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Information on EC 1.14.11.2 - procollagen-proline 4-dioxygenase and Organism(s) Homo sapiens and UniProt Accession Q9H6Z9

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IUBMB Comments
Requires Fe2+ and ascorbate.The enzyme, which is located within the lumen of the endoplasmic reticulum, catalyses the 4-hydroxylation of prolines in -X-Pro-Gly- sequences. The 4-hydroxyproline residues are essential for the formation of the collagen triple helix. The enzyme forms a complex with protein disulfide isomerase and acts not only on procollagen but also on more than 15 other proteins that have collagen-like domains.
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This record set is specific for:
Homo sapiens
UNIPROT: Q9H6Z9
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
prolyl 4-hydroxylase, prolyl-4-hydroxylase, p4ha1, egln3, p4ha2, hypoxia-inducible factor prolyl hydroxylase, hif prolyl hydroxylase, proline hydroxylase, c-p4h, prolyl-4-hydroxylases, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
HIF-P4H-3
-
prolyl hydroxylase domain containing protein
-
alpha (I) subunit
-
-
C-P4H
C-P4H alpha subunit (III)
-
C-P4H alpha(I)
-
-
collagen proline hydroxylase
-
-
-
-
collagen prolyl 4-hydroxylase
collagen prolyl 4-hydroxylase (type-II)
-
collagen prolyl 4-hydroxylase 1
-
collagen prolyl-4-hydroxylase alpha subunit 2
-
CP4H
-
-
Egl nine homolog
-
HIF prolyl hydroxylase
-
-
HIF-1alpha-specific prolyl-hydroxylase
-
-
HIF-P4H-1
-
HIF-P4H-2
-
HPH-2
-
-
hydroxylase, collagen proline
-
-
-
-
hypoxia inducible factor-prolyl hydroxylase
-
-
hypoxia-inducible factor prolyl hydroxylase
-
-
hypoxia-inducible factor-1alpha-prolyl-hydroxylase 2
-
-
P4H alpha1
-
P4ha1
P4H alpha 1 subunit
peptidyl proline hydroxylase
-
-
-
-
PHD-1
-
-
procollagen prolyl 4-hydroxylase
-
-
-
-
procollagen-proline dioxygenase
-
-
-
-
proline hydroxylase
-
-
-
-
proline protocollagen hydroxylase
-
-
-
-
proline, 2-oxoglutarate dioxygenase
-
-
-
-
proline,2-oxoglutarate 4-dioxygenase
-
-
-
-
prolyl 4-hydroxylase
prolyl hydroxylase
prolyl hydroxylase domain 1
-
-
prolyl hydroxylase domain containing protein
-
prolyl hydroxylase domain enzyme
-
-
prolyl hydroxylase domain protein 2
-
-
prolyl hydroxylase-1
-
-
prolyl hydroxylase-3
-
-
prolyl-4-hydroxylase
prolyl-4-hydroxylase alpha subunit 2
-
prolyl-4-hydroxylase alpha1
-
prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, 4-hydroxylating
-
-
-
-
prolylprotocollagen dioxygenase
-
-
-
-
prolylprotocollagen hydroxylase
-
-
-
-
protocollagen hydroxylase
-
-
-
-
protocollagen proline 4-hydroxylase
-
-
-
-
protocollagen proline dioxygenase
-
-
-
-
protocollagen proline hydroxylase
-
-
-
-
protocollagen prolyl hydroxylase
-
-
-
-
type I C-P4H
-
-
type I proyl 4-hydroxylase
-
-
type II proyl 4-hydroxylase
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
-
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
hydroxylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
procollagen-L-proline,2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)
Requires Fe2+ and ascorbate.The enzyme, which is located within the lumen of the endoplasmic reticulum, catalyses the 4-hydroxylation of prolines in -X-Pro-Gly- sequences. The 4-hydroxyproline residues are essential for the formation of the collagen triple helix. The enzyme forms a complex with protein disulfide isomerase and acts not only on procollagen but also on more than 15 other proteins that have collagen-like domains.
CAS REGISTRY NUMBER
COMMENTARY hide
9028-06-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-oxoglutarate + O2 + ascorbate
succinate + dehydroascorbate + CO2 + H2O
show the reaction diagram
-
-
-
?
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPAIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AIPMDDDFQL + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPAIPMDDDFQLRSFDQ + 2-oxoglutarate + O2
DLDLEMLAPAIPMDDDFQLRSFDQ trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPGIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLAPGIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMD + 2-oxoglutarate + O2
DLDLEMLAPYIPMD trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDD + 2-oxoglutarate + O2
DLDLEMLAPYIPMDD trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDF + 2-oxoglutarate + O2
DLDLEMLAPYIPMDDDF trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLAPYIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQLRSFDQ + 2-oxoglutarate + O2
DLDLEMLAPYIPMDDDFQLRSFDQ trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
-
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLAPYIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor alpha L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor alpha trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
isoform EGLN3 acts on the N-terminal oxygen-dependent degradation domain
-
-
?
hypoxia-inducible factor L-proline + 2-oxoglutarate + O2
hypoxia inducible factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
LAPYIPMDDDFQL + 2-oxoglutarate + O2
LAPYIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
(2S,4S)-4-fluoroproline + 2-oxoglutarate + O2
(2S)-4-oxoproline + fluoride
show the reaction diagram
-
development and evaluation of an assay method that continuously and directly detects turnover of the proline-containing substrate. The assay is based on (2S,4S)-4-fluoroproline, a proline analogue that is transformed into (2S)-4-oxoproline and inorganic fluoride by P4H using a fluoride ion-selective electrode for detection
-
-
?
(GPP)10 + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
-
?
(L-Pro-L-Pro-Gly)10 + 2-oxoglutarate + O2
(L-Pro-L-Pro-Gly)10-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
r
(L-Pro-L-Pro-Gly)2 + 2-oxoglutarate + O2
(L-Pro-L-Pro-Gly)2-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
r
(L-Pro-L-Pro-Gly)5 + 2-oxoglutarate + O2
(L-Pro-L-Pro-Gly)5-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
r
(Pro-Pro-Gly)10 + 2-oxoglutarate + O2
? + succinate + CO2
show the reaction diagram
(Pro-Pro-Gly)10 + 2-oxoglutarate + O2
trans-4-hydroxy-L-proline (Pro-Pro-Gly)10 + succinate + CO2
show the reaction diagram
-
-
-
?
(Pro-Pro-Gly)10 L-proline + 2-oxoglutarate + O2
(Pro-Pro-Gly)10 trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
(Pro-Pro-Gly)2 L-proline + 2-oxoglutarate + O2
(Pro-Pro-Gly)2 trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
?
(Pro-Pro-Gly)n + 2-oxoglutarate + O2
(Pro-4-hydroxy-Pro-Gly)n + succinate + CO2
show the reaction diagram
2-oxoglutarate + O2 + ascorbate
succinate + dehydroascorbate + CO2 + H2O
show the reaction diagram
Argonaute 2 + 2-oxoglutarate + O2
4-hydroxyproline-Argonaute 2 + succinate + CO2
show the reaction diagram
-
regulation of Ago 2 protein activity via substrate protein stability involving Ago Pro700 residue, the Ago protein mutant P700A is destabilized, overview
-
-
?
Argonaute protein + 2-oxoglutarate + O2
4-hydroxyproline-Argonaute protein + succinate + CO2
show the reaction diagram
-
i.e. GERp95 or Golgi endoplasmic reticulum protein 95 kDa. Recombinant substrate proteins expressed in HeLa S3 cells. Ago2 is a cytoplasmically exposed, peripheral membrane protein that exists in a protease-resistant complex. Hydroxylation of Pro700, which is important for Ago2 stability, but not of Ago1 or Ago3 stability, identification by mass spectrometric analysis. In vitro, both Ago2 and Ago4 seem to be more efficiently hydroxylated than Ago1 and Ago3 by recombinant human isozyme C-P4H(I)
-
-
?
biotin-Ahx-DLDLEALAP564YIPADDDFQL + 2-oxoglutarate + O2
?
show the reaction diagram
-
19mer HIF peptide not containing cysteine is used, in order to rule out an involvement of the cysteine nitrosylation
-
-
?
DALTLLAPAAGDTIISLDYG + 2-oxoglutarate + O2
?
show the reaction diagram
-
NODD peptide derived from native HIF-1alpha395-414
-
-
?
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
show the reaction diagram
-
-
-
?
dansyl-Gly-Phe-Pro-Gly-OEt + 2-oxoglutarate + O2
dansyl-Gly-Phe-4-hydroxy-L-Pro-Gly-OEt + succinate + CO2
show the reaction diagram
-
-
-
-
?
dansyl-Gly-Phe-Pro-Gly-OEt + 2-oxoglutarate + O2
dansyl-Gly-Phe-trans-4-hydroxy-L-proline-Gly-OEt + succinate + CO2
show the reaction diagram
-
-
-
-
?
DLDLEALAPYIPADDDFQL + 2-oxoglutarate + O2
?
show the reaction diagram
-
CODD peptide derived from native HIF-1alpha556-574. PHD2 preferred CODD by 20fold over NODD
-
-
?
DLDLEMLAPAIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AIPMDDDFQL + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPGIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLAPGIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMD + 2-oxoglutarate + O2
DLDLEMLAPYIPMD trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDD + 2-oxoglutarate + O2
DLDLEMLAPYIPMDD trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDF + 2-oxoglutarate + O2
DLDLEMLAPYIPMDDDF trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLAPYIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQLRSFDQ + 2-oxoglutarate + O2
DLDLEMLAPYIPMDDDFQLRSFDQ trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
DLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
-
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLAPYIPMDDDFQL trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
Gly-Val-Pro-Gly-Val + 2-oxoglutarate + O2
Gly-Val-4-hydroxyproline-Gly-Val + succinate + CO2
show the reaction diagram
-
-
?
hypoxia-induced factor alpha oxygen-dependent degradation domain L-proline + 2-oxoglutarate + O2
hypoxia-induced factor alpha oxygen-dependent degradation domain L-4-hydroxyproline + succinate + CO2
show the reaction diagram
-
-
in vitro hydroxylation of two proline residues, with preference for C-terminal proline
-
?
hypoxia-inducible factor alpha L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor alpha trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor L-proline + 2-oxoglutarate + O2
hypoxia inducible factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
?
hypoxia-inducible transcription factor + 2-oxoglutarate + O2
hypoxia-inducible transcription factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
L-Pro-L-Pro-Gly + 2-oxoglutarate + O2
L-Pro-L-Pro-Gly-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
r
PEG-Gly-Tyr-4-fluoroproline-GlyOEt + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
-
?
poly(ethylene glycol)-Gly-L-Tyr-(2S)-4-thiaproline-Gly-OCH2CH2OH + 2-oxoglutarate + O2
poly(ethylene glycol)-Gly-L-Tyr-L-(2S,4R)-thiaoxoproline-Gly-OCH2CH2OH + ? + CO2
show the reaction diagram
-
6% of the activity with L-prolyl peptide substrate
-
-
?
poly(ethylene glycol)-Gly-L-Tyr-L-(2S,4S)-4-fluoroproline-Gly-OCH2CH2OH + 2-oxoglutarate + O2
poly(ethylene glycol)-Gly-L-Tyr-L-(2S)-4-oxoproline-Gly-OCH2CH2OH + ? + CO2
show the reaction diagram
-
26% of the activity with L-prolyl peptide substrate
-
-
?
poly(ethylene glycol)-Gly-L-Tyr-L-Pro-Gly-OCH2CH2OH + 2-oxoglutarate + O2
poly(ethylene glycol)-Gly-L-Tyr-L-(2S,4R)-4-hydroxy-Pro-Gly-OCH2CH2OH + succinate + CO2
show the reaction diagram
-
-
-
-
?
poly(L-Pro) + 2-oxoglutarate + O2
poly(4-hydroxyproline) + succinate + CO2
show the reaction diagram
MW: 7000 and 44000
-
?
procollagen L-proline + 2-oxoglutarate + O2
procollagen trans-(2S,4R)-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
procollagen L-proline + 2-oxoglutarate + O2
procollagen trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
proline containing peptide + 2-oxoglutarate + O2
4-hydroxyproline containing peptide + succinate + CO2
show the reaction diagram
protocollagen + 2-oxoglutarate + O2
4-hydroxyproline containing protocollagen + succinate + CO2
show the reaction diagram
protocollagen type I L-proline+ 2-oxoglutarate + O2
protocollagen type I-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
r
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
hypoxia-inducible factor L-proline + 2-oxoglutarate + O2
hypoxia inducible factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
Argonaute 2 + 2-oxoglutarate + O2
4-hydroxyproline-Argonaute 2 + succinate + CO2
show the reaction diagram
-
regulation of Ago 2 protein activity via substrate protein stability involving Ago Pro700 residue, the Ago protein mutant P700A is destabilized, overview
-
-
?
hypoxia-inducible factor L-proline + 2-oxoglutarate + O2
hypoxia inducible factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible transcription factor + 2-oxoglutarate + O2
hypoxia-inducible transcription factor trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
procollagen L-proline + 2-oxoglutarate + O2
procollagen trans-(2S,4R)-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
?
procollagen L-proline + 2-oxoglutarate + O2
procollagen trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-oxoglutarate
-
-
ascorbate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
required for activity
Iron
-
iron(IV)-oxo species in the active site
NaCl
-
-
Zinc
-
PHD2 contains a MYND zinc finger domain (Myeloid translocation protein 8, Nervy, and DEAF1) that inhibits the catalytic activity in vivo
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
-
3-hydroxypyridine-2-carbonyl-glycine
-
N-[(6-chloro-3-hydroxyquinolin-2-yl)carbonyl]glycine
-
Pyridine-2,4-dicarboxylate
-
(Gly-Pro-Gly)n
-
competitive inhibitors with respect to the polypeptide substrate
(Pro-Ala-Gly)n
-
competitive inhibitors with respect to the polypeptide substrate
1,4-dihydrophenanthrolin-4-one-3-carboxylic acid
1,4,DPCA
2,2'-dipyridyl
-
-
2,3-Dihydroxybenzoate
-
-
2,4-pyridine dicarboxylate
-
-
3,4-dihydroxybenzoate
-
-
3,4-dihydroxybenzoic acid
-
-
3,4-Dihydroxyphenylacetate
-
-
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
3-hydroxypyridine-2-carbonyl-glycine
4-hydroxybenzoate
-
-
4-oxo-5,6-epoxyhexanoate
-
-
alpha,alpha'-dipyridyl
-
an Fe2+ chelator
benzyloxycarbonyl-Phe-Opr-Gly-benzyl ester
-
50% inactivation in 1 h at 0.0008 mM, the most effective inhibitor within oxaproline peptides
Benzyloxycarbonyl-Phe-oxaproline-Gly-benzyl ester
-
-
Beta-lactam antibiotics
-
-
bradykinin analogs
-
especially those in which the proline in the -X-Pro-Gly- triplet is replaced by certain proline analogues, the addition of a glutamyl residue to the N-terminal end of 3,4-dehydroprolyl- or trans-4-hydroxyprolyl-bradykinin considerably increases their effectiveness
-
catechol analogues
-
inhibitor of the reaction due in part to the chelation of Fe2+
-
Cd2+
-
competitive versus Fe2+
ciclopirox olamine
-
an Fe2+ chelator
Co2+
-
competitive versus Fe2+
cobalt chloride
-
inhibition of PHDs blocks the response of mTORC1 to amino acids
Coumalic acid
Cu2+
-
-
daunorubicin
deferoxamine mesylate
-
-
desferrioxamine
-
an Fe2+ chelator
dilantin
-
inhibitor of the reaction due in part to the chelation of Fe2+
dimethyloxallyl glycine
-
inhibition of PHDs blocks the response of mTORC1 to amino acids
DMOG
-
1 mM
doxorubicin
ethylpyridine-2,4-dicarboxylate
-
-
fumarate
-
-
glutamyl-3,4-dehydroprolyl-bradykinin
-
-
-
hydralazine
-
inhibitor of the reaction due in part to the chelation of Fe2+
N,N'-diethylpyridine 2,4-dicarboxamide
-
-
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
-
-
N-[(6-chloro-3-hydroxyquinolin-2-yl)carbonyl]glycine
-
Ni2+
-
competitive versus Fe2+
nitroblue tetrazolium
-
is capable of scavenging superoxide, competitive inhibitor with respect to O2
oxalylglycine
-
-
phenanthrolines
-
potent competitive inhibitors of collagen hydroxylation in foreskin fibroblasts in vitro
-
poly(L-Pro)
0.03 mM, 50% inhibition
poly(L-proline)
-
potassium bromide
-
over 80% inhibition at 500 mM
potassium chloride
-
over 80% inhibition at 500 mM
potassium fluoride
-
over 90% inhibition at 500 mM
potassium iodide
-
over 80% inhibition at 500 mM
Pyridine 2,4-dicarboxylate
Pyridine 2,5-dicarboxylate
-
-
Pyridine-2,4-dicarboxylate
Pyridine-2,5-dicarboxylate
0.007 mM, 50% inhibition
S-nitroso-N-acetylpenicillamine
-
hyperoxia attenuates the inhibitory effect of NO on HIF-1alpha prolyl hydroxylation
S-nitrosoglutathione
-
hyperoxia attenuates the inhibitory effect of NO on HIF-1alpha prolyl hydroxylation
sodium bromide
-
over 80% inhibition at 500 mM
sodium chloride
-
over 80% inhibition at 500 mM
sodium iodide
-
over 90% inhibition at 500 mM
succinate
-
product inhibition
tetracyclin
-
inhibitor of the reaction due in part to the chelation of Fe2+
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
required for activity
O2
activated by oxygen
ascorbate
bleomycin
-
activation
bovine serum albumin
-
activation
-
catalase
-
activation
-
Chelating agents
-
activation
cysteine
-
activation
dithiothreitol
-
activation
nucleoside triphosphates
-
stimulate
O2
activated by oxygen
Thymol
-
activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.055
2-oxoglutarate
-
0.14
ascorbate
-
0.01
DLDLEMLAPAIPMDDDFQL
C-terminal hydroxylation site of HIF-1alpha
0.05
DLDLEMLAPAIPMDDDFQLRSFDQ
-
0.02
DLDLEMLAPGIPMDDDFQL
C-terminal hydroxylation site of HIF-1alpha
0.03
DLDLEMLAPYIPMD
-
0.009
DLDLEMLAPYIPMDD
-
0.007
DLDLEMLAPYIPMDDDF
-
0.007
DLDLEMLAPYIPMDDDFQL
-
0.006
DLDLEMLAPYIPMDDDFQLRSFDQ
-
0.007
DLEMLAPYIPMDDDFQL
-
0.007
EMLAPYIPMDDDFQL
-
0.015
LAPYIPMDDDFQL
-
0.018 - 0.095
(L-Pro-L-Pro-Gly)10
-
2.6
(L-Pro-L-Pro-Gly)2
-
-
-
0.1 - 1.8
(L-Pro-L-Pro-Gly)5
-
0.01 - 0.095
(Pro-Pro-Gly)10
0.001 - 0.15
2-oxoglutarate
0.17 - 0.37
ascorbate
0.001 - 0.0042
DALTLLAPAAGDTIISLDYG
0.13 - 0.38
DALTLLAPAAGDTIISLFG
0.078
dansyl-Gly-Phe-Pro-Gly-OEt
-
-
0.001 - 0.0042
DLDLEALAPYIPADDDFQL
0.01 - 0.02
DLDLEMLAPAIPMDDDFQL
0.02
DLDLEMLAPGIPMDDDFQL
C-terminal hydroxylation site of HIF-1alpha
0.1
DLDLEMLAPYIPMD
-
0.06 - 0.1
DLDLEMLAPYIPMDD
0.05 - 0.07
DLDLEMLAPYIPMDDDF
0.007 - 0.008
DLDLEMLAPYIPMDDDFQL
0.006 - 0.008
DLDLEMLAPYIPMDDDFQLRSFDQ
0.007 - 0.014
DLEMLAPYIPMDDDFQL
0.035 - 0.08
EMLAPYIPMDDDFQL
0.0005 - 0.006
Fe2+
7.8 - 22
Gly-Val-Pro-Gly-Val
20
L-Pro-L-Pro-Gly
-
-
-
0.04 - 0.25
O2
0.5 - 1.2
PEG-Gly-Tyr-4-fluoroproline-GlyOEt
6.4
poly(ethylene glycol)-Gly-L-Tyr-(2S)-4-thiaproline-Gly-OCH2CH2OH
-
30°C, pH 7.8
1.6
poly(ethylene glycol)-Gly-L-Tyr-L-(2S,4S)-4-fluoroproline-Gly-OCH2CH2OH
-
30°C, pH 7.8
0.58
poly(ethylene glycol)-Gly-L-Tyr-L-Pro-Gly-OCH2CH2OH
-
30°C, pH 7.8
0.00000001 - 0.0011
Protocollagen
-
0.0002
protocollagen type I L-proline
-
-
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.22
(Pro-Pro-Gly)10
-
-
0.0101 - 0.0103
DALTLLAPAAGDTIISLDYG
0.15
dansyl-Gly-Phe-Pro-Gly-OEt
-
-
0.0188 - 0.02
DLDLEALAPYIPADDDFQL
4.5 - 6
PEG-Gly-Tyr-4-fluoroproline-GlyOEt
7.8
poly(ethylene glycol)-Gly-L-Tyr-(2S)-4-thiaproline-Gly-OCH2CH2OH
-
30°C, pH 7.8
4.2
poly(ethylene glycol)-Gly-L-Tyr-L-(2S,4S)-4-fluoroproline-Gly-OCH2CH2OH
-
30°C, pH 7.8
6
poly(ethylene glycol)-Gly-L-Tyr-L-Pro-Gly-OCH2CH2OH
-
30°C, pH 7.8
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.45 - 10.1
DALTLLAPAAGDTIISLDYG
4.76 - 18.8
DLDLEALAPYIPADDDFQL
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
-
0.001
3-hydroxypyridine-2-carbonyl-glycine
-
0.0002
N-[(6-chloro-3-hydroxyquinolin-2-yl)carbonyl]glycine
-
0.01
oxalglycine
-
0.008
Pyridine-2,4-dicarboxylate
-
0.005
3,4-dihydroxybenzoate
-
-
0.005 - 0.3
3,4-dihydroxybenzoic acid
0.002 - 0.03
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
0.0004 - 0.015
3-hydroxypyridine-2-carbonyl-glycine
3.2
4-hydroxybenzoate
-
-
17
Coumalic acid
-
S-parabolic competitive inhibition with respect to 2-oxoglutarate
0.04
doxorubicin
-
competitive inhibitor with respect to 2-oxoglutarate, in concentrations not exceeding 0.02 mM, competitive inhibition is also found with respect to ascorbate
0.05 - 0.19
fumarate
0.00006 - 0.0008
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
0.0002 - 0.0008
N-[(6-chloro-3-hydroxyquinolin-2-yl)carbonyl]glycine
0.008 - 0.05
oxalglycine
0.0019 - 0.05
oxalylglycine
0.00002 - 0.3
poly (L-proline)
-
0.00002 - 0.095
poly(L-proline)
-
0.001 - 0.04
Pyridine 2,4-dicarboxylate
0.0008 - 0.3
Pyridine 2,5-dicarboxylate
0.002 - 0.04
Pyridine-2,4-dicarboxylate
0.0008
Pyridine-2,5-dicarboxylate
-
-
0.35 - 0.46
succinate
0.0006
Zn2+
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.02 - 1.38
-
purified enzyme
1.3
-
purified enzyme
2300
-
-
77.8
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
7.8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
30
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 30
-
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
expression is suppressed by tumor necrosis factor TNFalpha via the MKK4-JNK1 pathway, which induces histone 4 lysine 12 acetylation within the TNFalpha response element in the prolyl-4-hydroxylase promoter
Manually annotated by BRENDA team
P4HA2 mRNA levels are significantly upregulated in breast cancer compared to normal mammary tissue
Manually annotated by BRENDA team
-
predominantly type I prolyl-4-hydroxylase
Manually annotated by BRENDA team
-
60 primary colorectal carcinoma tissues, PHD expression analysis, overview. expression of PHD3 is decreased in colorectal cancer, which is associated with higher tumor grade and metastasis, while expression of PHD1 is increased in colorectal tumors. Expression of PHD2 of colorectal tumors is similar to that of paired healthy colorectal tissues
Manually annotated by BRENDA team
-
fetus
Manually annotated by BRENDA team
-
a melanoma cell line
Manually annotated by BRENDA team
-
a melanoma cell line
Manually annotated by BRENDA team
-
a melanoma cell line
Manually annotated by BRENDA team
-
derived from primary melanoma
Manually annotated by BRENDA team
-
predominantly type I prolyl-4-hydroxylase
Manually annotated by BRENDA team
expression of enzyme alpha-I and alpha-II subunits mRNAs
Manually annotated by BRENDA team
-
a melanoma cell line
Manually annotated by BRENDA team
-
type II enzyme represents the main or only enzyme form
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
of endoplasmic reticulum, the catalytic site is inside the lumen
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
malfunction
metabolism
-
amino-acid starvation causes depletion of alpha-ketoglutarate that leads to PHD inactivation
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
EGLN3_HUMAN
239
0
27261
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15330
-
3 * 15330, X-ray crystallography
228000
-
gel filtration
230000 - 240000
-
gel filtration
27000
-
predicted molecular mass
400000 - 600000
-
value depending on salt concentration of buffer
40200
-
PHD1 generated by alternative internal translational initiation, SDS-PAGE
43700
-
PHD1, SDS-PAGE
46000
-
X-ray crystallography
61000
-
2 * 61000 + 2 * 640000
640000
-
2 * 61000 + 2 * 640000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotrimer
-
3 * 15330, X-ray crystallography
monomer
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of the PSB domain of the human C-P4H isoform II (PSB-II) complexed with and without various short proline-rich peptides are described
hanging drop vapour diffusion method
-
hanging-drop vapour diffusion, 0.002 ml of 10 mg/ml protein solution in 20 mM bis-Tris, 100 mM glycine, pH 6.8 is mixed with 0.002 ml reservoir solution containing 1.2-1.7 M ammonium phosphate, pH 8.2-8.6, crystals diffract to 3.0 A
-
recombinant catalytic domain of PHD2 in complex with the C-terminal oxygen-dependent degradation domain of HIF-1alpha, 20°C, 100 nl protein solution containing 40 mg/ml protein in 50 mM Tris-HCl, pH 7.5, 1 mM MnCl2, 1 mM NOG, and 0.1 mM HIF-1alpha CODD556-574 mixed with 100 nl of well solution consisting of 0.2 M MgCl2 and 20% PEG 3350, A tPHD2-Fe2+-B-CODD568-574 crystal is obtained by soaking preformed PHD2181-426-Fe2+-B crystals in 50% sodium malonate, pH 7.5, solution containing 10 mM 4R-hydroxylated Pro564 HIF-1alpha CODD556-574(Hyp564) peptide under anaerobic conditions for 72 h. The PHD2-Fe2+-inhibitor complexes crystallize in an apparently homotrimeric form, method optimization, X-ray diffraction structure determination and analysis at 2.0-2.3 A resolution, molecular replacement
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C150S
-
the mutation has no major effect on tetramer assembly, but the amount of tetramer is slightly reduced, being about 80% of that of the wild-type enzyme
C486S
-
the mutation totally prevents tetramer assembly
C511S
-
the mutation totally prevents tetramer assembly
D414A
-
site-directed mutagenesis, the mutation mimics the active site of a halogenase. The substitutions does not convert P4H into a halogenase, but the hydroxylase activity of D414A P4H cannot be rescued with small molecule, the mutant is inactive
D414G
-
site-directed mutagenesis, the mutation mimics the active site of a halogenase. The substitutions does not convert P4H into a halogenase, but the hydroxylase activity of D414A P4H cannot be rescued with small molecule, the mutant is inactive
D414H
-
site-directed mutagenesis, the mutation mimics the active site of a cysteine dioxygenase, the mutant is inactive
D414H/H483D
-
site-directed mutagenesis, the mutant is inactive
H131A/D315A
-
inactive mutant
H141S
-
the mutation has no effect on enzyme activity and does not inhibit tetramer assembly
H165S
-
the mutation produces a reduction of about 60% in enzyme activity per unit extractable cell protein relative to that obtained with the wild-type alpha subunit, the amount of tetramer is reduced by about 20-25%, the Km values for Fe2+, 2-oxoglutarate, ascorbate and the peptide substrate with the mutant are identical to those with the wild-type enzyme
H221S
-
the mutation produces a reduction of about 30% in enzyme activity per unit extractable cell protein relative to that obtained with the wild-type alpha subunit, the amount of tetramer is reduced by about 20-25%, the Km values for Fe2+, 2-oxoglutarate, ascorbate and the peptide substrate with the mutant are identical to those with the wild-type enzyme
H296S
-
the mutation has no effect on enzyme activity and does not inhibit tetramer assembly
H324S
-
the mutation totally prevents tetramer assembly
H412D/D414H
-
site-directed mutagenesis, the mutant is inactive
H412S
-
the mutation causes a complete inactivation of the enzyme with no effect on tetramer assembly or binding of the tetramer to poly(L-proline), role in the binding of Fe2+ to a catalytic site
H483S
-
the mutation causes a complete inactivation of the enzyme with no effect on tetramer assembly or binding of the tetramer to poly(L-proline), role in the binding of Fe2+ to a catalytic site
H501S
-
the mutation reduces the enzyme activity to about 4% with no effect on tetramer assembly or binding of the tetramer to poly(L-proline), role in the binding of Fe2+ to a catalytic site, the Km values for Fe2+, ascorbate and the peptide substrate with the mutant are identical to those with the wild-type enzyme, but the Km for 2-oxoglutarate is about 2.5fold higher. The main difference is that the Vmax determined from kinetic plots is consistently less than about 5% of that of the wild-type enzyme
H63S
-
the mutation has no effect on enzyme activity and does not inhibit tetramer assembly
N96Q/N242Q
-
the amount of enzyme activity observed with the double mutant alpha subunit is identical to that of the wild-type enzyme, the size of the double mutant alpha subunit is distinctly smaller than that of either the diglycosylated or monoglycosylated alpha subunit present in the wild-type enzyme, the difference being consistent with loss of all the carbohydrate
P191A
-
loss of hypoxic inducibility
P317R
-
naturally occuring mutation, near the Fe2+ binding site, causing erythrocytosis
R367K
no activity
R371H
-
naturally occuring mutation causing erythrocytosis
W243F
site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate reaches equilibrium within 10 ns. Replacement of Trp243 by Phe increases the accessibility to the oxidant
W243G
site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate equilibrium is not reached after 10 ns
Y140F
site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate reaches equilibrium within 10 ns, inactive mutant
Y140G
site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate reaches equilibrium within 10 ns
Y140G/W243G
site-directed mutagenesis, mutant structure analysis compared to the wild-type enzyme, the substrate equilibrium is not reached after 10 ns. The Y140G/W243G double mutant shows the accumulative effect of both the Y140G and W243G mutations
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
increased spontaneous inactivation at pH values above in the absence of an inactivating compound
439185
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
labile in tissue extracts
-
stabilization by NaCl, detergents
-
unstable in absence of 2-oxoglutarate and either Fe2+ or ascorbate
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
L-proline affinity chromatography and HiTrap Q Sepharose column chromatography
-
Ni-NTA column chromatography and gel filtration
-
Ni2+-affinity chromatography and HiLoad Superdex200 gel filtration
-
of the recombinant enzyme, using an affinity purification procedure based on the use of a histidine tag in the N terminus of the protein disulfide-isomerase/beta polypeptide
recombinant C-P4H alpha(I) subunit
-
recombinant isozymes
-
recombinant P4H, poly(proline)-affinity column, anion-exchange, gel filtration
-
recombinant wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3)
-
recombinant wild-type and mutant enzymes from Escherichia coli strain Origami DE3
-
using affinity chromatography on a column containing poly-(L-proline) linked to agarose, elution with the same polypeptide of a lower molecular weight, and gel filtration
-
using affinity chromatography, ion-exchange chromatography and gel filtration
-
using ammonium sulfate fractionation, affinity chromatography on poly(L-proline) coupled to Sepharose 4B, DEAE-cellulose chromatography, and gel filtration
-
using chromatography on DEAE-cellulose column, affinity column, anion-exchange chromatography and a second chromatography on DEAE-cellulose column
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Sf9 insect cells
in vitro transcription/translation in rabbit reticulocyte lysate
a human embryonic kidney (HEK) 293 cell line is generated expressing FLAG-tagged PHD2
-
alpha-subunit
-
beta-subunit
-
cloning of the alpha-II subunit, coexpression with the beta subunit in insect cells
co-expression of prolyl-4-hydroxylase with collagen type I and lysyl hydroxylase 3 in transgenic tobacco plants resulting in production of bioactive, post-translationally modified, heterotrimeric, human recombinant type-I collagen, overview
-
determination of PHD3 mRNA by real-time PCR
-
expressed in Escherichia coli
-
expressed in Escherichia coli strains BL21 and RB791
-
expressed in MCF7, U2OS, HEK-293T, MEF and HUVEC cells
-
expressed in Trichoplusia ni and Drosophila melanogaster S2 cells
-
expression in Escherichia coli
expression in insect cells and HEK-293 cells
expression in Sf9 insect cells
expression in Sf9 insect cells, HEK293T cells, in vitro transcription/translation in rabbit reticulocyte lysate
expression of histidine and cysteine mutant alpha subunits together with the wild-type beta subunit in insect cells by means of baculovirus vectors
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of wild-type and mutant enzymes in Escherichia coli strain Origami DE3
-
expression, of alpha (I) subunit in Escherichia coli
-
gene P4HA2, enzyme expression analysis, P4HA2 is associated with expression of Col1A1, Col3A1, and Col4A1 during breast cancer development and progression
gene P4halpha1, quantitative real-time PCR enzyme expression analysis
in vitro transcription/translation in rabbit reticulocyte lysate
infection of cells with recombinant viruses encoding type XII minicollagen together with various combinations of recombinant viruses encoding the wild-type or mutant enzyme, analysis of the contributions of the various cellular post-translational modifications to the assembly of trimeric type XII minicollagen, study of the conditions required for the production of disulfide-bonded type XII minicollagen in insect cells using the baculovirus expression system
-
preparation of cDNA clones for the two subunits, expression in Escherichia coli
-
recombinant expression of the three isozymes
-
recombinant human PHD2 (corresponding to residues 178-426 of the full-length PHD2 sequence) is expressed as a GST-fusion protein in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
endothelin-1 inhibits PHD2 expression and promoter activity by 50% to stabilize HIF-alpha. HIF-1alpha and HIF-2alpha accumulation in response to endothelins is specifically impaired in PHD2 overexpressing cells, indicating that re-expression of PHD2 is sufficient to counteract the ET-1- or ET-3-induced HIF-alpha expression
-
mechanical stretch increases MMP-2 and P4H alpha1 expression in human aortic smooth muscle cell via AKT-P38 MAPK-JNK signaling, thereby inducing vascular remodeling. p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 significantly attenuates the stretch-induced upregulation of P4H alpha1 expression, whereas blockade of the ERK1/2 pathway has no effect on P4H alpha1 expression
P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer
PHD2 is hypoxia-inducible by HIF-1alpha
-
the expressions of P4HAs and P4HB are regulated by multiple cellular factors, including cytokines, transcription factors, and microRNAs. P4HAs and P4HB are highly expressed in many tumors. P4HB expression is significantly upregulated in a variety of cancers, including HCC, RCC, glioma, GC, and melanoma, and its upregulation correlates with cancer metastasis and invasion
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
drug development
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pihlajaniemi, T.; Helaakoski, T.; Tasanen, K.; Myllyl, R.; Huhtala, M.L.; Koivu, J.; Kivirikko, K.I.
Molecular cloning of the beta-subunit of human prolyl 4-hydroxylase. This subunit and protein disulfide isomerase are products of the same gene
EMBO J.
6
643-649
1987
Homo sapiens
Manually annotated by BRENDA team
Kivirikko, K.I.; Myllyl, R.
The hydroxylation of prolyl and lysyl residues
Enzymol. Post- transl. Modif. Proteins (Freedman, R. B. , Hawkins, H. C. , eds. ) Academic Press, New York
1
53-104
1980
Gallus gallus, Homo sapiens, Rattus norvegicus
-
Manually annotated by BRENDA team
Kivirikko, K.I.; Myllyl, R.
Posttranslational enzymes in the biosynthesis of collagen: intracellular enzymes
Methods Enzymol.
82
245-304
1982
Gallus gallus, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Guzman, N.A.; Ascari, W.Q.; Cutroneo, K.R.; Desnick, R.J.
Comparison between avian and human prolyl 4-hydroxylases: studies on the holomeric enzymes and their constituent subunits
J. Cell. Biochem.
48
172-189
1992
Gallus gallus, Homo sapiens
Manually annotated by BRENDA team
Kivirikko, K.I.; Myllyl, R.; Pihlajaniemi, T.
Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit
FASEB J.
3
1609-1617
1989
Gallus gallus, Homo sapiens, Mus musculus, Volvox carteri
Manually annotated by BRENDA team
Gunzler, V.; Brocks, D.; Henke, S.; Myllyl, R.; Geiger, R.; Kivirikko, K.I.
Syncatalytic inactivation of prolyl 4-hydroxylase by synthetic peptides containing the unphysiologic amino acid 5-oxaproline
J. Biol. Chem.
263
19498-19504
1988
Gallus gallus, Homo sapiens
Manually annotated by BRENDA team
Gunzler, V.; Hanauske-Abel, H.M.; Myllyl, R.; Kaska, D.D.; Hanauske, A.; Kivirikko, K.I.
Syncatalytic inactivation of prolyl 4-hydroxylase by anthracyclines
Biochem. J.
251
365-372
1988
Gallus gallus, Homo sapiens
Manually annotated by BRENDA team
Gunzler, V.; Hanauske-Abel, H.M.; Myllyl, R.; Mohr, J.; Kivirikko, K.I.
Time-dependent inactivation of chick-embryo prolyl 4-hydroxylase by coumalic acid. Evidence for a syncatalytic mechanism
Biochem. J.
242
163-169
1987
Gallus gallus, Homo sapiens
Manually annotated by BRENDA team
Kivirikko, K.I.; Myllyl, R.
Recent developments in posttranslational modification: intracellular processing
Methods Enzymol.
144
96-114
1987
Gallus gallus, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Kuutti, L.R.; Tuderman, L.; Kivirikko, K.I.
Human prolyl hydroxylase. Purification, partial characterization and preparation of antiserum to the enzyme
Eur. J. Biochem.
57
181-188
1975
Homo sapiens
Manually annotated by BRENDA team
Helaakoski, T.; Vuori, K.; Myllyla, R.; Kivirikko, K.I.; Pihlajaniemi, T.
Molecular cloning of the a-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts
Proc. Natl. Acad. Sci. USA
86
4392-4396
1989
Homo sapiens
Manually annotated by BRENDA team
Lamberg, A.; Pihlajaniemi, T.; Kivirikko, K.I.
Site-directed mutagenesis of the a subunit of human prolyl 4-hydroxylase. Identification of three histidine residues critical for catalytic activity
J. Biol. Chem.
270
9926-9931
1995
Homo sapiens
Manually annotated by BRENDA team
Helaakoski, T.; Annunen, P.; Vuori, K.; MacNeil, I.A.; Pihlajaniemi, T.; Kivirikko, K.I.
Cloning, baculovirus expression, and characterization of a second mouse prolyl 4-hydroxylase a-subunit isoform: formation of an a2b2 tetramer with the protein disulfide-isomerase/b subunit
Proc. Natl. Acad. Sci. USA
92
4427-4431
1995
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Mazzorana, M.; Snellman, A.; Kivirikko, K.I.; van der Rest, M.; Pihlajaniemi, T.
Involvement of prolyl 4-hydroxylase in the assembly of trimeric minicollagen XII. Study in baculovirus expression system
J. Biol. Chem.
271
29003-29008
1996
Homo sapiens
Manually annotated by BRENDA team
Annunen, P.; Helaakoski, T.; Myllyharju, J.; Veijola, J.; Pihlajaniemi, T.; Kivirikko, K.I.
Cloning of the human prolyl 4-hydroxylase a subunit isoform a(II) and characterization of the type II enzyme tetramer. The a(I) and a(II) subunits do not form a mixed a(I)a(II)b2 tetramer
J. Biol. Chem.
272
17342-17348
1997
Gallus gallus, Homo sapiens (O15460), Homo sapiens
Manually annotated by BRENDA team
Annunen, P.; Autio-Harmainen, H.; Kivirikko, K.I.
The novel type II prolyl 4-hydroxylase is the main enzyme form in chondrocytes and capillary endothelial cells, whereas the type I enzyme predominates in most cells
J. Biol. Chem.
273
5989-5992
1998
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Annunen, P.; Koivunen, P.; Kivirikko, K.I.
Cloning of the a subunit of prolyl 4-hydroxylase from Drosophila and expression and characterization of the corresponding enzyme tetramer with some unique properties
J. Biol. Chem.
274
6790-6796
1999
Drosophila melanogaster, Homo sapiens
Manually annotated by BRENDA team
Franklin, T.J.; Morris, W.P.; Edwards, P.N.; Large, M.S.; Stephenson, R.
Inhibition of prolyl 4-hydroxylase in vitro and in vivo by members of a novel series of phenanthrolinones
Biochem. J.
353
333-338
2001
Gallus gallus, Homo sapiens, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Manually annotated by BRENDA team
ekkala, M.; Hieta, R.; Kursula, P.; Kivirikko, K.I.; Wierenga, R.K.; Myllyharju, J.
Crystallization of the proline-rich-peptide binding domain of human type I collagen prolyl 4-hydroxylase
Acta Crystallogr. Sect. D
59
940-942
2003
Homo sapiens
Manually annotated by BRENDA team
Nissi, R.; Bohling, T.; Autio-Harmainen, H.
Immunofluorescence localization of prolyl 4-hydroxylase isoenzymes and type I and II collagens in bone tumours: type I enzyme predominates in osteosarcomas and chondrosarcomas, whereas type II enzyme predominates in their benign counterparts
Acta Histochem.
106
111-121
2004
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Tuckerman, J.R.; Zhao, Y.; Hewitson, K.S.; Tian, Y.M.; Pugh, C.W.; Ratcliffe, P.J.; Mole, D.R.
Determination and comparison of specific activity of the HIF-prolyl hydroxylases
FEBS Lett.
576
145-150
2004
Homo sapiens, Homo sapiens (Q96KS0), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Hirsila, M.; Koivunen, P.; Gunzler, V.; Kivirikko, K.I.; Myllyharju, J.
Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor
J. Biol. Chem.
278
30772-30780
2003
Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Hieta, R.; Kukkola, L.; Permi, P.; Pirilae, P.; Kivirikko, K.I.; Kilpelaeinen, I.; Myllyharju, J.
The peptide-substrate-binding domain of human collagen prolyl 4-hydroxylases: backbone assignments, secondary structure, and binding of proline-rich peptides
J. Biol. Chem.
278
34966-34974
2003
Homo sapiens
Manually annotated by BRENDA team
Kukkola, L.; Hieta, R.; Kivirikko, K.I.; Myllyharju, J.
Identification and characterization of a third human, rat, and mouse collagen prolyl 4-hydroxylase isoenzyme
J. Biol. Chem.
278
47685-47693
2003
Rattus norvegicus (Q6W3E9), Mus musculus (Q6W3F0), Mus musculus, Homo sapiens (Q7Z4N8), Homo sapiens
Manually annotated by BRENDA team
Myllyharju, J.
Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis
Matrix Biol.
22
15-24
2003
Arabidopsis thaliana, Drosophila melanogaster, Paramecium bursaria Chlorella virus-1, Homo sapiens (O15460), Homo sapiens (P13674), Caenorhabditis elegans (Q20065)
Manually annotated by BRENDA team
Kersteen, E.A.; Higgin, J.J.; Raines, R.T.
Production of human prolyl 4-hydroxylase in Escherichia coli
Protein Expr. Purif.
38
279-291
2004
Homo sapiens
Manually annotated by BRENDA team
Li, H.C.; Huang, C.C.; Chen, S.F.; Chou, M.Y.
Assembly of homotrimeric type XXI minicollagen by coexpression of prolyl 4-hydroxylase in stably transfected Drosophila melanogaster S2 cells
Biochem. Biophys. Res. Commun.
336
375-385
2005
Homo sapiens
Manually annotated by BRENDA team
Tian, Y.M.; Mole, D.R.; Ratcliffe, P.J.; Gleadle, J.M.
Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation
Biochem. J.
397
179-186
2006
Homo sapiens
Manually annotated by BRENDA team
Cervera, A.M.; Apostolova, N.; Luna-Crespo, F.; Sanjuan-Pla, A.; Garcia-Bou, R.; McCreath, K.J.
An alternatively spliced transcript of the PHD3 gene retains prolyl hydroxylase activity
Cancer Lett.
233
131-138
2006
Homo sapiens
Manually annotated by BRENDA team
Callapina, M.; Zhou, J.; Schnitzer, S.; Metzen, E.; Lohr, C.; Deitmer, J.W.; Bruene, B.
Nitric oxide reverses desferrioxamine- and hypoxia-evoked HIF-1alpha accumulation--implications for prolyl hydroxylase activity and iron
Exp. Cell Res.
306
274-284
2005
Homo sapiens
Manually annotated by BRENDA team
Chen, L.; Shen, Y.H.; Wang, X.; Wang, J.; Gan, Y.; Chen, N.; Wang, J.; LeMaire, S.A.; Coselli, J.S.; Wang, X.L.
Human prolyl-4-hydroxylase alpha(I) transcription is mediated by upstream stimulatory factors
J. Biol. Chem.
281
10849-10855
2006
Homo sapiens
Manually annotated by BRENDA team
Neubauer, A.; Soini, J.; Bollok, M.; Zenker, M.; Sandqvist, J.; Myllyharju, J.; Neubauer, P.
Fermentation process for tetrameric human collagen prolyl 4-hydroxylase in Escherichia coli: improvement by gene optimisation of the PDI/beta subunit and repeated addition of the inducer anhydrotetracycline
J. Biotechnol.
128
308-321
2007
Homo sapiens
Manually annotated by BRENDA team
Neubauer, A.; Neubauer, P.; Myllyharju, J.
High-level production of human collagen prolyl 4-hydroxylase in Escherichia coli
Matrix Biol.
24
59-68
2005
Homo sapiens
Manually annotated by BRENDA team
Choi, K.O.; Lee, T.; Lee, N.; Kim, J.H.; Yang, E.G.; Yoon, J.M.; Kim, J.H.; Lee, T.G.; Park, H.
Inhibition of the catalytic activity of hypoxia-inducible factor-1alpha-prolyl-hydroxylase 2 by a MYND-type zinc finger
Mol. Pharmacol.
68
1803-1809
2005
Homo sapiens
Manually annotated by BRENDA team
Cummins, E.P.; Berra, E.; Comerford, K.M.; Ginouves, A.; Fitzgerald, K.T.; Seeballuck, F.; Godson, C.; Nielsen, J.E.; Moynagh, P.; Pouyssegur, J.; Taylor, C.T.
Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity
Proc. Natl. Acad. Sci. USA
103
18154-18159
2006
Homo sapiens
Manually annotated by BRENDA team
McDonough, M.A.; Li, V.; Flashman, E.; Chowdhury, R.; Mohr, C.; Lienard, B.M.; Zondlo, J.; Oldham, N.J.; Clifton, I.J.; Lewis, J.; McNeill, L.A.; Kurzeja, R.J.; Hewitson, K.S.; Yang, E.; Jordan, S.; Syed, R.S.; Schofield, C.J.
Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)
Proc. Natl. Acad. Sci. USA
103
9814-9819
2006
Homo sapiens
Manually annotated by BRENDA team
Meng, L.; Huang, M.; Ye, X.; Fan, M.; Bian, Z.
Increased expression of collagen prolyl 4-hydroxylases in Chinese patients with hereditary gingival fibromatosis
Arch. Oral Biol.
52
1209-1214
2007
Homo sapiens
Manually annotated by BRENDA team
Villar, D.; Vara-Vega, A.; Landazuri, M.O.; Del Peso, L.
Identification of a region on hypoxia-inducible-factor prolyl 4-hydroxylases that determines their specificity for the oxygen degradation domains
Biochem. J.
408
231-240
2007
Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Gorres, K.L.; Edupuganti, R.; Krow, G.R.; Raines, R.T.
Conformational preferences of substrates for human prolyl 4-hydroxylase
Biochemistry
47
9447-9455
2008
Homo sapiens
Manually annotated by BRENDA team
Zhang, C.; Zhang, M.; Shen, Y.H.; Burks, J.K.; Li, X.; LeMaire, S.A.; Yoshimura, K.; Aoki, H.; Matsuzaki, M.; An, F.; Engler, D.A.; Matsunami, R.K.; Coselli, J.S.; Zhang, Y.; Wang, X.L.
Role of NonO-histone interaction in TNFalpha-suppressed prolyl-4-hydroxylase alpha 1
Biochim. Biophys. Acta
1783
1517-1528
2008
Homo sapiens
Manually annotated by BRENDA team
Koivunen, P.; Tiainen, P.; Hyvaerinen, J.; Williams, K.E.; Sormunen, R.; Klaus, S.J.; Kivirikko, K.I.; Myllyharju, J.
An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha
J. Biol. Chem.
282
30544-30552
2007
Homo sapiens
Manually annotated by BRENDA team
Gorres, K.L.; Raines, R.T.
Direct and continuous assay for prolyl 4-hydroxylase
Anal. Biochem.
386
181-185
2009
Homo sapiens
Manually annotated by BRENDA team
Myllyharju, J.
Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets
Ann. Med.
40
402-417
2008
Caenorhabditis elegans, Chlamydomonas reinhardtii, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Stein, H.; Wilensky, M.; Tsafrir, Y.; Rosenthal, M.; Amir, R.; Avraham, T.; Ofir, K.; Dgany, O.; Yayon, A.; Shoseyov, O.
Production of bioactive, post-translationally modified, heterotrimeric, human recombinant type-I collagen in transgenic tobacco
Biomacromolecules
10
2640-2645
2009
Homo sapiens
Manually annotated by BRENDA team
Qi, H.H.; Ongusaha, P.P.; Myllyharju, J.; Cheng, D.; Pakkanen, O.; Shi, Y.; Lee, S.W.; Peng, J.; Shi, Y.
Prolyl 4-hydroxylation regulates Argonaute 2 stability
Nature
455
421-424
2008
Homo sapiens
Manually annotated by BRENDA team
Gorres, K.L.; Pua, K.H.; Raines, R.T.
Stringency of the 2-His-1-Asp active-site motif in prolyl 4-hydroxylase
PLoS ONE
4
e7635
2009
Homo sapiens
Manually annotated by BRENDA team
Chowdhury, R.; McDonough, M.A.; Mecinovic, J.; Loenarz, C.; Flashman, E.; Hewitson, K.S.; Domene, C.; Schofield, C.J.
Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases
Structure
17
981-989
2009
Homo sapiens
Manually annotated by BRENDA team
Xue, J.; Li, X.; Jiao, S.; Wei, Y.; Wu, G.; Fang, J.
Prolyl hydroxylase-3 is down-regulated in colorectal cancer cells and inhibits IKKbeta independent of hydroxylase activity
Gastroenterology
138
606-615
2010
Homo sapiens
Manually annotated by BRENDA team
Vogel, S.; Wottawa, M.; Farhat, K.; Zieseniss, A.; Schnelle, M.; Le-Huu, S.; von Ahlen, M.; Malz, C.; Camenisch, G.; Katschinski, D.M.
Prolyl hydroxylase domain (PHD) 2 affects cell migration and F-actin formation via RhoA/rho-associated kinase-dependent cofilin phosphorylation
J. Biol. Chem.
285
33756-33763
2010
Homo sapiens
Manually annotated by BRENDA team
Tennant, D.A.; Gottlieb, E.
HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression
J. Mol. Med.
88
839-849
2010
Homo sapiens
Manually annotated by BRENDA team
Spinella, F.; Rosano, L.; Del Duca, M.; Di Castro, V.; Nicotra, M.R.; Natali, P.G.; Bagnato, A.
Endothelin-1 inhibits prolyl hydroxylase domain 2 to activate hypoxia-inducible factor-1alpha in melanoma cells
PLoS ONE
5
e11241
2010
Homo sapiens
Manually annotated by BRENDA team
Pektas, S.; Knapp, M.J.
Substrate preference of the HIF-prolyl hydroxylase-2 (PHD2) and substrate-induced conformational change
J. Inorg. Biochem.
126
55-60
2013
Homo sapiens
Manually annotated by BRENDA team
Yum, S.; Choi, J.; Hong, S.; Park, M.H.; Lee, J.; Ha, N.C.; Jung, Y.
Hyperoxia attenuates the inhibitory effect of nitric oxide donors on HIF prolyl-4-hydroxylase-2: Implication on discriminative effect of nitric oxide on HIF prolyl-4-hydroxylase-2 and collagen prolyl-4-hydroxylase
Biochem. Pharmacol.
82
485-490
2011
Homo sapiens
Manually annotated by BRENDA team
Vasta, J.D.; Higgin, J.J.; Kersteen, E.A.; Raines, R.T.
Bioavailable affinity label for collagen prolyl 4-hydroxylase
Bioorg. Med. Chem.
21
3597-3601
2013
Caenorhabditis elegans, Homo sapiens
Manually annotated by BRENDA team
Song, D.; Li, L.S.; Heaton-Johnson, K.J.; Arsenault, P.R.; Master, S.R.; Lee, F.S.
Prolyl hydroxylase domain protein 2 (PHD2) binds a Pro-Xaa-Leu-Glu motif, linking it to the heat shock protein 90 pathway
J. Biol. Chem.
288
9662-9674
2013
Homo sapiens
Manually annotated by BRENDA team
Duran, R.V.; MacKenzie, E.D.; Boulahbel, H.; Frezza, C.; Heiserich, L.; Tardito, S.; Bussolati, O.; Rocha, S.; Hall, M.N.; Gottlieb, E.
HIF-independent role of prolyl hydroxylases in the cellular response to amino acids
Oncogene
32
4549-4556
2013
Homo sapiens
Manually annotated by BRENDA team
Xiong, G.; Deng, L.; Zhu, J.; Rychahou, P.G.; Xu, R.
Prolyl-4-hydroxylase alpha subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition
BMC Cancer
14
1-1
2014
Homo sapiens (O15460)
Manually annotated by BRENDA team
Liu, X.; Huang, X.; Chen, L.; Zhang, Y.; Li, M.; Wang, L.; Ge, C.; Wang, H.; Zhang, M.
Mechanical stretch promotes matrix metalloproteinase-2 and prolyl-4-hydroxylase alpha1 production in human aortic smooth muscle cells via Akt-p38 MAPK-JNK signaling
Int. J. Biochem. Cell Biol.
62
15-23
2015
Homo sapiens (P13674), Homo sapiens, Rattus norvegicus (P54001), Rattus norvegicus Wistar (P54001)
Manually annotated by BRENDA team
Timmins, A.; Saint-Andre, M.; de Visser, S.P.
Understanding how prolyl-4-hydroxylase structure steers a ferryl oxidant toward scission of a strong C-H bond
J. Am. Chem. Soc.
139
9855-9866
2017
Homo sapiens (P13674), Homo sapiens
Manually annotated by BRENDA team
Shi, R.; Gao, S.; Zhang, J.; Xu, J.; Graham, L.; Yang, X.; Li, C.
Collagen prolyl 4-hydroxylases modify tumor progression
Acta Biochim. Biophys. Sin. (Shanghai)
53
805-814
2021
Homo sapiens (O15460), Homo sapiens (P13674), Homo sapiens (Q7Z4N8)
Manually annotated by BRENDA team
Vasta, J.D.; Choudhary, A.; Jensen, K.H.; McGrath, N.A.; Raines, R.T.
Prolyl 4-hydroxylase substrate isosteres in which an (E)- or (Z)-alkene replaces the prolyl peptide bond
Biochemistry
56
219-227
2017
Chlamydomonas reinhardtii (A8IDI8), Chlamydomonas reinhardtii, Homo sapiens (P13674), Homo sapiens
Manually annotated by BRENDA team
Vasta, J.D.; Raines, R.T.
Collagen prolyl 4-hydroxylase as a therapeutic target
J. Med. Chem.
61
10403-10411
2018
Gallus gallus, Homo sapiens
Manually annotated by BRENDA team
Xiong, G.; Stewart, R.L.; Chen, J.; Gao, T.; Scott, T.L.; Samayoa, L.M.; OConnor, K.; Lane, A.N.; Xu, R.
Collagen prolyl 4-hydroxylase 1 is essential for HIF-1alpha stabilization and TNBC chemoresistance
Nat. Commun.
9
4456
2018
Homo sapiens (P13674), Homo sapiens
Manually annotated by BRENDA team
Murthy, A.V.; Sulu, R.; Koski, M.K.; Tu, H.; Anantharajan, J.; Sah-Teli, S.K.; Myllyharju, J.; Wierenga, R.K.
Structural enzymology binding studies of the peptide-substrate-binding domain of human collagen prolyl 4-hydroxylase (type-II) High affinity peptides have a PxGP sequence motif
Protein Sci.
27
1692-1703
2018
Homo sapiens (O15460), Homo sapiens
Manually annotated by BRENDA team