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Information on EC 3.5.3.15 - protein-arginine deiminase and Organism(s) Mus musculus and UniProt Accession Q08642
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3.5.3.15 protein-arginine deiminaseIUBMB Comments
Also acts on N-acyl-L-arginine and, more slowly, on L-arginine esters.
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Word Map
- 3.5.3.15
-
citrullination
-
rheumatoid
- arthritis
- histone
- autoimmune
-
deimination
- autoantibody
-
anti-citrullinated
- chromatin
-
acpas
- epitope
- synovial
-
padis
- porphyromonas
-
anti-ccp
-
netosis
- periodontitis
- gingivalis
- sclerosis
- fibrinogen
-
anti-cyclic
- vimentin
-
hla-drb1
- elastase
- autoantigens
- ptpn22
-
decondensation
- cl-amidine
-
lupus
- erythematosus
- myeloperoxidase
- pharmacology
-
self-antigens
-
ra-associated
-
gingipains
- synoviocytes
-
rheumatology
- medicine
-
arginyl
-
erosive
- analysis
- drug development
- fibrin
-
non-hla
- filaggrin
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
padi4, peptidylarginine deiminase, padi2, peptidyl arginine deiminase, peptidylarginine deiminase 4, padi3, pad-4, padi1, peptidylarginine deiminase type 4, protein arginine deiminase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
deiminase, protein (arginine)
-
-
-
-
HL-60 PAD
-
-
-
-
PAD
PAD-H19
-
-
-
-
PAD-R11
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-
-
-
PAD-R4
-
-
-
-
PAD4
peptidylarginine deiminase
Peptidylarginine deiminase type alpha
-
-
-
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protein arginine deiminase
-
-
-
-
PAD
-
-
-
-
peptidylarginine deiminase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amidine hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
protein-L-arginine iminohydrolase
Also acts on N-acyl-L-arginine and, more slowly, on L-arginine esters.
CAS REGISTRY NUMBER
COMMENTARY
75536-80-0
-
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
benzoyl-L-arginine ethyl ester + H2O
benzoyl-L-citrulline ethyl ester + NH3
-
-
-
?
glial fibrillary acidic protein-L-Arg + H2O
glial fibrillary acidic protein-L-citrulline + NH3
-
-
-
?
heat shock protein 8 L-Arg + H2O
heat shock protein 8 L-citrulline + NH3
-
-
-
?
myelin basic protein L-arginine + H2O
myelin basic protein L-citrulline + NH3
-
-
-
?
myelin basic protein-L-Arg + H2O
myelin basic protein-L-citrulline + NH3
-
-
-
?
myelin basic protein-L-arginine + H2O
myelin basic protein-L-citrulline + NH3
-
-
-
?
neuron-specific enolase 2 L-Arg + H2O
neuron-specific enolase 2 L-citrulline + NH3
-
-
-
?
peptidylprolyl isomerase A L-Arg + H2O
peptidylprolyl isomerase A L-citrulline + NH3
-
-
-
?
voltage-dependent anion channel 1 L-Arg + H2O
voltage-dependent anion channel 1 L-citrulline + NH3
-
-
-
?
[mitochondrial malate dehydrogenase 2]-L-arginine + H2O
[mitochondrial malate dehydrogenase 2]-L-citrulline + NH3
-
-
-
?
benzoyl-Arg methyl ester + H2O
benzoyl-citrulline methyl ester + NH3
-
-
-
-
?
benzoyl-L-Arg-NH2 + H2O
benzoyl-L-citrullineamide + NH3
-
peptidyl arginine deiminase I shows highest activity towards
-
-
?
myelin basic protein-L-arginine + H2O
myelin basic protein-L-citrulline + NH3
-
-
-
?
N-alpha-benzoyl-L-arginine ethyl ester + H2O
N-alpha-benzoyl-L-citrulline ethyl ester + NH3
-
-
-
-
?
Nalpha-benzoyl-L-arginine ethyl ester + H2O
Nalpha-benzoyl-L-citrulline ethyl ester + NH3
-
-
-
-
?
protamine + H2O
? + NH3
-
peptidyl arginine deiminase III shows highest activity towards
-
-
?
benzoyl-Arg ethyl ester + H2O
benzoyl-citrulline ethyl ester + NH3
-
-
-
?
benzoyl-Arg ethyl ester + H2O
benzoyl-citrulline ethyl ester + NH3
-
peptidyl arginine deiminase II shows highest activity towards
-
-
?
protein L-Arg + H2O
?
-
expression of the enzyme in luminal and glandular epithelia of the uterus is controlled by amount of the steroid hormones estrogen and progesterone
-
-
?
protein-L-arginine + H2O
protein-L-citrulline + NH3
-
development and evaluation of a highly sensitive antibody-based assay method for PAD activity determination, overview
-
-
?
additional information
?
-
proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis. Pressure-induced translational control of PAD2 expression is consistent with a possible role for PAD2 and citrullination in primary open-angle glaucoma
-
-
?
additional information
?
-
-
proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis. Pressure-induced translational control of PAD2 expression is consistent with a possible role for PAD2 and citrullination in primary open-angle glaucoma
-
-
?
additional information
?
-
the cortical granule enzyme plays a role in preimplantation embryonic development
-
-
?
additional information
?
-
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the cortical granule enzyme plays a role in preimplantation embryonic development
-
-
?
additional information
?
-
PAD 6 is essential for oocyte cytoskeletal sheet formation and female fertility, it plays an important role in germ-cell-specific structures in zygote/embryo development, citrullination is a regulator of fertility, overview
-
-
?
additional information
?
-
-
IKKgamma and PAD2 can coimmunoprecipitate in the presence of the Ca2+ ionophore
-
-
?
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
myelin basic protein-L-arginine + H2O
myelin basic protein-L-citrulline + NH3
-
-
-
?
myelin basic protein-L-arginine + H2O
myelin basic protein-L-citrulline + NH3
-
-
-
?
protein L-Arg + H2O
?
-
expression of the enzyme in luminal and glandular epithelia of the uterus is controlled by amount of the steroid hormones estrogen and progesterone
-
-
?
additional information
?
-
proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis. Pressure-induced translational control of PAD2 expression is consistent with a possible role for PAD2 and citrullination in primary open-angle glaucoma
-
-
?
additional information
?
-
-
proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis. Pressure-induced translational control of PAD2 expression is consistent with a possible role for PAD2 and citrullination in primary open-angle glaucoma
-
-
?
additional information
?
-
the cortical granule enzyme plays a role in preimplantation embryonic development
-
-
?
additional information
?
-
-
the cortical granule enzyme plays a role in preimplantation embryonic development
-
-
?
additional information
?
-
PAD 6 is essential for oocyte cytoskeletal sheet formation and female fertility, it plays an important role in germ-cell-specific structures in zygote/embryo development, citrullination is a regulator of fertility, overview
-
-
?
additional information
?
-
-
IKKgamma and PAD2 can coimmunoprecipitate in the presence of the Ca2+ ionophore
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
-
half-maximal activity: 2 mM for peptidyl arginine deiminase I and 4 mM for peptidyl arginine deiminase III
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lipid vesicle
binding of substrate myelin basic protein to lipid vesicles, consisting of 7.8% phosphatidylserine and 92.2% phosphatidylcholine, increases deimination activity, but in the 40 mino acid C-terminal region, where the arginyl residues are no longer deiminated, while they are deiminated in aqueous solution
-
lipid vesicle
binding of substrate myelin basic protein to lipid vesicles, consisting of 7.8% phosphatidylserine and 92.2% phosphatidylcholine, increases deimination activity, but in the 40 mino acid C-terminal region, where the arginyl residues are no longer deiminated, while they are deiminated in aqueous solution
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lipid vesicle
binding of substrate myelin basic protein to lipid vesicles, consisting of 7.8% phosphatidylserine and 92.2% phosphatidylcholine, increases deimination activity, but in the 40 amino acid residue C-terminal region, where the arginyl residues are no longer deiminated, while they are deiminated in aqueous solution
-
lipid vesicle
binding of substrate myelin basic protein to lipid vesicles, consisting of 7.8% phosphatidylserine and 92.2% phosphatidylcholine, increases deimination activity, but in the 40 amino acid residue C-terminal region, where the arginyl residues are no longer deiminated, while they are deiminated in aqueous solution
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
development and evaluation of a highly sensitive antibody-based assay method for PAD activity determination, overview
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
from older, glaucomatous DBA/2J mice (primary open-angle glaucoma), but not in younger DGB/2J or control C57BL6J mice
-
the level of the enzyme in theses cells decreases as the cells differentiate
additional information
-
tissue distribution, no activity in testis and liver, overview
pressure-treated astrocytes exhibit elevated PAD2 and citrullination without apparent change in PAD2 mRNA
PAD2 immunoreactivity is increased in Scrapie-infected brains, with staining detected primarily in reactive astrocytes
expression levels of PAD2 protein as well as its enzyme activity are significantly increased in brain sections of Scrapie-infected mice, including hippocampus, brain stem, and striatum
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Pad6 mRNA expression is localized to oocytes from primordial through antral follicles, but excluded from granulosa cells, theca cells, and corpora lutea
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ovariectomized, amount of the enzyme in the uterus is considerably diminished by ovariectomy, the expression of the enzyme in luminal andd glandular epithelia is controlled by the amount of the steroid hormones estrogen and progesterone
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PAD4 associated with chromatin and with intermediate filaments in the axon
-
in mouse in vitro fertilized embryos, nuclear translocation starts from the 2-cell stage and gradually increases up to blastocyst
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
in fetal testes from Sox9 knockout mice, Pai2 expression is greatly reduced. Padi-/- XY mice are fertile and show no apparent reproductive anomalies. No significant difference in H3 citrullination between wildtype and Padi2-/- XY gonads is observed
malfunction
-
overexpressing PAD2 reduces LPS-mediated COX-2 up-regulation by 50%. PAD2 overexpression also reduces NF-kappaB activity
physiological function
physiological function
-
despite PAD2's normally inactive status, it becomes active and citrullinates cellular proteins, but only when the intracellular Ca2+ balance is upset during neurodegenerative changes. Abnormal protein citrullination by PAD2 is closely associated with the pathogenesis of neurodegenerative disorders such as Alzheimers disease and prion disease
physiological function
-
incubation of purified PAD2 and IKKgamma proteins in the presence of Ca2+ citrullinate IKKgamma. Results demonstrate that PAD2 interacts with IKKgamma and suppresses NF-kappaB activity
physiological function
-
the target of citrullination is histone protein (H3), not B23. Therefore the presence of PAD4 and citrullinated histone H3 in oocytes and embryos suggests a possible role for PAD4 in preimplantation embryonic development
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). PADI2_MOUSE
673
0
76250
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
75000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
no modification
-
the potential Asn-linked glycosylation site, Asn542-Glu543-Ser544 has no carbohydrate moiety
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DELTA1-385
-
IKKgamma co-immunoprecipitates truncation mutants, PAD2(1-385) and PAD2(355-672)
DELTA355-672
-
IKKgamma co-immunoprecipitates truncation mutants, PAD2(1-385) and PAD2(355-672)
Q358A
-
substitution of Gln-358 (a putative ligand for Ca2+ binding) with an Ala abolishes co-immunoprecipitation with IKKgamma
additional information
additional information
inactivation of PAD2 does not affect PAD4 activity, but leads to limited deimination due to the narrower cleavage spectrum of arginyl residues in myelin basic protein for PAD4, overview
additional information
inactivation of PAD2 does not affect PAD4 activity, but leads to limited deimination due to the narrower cleavage spectrum of arginyl residues in myelin basic protein for PAD4, overview
additional information
generation of PAD6-deficient mice, enzyme inactivation affects female, but not male, fertility, it results in dispersal of the cytoskeletal sheets in oocytes, phenotype, overview
additional information
inactivation of PAD2 does not affect PAD4 activity, but leads to limited deimination due to the narrower cleavage spectrum of arginyl residues in myelin basic protein for PAD4, overview
additional information
inactivation of PAD2 does not affect PAD4 activity, but leads to limited deimination due to the narrower cleavage spectrum of arginyl residues in myelin basic protein for PAD4, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
SOX9 positively regulates Padi2 transcription and FOXL2 antagonizes it in TM3 cells
PAD2 mRNA expression is detected in the brains of mice as early as embryonic day 15, and its expression in cerebral cortex, hippocampus, and cerebellum increases significantly as the animals age from 3 to 30 months old, PAD2 mRNA levels in the cerebral cortex, cerebellum, and hippocampus at 30 months were about 1.6fold,1.5fold, and 1.6fold higher, respectively, than in 3-month-old animals
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peptidylarginine deiminase 6 is downregulated in newborn ovary homeobox-null ovaries
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Takahara, H.; Kusubata, M.; Tsuchida, M.; Kohsaka, T.; Tagami, S.; Sugawara, K.
Expression of peptidylarginine deiminase in the uterine epithelial cells of mouse is dependent on estrogen
J. Biol. Chem.
267
520-525
1992
Mus musculus
Tsuchida, M.; Takahara, H.; Ninami, N.; Arai, T.; Kobayashi, Y.; Tsujimoto, H.; Fukazawa, C.; Sugawara, K.
cDNA nucleotide sequence and primary structure of mouse uterine peptidylarginine deiminase. Detection of a 3'-untranslated nucleotide sequence common to the mRNA of transiently expressed genes and rapid turnover of this enzymes mRNA in the estrous cycle
Eur. J. Biochem.
215
677-685
1993
Mus musculus
Ohsugi, I.; Takahara, H.; Shiraiwa, M.; Sugawara, K.
Expression of mouse uterine peptidylarginine deiminase in Escherichia coli: construction of expression plasmid and properties of the recombinant enzyme
Arch. Biochem. Biophys.
317
62-68
1995
Mus musculus
Terakawa, H.; Takahara, H.; Sugawara, K.
Three types of mouse peptidylarginine deiminase: characterization and tissue distribution
J. Biochem.
110
661-666
1991
Mus musculus
Nagata, S.; Senshu, T.
Peptidylarginine deiminase in rat and mouse hemopoietic cells
Experientia
46
72-74
1990
Mus musculus, Rattus norvegicus
Pritzker, L.B.; Nguyen, T.A.; Moscarello, M.A.
The developmental expression and activity of peptidylarginine deiminase in the mouse
Neurosci. Lett.
266
161-164
1999
Mus musculus
Koike, H.; Shiraiwa, M.; Sugawara, K.; Kohsaka, T.; Takahara, H.
Existence and differential changes of peptidylarginine deiminase type II in mouse yolk-sac erythroid cells
Biosci. Biotechnol. Biochem.
59
552-554
1995
Mus musculus
Bhattacharya, S.K.; Crabb, J.S.; Bonilha, V.L.; Gu, X.; Takahara, H.; Crabb, J.W.
Proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis
Invest. Ophthalmol. Vis. Sci.
47
2508-2514
2006
Mus musculus (Q08642), Mus musculus
Liu, M.; Oh, A.; Calarco, P.; Yamada, M.; Coonrod, S.A.; Talbot, P.
Peptidylarginine deiminase (PAD) is a mouse cortical granule protein that plays a role in reimplantation embryonic development
Reprod. Biol. Endocrinol.
3
42
2005
Mus musculus (Q8K3V4), Mus musculus
Zendman, A.J.; Raijmakers, R.; Nijenhuis, S.; Vossenaar, E.R.; Tillaart, M.; Chirivi, R.G.; Raats, J.M.; van Venrooij, W.J.; Drijfhout, J.W.; Pruijn, G.J.
ABAP: antibody-based assay for peptidylarginine deiminase activity
Anal. Biochem.
369
232-240
2007
Oryctolagus cuniculus, Mus musculus, Homo sapiens (Q9Y2J8), Homo sapiens, Mus musculus C57BL/6 / 129S
Wood, D.D.; Ackerley, C.A.; Brand, B.; Zhang, L.; Raijmakers, R.; Mastronardi, F.G.; Moscarello, M.A.
Myelin localization of peptidylarginine deiminases 2 and 4: comparison of PAD2 and PAD4 activities
Lab. Invest.
88
354-364
2008
Homo sapiens, Mus musculus (Q08642), Mus musculus (Q9Z183), Mus musculus CD-1 (Q08642), Mus musculus CD-1 (Q9Z183)
Esposito, G.; Vitale, A.M.; Leijten, F.P.; Strik, A.M.; Koonen-Reemst, A.M.; Yurttas, P.; Robben, T.J.; Coonrod, S.; Gossen, J.A.
Peptidylarginine deiminase (PAD) 6 is essential for oocyte cytoskeletal sheet formation and female fertility
Mol. Cell. Endocrinol.
273
25-31
2007
Mus musculus (Q8K3V4)
Jang, B.; Kim, E.; Choi, J.K.; Jin, J.K.; Kim, J.I.; Ishigami, A.; Maruyama, N.; Carp, R.I.; Kim, Y.S.; Choi, E.K.
Accumulation of citrullinated proteins by up-regulated peptidylarginine deiminase 2 in brains of scrapie-infected mice: a possible role in pathogenesis
Am. J. Pathol.
173
1129-1142
2008
Mus musculus (Q08642)
Choi, M.; Lee, O.H.; Jeon, S.; Park, M.; Lee, D.R.; Ko, J.J.; Yoon, T.K.; Rajkovic, A.; Choi, Y.
The oocyte-specific transcription factor, Nobox, regulates the expression of Pad6, a peptidylarginine deiminase in the oocyte
FEBS Lett.
584
3629-3634
2010
Mus musculus
Shimada, N.; Handa, S.; Uchida, Y.; Fukuda, M.; Maruyama, N.; Asaga, H.; Choi, E.K.; Lee, J.; Ishigami, A.
Developmental and age-related changes of peptidylarginine deiminase 2 in the mouse brain
J. Neurosci. Res.
88
798-806
2010
Mus musculus
Lee, H.J.; Joo, M.; Abdolrasulnia, R.; Young, D.G.; Choi, I.; Ware, L.B.; Blackwell, T.S.; Christman, B.W.
Peptidylarginine deiminase 2 suppresses inhibitory {kappa}B kinase activity in lipopolysaccharide-stimulated RAW 264.7 macrophages
J. Biol. Chem.
285
39655-39662
2010
Mus musculus
Brahmajosyula, M.; Miyake, M.
Localization and expression of peptidylarginine deiminase 4 (PAD4) in mammalian oocytes and preimplantation embryos
Zygote
21
314-324
2013
Mus musculus, Sus scrofa
Tsuji-Hosokawa, A.; Kashimada, K.; Kato, T.; Ogawa, Y.; Nomura, R.; Takasawa, K.; Lavery, R.; Coschiera, A.; Schlessinger, D.; Harley, V.R.; Takada, S.; Morio, T.
Peptidyl arginine deiminase 2 (Padi2) is expressed in Sertoli cells in a specific manner and regulated by SOX9 during testicular development
Sci. Rep.
8
13263
2018
Mus musculus (Q08642)
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