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Information on EC 3.4.22.40 - bleomycin hydrolase and Organism(s) Homo sapiens and UniProt Accession Q13867
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3.4.22.40 bleomycin hydrolaseSpecify your search results
Word Map
- 3.4.22.40
-
luteinizing
- paraoxonase
- thiolactone
- helveticus
- peplomycin
-
lutropins
- corneocytes
-
homocysteinylation
- beta-naphthylamide
- medicine
-
hcy-thiolactone
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Inactivates bleomycin B2 (a cytotoxic glycometallopeptide) by hydrolysis of a carboxyamide bond of beta-aminoalanine, but also shows general aminopeptidase activity. The specificity varies somewhat with source, but amino acid arylamides of Met, Leu and Ala are preferred
Synonyms
blh, bleomycin hydrolase, blm hydrolase, htlase, homocysteine thiolactonase, hcy-thiolactonase, aminopeptidase c, aminopeptidase h, hydrolase h, gal6p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminopeptidase C
-
-
-
-
aminopeptidase H
-
-
-
-
BANA-hydrolase
-
-
-
-
Bleomycin hydrolase
-
-
-
-
Blh1p
-
-
-
-
BLM hydrolase
-
-
-
-
BMH
Gal6p
-
-
-
-
Hcy-thiolactonase
-
the bleomycin hydrolase is identical with the homocysteine thiolactonase, overview
homocysteine thiolactonase
-
the bleomycin hydrolase is identical with the homocysteine thiolactonase, overview
HTLase
-
the bleomycin hydrolase is identical with the homocysteine thiolactonase, overview
hydrolase H
-
-
-
-
PEPC
-
-
-
-
BMH
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
53096-17-6
-
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
6'-deoxy bleomycin A2 + H2O
6'-deoxy deamido bleomycin A2 + NH3
recombinant enzyme shows rapid and efficient hydrolysis of all bleomycins tested, exhibiting a superior catalytic efficiency for bleomycin B2
-
-
?
6'-deoxy bleomycin Z + H2O
6'-deoxy deamido bleomycin Z + NH3
recombinant enzyme shows rapid and efficient hydrolysis of all bleomycins tested, exhibiting a superior catalytic efficiency for bleomycin B2
-
-
?
bleomycin Z + H2O
deamido bleomycin Z + NH3
recombinant enzyme shows rapid and efficient hydrolysis of all bleomycins tested, exhibiting a superior catalytic efficiency for bleomycin B2
-
-
?
citrulline-4-methylcoumarin 7-amide + H2O
citrulline + 7-amino-4-methylcoumarin
-
-
-
-
?
citrulline-7-amido-4-methylcoumarin + H2O
citrulline + 7-amino-4-methylcoumarin
-
-
-
-
?
huntingtin + H2O
?
-
the enzyme is involved in a specific cleavage step at the N-terminal fragment cp-2 site of huntingtin
-
-
?
bleomycin A2 + H2O
deamido bleomycin A2 + NH3
the enzyme hydrolyzes bleomycins into the biologically inactive deamido bleomycins
-
-
?
bleomycin A2 + H2O
deamido bleomycin A2 + NH3
recombinant enzyme shows rapid and efficient hydrolysis of all bleomycins tested, exhibiting a superior catalytic efficiency for bleomycin B2
-
-
?
bleomycin B2 + H2O
deamido bleomycin B2 + NH3
the enzyme hydrolyzes bleomycins into the biologically inactive deamido bleomycins
-
-
?
bleomycin B2 + H2O
deamido bleomycin B2 + NH3
recombinant enzyme shows rapid and efficient hydrolysis of all bleomycins tested, exhibiting a superior catalytic efficiency for bleomycin B2
-
-
?
bleomycin + H2O
?
-
bleomycin is a cytotoxic agent inducing pneumonitis, detoxification reaction
-
-
?
bleomycin + H2O
?
-
detoxification reaction, high enzyme expression level leads to resistance against the drug
-
-
?
deiminated filaggrin + H2O
?
-
neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids
-
-
?
deiminated filaggrin + H2O
?
-
recombinant human filaggrin is a component of the cornified cell envelope and the precursor of free amino acids acting as a natural moisturizing factor in the stratum corneum. Profilaggrin is synthesized as a large, extremely insoluble phosphoprotein. Deimination is critical for the degradation of filaggrin into free amino acids, deimination of filaggrin is catalyzed by murine PAD3
-
-
?
additional information
?
-
bleomycin hydrolase as an essential component of chemotherapy regimens for disseminated testicular germ-cell cancer analyzed, study on relation of single nucleotide polymorphism (SNP) A1450G of the bleomycin hydrolase gene with survival according to genotype analyzed
-
-
?
additional information
?
-
-
bleomycin hydrolase as an essential component of chemotherapy regimens for disseminated testicular germ-cell cancer analyzed, study on relation of single nucleotide polymorphism (SNP) A1450G of the bleomycin hydrolase gene with survival according to genotype analyzed
-
-
?
additional information
?
-
-
the enzyme exhibits protection against homocysteine toxicity, role and mechanisms of bleomycin hydrolase, overview
-
-
?
additional information
?
-
-
the substrate specificity is controlled by the opening of the barrel structure and the positioning of the enzyme's C-terminus in the active site as opposed to the features of the substrate, mechanism, overview
-
-
?
additional information
?
-
-
bleomycin hydrolase is a neutral cysteine protease, the enzyme releases various amino acids except Pro from beta-naphthylamide derivatives and hydrolyzed citrulline-beta-naphthylamide most effectively, overview
-
-
?
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
bleomycin A2 + H2O
deamido bleomycin A2 + NH3
the enzyme hydrolyzes bleomycins into the biologically inactive deamido bleomycins
-
-
?
bleomycin B2 + H2O
deamido bleomycin B2 + NH3
the enzyme hydrolyzes bleomycins into the biologically inactive deamido bleomycins
-
-
?
deiminated filaggrin + H2O
?
-
neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids
-
-
?
huntingtin + H2O
?
-
the enzyme is involved in a specific cleavage step at the N-terminal fragment cp-2 site of huntingtin
-
-
?
additional information
?
-
-
the enzyme exhibits protection against homocysteine toxicity, role and mechanisms of bleomycin hydrolase, overview
-
-
?
bleomycin + H2O
?
-
bleomycin is a cytotoxic agent inducing pneumonitis, detoxification reaction
-
-
?
bleomycin + H2O
?
-
detoxification reaction, high enzyme expression level leads to resistance against the drug
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
response to chemotherapy dependent on gene polymorphism of bleomycin hydrolase analyzed, homozygous variant G/G of bleomycin hydrolase gene SNP A1450G associated with reduced survival and higher prevalence of early relapses in testicular germ-cell cancer patients treated with bleomycin-containing chemotherapy
additional information
-
response to chemotherapy dependent on gene polymorphism of bleomycin hydrolase analyzed, homozygous variant G/G of bleomycin hydrolase gene SNP A1450G associated with reduced survival and higher prevalence of early relapses in testicular germ-cell cancer patients treated with bleomycin-containing chemotherapy
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
encoded by Blmh gene; patient study, testicular germ-cell cancer
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
testicular germ-cell cancer, response to chemotherapy dependent on gene polymorphism of bleomycin hydrolase analyzed
-
the enzyme co-localizes with fillagrin in the granular layer, immunohistochemic analysis
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
Ubc9 plays different roles of action in antitumor agents in chemotherapy. The process requires bleomycin hydrolase and poly(ADP-ribose) polymerase-1
malfunction
malfunction
-
knockdown of bleomycin hydrolase reduces cp-2 cleavage, and ameliorates mutant huntingtin induced toxicity
malfunction
-
the sensitivity to bleomycin is increased in HeLa cells after knockdown of bleomycin hydrolase
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). BLMH_HUMAN
455
0
52562
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C73S
-
ectopic expression of enzyme increases the secretion of amyloid precursor protein, increase is blocked in mutant
truncated C-terminus
-
C-terminus is essential for protection against bleomycin induced chromatin breaks
V443I
-
the naturally occurring polymorphism of the gene encoding the enzyme is associated to sporadic Alzheimer's disease and to the amyloid precursor protein
additional information
-
naturally occurring polymorphism A1450G in the BMH gene, causing a C-terminal amino acid substitution, is not responsible for development of bleomycin-induced pneumonitis, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme 4300fold from newborn rat epidermis by gel filtration, and two steps of anion exchange chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography to homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
determination of DNA sequence and genotypes in 340 different male germ cell probes
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
bleomycin hydrolase expression is up-regulated via IRF-1/2, MZF-1 and Sp-1. mRNA is up-regulated in keratinocytes when cultured at high calcium concentration (6.8fold)
-
interferon-gamma significantly reduces the expression of bleomycin hydrolase. The enzyme activity and expression are markedly decreased in atopic dermatitis lesional and non-lesional skin (to 27.1 and 8.8%, respectively)
-
interleukin-4 does not show any direct effect on bleomycin hydrolase expression
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
medicine
patient study, patients with testicular germ-cell cancer treated with bleomycin-containing chemotherapy, response to chemotherapy determined by gene polymorphisms involved in metabolism of cytotoxic drugs analyzed, importance for risk classification and selection for alternative treatment strategies suggested
medicine
the bleomycins (BLMs) are widely used in combination therapies for the treatment of various cancers. Dose-dependent and cumulative pulmonary toxicity is the major cause of BLM-associated morbidity, limiting the broad uses of BLMs as anticancer drugs. Opportunities to overcome bleomycin-induced pulmonary toxicity in chemotherapies, potentially by exploring BLM B2 as the preferred congener, engineering designer bleomycins with optimized activity for recombinant human bleomycin hydrolase (rhBLMH), or co-administrating rhBLMH directly into the lung as a potential protein therapeutic
medicine
-
is thought to be the major cause of tumor cell resistance to bleomycin chemotherapy
medicine
-
ectopic expression of enzyme alters processing of amyloid precursor protein and increases significantly release of beta-amyloid
medicine
-
ectopic expression of enzyme increases the secretion of amyloid precursor protein, increase is blocked in mutant C73S
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lefterov, I.M.; Koldamova, R.P.; King, J.; Lazo, J.S.
The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage
Mutat. Res.
421
1-7
1998
Homo sapiens
Sebti, S.M.; Mignano, J.E.; Jani, J.P.; Srimatkandada, S.; Lazo, J.S.
Bleomycin hydrolase: molecular cloning, sequencing, and biochemical studies reveal membership in the cysteine proteinase family
Biochemistry
28
6544-6548
1989
Gallus gallus, Homo sapiens, Lithobates catesbeianus, Mus musculus, Oryctolagus cuniculus, Papio hamadryas, Rattus norvegicus
Broemme, D.; Rossi, A.B.; Smeekens, S.P.; Anderson, D.C.; Payan, D.G.
Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization
Biochemistry
35
6706-6714
1996
Homo sapiens
O'Farrel, P.; Gonzalez, F.; Zheng, W.; Johnston, S.A.; Joshua-Tor, L.
Crystal structure of human bleomycin hydrolase, a self-compartmentalizing cysteine protease
Structure Fold. Des.
15
619-627
1999
Homo sapiens
-
Lazo, J.S.; Boland, C.J.; Schwartz, P.E.
Bleomycin hydrolase activity and cytotoxicity in human tumors
Cancer Res.
42
4026-4031
1982
Homo sapiens
Lefterov, I.M.; Koldamova, R.P.; Lefterova, M.; Schwartz, D-R.; Lazo, J.S.
Cysteine 73 in bleomycin hydrolase is critical for amyloid precursor protein processing
Biochem. Biophys. Res. Commun.
283
994-999
2001
Homo sapiens
Lefterov, I.M.; Koldamova, R.P.; Lazo, J.S.
Human bleomycin hydrolase regulates the secretion of amyloid precursor protein
FASEB J.
14
1837-1847
2000
Homo sapiens
Joshua-Tor, L.; Johnston, S.A.
Bleomycin hydrolase
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. )Academic Press
2
1197-1201
2004
Saccharomyces cerevisiae, Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus, Streptomyces verticillus
-
Zimny, J.; Sikora, M.; Guranowski, A.; Jakubowski, H.
Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase
J. Biol. Chem.
281
22485-22492
2006
Homo sapiens, Saccharomyces cerevisiae
Nuver, J.; Lutke Holzik, M.F.; van Zweeden, M.; Hoekstra, H.J.; Meijer, C.; Suurmeijer, A.J.; Groen, H.J.; Hofstra, R.M.; Sluiter, W.J.; Groen, H.; Sleijfer, D.T.; Gietema, J.A.
Genetic variation in the bleomycin hydrolase gene and bleomycin-induced pulmonary toxicity in germ cell cancer patients
Pharmacogenet. Genomics
15
399-405
2005
Homo sapiens
de Haas, E.C.; Zwart, N.; Meijer, C.; Nuver, J.; Boezen, H.M.; Suurmeijer, A.J.; Hoekstra, H.J.; van der Steege, G.; Sleijfer, D.T.; Gietema, J.A.
Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer
J. Clin. Oncol.
26
1817-1823
2008
Homo sapiens (Q13867), Homo sapiens
Kamata, Y.; Taniguchi, A.; Yamamoto, M.; Nomura, J.; Ishihara, K.; Takahara, H.; Hibino, T.; Takeda, A.
Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids
J. Biol. Chem.
284
12829-12836
2009
Homo sapiens, Rattus norvegicus
Ratovitski, T.; Chighladze, E.; Waldron, E.; Hirschhorn, R.R.; Ross, C.A.
Cysteine proteases bleomycin hydrolase and cathepsin Z mediate N-terminal proteolysis and toxicity of mutant huntingtin
J. Biol. Chem.
286
12578-12589
2011
Homo sapiens
Kamata, Y.; Yamamoto, M.; Kawakami, F.; Tsuboi, R.; Takeda, A.; Ishihara, K.; Hibino, T.
Bleomycin hydrolase is regulated biphasically in a differentiation- and cytokine-dependent manner: relevance to atopic dermatitis
J. Biol. Chem.
286
8204-8212
2011
Homo sapiens
Chen, J.; Chen, Y.; He, Q.
Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1
Int. J. Oncol.
41
2245-2252
2012
Homo sapiens
Crnovcic, I.; Gan, F.; Yang, D.; Dong, L.B.; Schultz, P.G.; Shen, B.
Activities of recombinant human bleomycin hydrolase on bleomycins and engineered analogues revealing new opportunities to overcome bleomycin-induced pulmonary toxicity
Bioorg. Med. Chem. Lett.
28
2670-2674
2018
Homo sapiens (Q13867), Homo sapiens
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