PADI1

Summary

PADI1 (peptidyl arginine deiminase 1, HGNC:18367) is a protein-coding gene on chromosome 1p36.13, encoding Protein-arginine deiminase type-1 (Q9ULC6). Catalyzes the deimination of arginine residues of proteins.

This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type I enzyme is involved in the late stages of epidermal differentiation, where it deiminates filaggrin and keratin K1, which maintains hydration of the stratum corneum, and hence the cutaneous barrier function. This enzyme may also play a role in hair follicle formation. This gene exists in a cluster with four other paralogous genes.

Source: NCBI Gene 29943 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 130 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_013358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18367
Approved symbol	PADI1
Name	peptidyl arginine deiminase 1
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	HPAD10, PDI1, PDI, PAD1
Ensembl gene	ENSG00000142623
Ensembl biotype	protein_coding
OMIM	607934
Entrez	29943

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375471, ENST00000460293, ENST00000483501, ENST00000648847

RefSeq mRNA: 1 — MANE Select: NM_013358 NM_013358

CCDS: CCDS178

Canonical transcript exons

ENST00000375471 — 16 exons

Exon	Start	End
ENSE00000955380	17240635	17240760
ENSE00001626162	17232819	17232970
ENSE00001635738	17230572	17230679
ENSE00001652409	17222290	17222470
ENSE00001654956	17228948	17229051
ENSE00001656389	17223621	17223693
ENSE00001671968	17228625	17228797
ENSE00001673194	17230085	17230208
ENSE00001821486	17244010	17246007
ENSE00002209398	17205128	17205309
ENSE00003476461	17238616	17238709
ENSE00003542293	17225811	17225928
ENSE00003573493	17224367	17224428
ENSE00003646953	17226033	17226158
ENSE00003690888	17237314	17237458
ENSE00003691076	17239704	17239783

Expression profiles

Bgee: expression breadth broad, 97 present calls, max score 99.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0555 / max 242.5618, expressed in 124 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
987	0.9924	95
988	0.0500	22
989	0.0131	6

Top tissues by expression

119 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.63	gold quality
esophagus mucosa	UBERON:0002469	96.55	gold quality
vagina	UBERON:0000996	79.07	gold quality
skin of leg	UBERON:0001511	77.05	gold quality
zone of skin	UBERON:0000014	76.59	gold quality
skin of abdomen	UBERON:0001416	75.59	gold quality
esophagus	UBERON:0001043	72.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	71.96	gold quality
placenta	UBERON:0001987	70.56	gold quality
tonsil	UBERON:0002372	70.45	gold quality
substantia nigra	UBERON:0002038	62.82	gold quality
minor salivary gland	UBERON:0001830	60.01	gold quality
mucosa of transverse colon	UBERON:0004991	59.62	gold quality
rectum	UBERON:0001052	59.51	gold quality
ectocervix	UBERON:0012249	59.01	gold quality
saliva-secreting gland	UBERON:0001044	58.09	gold quality
uterine cervix	UBERON:0000002	57.86	gold quality
urinary bladder	UBERON:0001255	54.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	54.07	gold quality
hypothalamus	UBERON:0001898	53.70	gold quality
islet of Langerhans	UBERON:0000006	50.62	gold quality
endocervix	UBERON:0000458	48.15	gold quality
metanephros cortex	UBERON:0010533	48.09	gold quality
right lobe of liver	UBERON:0001114	47.53	gold quality
transverse colon	UBERON:0001157	46.77	gold quality
lower esophagus	UBERON:0013473	46.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	46.47	gold quality
putamen	UBERON:0001874	46.10	gold quality
pancreas	UBERON:0001264	45.39	gold quality
liver	UBERON:0002107	45.26	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MZF1, NFKB1, NFKB, RELA, SP1, SP3

miRNA regulators (miRDB)

71 targeting PADI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-208A-5P	99.42	70.83	1913

Literature-anchored findings (GeneRIF, showing 13)

• cloning, gene organization, and expression analysis (PMID:12416996)
• peptidylarginine deiminase types 1 and 3 loci map to chromosomal band 1p36.13 (PMID:15150696)
• PAD1 and 3 are able to modify filaggrin (PMID:15675958)
• PAD1 is co-located with filaggrin within the filamentous matrix of the deeper corneocytes where the protein is deiminated. (PMID:16091842)
• MZF1 and Sp1/Sp3 binding to the promoter region drive the PADI1 expression in keratinocytes (PMID:17851584)
• The expressoin of COL1A1-PADI1 genes were particularly effective in distinguishing OCSS from normal tissue. (PMID:18669583)
• peptidylarginine deiminase citrullinates the chemokine CXCL8, and thus may dampen neutrophil extravasation during acute or chronic inflammation (PMID:18710930)
• NF-kappaB-mediated signaling pathway is involved in PADI1 regulation in human epidermal keratinocytes (PMID:20596086)
• Identify acefylline as an activator of peptidylarginine deiminase 1 and 3 in the epidermis, resulting in filaggrin deimination. (PMID:26616205)
• Authors showed that PAD1 interacts with and citrullinates MEK1 thereby disrupting MEK1-catalyzed ERK1/2 phosphorylation, thus leading to the MMP2 overexpression. (PMID:28844713)
• Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases. (PMID:31952341)
• Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation. (PMID:33741961)
• IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes: Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation. (PMID:34352263)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	padi2	ENSDARG00000044167
mus_musculus	Padi1	ENSMUSG00000025329
rattus_norvegicus	Padi1	ENSRNOG00000007067

Paralogs (4): PADI2 (ENSG00000117115), PADI3 (ENSG00000142619), PADI4 (ENSG00000159339), PADI6 (ENSG00000276747)

Protein

Protein identifiers

Protein-arginine deiminase type-1 — Q9ULC6 (reviewed: Q9ULC6)

Alternative names: Peptidylarginine deiminase I, Protein-arginine deiminase type I

All UniProt accessions (1): Q9ULC6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the deimination of arginine residues of proteins.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in epidermal keratinocytes (at protein level). Epidermis, prostate, testis, placenta, spleen and thymus.

Similarity. Belongs to the protein arginine deiminase family.

RefSeq proteins (1): NP_037490* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004303	PAD	Family
IPR008972	Cupredoxin	Homologous_superfamily
IPR013530	PAD_C	Domain
IPR013732	PAD_N	Domain
IPR013733	Prot_Arg_deaminase_cen_dom	Domain
IPR036556	PAD_central_sf	Homologous_superfamily
IPR038685	PAD_N_sf	Homologous_superfamily

Pfam: PF03068, PF08526, PF08527

Enzyme classification (BRENDA):

• EC 3.5.3.15 — protein-arginine deiminase (BRENDA: 14 organisms, 435 substrates, 132 inhibitors, 239 Km, 204 kcat entries)

Substrate kinetics (BRENDA)

63 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-ALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.1–30	62
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.27–2.77	21
NALPHA-BENZOYL L-ARGININE ETHYL ESTER	0.44–1.7	20
[HISTONE H4]-L-ARG	0.088–0.35	17
BENZOYL-L-ARG	0.0029–33.6	6
ACETYL-L-ARG METHYL ESTER	1.19–66.3	5
BENZOYL-ARG ETHYL ESTER	0.33–0.78	4
BENZOYL-L-ARG ETHYL ESTER	0.35–7.5	4
N-ALPHA-BENZOYL-L-ARGININE AMIDE	0.16–17.5	4
AC-SER-GLY-ARG-GLY-ACETYL-LYS-GLY-GLY-ACETYL-LYS	0.15–1.07	3
AC-SER-GLY-ARG-GLY-LYS-GLY-GLY-LYS-GLY-LEU-GLY-L	0.15–0.59	3
AC-SER-GLY-ARG-GLY-LYS-GLY-GLY-LYS-GLY-LEU-GLY-L	0.22–1.95	3
AC-SER-GLY-ARG-GLY-LYS-GLY-GLY-LYS-GLY-LEU-GLY-L	0.21–0.64	3
AC-SER-GLY-ARG-GLY-LYS-GLY-GLY-LYS-GLY-LEU-GLY-L	0.48–3.27	3
ACETYL-L-ARG	0.91–11.3	3

Catalyzed reactions (Rhea), 1 shown:

• L-arginyl-[protein] + H2O = L-citrullyl-[protein] + NH4(+) (RHEA:18089)

UniProt features (90 total): strand 45, helix 18, binding site 17, turn 5, sequence conflict 2, chain 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5HP5	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULC6-F1	94.70	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 645 (nucleophile)

Ligand- & substrate-binding residues (17): 179; 351; 353; 364; 371; 372; 375; 409; 412; 153; 155; 155 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3247509	Chromatin modifying enzymes

MSigDB gene sets: 83 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, TGGNNNNNNKCCAR_UNKNOWN, SHEN_SMARCA2_TARGETS_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS_IN_LINEAR_AMIDINES, MZF1_01, YOSHIMURA_MAPK8_TARGETS_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS, chr1p36, LEE_BMP2_TARGETS_UP, KRIEG_HYPOXIA_NOT_VIA_KDM3A, RATTENBACHER_BOUND_BY_CELF1, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, PRC1_BMI_UP.V1_DN

GO Biological Process (0):

GO Molecular Function (5): protein-arginine deiminase activity (GO:0004668), calcium ion binding (GO:0005509), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines	1
metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PADI1	FLG2	Q5D862	589
PADI1	FLG	P20930	571
PADI1	EDEM1	Q92611	553
PADI1	TCHH	Q07283	530
PADI1	TRIM3	O75382	471
PADI1	ELANE	P08246	432
PADI1	MPO	P05164	415
PADI1	KDELR1	P24390	398
PADI1	CFAP95	Q5VTT2	393
PADI1	BLZF1	Q9H2G9	390
PADI1	ARG2	P78540	373
PADI1	SEC61A1	P38378	351
PADI1	DNAJC10	Q8IXB1	348
PADI1	LEF1	Q9UJU2	340
PADI1	DERL1	Q9BUN8	325

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PADI1	STAP2	psi-mi:“MI:0915”(physical association)	0.590
TP53	PADI1	psi-mi:“MI:0915”(physical association)	0.400
PADI3	NFKB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): PADI1 (Reconstituted Complex), PADI1 (Proximity Label-MS), STAP2 (Affinity Capture-MS), PADI1 (Affinity Capture-MS), SQSTM1 (Protein-peptide), PADI1 (Affinity Capture-MS), PADI1 (Affinity Capture-MS), PADI1 (Affinity Capture-MS), PADI1 (Affinity Capture-MS), STAP2 (Affinity Capture-MS), PADI1 (Positive Genetic)

ESM2 similar proteins: A6NC97, A8MVJ9, F4IRQ5, F4ISV6, F4IY62, G5ECQ8, O02849, O15091, O64967, O88806, P10759, P17532, P20717, P23109, P53215, P70708, Q05B50, Q08642, Q0EAB8, Q2HZ26, Q3V1D3, Q4R366, Q54E29, Q5K651, Q5M965, Q6BKD4, Q6CW75, Q6CY84, Q6DDV1, Q6FPX3, Q75DJ3, Q7SDM8, Q86VD1, Q8C5W4, Q8CGU9, Q8CGV2, Q8IVG5, Q8IWU9, Q8L627, Q9CY52

Diamond homologs: O02849, O88806, O88807, P20717, P70708, Q08642, Q6TGC4, Q8K3V4, Q9ULC6, Q9ULW8, Q9UM07, Q9Y2J8, Q9Z183, Q9Z184, Q9Z185

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

130 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2420 predictions. Top by Δscore:

Variant	Effect	Δscore
1:17205308:AGG:A	donor_loss	1.0000
1:17205311:T:G	donor_loss	1.0000
1:17225803:T:TA	acceptor_gain	1.0000
1:17225809:A:AG	acceptor_gain	1.0000
1:17225810:G:GG	acceptor_gain	1.0000
1:17225924:GGCTG:G	donor_gain	1.0000
1:17225925:GCTG:G	donor_gain	1.0000
1:17225925:GCTGG:G	donor_gain	1.0000
1:17226031:A:AG	acceptor_gain	1.0000
1:17226032:G:GT	acceptor_gain	1.0000
1:17226032:GAC:G	acceptor_gain	1.0000
1:17226135:GA:G	donor_gain	1.0000
1:17226137:G:GG	donor_gain	1.0000
1:17226371:G:GT	donor_gain	1.0000
1:17228622:TAG:T	acceptor_loss	1.0000
1:17228624:G:GT	acceptor_loss	1.0000
1:17228946:A:AG	acceptor_gain	1.0000
1:17228946:A:G	acceptor_loss	1.0000
1:17228947:G:GT	acceptor_gain	1.0000
1:17228947:GA:G	acceptor_gain	1.0000
1:17228947:GAC:G	acceptor_gain	1.0000
1:17228947:GACC:G	acceptor_gain	1.0000
1:17228947:GACCC:G	acceptor_gain	1.0000
1:17229037:GCT:G	donor_gain	1.0000
1:17229049:CAG:C	donor_loss	1.0000
1:17229051:GGT:G	donor_loss	1.0000
1:17229052:G:GC	donor_loss	1.0000
1:17229053:T:G	donor_loss	1.0000
1:17230080:TACA:T	acceptor_loss	1.0000
1:17230081:ACAG:A	acceptor_loss	1.0000

AlphaMissense

4393 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:17232900:A:C	S415R	0.999
1:17232902:C:A	S415R	0.999
1:17232902:C:G	S415R	0.999
1:17230200:T:A	W349R	0.997
1:17230200:T:C	W349R	0.997
1:17237399:T:A	W467R	0.996
1:17237399:T:C	W467R	0.996
1:17232890:C:A	N411K	0.995
1:17232890:C:G	N411K	0.995
1:17229002:T:A	W294R	0.994
1:17229002:T:C	W294R	0.994
1:17230202:G:C	W349C	0.994
1:17230202:G:T	W349C	0.994
1:17230573:A:T	D352V	0.994
1:17244204:G:C	R651S	0.994
1:17244204:G:T	R651S	0.994
1:17230572:G:C	D352H	0.993
1:17230573:A:C	D352A	0.993
1:17232892:T:C	L412P	0.993
1:17238619:T:C	F488L	0.993
1:17238621:C:A	F488L	0.993
1:17238621:C:G	F488L	0.993
1:17244203:G:C	R651T	0.992
1:17232943:G:C	R429P	0.991
1:17232886:G:T	G410V	0.990
1:17240654:G:C	R551P	0.990
1:17244015:C:A	N588K	0.990
1:17244015:C:G	N588K	0.990
1:17244186:T:G	C645W	0.990
1:17230194:G:C	D347H	0.989

dbSNP variants (sampled 300 via entrez): RS1000027270 (1:17236922 G>A), RS1000060758 (1:17217497 A>G,T), RS1000454142 (1:17221693 C>A), RS1000488515 (1:17227821 C>T), RS1000542627 (1:17232495 G>T), RS1000609479 (1:17232237 C>G,T), RS1000674422 (1:17203774 C>A,T), RS1000726567 (1:17203946 T>C), RS1000787493 (1:17227556 A>C), RS1000839259 (1:17228084 G>A), RS1000845754 (1:17221893 G>C), RS1000859829 (1:17214054 A>C), RS1000863169 (1:17208109 G>A,C,T), RS1000920025 (1:17243431 C>G,T), RS1000920937 (1:17209211 G>A)

Disease associations

OMIM: gene MIM:607934 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002655_13	IgA nephropathy	2.000000e-06
GCST009391_1730	Metabolite levels	2.000000e-06
GCST011680_2	Depression in multiple sclerosis	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010375	phosphatidylcholine 34:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1909486 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,337 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11417	STREPTONIGRIN	2	43,337

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 3.5.3.15 Peptidyl arginine deiminases (PADI)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
o-F-amidine	Irreversible inhibition	5.85	pIC50

ChEMBL bioactivities

11 potent at pChembl≥5 of 19 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	IC50	70	nM	CHEMBL58150
6.10	IC50	800	nM	CHEMBL5715918
6.10	IC50	800	nM	CHEMBL1910972
6.08	IC50	840	nM	CHEMBL1910971
6.02	IC50	960	nM	CHEMBL60908
6.02	IC50	950	nM	CHEMBL57818
5.85	IC50	1400	nM	CHEMBL1910970
5.64	IC50	2270	nM	CHEMBL3113470
5.34	IC50	4550	nM	CHEMBL1714002
5.07	IC50	8500	nM	CHEMBL5093554
5.03	Ki	9400	nM	CHEMBL1910970

PubChem BioAssay actives

10 with measured affinity, of 130 total; 9 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-(7-amino-5,8-dioxoquinolin-2-yl)pyridine-2-carboxylic acid	1069622: Inhibition of recombinant wild-type PAD1 (unknown origin) using N-alpha-Benzoyl-L-arginine amide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	0.0700	uM
N-[(2S)-1-amino-5-[(1-amino-2-chloroethylidene)amino]-1-oxopentan-2-yl]benzamide;2,2,2-trifluoroacetic acid	627372: Irreversible inhibition of PAD1 assessed as hydrolysis of benzoyl-L-arginine ethyl ester preincubated for 15 mins measured after 15 mins by fluorometric analysis	ic50	0.8000	uM
2-[[(2S)-1-amino-5-[(1-amino-2-chloroethylidene)amino]-1-oxopentan-2-yl]carbamoyl]benzoic acid;2,2,2-trifluoroacetic acid	627372: Irreversible inhibition of PAD1 assessed as hydrolysis of benzoyl-L-arginine ethyl ester preincubated for 15 mins measured after 15 mins by fluorometric analysis	ic50	0.8400	uM
7-amino-2-pyridin-2-ylquinoline-5,8-dione	1069622: Inhibition of recombinant wild-type PAD1 (unknown origin) using N-alpha-Benzoyl-L-arginine amide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	0.9500	uM
7-aminoquinoline-5,8-dione	1069622: Inhibition of recombinant wild-type PAD1 (unknown origin) using N-alpha-Benzoyl-L-arginine amide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	0.9600	uM
2-[[(2S)-1-amino-5-[(1-amino-2-fluoroethylidene)amino]-1-oxopentan-2-yl]carbamoyl]benzoic acid;2,2,2-trifluoroacetic acid	627372: Irreversible inhibition of PAD1 assessed as hydrolysis of benzoyl-L-arginine ethyl ester preincubated for 15 mins measured after 15 mins by fluorometric analysis	ic50	1.4000	uM
7-amino-6-bromoquinoline-5,8-dione	1069622: Inhibition of recombinant wild-type PAD1 (unknown origin) using N-alpha-Benzoyl-L-arginine amide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	2.2700	uM
7-bromo-6-methoxyquinoline-5,8-dione	1069622: Inhibition of recombinant wild-type PAD1 (unknown origin) using N-alpha-Benzoyl-L-arginine amide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by COLDER assay	ic50	4.5500	uM
(3S)-3-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-4-[[(2S)-1-amino-5-[(1-amino-2-fluoroethylidene)amino]-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1813079: Inhibition of PAD1 (unknown origin)	ic50	8.5000	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Estradiol	affects cotreatment, increases expression, increases reaction	3
bisphenol A	decreases methylation, increases expression	2
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

29 unique, capped per target: 28 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1912611	Binding	Irreversible inhibition of PAD1 assessed as citrulline formation at 1 mM measured after 20 hrs by colorimetric assay in presence of 2 mM benzoyl-L-arginine ethyl ester	The development of N-α-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-α-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors. — J Med Chem
CHEMBL5723214	Functional	Affinity Biochemical interaction: (enzyme inhibition, measure production of citrulline colorimetrically) EUB0002538aAD PADI1	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.