
medicine
-
coexpression of formylglycine-generating enzyme is essential for gene therapy of metachromatic leukodystrophy
biotechnology
site-specific bioconjugation. Formylglycine-generating enzymes allow to posttranslationally introduce the amino acid Calpha-formylglycine (FGly) into recombinant proteins, starting from cysteine or serine residues within distinct consensus motifs
biotechnology
site-specific conjugation strategy for dual antibody-drug conjugates using aerobic formylglycine-generating enzymes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Dierks, T.; Schmidt, B.; Borissenko, L.V; Peng, J.; Preusser, A.; Mariappan, M.; von Figura, K.
Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme
Cell
113
435-444
2003
Homo sapiens (Q8NBK3)
Dierks, T.; Dickmanns, A.; Preusser-Kunze, A.; Schmidt, B.; Mariappan. M.; von Figura, K.; Ficner, R.; Rudolph, M.G.
Molecular Basis or Multiple Sulfatase Deficiency and Mechanism for Formylglycine Generation of the Human Formylglycine-Generating Enzyme
Cell
121
541-552
2005
Homo sapiens (Q8NBK3), Homo sapiens
Roeser, D.; Schmidt, B.; Preusser-Kunze, A.; Rudolph, M.G.
Probing the oxygen-binding site of the human formylglycine-generating enzyme using halide ions
Acta Crystallogr. Sect. D
63
621-627
2007
Homo sapiens (Q8NBK3), Homo sapiens
Dierks, T.; Dickmanns, A.; Preusser-Kunze, A.; Schmidt, B.; Mariappan, M.; von Figura, K.; Ficner, R.; Rudolph, M.G.
Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme
Cell
121
541-552
2005
Homo sapiens (Q8NBK3), Homo sapiens
Bojarova, P.; Williams, S.
Sulfotransferases, sulfatases and formylglycine-generating enzymes a sulfation fascination
Curr. Opin. Chem. Biol.
12
573-581
2008
Homo sapiens
Schlotawa, L.; Radhakrishnan, K.; Baumgartner, M.; Schmid, R.; Schmidt, B.; Dierks, T.; Gaertner, J.
Rapid degradation of an active formylglycine generating enzyme variant leads to a late infantile severe form of multiple sulfatase deficiency
Eur. J. Hum. Genet.
21
1020-1023
2013
Homo sapiens (Q8NBK3), Homo sapiens
Gande, S.L.; Mariappan, M.; Schmidt, B.; Pringle, T.H.; von Figura, K.; Dierks, T.
Paralog of the formylglycine-generating enzyme - retention in the endoplasmic reticulum by canonical and noncanonical signals
FEBS J.
275
1118-1130
2008
Homo sapiens (Q8NBK3), Homo sapiens
Peng, J.; Alam, S.; Radhakrishnan, K.; Mariappan, M.; Rudolph, M.G.; May, C.; Dierks, T.; von Figura, K.; Schmidt, B.
Eukaryotic formylglycine-generating enzyme catalyses a monooxygenase type of reaction
FEBS J.
282
3262-3274
2015
Homo sapiens (Q8NBK3)
Takakusaki, Y.; Hisayasu, S.; Hirai, Y.; Shimada, T.
Coexpression of formylglycine-generating enzyme is essential for synthesis and secretion of functional arylsulfatase A in a mouse model of metachromatic leukodystrophy
Hum. Gene Ther.
16
929-936
2005
Homo sapiens
Schlotawa, L.; Steinfeld, R.; von Figura, K.; Dierks, T.; Gaertner, J.
Molecular analysis of SUMF1 mutations stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency
Hum. Mutat.
29
205
2008
Homo sapiens (Q8NBK3)
Mariappan, M.; Preusser-Kunze, A.; Balleininger, M.; Eiselt, N.; Schmidt, B.; Gande, S.L.; Wenzel, D.; Dierks, T.; von Figura, K.
Expression, localization, structural, and functional characterization of pFGE, the paralog of the Calpha-formylglycine-generating enzyme
J. Biol. Chem.
280
15173-15179
2005
Homo sapiens (Q8NBK3)
Dickmanns, A.; Schmidt, B.; Rudolph, M.G.; Mariappan, M.; Dierks, T.; von Figura, K.; Ficner, R.
Crystal structure of human pFGE, the paralog of the Calpha-formylglycine-generating enzyme
J. Biol. Chem.
280
15180-15187
2005
Homo sapiens (Q8NBK3), Homo sapiens
Mariappan, M.; Gande, S.L.; Radhakrishnan, K.; Schmidt, B.; Dierks, T.; von Figura, K.
The non-catalytic N-terminal extension of formylglycine-generating enzyme is required for its biological activity and retention in the endoplasmic reticulum
J. Biol. Chem.
283
11556-11564
2008
Homo sapiens (Q8NBK3)
Mariappan, M.; Radhakrishnan, K.; Dierks, T.; Schmidt, B.; von Figura, K.
ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum
J. Biol. Chem.
283
6375-6383
2008
Homo sapiens (Q8NBK3)
Ennemann, E.C.; Radhakrishnan, K.; Mariappan, M.; Wachs, M.; Pringle, T.H.; Schmidt, B.; Dierks, T.
Proprotein convertases process and thereby inactivate formylglycine-generating enzyme
J. Biol. Chem.
288
5828-5839
2013
Homo sapiens (Q8NBK3), Homo sapiens
Holder, P.G.; Jones, L.C.; Drake, P.M.; Barfield, R.M.; Banas, S.; de Hart, G.W.; Baker, J.; Rabuka, D.
Reconstitution of formylglycine-generating enzyme with copper(II) for aldehyde tag conversion
J. Biol. Chem.
290
15730-15745
2015
Homo sapiens (Q8NBK3), Streptomyces coelicolor (Q9F3C7)
Meshach Paul, D.; Chadah, T.; Senthilkumar, B.; Sethumadhavan, R.; Rajasekaran, R.
Structural distortions due to missense mutations in human formylglycine-generating enzyme leading to multiple sulfatase deficiency
J. Biomol. Struct. Dyn.
36
3575-3585
2017
Homo sapiens
Roeser, D.; Preusser-Kunze, A.; Schmidt, B.; Gasow, K.; Wittmann, J.G.; Dierks, T.; von Figura, K.; Rudolph, M.G.
A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme
Proc. Natl. Acad. Sci. USA
103
81-86
2006
Homo sapiens (Q8NBK3), Homo sapiens
Boschanski, M.; Krueger, T.; Karsten, L.; Falck, G.; Alam, S.; Gerlach, M.; Mueller, B.; Mueller, K.M.; Sewald, N.; Dierks, T.
Site-specific conjugation strategy for dual antibody-drug conjugates using aerobic formylglycine-generating enzymes
Bioconjug. Chem.
32
1167-1174
2021
Mycobacterium tuberculosis, Streptomyces coelicolor, Homo sapiens (Q8NBK3)
EXTERNAL LINKS (specific for EC-Number 1.8.3.7)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
