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Information on EC 2.3.1.37 - 5-aminolevulinate synthase and Organism(s) Homo sapiens and UniProt Accession P13196
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2.3.1.37 5-aminolevulinate synthaseIUBMB Comments
A pyridoxal-phosphate protein. The enzyme in erythrocytes is genetically distinct from that in other tissues.
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Word Map
- 2.3.1.37
- heme
- porphyria
-
sideroblastic
- oxygenase
- anemia
-
x-linked
-
ferrochelatase
- hemoglobin
- marrow
- porphobilinogen
- dehydratase
- pyridoxal
- uroporphyrinogen
- protoporphyria
-
iron-responsive
- hemoprotein
- erythroblast
- phenobarbital
-
erythropoietic
- tetrapyrrole
- rhodopseudomonas
- rhodobacter
-
microcytic
-
porphyrinogenic
- erythroleukemia
-
delta-aminolaevulinate
-
allylisopropylacetamide
-
uroporphyrin
- medicine
- synthesis
-
hypochromic
- pharmacology
- gata1
- aip
- hexachlorobenzene
-
plp-dependent
-
cutanea
-
5'-phosphate-dependent
-
phenobarbital-induced
- biotechnology
-
neurovisceral
- nutrition
-
rate-controlling
-
pyrrolase
- protoporphyrinogen
-
heme-mediated
- tarda
-
5-aminolaevulinate
-
succinyl-coenzyme
- bacteriochlorophyll
- coproporphyrinogen
- agriculture
-
harderian
- succinylacetone
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
alas2, ala synthase, 5-aminolevulinate synthase, ala-s, delta-aminolevulinate synthase, delta-aminolevulinic acid synthase, delta-aminolevulinic acid synthetase, 5-aminolevulinic acid synthase, aminolevulinate synthase, delta-aminolevulinate synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5-aminolevulinate synthetase
-
-
-
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5-aminolevulinic acid synthetase
-
-
-
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ALA synthase
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-
-
-
ALA synthetase
-
-
-
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ALAS
ALAS2
alpha-aminolevulinic acid synthase
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-
-
-
aminolevulinate synthase
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-
-
-
aminolevulinate synthetase
-
-
-
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aminolevulinic acid synthase
-
-
-
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aminolevulinic acid synthetase
-
-
-
-
aminolevulinic synthetase
-
-
-
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delta-aminolevulinate synthase
delta-aminolevulinate synthetase
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-
-
-
delta-aminolevulinic acid synthase
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-
-
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delta-aminolevulinic acid synthetase
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-
-
-
delta-aminolevulinic synthetase
-
-
-
-
synthase, aminolevulinate
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-
-
-
synthetase, aminolevulinate
-
-
-
-
ALAS
-
-
-
-
delta-aminolevulinate synthase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -
SYSTEMATIC NAME
IUBMB Comments
succinyl-CoA:glycine C-succinyltransferase (decarboxylating)
A pyridoxal-phosphate protein. The enzyme in erythrocytes is genetically distinct from that in other tissues.
CAS REGISTRY NUMBER
COMMENTARY
9037-14-3
-
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
alpha-glutamyl-CoA + glycine
6-amino-5-oxohexanoate + CoA + CO2
-
at 9% the rate of the reaction with succinyl-CoA
-
-
?
succinyl-CoA-monomethyl ester + glycine
5-aminolevulinic acid methyl ester + CoA + CO2
-
at 80% the rate of the reaction with succinyl-CoA
-
-
?
additional information
?
-
-
enzyme deficiency causes X-linked sideroblastic anemia
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
absolute requirement for glycine
-
ir
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
absolutely specific for glycine
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
regulatory mechanisms in hepatic and erythroid cells
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
ALAS2 synthesizes heme specifically for haemoglobin
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
first and rate-limiting step of heme biosynthesis. Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways
-
-
?
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
additional information
?
-
-
enzyme deficiency causes X-linked sideroblastic anemia
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
regulatory mechanisms in hepatic and erythroid cells
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
-
ALAS2 synthesizes heme specifically for haemoglobin
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
dependent on, succinyl-CoA binding effects the cofactor-binding site of wild-type and mutant enzymes and induces distinct changes to the chiral environment of the cofactor, overview
pyridoxal 5'-phosphate
dependent on, wild-type Km is 0.0000215 nM, Km values of mutant enzymes are between 0.0000062 nM and 0.00065 nM
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Iron
-
regulation of erythroid-specific isoform ALAS-2 via 5'-iron responsive element, i.e. IRE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
isoniazid
about 25% residual activity at 0.01 mM. Isoniazid directly inhibits the enzyme, noncompetitively or uncompetitively. about 0.4 mM pyridoxal 5'-phosphate and PMP reduce the effect of isoniazid on isoform ALAS2 inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ClpX
-
the mitochondrial AAA+ unfoldase ClpX participates in both heme-dependent degradation of the enzyme and its activation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten steady-state kinetics, two-step sequential kinetic mechanism , and thermodynamics. Both the reaction for wild-type hALAS2 and those for the X-linked protoporphyria variants comprised a single kinetic step associated with quinonoid intermediate formation followed by one decay step. Rates for the two steps range from 9.8-14.3/s and from 1.37-1.97 s for the reactions of the XLPP variants, whereas those for the wild-type hALAS2-catalyzed reaction are 6.6/s and 0.70/s
-
additional information
additional information
-
Michaelis-Menten steady-state kinetics, two-step sequential kinetic mechanism , and thermodynamics. Both the reaction for wild-type hALAS2 and those for the X-linked protoporphyria variants comprised a single kinetic step associated with quinonoid intermediate formation followed by one decay step. Rates for the two steps range from 9.8-14.3/s and from 1.37-1.97 s for the reactions of the XLPP variants, whereas those for the wild-type hALAS2-catalyzed reaction are 6.6/s and 0.70/s
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0012
isoniazid
apparent value, pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
sodium butyrate treatment activates ALAS2 gene transcription
-
rapid stimulation of ALA-s mRNA by ACTH which acts through cyclic AMP
additional information
-
enzyme in erythrocytes is genetically distinct from that in other tissue
-
erythroid induction cultures of CD34+ hematopoietic stem/progenitor cells
additional information
-
enzyme is synthezised in the cytosol as the precursor protein and then imported into the mitochondria matrix and cleaved to the mature enzyme, the targeting information is encoded in nonoverlapping regions of the presequence
additional information
-
enzyme is synthezised in the cytosol as the precursor protein and then imported into the mitochondria matrix and cleaved to the mature enzyme, the targeting information is encoded in nonoverlapping regions of the presequence
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
synthesized in microsomes and then migrates to the mitochondria
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
vertebrate genomes encode two highly conserved, but differentially expressed, ALAS genes, a housekeeping gene (ALAS1)5,6 and an erythroid-specific gene (ALAS2)
malfunction
metabolism
the enzyme catalyzes the first and rate-limiting step of heme formation
physiological function
additional information
malfunction
mutations in the C-terminal region of human erythroid-specific enzyme ALAS are associated with X-linked protoporphyria, a disease characterized by extreme photosensitivity, with elevated blood concentrations of free protoporphyrin IX and zinc protoporphyrin. The protein conformational transition step associated with product release is predominantly affected, because the mutations alter the microenvironment of the pyridoxal 5'-phosphate cofactor, which undergoes further and specific alterations upon succinyl-CoA binding. This results in enhanced activities of the XLPP mutant enzyme variants due to accelerations in the rate at which the product 5-aminolevulinate is released from the enzyme. The erythroid 5-aminolevulinate synthase mutations disrupt the conformational equilibrium. Molecular mechanism, overview
malfunction
X-linked protoporphyria is a erythropoietic porphyria due to gain-of-function mutations in the erythroid-specific aminolevulinate synthase gene (ALAS2). Two exon 11 small deletions, c.1699_1670DELTAAT and c.1706_1709DELTAAGTG (DELTAAGTG), that prematurely truncate or elongate the ALAS2 polypeptide, are reported to increase enzymatic activity 20 to 40fold, causing the erythroid accumulation of protoporphyrins, cutaneous photosensitivity and liver disease
malfunction
enzyme mutations are associated with two different blood disorders, X-linked sideroblastic anemia and X-linked protoporphyria
physiological function
silencing by shRNA results in a decrease in iron-induced expression of band 3 protein
physiological function
the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, regulation of 5-aminolevulinate synthase is at the origin of balanced heme production in mammals
additional information
the N-terminal region, designated as region 2 and encoded by exons 3 and 4 of the human ALAS2 gene, is not required for activity and contains an heme-regulatory motif
additional information
-
the N-terminal region, designated as region 2 and encoded by exons 3 and 4 of the human ALAS2 gene, is not required for activity and contains an heme-regulatory motif
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). HEM1_HUMAN
640
0
70581
Swiss-Prot
Mitochondrion (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
52000
x * 54000, recombinant wild-type enzyme, SDS-PAGE, x * 52000, recombinant mutant F557X, SDS-PAGE
54000
x * 54000, recombinant wild-type enzyme, SDS-PAGE, x * 52000, recombinant mutant F557X, SDS-PAGE
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
x * 54000, recombinant wild-type enzyme, SDS-PAGE, x * 52000, recombinant mutant F557X, SDS-PAGE
additional information
two heme-binding motifs in the leader sequence, as well as one present in the N-terminus of the mature enzyme, function in vivo in the heme-regulated translocation of enzyme
additional information
-
splice variant lacking exon 4-encoded sequence produces a functional enzyme with slightly reduced activity compared to full-length enzyme. Interaction of both full-length enzyme and splice variant lacking exon 4-encoded sequence with succinyl CoA synthase
additional information
-
three-dimensional structural model of enzyme, comparison with Rhodobacter sphaeroides enzyme. Mapping of a range of human mutants that give rise to X-linked sideroblastic anemia
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
first 49 amino acids of enzyme pre-protein are mitochondrial targeting sequence
ubiquitinylation
-
ALAS2 appears to be ubiquitinated as rapidly as at is produced
additional information
additional information
two heme-binding motifs in the leader sequence, as well as one present in the N-terminus of the mature enzyme, function in vivo in the heme-regulated translocation of enzyme
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F557X
site-directed mutagenesis, a ALAS2 exon 11, c.1670-1671TC>GA mutation
M567I
-
mutant shows 25% of wild-type activity, while its half-life is longer than that of wild-type
Q548X
S568G
-
mutant shows decreased catalytic activity in vitro (20% compared to wild-type), but a higher half-life compared to those of wild-type ALAS2
V562A
-
mutant shows a higher catalytic activity in vitro, but a shorter half-life in vivo compared to those of wild-type ALAS2
additional information
Q548X
naturally occuring mutation involved in X-linked protoporphyria, 1.6fold increased activity compared to the wild-type enzyme. The increased activity Q548X enzyme does not bind to succinyl-CoA synthetase
Q548X
site-directed mutagenesis, an X-linked protoporphyria-related mutant
additional information
-
analysis of the 5' regulatory region of 5-aminolevulinate synthase gene in variegate porphyria patients heterozygous for the causative R59W mutation in the protoporphyrinogen oxidase gene. In the presence of estrogen and ERalpha, the wild-type -853C/-1253T allele induces a 47% increase in transcription, while the -853T/-1253A double mutant allele showed a 35% increase in transcription. The highest induction is observed for the mutant -853T/1253T allele generating an increase of 66%
additional information
-
the deletion of 33 amino acids at C-terminal end results in higher catalytic activity both in vitro and in vivo with the longer half-life compared to wild-type
additional information
generation of two deletion mutants DELTAAT and DELTAAGTG enzymes. Compared to the purified wild-type enzyme, the deletion mutants show 1.8 and 3.1fold increased activity,respectively, compared to the wild-type enzyme
additional information
generation of X-linked protoporphyria-related deletion mutants delAT and delAGTG, the mutant delAGTG has a significantly increased affinity for the glycine substrate
additional information
-
generation of X-linked protoporphyria-related deletion mutants delAT and delAGTG, the mutant delAGTG has a significantly increased affinity for the glycine substrate
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
t1/2 of the wild-type is 11.7 min, and t1/2 of mutant enzymes are between 3.8 and 12.8 min
additional information
additional information
comparison of thermostability of wild-type and mutant ALAS2 aApoenzymes, overview
additional information
t1/2 is 48.6°C, 52.5°C, 49.9°C, and 51.4°C for wild-type hALAS2, delAT, delAGTG, and Q548X, respectively
additional information
-
t1/2 is 48.6°C, 52.5°C, 49.9°C, and 51.4°C for wild-type hALAS2, delAT, delAGTG, and Q548X, respectively
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant MBP-fusion wild-type and mutant enzymes 29-114fold by amylose affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene ALAS2, expression of N-terminally His-tagged wild-type enzyme, deletion mutants delAT and delAGTG, and mutant Q548X in Escherichia coli strain BL21(DE3), transient expression of the wild-type enzyme in HeLa cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
analysis of the 5' regulatory region of 5-aminolevulinate synthase gene in variegate porphyria patients heterozygous for the causative R59W mutation in the protoporphyrinogen oxidase gene. In the presence of estrogen and ERalpha, the wild-type -853C/-1253T allele induces a 47% increase in transcription, while the -853T/-1253A double mutant allele showed a 35% increase in transcription. The highest induction is observed for the mutant -853T/1253T allele generating an increase of 66%
-
elevated mRNA and protein levels of isoform ALAS2 are observed among patients with erythropoietic protoporphyria. Iron deprivation increases the amount of isoform ALAS2 mRNA
HIF1R knockdown by RNA interference decreased the level of ALAS2 expression. In silico analysis reveal three potential hypoxia-response elements (HREs) that are located 611, 621, and 741 bp downstream of the ALAS2 gene
-
increased expression of erythroid specific 5-aminolevulinate synthase ALAS2 and gamma-globin mRNAs after 48 h of hypoxia. Exogenous TGF-beta1 induces hemoglobinization and the expression of ALAS2 mRNA in YN-1-0-A cells, but not of c-globin and mitoferrin mRNAs. A specific inhibitor of intracellular TGF-b signaling markedly reduces the degree of the hypoxia-mediated increase in the expression of ALAS2 mRNA in YN-1-0-A cells
-
the presence of low-activity mitochondrial AAA+ unfoldase CLPX increases the posttranslational stability of the enzyme, causing increased protein level
-
the relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, is significantly reduced by nearly 90% in patients with Alzheimer's disease compared to control. The relative expression of porphobilinogen deaminase mRNA, the third enzyme in the heme synthesis pathway and a secondary rate-limiting enzyme in heme biosynthesis, is also significantly reduced by nearly 60% in brain of patients with Alzheimer's disease and significantly related to apolipoprotein E genotype. The relative expression of aminolevulinate dehydratase mRNA, the second and a non-rate-limiting enzyme for heme biosynthesis, is unchanged between the two groups
-
under hypoxic conditions, significantly increased ALAS2 mRNA and protein levels are detected in K562 cells and erythroid induction cultures of CD34+ hematopoietic stem/progenitor cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
three-dimensional structural model of enzyme, mapping of a range of human mutants that give rise to X-linked sideroblastic anemia
medicine
-
hypoxia induces the expression of TGF-beta1 and mitoferrin mRNAs through separate mechanisms in erythroid cells. TGF-beta1 subsequently induces erythroidspecific 5-aminolevulinate synthase ALAS2 expression
medicine
-
the relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, is significantly reduced by nearly 90% in patients with Alzheimer's disease compared to control. The relative expression of porphobilinogen deaminase mRNA, the third enzyme in the heme synthesis pathway and a secondary rate-limiting enzyme in heme biosynthesis, is also significantly reduced by nearly 60% in brain of patients with Alzheimer's disease and significantly related to apolipoprotein E genotype. The relative expression of aminolevulinate dehydratase mRNA, the second and a non-rate-limiting enzyme for heme biosynthesis, is unchanged between the two groups
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bishop, D.F.; Henderson, A.S.; Astrin, K.H.
Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome
Genomics
7
207-214
1990
Homo sapiens
Jordan, P.M.; Shemin, D.
delta-Aminolevulinic acid synthetase
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
7
339-356
1972
Saccharomyces cerevisiae, Cavia porcellus, Gallus gallus, Oryctolagus cuniculus, Homo sapiens, no activity in Chromatium sp., Propionibacterium freudenreichii subsp. shermanii, Rattus norvegicus, Cereibacter sphaeroides, Rhodospirillum rubrum, Spinacia oleracea, Novispirillum itersonii
-
Ferreira, G.C.; Gong, J.
5-Aminolevulinate synthase and the first step of heme biosynthesis
J. Bioenerg. Biomembr.
27
151-159
1995
Agrobacterium tumefaciens, Aspergillus nidulans, Bradyrhizobium japonicum, Saccharomyces cerevisiae, Gallus gallus, Euglena gracilis, Homo sapiens, Paracoccus denitrificans, Mus musculus, Rattus norvegicus, Sinorhizobium meliloti, Rhodobacter capsulatus, Cereibacter sphaeroides
Dailey, H.A.; Dailey, T.A.
Expression and purification of mammalian 5-aminolevulinate synthase
Methods Enzymol.
281
336-340
1997
Gallus gallus, Homo sapiens, Mus musculus, Rattus norvegicus
Dailey, T.A.; Woodruff, J.H.; Dailey, H.A.
Examination of mitochondrial protein targeting of haem synthetic enzymes: in vivo identification of three functional haem-responsive motifs in 5-aminolaevulinate synthase
Biochem. J.
386
381-386
2005
Homo sapiens (P13196)
Shoolingin-Jordan, P.M.; Al-Daihan, S.; Alexeev, D.; Baxter, R.L.; Bottomley, S.S.; Kahari, I.D.; Roy, I.; Sarwar, M.; Sawyer, L.; Wang, S.F.
5-Aminolevulinic acid synthase: mechanism, mutations and medicine
Biochim. Biophys. Acta
1647
361-366
2003
Homo sapiens, Cereibacter sphaeroides
Cox, T.C.; Sadlon, T.J.; Schwarz, Q.P.; Matthews, C.S.; Wise, P.D.; Cox, L.L.; Bottomley, S.S.; May, B.K.
The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis
Int. J. Biochem. Cell Biol.
36
281-295
2004
Homo sapiens
Guberman, A.S.; Scassa, M.E.; Canepa, E.T.
Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways
Arch. Biochem. Biophys.
436
285-296
2005
Homo sapiens
Abu-Farha, M.; Niles, J.; Willmore, W.G.
Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition
Biochem. Cell Biol.
83
620-630
2005
Homo sapiens
Han, L.; Zhong, Y.; Huang, B.; Han, L.; Pan, L.; Xu, X.; Wang, X.; Huang, B.; Lu, J.
Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter
Blood Cells Mol. Dis.
41
148-153
2008
Homo sapiens (P22557)
Martini, C.N.; Romero, D.G.; Yanes, L.L.; Vila, M.d.e.l..C.
Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis
Life Sci.
81
19-25
2007
Homo sapiens, Rattus norvegicus
Huang, Q.; Li, J.; Feng, W.; Xu, Y.; Huang, Z.; Lv, S.; Zhou, H.; Gao, L.
Erythroid 5-aminolevulinate synthase mediates the upregulation of membrane band 3 protein expression by iron
Cell Biochem. Funct.
28
122-125
2010
Homo sapiens (P22557)
du Plessis, N.; Kimberg, M.; Zaahl, M.G.; Sadie, A.; Venter, M.; van der Merwe, L.; Louw, A.; Warnich, L.
Functional analysis of the 5 regulatory region of the 5-aminolevulinate synthase (ALAS1) gene in response to estrogen
Cell. Mol. Biol.
55
20-30
2009
Homo sapiens
Kaneko, K.; Furuyama, K.; Aburatani, H.; Shibahara, S.
Hypoxia induces erythroid-specific 5-aminolevulinate synthase expression in human erythroid cells through transforming growth factor-beta signaling
FEBS J.
276
1370-1382
2009
Homo sapiens
Dwyer, B.E.; Smith, M.A.; Richardson, S.L.; Perry, G.; Zhu, X.
Down-regulation of aminolevulinate synthase, the rate-limiting enzyme for heme biosynthesis in Alzheimers disease
Neurosci. Lett.
460
180-184
2009
Homo sapiens
Zhang, F.L.; Shen, G.M.; Liu, X.L.; Wang, F.; Zhao, H.L.; Yu, J.; Zhang, J.W.
Hypoxic induction of human erythroid-specific sigma-aminolevulinate synthase mediated by hypoxia-inducible factor 1
Biochemistry
50
1194-1202
2011
Homo sapiens
Kadirvel, S.; Furuyama, K.; Harigae, H.; Kaneko, K.; Tamai, Y.; Ishida, Y.; Shibahara, S.
The carboxyl-terminal region of erythroid-specific 5-aminolevulinate synthase acts as an intrinsic modifier for its catalytic activity and protein stability
Exp. Hematol.
40
477-486.e1
2012
Homo sapiens
Fratz, E.J.; Clayton, J.; Hunter, G.A.; Ducamp, S.; Breydo, L.; Uversky, V.N.; Deybach, J.C.; Gouya, L.; Puy, H.; Ferreira, G.C.
Human erythroid 5-aminolevulinate synthase mutations associated with X-linked protoporphyria disrupt the conformational equilibrium and enhance product release
Biochemistry
54
5617-5631
2015
Homo sapiens (P22557), Homo sapiens
Bishop, D.F.; Tchaikovskii, V.; Nazarenko, I.; Desnick, R.J.
Molecular expression and characterization of erythroid-specific 5-aminolevulinate synthase gain-of-function mutations causing X-linked protoporphyria
Mol. Med.
19
18-25
2013
Homo sapiens (P22557)
Fratz-Berilla, E.J.; Breydo, L.; Gouya, L.; Puy, H.; Uversky, V.N.; Ferreira, G.C.
Isoniazid inhibits human erythroid 5-aminolevulinate synthase Molecular mechanism and tolerance study with four X-linked protoporphyria patients
Biochim. Biophys. Acta
1863
428-439
2017
Homo sapiens (P22557), Homo sapiens
Barman-Aksoezen, J.; Halloy, F.; Iyer, P.S.; Schuemperli, D.; Minder, A.E.; Hall, J.; Minder, E.I.; Schneider-Yin, X.
Delta-aminolevulinic acid synthase 2 expression in combination with iron as modifiers of disease severity in erythropoietic protoporphyria
Mol. Genet. Metab.
128
304-308
2019
Homo sapiens (P22557), Homo sapiens
Yien, Y.Y.; Ducamp, S.; van der Vorm, L.N.; Kardon, J.R.; Manceau, H.; Kannengiesser, C.; Bergonia, H.A.; Kafina, M.D.; Karim, Z.; Gouya, L.; Baker, T.A.; Puy, H.; Phillips, J.D.; Nicolas, G.; Paw, B.H.
Mutation in human CLPX elevates levels of delta-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria
Proc. Natl. Acad. Sci. USA
114
E8045-E8052
2017
Homo sapiens
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