ART1

Summary

ART1 (ADP-ribosyltransferase 1, HGNC:723) is a protein-coding gene on chromosome 11p15.4, encoding GPI-linked NAD(P)(+)–arginine ADP-ribosyltransferase 1 (P52961). Has ADP-ribosyltransferase activity toward GLP1R.

ADP-ribosyltransferase catalyzes the ADP-ribosylation of arginine residues in proteins. Mono-ADP-ribosylation is a posttranslational modification of proteins that is interfered with by a variety of bacterial toxins including cholera, pertussis, and heat-labile enterotoxins of E. coli. The amino acid sequence consists of predominantly hydrophobic N- and C-terminal regions, which is characteristic of glycosylphosphatidylinositol (GPI)-anchored proteins. This gene was previously designated ART2.

Source: NCBI Gene 417 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 86 total
• Druggable target: yes
• MANE Select transcript: NM_004314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:723
Approved symbol	ART1
Name	ADP-ribosyltransferase 1
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	ART2, CD296, ARTC1
Ensembl gene	ENSG00000129744
Ensembl biotype	protein_coding
OMIM	601625
Entrez	417

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000250693, ENST00000529556, ENST00000948756, ENST00000948757

RefSeq mRNA: 1 — MANE Select: NM_004314 NM_004314

CCDS: CCDS7744

Canonical transcript exons

ENST00000250693 — 5 exons

Exon	Start	End
ENSE00000693077	3661372	3661413
ENSE00000693081	3659583	3660363
ENSE00001121212	3664092	3664416
ENSE00002164737	3645128	3645179
ENSE00003463386	3659162	3659276

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 89.87.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2030 / max 75.1895, expressed in 35 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112731	0.2030	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	89.87	gold quality
gastrocnemius	UBERON:0001388	88.90	gold quality
muscle of leg	UBERON:0001383	87.91	gold quality
skeletal muscle organ	UBERON:0014892	81.02	gold quality
muscle organ	UBERON:0001630	81.00	gold quality
tibialis anterior	UBERON:0001385	74.57	silver quality
pancreatic ductal cell	CL:0002079	68.20	silver quality
skeletal muscle tissue	UBERON:0001134	67.90	gold quality
diaphragm	UBERON:0001103	67.78	gold quality
parotid gland	UBERON:0001831	65.43	gold quality
muscle tissue	UBERON:0002385	64.59	gold quality
tendon of biceps brachii	UBERON:0008188	64.04	gold quality
deltoid	UBERON:0001476	62.03	silver quality
cranial nerve II	UBERON:0000941	60.97	gold quality
buccal mucosa cell	CL:0002336	60.73	gold quality
olfactory bulb	UBERON:0002264	60.63	gold quality
ileal mucosa	UBERON:0000331	60.43	silver quality
type B pancreatic cell	CL:0000169	60.38	gold quality
quadriceps femoris	UBERON:0001377	59.71	gold quality
skin of hip	UBERON:0001554	58.64	gold quality
vastus lateralis	UBERON:0001379	58.49	gold quality
triceps brachii	UBERON:0001509	57.80	gold quality
biceps brachii	UBERON:0001507	57.63	gold quality
medial globus pallidus	UBERON:0002477	57.14	gold quality
gluteal muscle	UBERON:0002000	56.84	gold quality
decidua	UBERON:0002450	56.55	gold quality
myocardium	UBERON:0002349	55.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	55.53	gold quality
sural nerve	UBERON:0015488	55.44	silver quality
heart right ventricle	UBERON:0002080	55.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, MYOG, RUNX1

miRNA regulators (miRDB)

1 targeting ART1, 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-6856-3P	96.47	66.27	781

Literature-anchored findings (GeneRIF, showing 10)

• ADP-ribosylation of HNP-1 appears to be primarily an activity of ART1 and occurs in inflammatory conditions and disease (PMID:16627471)
• ADPRT Ala762Val polymorphism may play a role in the etiology of squamous cell carcinoma of the head and neck or in linkage disequilibrium with other untyped protective alleles. (PMID:17614107)
• This study provides evidence that ARTC1 is activated during the endoplasmic-reticulum stress response, which results in acute ADP-ribosylation of GRP78/BiP paralleling translational inhibition. (PMID:25292337)
• The altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD. (PMID:26307000)
• Arginine ADP-ribosyltransferase 1 promotes angiogenesis in colorectal cancer via the PI3K/Akt pathway (PMID:26847718)
• Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/beta-catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E-cadherin) and that it therefore plays an important role in the progression of colon carcinoma. (PMID:27277835)
• up-regulation of ART1 expression is associated with the aggressiveness of glioma. (PMID:27466078)
• Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer. (PMID:35294260)
• ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis. (PMID:37381178)
• ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells. (PMID:38504172)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-145b13.6	ENSDARG00000069998
mus_musculus	Art1	ENSMUSG00000030996
rattus_norvegicus	Art1	ENSRNOG00000020251

Paralogs (3): ART4 (ENSG00000111339), ART3 (ENSG00000156219), ART5 (ENSG00000167311)

Protein

Protein identifiers

GPI-linked NAD(P)(+)–arginine ADP-ribosyltransferase 1 — P52961 (reviewed: P52961)

Alternative names: ADP-ribosyltransferase C2 and C3 toxin-like 1, Mono(ADP-ribosyl)transferase 1

All UniProt accessions (1): P52961

UniProt curated annotations — full annotation on UniProt →

Function. Has ADP-ribosyltransferase activity toward GLP1R.

Subcellular location. Sarcoplasmic reticulum membrane.

Similarity. Belongs to the Arg-specific ADP-ribosyltransferase family.

RefSeq proteins (1): NP_004305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000768	ART	Family
IPR050999	ADP-ribosyltransferase_ARG	Family

Pfam: PF01129

Enzyme classification (BRENDA):

• EC 2.4.2.31 — NAD+-protein-arginine ADP-ribosyltransferase (BRENDA: 29 organisms, 161 substrates, 61 inhibitors, 61 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0007–8.67	44
AGMATINE	1–9.4	3
ARGININE METHYL ESTER	1.3–3	3
1-(4-AMINOBUTYL)GUANIDINE	0.26–15	2
ALPHA-ACTIN-L-ARGININE	0.0025	1
BETA/GAMMA-ACTIN-L-ARGININE	0.015	1
GAMMA-ACTIN-L-ARGININE	0.01	1
NOMEGA-(ADP-D-RIBOSYL)-AGMATINE-L-ARGININE	0.272	1
PROTEIN L-ARGININE	4.1	1
PROTEIN L-ARGININE METHYL ESTER	1.3	1
PROTEIN NALPHA-ACETYL-L-ARGININE	6.3	1
PROTEIN NALPHA-ACETYL-L-ARGININE METHYL ESTER	0.9	1

Catalyzed reactions (Rhea), 1 shown:

• L-arginyl-[protein] + NAD(+) = N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] + nicotinamide + H(+) (RHEA:19149)

UniProt features (18 total): sequence variant 3, active site 3, binding site 3, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52961-F1	85.03	0.66

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 (3): 179; 202; 240

Ligand- & substrate-binding residues (3): 121; 179; 233

Post-translational modifications (1): 295

Disulfide bonds (2): 53–277, 174–224

Glycosylation sites (2): 65, 253

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1462054	Alpha-defensins
R-HSA-1461973	Defensins
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 78 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GAANYNYGACNY_UNKNOWN, MODULE_64, GOCC_CELL_SURFACE, CAGCTG_AP4_Q5, MARTINEZ_RB1_TARGETS_UP, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, WINTER_HYPOXIA_METAGENE, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GOCC_SARCOPLASMIC_RETICULUM_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_SARCOPLASM, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (0):

GO Molecular Function (5): NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), NAD+-protein-arginine ADP-ribosyltransferase activity (GO:0106274), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), sarcoplasmic reticulum membrane (GO:0033017), side of membrane (GO:0098552), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Defensins	1
Antimicrobial peptides	1
Immune System	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
pentosyltransferase activity	1
transferase activity, transferring phosphorus-containing groups	1
NAD+-protein mono-ADP-ribosyltransferase activity	1
catalytic activity	1
transferase activity	1
cell periphery	1
endoplasmic reticulum membrane	1
sarcoplasmic reticulum	1
bounding membrane of organelle	1
leaflet of membrane bilayer	1
endoplasmic reticulum	1
sarcoplasm	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ART1	SEPTIN4	O43236	764
ART1	PARG	Q86W56	744
ART1	ODF1	Q14990	696
ART1	DEFA1	P11479	549
ART1	DEFA4	P12838	549
ART1	DEFA6	Q01524	491
ART1	DEFA1	P11479	490
ART1	DEFB1	P60022	465
ART1	DEFA5	Q01523	463
ART1	DEFB4A	O15263	446
ART1	P2RX7	Q99572	445
ART1	ADPRH	P54922	429
ART1	HBB	P02023	415
ART1	ITIH4	Q14624	403
ART1	PCBP3	P57721	387

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ART1	IMPDH1	psi-mi:“MI:0914”(association)	0.350
OR52N5	ART1	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): ART1 (Affinity Capture-MS), SIRT2 (Affinity Capture-MS), ATR (Affinity Capture-MS), IMPDH1 (Affinity Capture-MS), GHITM (Affinity Capture-MS), ART1 (Affinity Capture-MS), ERMP1 (Affinity Capture-MS)

ESM2 similar proteins: D0G895, F1M928, O15466, O35696, O35975, O43173, P16368, P17981, P17982, P20974, P35625, P39876, P48032, P48794, P52961, P55806, P55807, P61269, P61644, P61646, P61647, P61648, P70126, P79121, Q03515, Q07977, Q0VC22, Q13508, Q3V5L5, Q5PXZ9, Q5XHY4, Q60813, Q60935, Q64663, Q64689, Q6W3E5, Q6ZXC8, Q765H6, Q812F3, Q8C8H8

Diamond homologs: O35975, P17981, P17982, P20974, P52961, P55806, P55807, P70352, Q03515, Q0VC22, Q13508, Q5XHY4, Q60935, Q8R2G4, Q92080, Q93070, Q95NE0, Q96L15, Q9CRA0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NPR1	“down-regulates activity”	ART1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1356 predictions. Top by Δscore:

Variant	Effect	Δscore
11:3666560:CTTCC:C	acceptor_gain	1.0000
11:3645174:GCC:G	donor_gain	0.9900
11:3645181:T:G	donor_loss	0.9900
11:3659580:CAGGC:C	acceptor_loss	0.9900
11:3659581:AGGC:A	acceptor_loss	0.9900
11:3659581:AGGCC:A	acceptor_gain	0.9900
11:3659582:G:GT	acceptor_loss	0.9900
11:3659625:G:C	acceptor_gain	0.9900
11:3666563:CC:C	acceptor_gain	0.9900
11:3666564:CC:C	acceptor_gain	0.9900
11:3666565:C:CC	acceptor_gain	0.9900
11:3667224:CTGCT:C	donor_loss	0.9900
11:3667226:GCTCA:G	donor_loss	0.9900
11:3667227:CT:C	donor_loss	0.9900
11:3667228:TCAC:T	donor_loss	0.9900
11:3667229:CA:C	donor_loss	0.9900
11:3667230:A:AC	donor_gain	0.9900
11:3667230:A:C	donor_loss	0.9900
11:3667231:C:CC	donor_gain	0.9900
11:3659580:CAGG:C	acceptor_gain	0.9800
11:3659581:A:AG	acceptor_gain	0.9800
11:3659582:G:GG	acceptor_gain	0.9800
11:3660350:C:T	donor_gain	0.9800
11:3660359:CAAAG:C	donor_loss	0.9800
11:3660360:AAAGG:A	donor_loss	0.9800
11:3660361:AAGG:A	donor_loss	0.9800
11:3660362:AG:A	donor_loss	0.9800
11:3660363:GG:G	donor_loss	0.9800
11:3660364:GTAGG:G	donor_loss	0.9800
11:3660365:T:C	donor_loss	0.9800

AlphaMissense

2132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:3660117:T:C	F200L	0.992
11:3660119:T:A	F200L	0.992
11:3660119:T:G	F200L	0.992
11:3660264:T:C	F249L	0.991
11:3660266:C:A	F249L	0.991
11:3660266:C:G	F249L	0.991
11:3659964:T:C	F149L	0.985
11:3659966:C:A	F149L	0.985
11:3659966:C:G	F149L	0.985
11:3659985:T:C	F156L	0.985
11:3659987:C:A	F156L	0.985
11:3659987:C:G	F156L	0.985
11:3660118:T:G	F200C	0.984
11:3660156:T:C	F213L	0.984
11:3660158:T:A	F213L	0.984
11:3660158:T:G	F213L	0.984
11:3660265:T:G	F249C	0.984
11:3659975:G:C	K152N	0.982
11:3659975:G:T	K152N	0.982
11:3659970:T:C	F151L	0.980
11:3659972:C:A	F151L	0.980
11:3659972:C:G	F151L	0.980
11:3660260:G:C	E247D	0.980
11:3660260:G:T	E247D	0.980
11:3659756:G:C	W79C	0.979
11:3659756:G:T	W79C	0.979
11:3660247:T:C	I243T	0.977
11:3659655:T:C	F46L	0.976
11:3659657:T:A	F46L	0.976
11:3659657:T:G	F46L	0.976

dbSNP variants (sampled 300 via entrez): RS1000016785 (11:3646991 G>A), RS1000059361 (11:3651585 G>A), RS1000067978 (11:3654795 C>G,T), RS1000089978 (11:3651754 C>A,G), RS1000141938 (11:3655112 C>G), RS1000358097 (11:3654602 C>A,T), RS1000579759 (11:3652937 CCTT>C), RS1000650422 (11:3661064 C>A), RS1000654746 (11:3653204 C>T), RS1000661713 (11:3661340 G>A,T), RS1000776107 (11:3662593 C>T), RS1000789391 (11:3661862 G>C), RS1001208640 (11:3662155 G>A), RS1001215482 (11:3656797 T>C), RS1001355052 (11:3647621 G>A)

Disease associations

OMIM: gene MIM:601625 | 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
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2158 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	decreases expression	1
pinosylvin	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL636752	Binding	Inhibition of ADP-ribosyltransferase 1 that catalyze ADP-ribosyltransferase was measured at 0 uM concentration	Specific inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7KI	Ubigene A-549 ART1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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