TGM2

Summary

TGM2 (transglutaminase 2, HGNC:11778) is a protein-coding gene on chromosome 20q11.23, encoding Protein-glutamine gamma-glutamyltransferase 2 (P21980). Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectiv….

Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. The protein encoded by this gene acts as a monomer, is induced by retinoic acid, and appears to be involved in apoptosis. Finally, the encoded protein is the autoantigen implicated in celiac disease. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7052 — RefSeq curated summary.

At a glance

• Gene–disease (curated): type 2 diabetes mellitus (Limited, GenCC)
• Clinical variants (ClinVar): 140 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11778
Approved symbol	TGM2
Name	transglutaminase 2
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	TGC, TG2
Ensembl gene	ENSG00000198959
Ensembl biotype	protein_coding
OMIM	190196
Entrez	7052

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 retained_intron

ENST00000361475, ENST00000373403, ENST00000453095, ENST00000468262, ENST00000469269, ENST00000474777, ENST00000879170, ENST00000879171, ENST00000879172, ENST00000954626, ENST00000954627, ENST00000954628

RefSeq mRNA: 5 — MANE Select: NM_004613 NM_001323316, NM_001323317, NM_001323318, NM_004613, NM_198951

CCDS: CCDS13302

Canonical transcript exons

ENST00000361475 — 13 exons

Exon	Start	End
ENSE00001922845	38165189	38165270
ENSE00003032232	38132340	38132500
ENSE00003083927	38138113	38138385
ENSE00003458407	38155847	38156089
ENSE00003459761	38146717	38146894
ENSE00003554130	38147961	38148089
ENSE00003566870	38127385	38130369
ENSE00003568466	38150939	38151057
ENSE00003570319	38142064	38142199
ENSE00003597950	38161420	38161599
ENSE00003619583	38139412	38139654
ENSE00003625812	38141282	38141385
ENSE00003636374	38131093	38131229

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 166.7336 / max 5141.9001, expressed in 1547 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187236	162.6363	1540
187235	0.8670	412
187220	0.5453	291
187213	0.4215	249
187218	0.3284	182
187211	0.3185	140
187237	0.3084	166
187214	0.2958	160
187239	0.2603	120
187216	0.2496	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	99.74	gold quality
right coronary artery	UBERON:0001625	99.73	gold quality
left coronary artery	UBERON:0001626	99.60	gold quality
endocervix	UBERON:0000458	99.56	gold quality
coronary artery	UBERON:0001621	99.55	gold quality
popliteal artery	UBERON:0002250	99.50	gold quality
tibial artery	UBERON:0007610	99.50	gold quality
right uterine tube	UBERON:0001302	99.34	gold quality
right atrium auricular region	UBERON:0006631	99.34	gold quality
upper lobe of left lung	UBERON:0008952	99.33	gold quality
aorta	UBERON:0000947	99.20	gold quality
upper lobe of lung	UBERON:0008948	99.19	gold quality
decidua	UBERON:0002450	99.18	gold quality
cardiac atrium	UBERON:0002081	99.10	gold quality
apex of heart	UBERON:0002098	99.03	gold quality
stromal cell of endometrium	CL:0002255	99.00	gold quality
right lung	UBERON:0002167	98.97	gold quality
body of uterus	UBERON:0009853	98.92	gold quality
ascending aorta	UBERON:0001496	98.89	gold quality
thoracic aorta	UBERON:0001515	98.88	gold quality
left uterine tube	UBERON:0001303	98.86	gold quality
gall bladder	UBERON:0002110	98.77	gold quality
heart left ventricle	UBERON:0002084	98.74	gold quality
cardiac ventricle	UBERON:0002082	98.62	gold quality
heart	UBERON:0000948	98.58	gold quality
placenta	UBERON:0001987	98.56	gold quality
descending thoracic aorta	UBERON:0002345	98.50	gold quality
pericardium	UBERON:0002407	98.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.18	gold quality
lower esophagus	UBERON:0013473	98.14	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	8874.11
E-MTAB-8559	yes	2379.33
E-HCAD-24	yes	1828.56
E-HCAD-38	yes	667.91
E-MTAB-9689	yes	437.52
E-MTAB-6108	yes	383.02
E-MTAB-6701	yes	133.86
E-MTAB-10553	yes	42.95
E-CURD-112	yes	41.64
E-GEOD-135922	yes	41.36
E-HCAD-35	yes	21.36
E-HCAD-9	yes	18.30
E-MTAB-7249	yes	11.42
E-HCAD-11	yes	8.44
E-MTAB-9543	yes	7.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESR2, IRF6, MTA1, MYCN, NFKB, POU2F1, RARA, RELA, SMAD3

miRNA regulators (miRDB)

32 targeting TGM2, 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-6793-5P	99.97	65.95	758
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6737-5P	97.75	66.54	1044

Literature-anchored findings (GeneRIF, showing 40)

• N-terminal and C-terminal regions of TGM2 interact with each other in determining the structure of the native protein (PMID:10561600)
• GTP is required to stabilize and display transamidation activity of transglutaminase 2. (PMID:12061780)
• specificity is involved in selection of gluten T cell epitopes and the deamidation reaction of gluten peptides in celiac disease is taking place in slightly acidic environments (PMID:12093810)
• Detection of a putative mutation in a MODY patient identifies transglutaminase 2 as a potential candidate gene in type 2 diabetes (PMID:12205028)
• products accumulate abnormaly in skeletal muscle and erythrocytes of chorea-acanthocytosis patients (PMID:12387450)
• tissue transglutaminase expression in the small intestine in children with coeliac disease (PMID:12410804)
• TGM2 was identified using a trifunctional phenyl sulfonate probe. (PMID:12438565)
• These data indicate that the in situ activity of TGase 2 gives different results with different substrates, and suggest the possibility of overrepresentation of in situ TGase 2 activity when assayed with BP (PMID:12527383)
• Transglutaminase 2 isoform colocalizes with both huntingtin protein and epsilon-(gamma-glutamyl) lysine covalent cross-links in intranuclear inclusions in Huntington disease. (PMID:12528814)
• results showed that Fas and/or Fas-Ligand, Bcl-2, and tissue transglutaminase may be involved in apoptotic pathways leading to mucosal atrophy in children with coeliac disease (PMID:12698366)
• Tissue transglutaminase directly regulates adenylyl cyclase resulting in enhanced cAMP-response element-binding protein (CREB) activation. (PMID:12743114)
• Tissue-type transglutaminase TGM2 plays a significant role in mediating CD8+ T cell migration across cytokine-activated endothelium and infiltration of tissues during inflammation. (PMID:12960346)
• the level of TGase 2 expression was found to be specifically increased in polymyositis and dermatomyositis, but not in Duchenne muscular dystrophy and normal controls. (PMID:14631123)
• six lysine residues of TG2 were found to participate in isopeptide bond formation with gliadin (PMID:14747475)
• transglutaminase 2 is activated by oxidative stress or ultraviolet irradiation and has a role in transglutaminase 2 in age-related cataractogenesis (PMID:14752105)
• Inhibiting the interaction of calmodulin with transglutaminase and huntingtin protein could decrease cross-linking and diminish huntingtin aggregate formation in the HD brain (PMID:14985437)
• Iintramolecular crosslinking of the cytoplasmic soluble phospho-Ser alpha-synuclein monomer is initially catalyzed by tissue transglutaminase. (PMID:15001552)
• Tissue transglutaminase has intrinsic kinase activity and is an insulin-like growth factor-binding protein-3 kinase (PMID:15069073)
• transglutaminase 2 has a role in fibroblast wound healing and extracellular matrix remodelling (PMID:15199098)
• Correlated with initiation and progression of scarring on sequential biopsies from renal-allograft recipients with chronic allograft nephropathy(CAN). Elevated tTg may predict of development of CAN. tTg may be attractive therapeutic target. (PMID:15201665)
• GTP-bound G(h)/TG2has a role in inhibiting cell migration migration through interaction with cytoplasmic tail of integrin alpha subunits (PMID:15220331)
• EGF failed to block RA-induced TGase expression; EGF alone potently up-regulated TGase expression and activation in breast cancer cells; results suggest that TGase activation is necessary and sufficient for the antiapoptotic properties of EGF (PMID:15272014)
• Data describe the role of the MT1-MMP/MMP-2 protease tandem in the regulation of cell receptors and explain the underlying biochemical mechanisms of tissue transglutaminase proteolysis at the normal tissue/tumor boundary. (PMID:15362860)
• Tissue transglutaminase is unlikely to be a contributing factor to the formation of aggregates of alpha-synuclein in a stable cell model. (PMID:15460447)
• Transglutaminase 2 induces nuclear factor-kappaB activation via a novel pathway (PMID:15471861)
• Overexpression of TGM2 accelerates the erythroid differentiation of chronic myeloid leukemia cell line through PI3K/akt signaling pathway. (PMID:15556610)
• up-regulation of TG2 expression is associated with drug-resistance and metastasis of breast cancer (PMID:15585642)
• externalized GTP-bound TG2 serves as a molecular switch for differentiation of chondrocytes to a hypertrophic, calcifying phenotype in a manner that does not require either TG2 transamidation activity or fibronectin binding (PMID:15691824)
• In HEK 293T cell culture, transglutaminase 2 cross-links the N-terminal fragments of mutant huntingtin protein, therefore it could be involved in the cross-linking of huntingtin into intranuclear inclusions in Huntington disease. (PMID:15715085)
• Autoantigen in celiac disease. Review. (PMID:15746535)
• immunostaining for TG2 revealed substantial presence of this protein in single, damaged muscle fibers and a weak reaction in regenerating fibers appearing in polymyositis/dermatomyositis patients’ specimens (PMID:15752564)
• tTG actively participates in adhesion events at the embryo-maternal interface through its interaction with FN, at least in part, by activating integrin-signaling pathways (PMID:15886239)
• TG2 expression can contribute to the development of drug-resistant and metastatic cancer cell phenotypes [review] (PMID:16146723)
• review of protein modifications mediated by transglutaminase 2 in human viral diseases [review] (PMID:16146727)
• Tissue transglutaminase (TG2) is a wound response enzyme [review] (PMID:16146777)
• TG2-induced alterations in the extracellular matrix could effectively inhibit the process of metastasis (PMID:16153302)
• novel and unexpected biological role for surface TG2 in the pathogenesis of celiac disease (PMID:16285941)
• transglutaminase 2-mediated cross-linking of serine protease inhibitors elafin and trappin-2 to neutrophil serine proteinases preserves their inhibitory capacities (PMID:16300411)
• Yeast 2-Hybrid experiments identified a strong and novel interaction between the transglutaminase moiety and protein kinase A anchor protein 13 (AKAP13) (PMID:16301118)
• TG2 modification of tumor protein p53 could be an additional mechanism whereby TG2 could facilitate apoptosis (PMID:16313886)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tgm2a	ENSDARG00000070157
danio_rerio	tgm2b	ENSDARG00000074094
mus_musculus	Tgm2	ENSMUSG00000037820

Paralogs (8): TGM1 (ENSG00000092295), TGM5 (ENSG00000104055), F13A1 (ENSG00000124491), TGM3 (ENSG00000125780), TGM7 (ENSG00000159495), TGM4 (ENSG00000163810), EPB42 (ENSG00000166947), TGM6 (ENSG00000166948)

Protein

Protein identifiers

Protein-glutamine gamma-glutamyltransferase 2 — P21980 (reviewed: P21980)

Alternative names: Erythrocyte transglutaminase, Heart G alpha(h), Isopeptidase TGM2, Protein G alpha(h), Protein-glutamine deamidase TGM2, Protein-glutamine dopaminyltransferase TGM2, Protein-glutamine histaminyltransferase TGM2, Protein-glutamine noradrenalinyltransferase TGM2, Protein-glutamine serotonyltransferase TGM2, Tissue transglutaminase, Transglutaminase C, Transglutaminase H, Transglutaminase II, Transglutaminase-2

All UniProt accessions (5): P21980, A2A299, A2A2A0, B4DIT7, V9HWG3

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively. Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis. Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54. Under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses. When secreted, catalyzes cross-linking of proteins of the extracellular matrix, such as FN1 and SPP1 resulting in the formation of scaffolds. Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components. In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively. Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases. Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3. Catalyzes serotonylation of ‘Gln-5’ of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription. Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of ‘Gln-5’ of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system. Regulates vein remodeling by mediating serotonylation and subsequent inactivation of ATP2A2/SERCA2. Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate. Catalyzes specific deamidation of protein gliadin, a component of wheat gluten in the diet. May also act as an isopeptidase cleaving the previously formed cross-links. Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism. Has cytotoxic activity: is able to induce apoptosis independently of its acyltransferase activity.

Subunit / interactions. Monomer. Interacts with phospholipase C; promoting alpha-1 adrenergic receptor signaling. Interacts with PLCD1. Homooligomer.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Chromosome. Secreted. Extracellular space. Extracellular matrix. Cell membrane. Mitochondrion Cytoplasm. Perinuclear region.

Post-translational modifications. Disulfide bond formation inactivates the calcium-dependent acyltransferase activity. Cys-370 can form disulfide bonds with both Cys-230 and Cys-371: formation of a disulfide bond between Cys-230 and Cys-370 facilitates formation of the disulfide between Cys-370 and Cys-371, which promotes inactivation of the acyltransferase activity. May also form interchain disulfids between Cys-230 and Cys-370. Ca(2+) protects against disulfide bond formation and inactivation. Auto-transglutaminated: Forms covalent cross-links mediated by transglutaminase between Gln-633 and the epsilon-amino group of a lysine residue of itself or HMGB1, forming homopolymers and heteropolymers, respectively. S-nitrosylated, leading to inactivation of the acyltransferase activity.

Disease relevance. TGM2 constitutes the major autoantigen in celiac disease, a multifactorial chronic disorder of the small intestine caused by intolerance to gluten. Celiac disease is characterized by immune-mediated enteropathy associated with failed intestinal absorption and malnutrition: intestinal inflammation is precipitated by ingestion of the protein gliadin, a component of wheat gluten in the diet. TGM2 is the main target for celiac disease-associated anti-endomysium autoantibodies. It mediates its effect by catalyzing specific deamidation of gliadin; this deamidation creates an epitope that binds efficiently to HLA-DQ2 and is recognized by gut-derived T-cells.

Activity regulation. Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites. In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form. In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity. Extracellularly reduced and activated by CLIC3. Specifically inhibited by compound VA4 ((S)-Benzyl (6-Acrylamido-1-(4-((5-(dimethylamino)naphthalen-1-yl)sulfonyl)piperazin-1-yl)-1-oxohexan-2-yl)carbamate), which specifically abolishes both the transamidation and GTP-binding activities.

Induction. By retinoic acid.

Similarity. Belongs to the transglutaminase superfamily. Transglutaminase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P21980-1	1	yes
P21980-2	2, TGase-S
P21980-3	3, TGH2

RefSeq proteins (5): NP_001310245, NP_001310246, NP_001310247, NP_004604, NP_945189 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001102	Transglutaminase_N	Domain
IPR002931	Transglutaminase-like	Domain
IPR008958	Transglutaminase_C	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013808	Transglutaminase_AS	Active_site
IPR014756	Ig_E-set	Homologous_superfamily
IPR023608	Transglutaminase_animal	Family
IPR036238	Transglutaminase_C_sf	Homologous_superfamily
IPR036985	Transglutaminase-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050779	Transglutaminase	Family

Pfam: PF00868, PF00927, PF01841

Enzyme classification (BRENDA):

• EC 2.3.2.13 — protein-glutamine gamma-glutamyltransferase (BRENDA: 68 organisms, 476 substrates, 772 inhibitors, 122 Km, 49 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
PUTRESCINE	0.035–9.63	13
L-LYSINE	2.9–15.8	6
N-CBZ-GLN-GLY	12.83–59.5	5
HYDROXYLAMINE	1.37–61.9	4
NALPHA-BENZYLOXYCARBONYL-L-GLN-GLY	11.2–30	4
CASEIN	0.006–0.012	3
CBZ-GLN-GLY	0.0169–5.9	3
CBZ-GLN-GLY-OH	3.53–8.55	3
METHYLAMINE	0.024–0.061	3
MONODANSYLCADAVERINE	0.01–0.034	3
N-CARBOXYBENZOYL-L-GLUTAMINYL-GLYCINE	0.0547–69.4	3
PENTYLAMINE	0.0029–0.0203	3
Z-GLN-GLY	1.8–11.6	3
ACETYL-ALPHAS1-CASEIN	0.0029–0.0032	2
GTP	0.0044–0.01	2

Catalyzed reactions (Rhea), 6 shown:

• L-glutaminyl-[protein] + H2O = L-glutamyl-[protein] + NH4(+) (RHEA:16441)
• L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+) (RHEA:54816)
• L-glutaminyl-[protein] + serotonin = 5-serotonyl-L-glutamyl-[protein] + NH4(+) (RHEA:66552)
• L-glutaminyl-[protein] + dopamine = 5-dopaminyl-L-glutamyl-[protein] + NH4(+) (RHEA:66556)
• L-glutaminyl-[protein] + (R)-noradrenaline = 5-(R)-noradrenalinyl-L-glutamyl-[protein] + NH4(+) (RHEA:66560)
• L-glutaminyl-[protein] + histamine = 5-histaminyl-L-glutamyl-[protein] + NH4(+) (RHEA:66564)

UniProt features (133 total): strand 46, mutagenesis site 22, helix 16, turn 12, binding site 8, sequence variant 8, sequence conflict 5, splice variant 4, modified residue 3, active site 3, disulfide bond 2, initiator methionine 1, chain 1, site 1, cross-link 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9BC4	X-RAY DIFFRACTION	1.84
2Q3Z	X-RAY DIFFRACTION	2
3S3J	X-RAY DIFFRACTION	2.25
3S3S	X-RAY DIFFRACTION	2.3
3S3P	X-RAY DIFFRACTION	2.5
9BC3	X-RAY DIFFRACTION	2.52
6A8P	X-RAY DIFFRACTION	2.54
9BC2	X-RAY DIFFRACTION	2.75
1KV3	X-RAY DIFFRACTION	2.8
4PYG	X-RAY DIFFRACTION	2.8
3LY6	X-RAY DIFFRACTION	3.14
8TR9	ELECTRON MICROSCOPY	3.2
6KZB	X-RAY DIFFRACTION	3.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21980-F1	92.91	0.80

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 (4): 516 (important for catalytic activity); 277; 335; 358

Ligand- & substrate-binding residues (8): 476–483; 539; 580–583; 398; 400; 437; 447; 452

Post-translational modifications (4): 2, 60, 468, 633

Disulfide bonds (2): 230–370, 370–371

Mutagenesis-validated functional residues (22):

Position	Phenotype
277	abolished protein-glutamine gamma-glutamyltransferase activity without affecting cytotoxic activity.
171	abolishes gtp-binding and transglutaminase activities. does not have cytotoxic activity when overexpressed.
180	abolished isopeptidase activity and reduced transamidase activity.
180	abolished isopeptidase and transamidase activities.
224	displays lower ca(2+)-binding affinity and reduced transglutaminase activity.
230	does not affect the protein-glutamine deamidase activity.
241	abolished isopeptidase and transamidase activities.
277	abolished protein-glutamine gamma-glutamyltransferase activity without affecting alpha-1 adrenergic receptor signaling.
277	dominant negative mutant. abolishes wdr54 cross-linking.
278	in tg2-t; strongly reduced isopeptidase activity without affecting the transamidase activity.
278	abolished isopeptidase and transamidase activities.
332	in tg2-i; strongly reduced transamidase activity without affecting the isopeptidase activity.
332	abolished isopeptidase and transamidase activities.
334	abolished isopeptidase and transamidase activities.
337	reduced isopeptidase and transamidase activities.
337	abolished isopeptidase and transamidase activities.
370	impaired substrate recognition for the protein-glutamine deamidase activity.
371	impaired substrate recognition for the protein-glutamine deamidase activity.
437	impaired ca(2+)-binding leading to reduced transglutaminase activity.
516	no effect on isopeptidase and transamidase activities.
539	impaired ca(2+)-binding leading to reduced transglutaminase activity.
665–672	substitution with f13a1 sequence. abolished interaction with phospholipase c and ability to promote alpha-1 adrenergic r

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 496 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_GLAND_MORPHOGENESIS, HARRIS_HYPOXIA, GOBP_RESPONSE_TO_COCAINE, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SALIVARY_GLAND_DEVELOPMENT, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_PEPTIDE_CROSS_LINKING, GOZGIT_ESR1_TARGETS_DN

GO Biological Process (25): proteolysis (GO:0006508), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), peptide cross-linking (GO:0018149), protein deamination (GO:0018277), negative regulation of endoplasmic reticulum calcium ion concentration (GO:0032471), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), apoptotic cell clearance (GO:0043277), positive regulation of GTPase activity (GO:0043547), positive regulation of cell adhesion (GO:0045785), positive regulation of neurogenesis (GO:0050769), positive regulation of small GTPase mediated signal transduction (GO:0051057), protein homooligomerization (GO:0051260), positive regulation of mitochondrial calcium ion concentration (GO:0051561), bone development (GO:0060348), branching involved in salivary gland morphogenesis (GO:0060445), salivary gland cavitation (GO:0060662), cellular response to cocaine (GO:0071314), cellular response to dopamine (GO:1903351), positive regulation of sprouting angiogenesis (GO:1903672), cellular response to serotonin (GO:1904015), regulation of apoptotic cell clearance (GO:2000425), chromatin remodeling (GO:0006338), gene expression (GO:0010467), dopamine secretion (GO:0014046)

GO Molecular Function (17): protein-glutamine gamma-glutamyltransferase activity (GO:0003810), calcium ion binding (GO:0005509), GTP binding (GO:0005525), peptidase activity (GO:0008233), protein-glutamine glutaminase activity (GO:0050568), histone serotonyltransferase activity (GO:0120295), histone dopaminyltransferase activity (GO:0120297), peptide noradrenalinyltransferase activity (GO:0120298), peptide histaminyltransferase activity (GO:0120299), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), peptide serotonyltransferase activity (GO:0120294), peptide dopaminyltransferase activity (GO:0120296)

GO Cellular Component (15): chromatin (GO:0000785), nucleosome (GO:0000786), nucleus (GO:0005634), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), extracellular matrix (GO:0031012), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), extracellular region (GO:0005576), chromosome (GO:0005694), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
acyltransferase activity, transferring groups other than amino-acyl groups	4
cytoplasm	4
catalytic activity, acting on a protein	3
intracellular membrane-bounded organelle	3
protein modification process	2
apoptotic process	2
salivary gland morphogenesis	2
histone modifying activity	2
catalytic activity	2
protein metabolic process	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
endoplasmic reticulum calcium ion homeostasis	1
regulation of programmed cell death	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
phagocytosis	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
small GTPase-mediated signal transduction	1
regulation of small GTPase mediated signal transduction	1
positive regulation of intracellular signal transduction	1
protein complex oligomerization	1
mitochondrial calcium ion homeostasis	1
skeletal system development	1
animal organ development	1
morphogenesis of a branching epithelium	1
tube lumen cavitation	1
response to cocaine	1
cellular response to alkaloid	1
cellular response to oxygen-containing compound	1

Protein interactions and networks

STRING

2414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGM2	FN1	P02751	986
TGM2	TOR1A	O14656	925
TGM2	ADGRG1	Q9Y653	849
TGM2	ARNT	P27540	663
TGM2	SDC4	P31431	650
TGM2	SBSN	Q6UWP8	634
TGM2	TGFB2	P08112	604
TGM2	ANXA1	P04083	592
TGM2	SPP1	P10451	583
TGM2	TPO	P07202	572
TGM2	COL18A1	P39060	564
TGM2	KRT8	P05787	555
TGM2	TFRC	P02786	554
TGM2	PPHLN1	Q8NEY8	549
TGM2	POSTN	Q15063	547

IntAct

129 interactions, top by confidence:

A	B	Type	Score
	FN1	psi-mi:“MI:0407”(direct interaction)	0.840
TGM2	FN1	psi-mi:“MI:0407”(direct interaction)	0.810
TGM2	FN1	psi-mi:“MI:0414”(enzymatic reaction)	0.810
FN1	TGM2	psi-mi:“MI:0407”(direct interaction)	0.810
	TGM2	psi-mi:“MI:0407”(direct interaction)	0.760
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TGM2	E7	psi-mi:“MI:0915”(physical association)	0.630
E7	TGM2	psi-mi:“MI:0407”(direct interaction)	0.630
E7	TGM2	psi-mi:“MI:0915”(physical association)	0.630
APP	TGM2	psi-mi:“MI:0407”(direct interaction)	0.620
TGM2	APP	psi-mi:“MI:0407”(direct interaction)	0.620
TGM2	VHL	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (261): TGM2 (Biochemical Activity), TGM2 (Affinity Capture-Western), PINK1 (Affinity Capture-Western), TGM2 (Reconstituted Complex), CDK11B (Affinity Capture-MS), COL5A1 (Affinity Capture-MS), COL5A2 (Affinity Capture-MS), CDC42BPA (Affinity Capture-MS), PLOD3 (Affinity Capture-MS), SRGAP3 (Affinity Capture-MS), MVP (Affinity Capture-MS), SF3B4 (Affinity Capture-MS), ENOPH1 (Affinity Capture-MS), RBM25 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JDV3, A0A2P1BRP3, A0A2P1BRQ0, A0ZSK3, A0ZSK4, A1L314, A7RS11, A8MVJ9, E7F9T0, O08619, O81025, P08587, P21980, P21981, P27473, P49221, P52181, Q0GUM3, Q1LYL8, Q1MT80, Q2EMV9, Q3T9E4, Q53G44, Q5K651, Q62293, Q63663, Q66S13, Q66S21, Q66S25, Q69Z37, Q6P5U7, Q6ZN66, Q7EYV7, Q8BV66, Q8CBA2, Q8IVG5, Q8N8V2, Q8T773, Q8TCB0, Q91453

Diamond homologs: A6QP57, D4A5U3, O08619, O43548, O46510, O95932, P00488, P08587, P16452, P21980, P21981, P22735, P22758, P23606, P49221, P51176, P52181, P52183, Q01841, Q05187, Q08188, Q08189, Q8BH61, Q8BZH1, Q96PF1, Q99041, Q9D7I9, Q9GLK0, Q9JLF6, Q9WVJ6, P49222, P12260

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TGM2	unknown	H3C1	phosphorylation
TGM2	unknown	“Histone H3”	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TAK1-dependent IKK and NF-kappa-B activation	7	27.7×	4e-06
Interleukin-1 family signaling	5	17.9×	3e-04
Gastrulation	5	17.1×	4e-04
Toll Like Receptor 10 (TLR10) Cascade	6	17.0×	2e-04
Toll Like Receptor 5 (TLR5) Cascade	6	17.0×	2e-04
MyD88 cascade initiated on plasma membrane	6	16.1×	2e-04
Toll Like Receptor 3 (TLR3) Cascade	6	15.3×	2e-04
TRIF (TICAM1)-mediated TLR4 signaling	6	15.0×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	17.7×	1e-03
hematopoietic progenitor cell differentiation	5	14.5×	3e-03
transforming growth factor beta receptor signaling pathway	7	13.6×	2e-04
lung development	5	12.1×	5e-03
response to endoplasmic reticulum stress	5	10.2×	6e-03
cellular response to tumor necrosis factor	5	10.0×	6e-03
cell morphogenesis	5	9.6×	6e-03
regulation of gene expression	9	9.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	17
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

1747 predictions. Top by Δscore:

Variant	Effect	Δscore
20:38130365:CTGGG:C	acceptor_gain	1.0000
20:38130366:TGGG:T	acceptor_gain	1.0000
20:38130366:TGGGC:T	acceptor_loss	1.0000
20:38130367:GGG:G	acceptor_gain	1.0000
20:38130368:GG:G	acceptor_gain	1.0000
20:38130369:GCT:G	acceptor_loss	1.0000
20:38130370:C:CC	acceptor_gain	1.0000
20:38131090:TA:T	donor_loss	1.0000
20:38131091:A:AC	donor_gain	1.0000
20:38131091:AC:A	donor_loss	1.0000
20:38131091:ACAT:A	donor_gain	1.0000
20:38131092:C:CA	donor_gain	1.0000
20:38131092:CA:C	donor_gain	1.0000
20:38131092:CAT:C	donor_gain	1.0000
20:38131092:CATC:C	donor_gain	1.0000
20:38131092:CATCT:C	donor_gain	1.0000
20:38131225:AGGAT:A	acceptor_gain	1.0000
20:38131226:GGAT:G	acceptor_gain	1.0000
20:38131227:GAT:G	acceptor_gain	1.0000
20:38131228:AT:A	acceptor_gain	1.0000
20:38131228:ATCT:A	acceptor_loss	1.0000
20:38131229:TCT:T	acceptor_loss	1.0000
20:38131230:C:CC	acceptor_gain	1.0000
20:38131230:CTG:C	acceptor_loss	1.0000
20:38132334:CCTTA:C	donor_loss	1.0000
20:38132335:CTTA:C	donor_loss	1.0000
20:38132336:TTA:T	donor_loss	1.0000
20:38132337:TAC:T	donor_loss	1.0000
20:38132338:A:AC	donor_gain	1.0000
20:38132338:AC:A	donor_gain	1.0000

AlphaMissense

4531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:38139486:C:T	G423E	0.999
20:38139487:C:A	G423W	0.999
20:38141373:G:C	C336W	0.999
20:38141378:G:C	H335D	0.999
20:38141379:G:C	F334L	0.999
20:38141379:G:T	F334L	0.999
20:38141381:A:G	F334L	0.999
20:38146805:G:C	S257R	0.999
20:38146805:G:T	S257R	0.999
20:38146807:T:G	S257R	0.999
20:38139422:T:A	K444N	0.998
20:38139422:T:G	K444N	0.998
20:38139487:C:G	G423R	0.998
20:38139487:C:T	G423R	0.998
20:38139578:A:C	F392L	0.998
20:38139578:A:T	F392L	0.998
20:38139580:A:G	F392L	0.998
20:38141295:C:A	Q362H	0.998
20:38141295:C:G	Q362H	0.998
20:38141372:A:G	W337R	0.998
20:38141372:A:T	W337R	0.998
20:38141376:G:C	H335Q	0.998
20:38141376:G:T	H335Q	0.998
20:38142065:A:G	W332R	0.998
20:38142065:A:T	W332R	0.998
20:38146736:G:C	F280L	0.998
20:38146736:G:T	F280L	0.998
20:38146738:A:G	F280L	0.998
20:38146745:G:C	C277W	0.998
20:38146853:C:A	W241C	0.998

dbSNP variants (sampled 300 via entrez): RS1000074361 (20:38137273 C>T), RS1000081758 (20:38137472 GCAAA>G,GCAAACAAA), RS1000181313 (20:38165411 G>C,T), RS1000259380 (20:38157280 C>T), RS1000268613 (20:38169653 G>A), RS1000322680 (20:38169414 C>T), RS1000434927 (20:38143298 C>G), RS1000511226 (20:38138864 C>A), RS1000593859 (20:38133538 T>C), RS1000658580 (20:38158405 G>T), RS1000749465 (20:38128823 G>A), RS1000823531 (20:38128344 C>T), RS1000864939 (20:38159545 A>C), RS1000920304 (20:38159360 G>T), RS1000958509 (20:38142719 A>G)

Disease associations

OMIM: gene MIM:190196 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
type 2 diabetes mellitus	Limited	Autosomal dominant

Mondo (1): type 2 diabetes mellitus (MONDO:0005148)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2730 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,504 (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
CHEMBL4081588	ZED-1227	2	167

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.3.2.13 Transglutaminases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
JAK3 inhibitor IV	Inhibition	8.0	pIC50
vilagletistat	Inhibition	7.28	pIC50
ERW1041E	Inhibition	5.8	pIC50
compound 11 [PMID: 37449845]	Inhibition	4.16	pKd

Binding affinities (BindingDB)

76 measured of 95 human assays (96 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(4-Methoxycarbonylphenyl)methyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate (6b)	IC50	2.1 nM
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]-2-bromo-acetamide (6e)	IC50	3.9 nM
1-Adamantylmethyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate (6f)	IC50	6.29 nM
(6-Methoxycarbonyl-2-naphthyl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate (6n)	IC50	6.65 nM
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]-2-chloro-acetamide (6o)	IC50	8.75 nM
CHEMBL2086528	IC50	10 nM
7-oxido-2-[4-(3-phenoxypropanoyl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	14 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-Naphthylmethyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate (6c)	IC50	29 nM
2-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	45 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(3,4-dimethoxybenzoyl)piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	54 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-ethylsulfonylpiperazine-1-carbonyl)-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	61 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(2-methylpropanoyl)piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	62 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-acetylpiperazine-1-carbonyl)-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	62 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(3,4-dimethoxybenzoyl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-3-one	IC50	65 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
7-oxido-2-[4-(pyridine-2-carbonyl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	72 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(3-phenoxypropanoyl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-3-one	IC50	110 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(2-aminoacetyl)piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	120 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-butanoylpiperidine-1-carbonyl)-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	120 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]prop-2-enamide (3e)	IC50	125 nM
7-oxido-2-[4-(pyridine-4-carbonyl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	130 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
7-oxido-2-[4-(6-pyrrolidin-1-ylpyridazin-3-yl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	140 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
7-oxido-2-(3-oxopiperazine-1-carbonyl)-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	150 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
4-(7-oxido-3-oxo-[1,2]thiazolo[5,4-b]pyridin-7-ium-2-carbonyl)piperazine-1-sulfonamide	IC50	200 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(methylamino)piperidine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	240 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-methylsulfonylpiperazine-1-carbonyl)-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	250 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(morpholine-4-carbonyl)-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	270 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-acetylpiperazine-1-carbonyl)-[1,2]thiazolo[5,4-b]pyridin-3-one	IC50	340 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	340 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
N-[(3,4-dimethoxyphenyl)methyl]-7-oxido-3-oxo-[1,2]thiazolo[5,4-b]pyridin-7-ium-2-carboxamide	IC50	370 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-3-one	IC50	420 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-ethylsulfonylpiperazine-1-carbonyl)-[1,2]thiazolo[5,4-b]pyridin-3-one	IC50	430 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
CHEMBL2152196	IC50	660 nM
2-[4-(3-methoxypropanoyl)piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	750 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
[2-[[2-[4-(1-Adamantylmethoxycarbonyl)piperazin-1-yl]-2-oxo-ethyl]amino]-2-oxoethyl]-dimethyl-sulfonium bromide (1f)	IC50	775 nM
3-oxo-N-[(2S,3R,4S,5R)-3,4,5,6-tetrahydroxyoxan-2-yl]-[1,2]thiazolo[5,4-b]pyridine-2-carboxamide	IC50	800 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
alpha-Cyano-(3,4-dihydroxy)thiocinnamide	KI	850 nM
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]ethenesulfonamide (2e)	IC50	875 nM
[2-[[2-[4-(Adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]amino]-2-oxo-ethyl]-dimethyl-sulfonium bromide (1e)	IC50	889 nM
7-oxido-2-[4-[(2S)-5-oxopyrrolidine-2-carbonyl]piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	1000 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
4-[4-(3-oxo-[1,2]thiazolo[5,4-b]pyridine-2-carbonyl)piperazin-1-yl]benzonitrile	IC50	1100 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
7-oxido-2-(piperazine-1-carbonyl)-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	1200 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
[(2R,3S,4R,5R,6S)-3,4,6-triacetyloxy-5-[(3-oxo-[1,2]thiazolo[5,4-b]pyridine-2-carbonyl)amino]oxan-2-yl]methyl acetate	IC50	1400 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
1-Adamantylmethyl 4-[2-(prop-2-enoylamino)acetyl]piperazine-1-carboxylate (3f)	IC50	1620 nM
2-[4-[2-methyl-2-(methylamino)propanoyl]piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	1700 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
4-(7-oxido-3-oxo-[1,2]thiazolo[5,4-b]pyridin-7-ium-2-carbonyl)piperazine-1-carboxamide	IC50	1700 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
Benzyl 4-[2-(vinylsulfonylamino)acetyl]piperazine-1-carboxylate (2a)	IC50	1720 nM
2-[4-[2-(ethylamino)acetyl]piperazine-1-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	2000 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-(4-hydroxypiperidine-1-carbonyl)-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	2100 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
7-oxido-2-[4-[(2S)-pyrrolidine-2-carbonyl]piperazine-1-carbonyl]-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	2300 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals
2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-7-oxido-[1,2]thiazolo[5,4-b]pyridin-7-ium-3-one	IC50	2900 nM	US-9260454: Isothiazolopyridine-2-carboxamides and their use as pharmaceuticals

ChEMBL bioactivities

577 potent at pChembl≥5 of 731 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	IC50	6	nM	CHEMBL4076082
8.02	IC50	9.6	nM	CHEMBL3423198
8.00	IC50	10	nM	CHEMBL2086528
7.92	IC50	12	nM	CHEMBL5842415
7.85	IC50	14	nM	CHEMBL2086544
7.85	IC50	14	nM	CHEMBL2203451
7.85	IC50	14	nM	CHEMBL3949090
7.85	IC50	14	nM	CHEMBL6009354
7.82	IC50	15	nM	CHEMBL2086541
7.80	IC50	16	nM	CHEMBL6029478
7.80	IC50	16	nM	CHEMBL6019101
7.70	IC50	20	nM	CHEMBL2086523
7.70	IC50	20	nM	CHEMBL3092843
7.60	IC50	25	nM	CHEMBL2086530
7.60	IC50	25	nM	CHEMBL2086889
7.58	IC50	26	nM	CHEMBL2086524
7.58	IC50	26	nM	CHEMBL2086542
7.58	IC50	26	nM	CHEMBL5963787
7.57	IC50	27	nM	CHEMBL5912424
7.52	IC50	30	nM	CHEMBL3092841
7.50	IC50	32	nM	CHEMBL2086480
7.50	IC50	32	nM	CHEMBL5932274
7.50	IC50	32	nM	CHEMBL5747952
7.47	IC50	34	nM	CHEMBL2367730
7.46	IC50	35	nM	CHEMBL2086531
7.46	IC50	35	nM	CHEMBL5856535
7.44	IC50	36	nM	CHEMBL5827711
7.43	IC50	37	nM	CHEMBL2086525
7.42	IC50	38	nM	CHEMBL6018716
7.40	IC50	40	nM	STREPTONIGRIN
7.39	IC50	41	nM	CHEMBL2086526
7.39	IC50	41	nM	CHEMBL5778990
7.36	IC50	44	nM	CHEMBL2086519
7.35	IC50	45	nM	CHEMBL3968388
7.35	IC50	45	nM	ZED-1227
7.34	IC50	46	nM	CHEMBL2086506
7.34	IC50	46	nM	CHEMBL3423193
7.32	IC50	48	nM	CHEMBL3423194
7.32	IC50	48	nM	CHEMBL3423202
7.32	IC50	48	nM	CHEMBL5806048
7.30	IC50	50	nM	CHEMBL3423195
7.28	IC50	52	nM	CHEMBL2086532
7.27	IC50	54	nM	CHEMBL2086507
7.27	IC50	54	nM	CHEMBL2086515
7.27	IC50	54	nM	CHEMBL2203467
7.27	IC50	54	nM	CHEMBL3092842
7.27	IC50	54	nM	CHEMBL3932512
7.26	IC50	55	nM	CHEMBL2086529
7.26	IC50	55	nM	CHEMBL2203473
7.25	IC50	56	nM	CHEMBL5944421

PubChem BioAssay actives

476 with measured affinity, of 1282 total; 50 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
(4-methoxycarbonylphenyl)methyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0021	uM
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxoethyl]-2-bromoacetamide	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0039	uM
N-[2-[4-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperazin-1-yl]-2-oxoethyl]prop-2-enamide	1469839: Inhibition of recombinant human TG2 by fluorescence assay	ic50	0.0060	uM
1-adamantylmethyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0063	uM
(6-methoxycarbonylnaphthalen-2-yl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0066	uM
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxoethyl]-2-chloroacetamide	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0088	uM
(2S,3R)-2-N-(4-bromo-3-chlorophenyl)oxirane-2,3-dicarboxamide	1204604: Inhibition of transglutaminase 2 (unknown origin)	ic50	0.0096	uM
N-[4-[4-(adamantane-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	1922388: Inhibition of TG2 (unknown origin)	ic50	0.0100	uM
2,6-dibromo-4-[(Z)-(5-iodo-2-methylidene-1H-indol-3-ylidene)methyl]phenol	1799534: BP Incorporation Assay from Article 10.1016/j.chembiol.2008.07.015: “Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries.”	ic50	0.0100	uM
N-[5-[4-(adamantane-1-carbonyl)piperazin-1-yl]sulfonylpyrimidin-2-yl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0140	uM
N-[(5S)-6-[4-(6-methyl-2-pyridinyl)piperazin-1-yl]-6-oxo-5-[(2-phenylacetyl)amino]hexyl]prop-2-enamide	712442: Irreversible inhibition of transglutaminase 2	ic50	0.0140	uM
N-[5-[4-(adamantane-1-carbonyl)piperazin-1-yl]sulfonyl-2-pyridinyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0150	uM
(6-methoxycarbonylnaphthalen-2-yl)methyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0150	uM
N-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0200	uM
ethyl (E,6S)-7-[[(2S)-5-amino-1-[(2S)-2-[[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-7-oxo-6-(phenylmethoxycarbonylamino)hept-2-enoate	1059555: Inhibition of human TGase2	ic50	0.0200	uM
N-[4-[4-(3-methyl-2-pyridinyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0250	uM
1-ethyl-3-(4-methoxyphenyl)-6-methylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0250	uM
N-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2H-quinoline-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0260	uM
tert-butyl 4-[2-(prop-2-enoylamino)pyrimidin-5-yl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0260	uM
naphthalen-2-ylmethyl 4-[2-[(2-bromoacetyl)amino]acetyl]piperazine-1-carboxylate	1801716: TG Activity Assays from Article 10.1016/j.chembiol.2015.08.013: “Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.”	ic50	0.0290	uM
ethyl (E,6S)-7-[[(2S)-1-[(2S)-2-[[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-7-oxo-6-(phenylmethoxycarbonylamino)hept-2-enoate	1059555: Inhibition of human TGase2	ic50	0.0300	uM
N-[4-[4-(cyclopentanecarbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0320	uM
N-[4-[4-[(1S,2S)-2-phenylcyclopropanecarbonyl]piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0340	uM
N-[4-[4-(6-methyl-2-pyridinyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0350	uM
N-[4-[4-(piperidine-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0370	uM
N-[4-[4-(4,4-difluoropiperidine-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0410	uM
cyclopentyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0440	uM
methyl (E,6S)-7-[[1-[2-(2-ethylbutylamino)-2-oxoethyl]-2-oxo-3-pyridinyl]amino]-6-[(3-methylimidazole-4-carbonyl)amino]-7-oxohept-2-enoate	1469834: Inhibition of human TG2 using glycine methyl ester/Abz-APE as substrate after 5 mins	ic50	0.0450	uM
(2R,3S)-2-N-(4-phenoxyphenyl)oxirane-2,3-dicarboxamide	1204604: Inhibition of transglutaminase 2 (unknown origin)	ic50	0.0460	uM
(2,3-difluorophenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0460	uM
(2R,3S)-2-N-(3-chlorophenyl)oxirane-2,3-dicarboxamide	1204604: Inhibition of transglutaminase 2 (unknown origin)	ic50	0.0480	uM
(2S,3R)-2-N-[4-(4-aminophenoxy)phenyl]oxirane-2,3-dicarboxamide	1204604: Inhibition of transglutaminase 2 (unknown origin)	ic50	0.0480	uM
(2R,3S)-2-N-(3-phenoxyphenyl)oxirane-2,3-dicarboxamide	1204604: Inhibition of transglutaminase 2 (unknown origin)	ic50	0.0500	uM
N-[4-[4-[3-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0520	uM
(3-phenoxyphenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0540	uM
(4-fluorophenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0540	uM
methyl (2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[(E,2S)-6-methylsulfonyl-2-(phenylmethoxycarbonylamino)hex-5-enoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoate	1059555: Inhibition of human TGase2	ic50	0.0540	uM
benzyl N-[(2S)-1-oxo-1-(4-phenylpiperidin-1-yl)-6-(prop-2-enoylamino)hexan-2-yl]carbamate	712442: Irreversible inhibition of transglutaminase 2	ic50	0.0540	uM
N-[4-(4-pyridin-2-ylpiperazin-1-yl)sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0550	uM
benzyl N-[(2S)-1-[4-(6-methyl-2-pyridinyl)piperazin-1-yl]-1-oxo-6-(prop-2-enoylamino)hexan-2-yl]carbamate	712442: Irreversible inhibition of transglutaminase 2	ic50	0.0550	uM
(2S,3R)-2-N-(4-bromophenyl)oxirane-2,3-dicarboxamide	1204604: Inhibition of transglutaminase 2 (unknown origin)	ic50	0.0570	uM
N-[4-[4-(pyrrolidine-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0570	uM
(4-phenoxyphenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0600	uM
benzyl N-[(2S)-1-[4-(2-chlorophenyl)piperazin-1-yl]-1-oxo-6-(prop-2-enoylamino)hexan-2-yl]carbamate	712442: Irreversible inhibition of transglutaminase 2	ic50	0.0620	uM
benzyl N-[1-[4-(2-chlorophenyl)piperazin-1-yl]-1-oxo-6-(prop-2-enoylamino)hexan-2-yl]carbamate	1922388: Inhibition of TG2 (unknown origin)	ic50	0.0620	uM
benzyl 4-[2-(prop-2-enoylamino)pyrimidin-5-yl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0690	uM
(3,5-difluorophenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0700	uM
(2-methylphenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0700	uM
ethyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0720	uM
N-[4-[4-[5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683883: Inhibition of human recombinant TG2 by fluorescent transamidation assay	ic50	0.0760	uM

CTD chemical–gene interactions

133 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases reaction, affects cotreatment, affects localization, affects reaction, affects response to substance (+3 more)	18
Estradiol	affects reaction, increases expression, affects expression, affects cotreatment, decreases expression	6
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	6
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	5
Alitretinoin	affects binding, affects cotreatment, increases reaction, increases activity, increases expression (+1 more)	4
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	4
Doxorubicin	decreases reaction, increases expression, affects response to substance	4
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects cotreatment, decreases expression	4
Cyclosporine	decreases expression, increases expression	4
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	4
cobaltous chloride	decreases expression, increases expression	3
Am 580	affects cotreatment, increases activity, increases expression	3
Arsenic Trioxide	decreases reaction, increases expression, affects cotreatment, affects reaction	3
Acetaminophen	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects binding, increases reaction	2
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	increases expression, decreases reaction	2
phenylsaligenin cyclic phosphate	affects activity, increases activity, increases expression	2
(+)-JQ1 compound	affects cotreatment, decreases expression	2
Ethanol	increases reaction, affects cotreatment, decreases expression, decreases reaction, increases activity (+3 more)	2
Calcitriol	increases expression, affects cotreatment	2
Nickel	increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Silicon Dioxide	increases expression	2
Smoke	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
bisphenol F	increases expression	1
4-oxoretinoic acid	increases expression	1
7-ketocholesterol	decreases reaction, increases expression	1

ChEMBL screening assays

127 unique, capped per target: 127 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1243703	Binding	Inhibition of tissue transglutaminase	Mechanisms, biology and inhibitors of deubiquitinating enzymes. — Nat Chem Biol

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7K2	SEES3-1V human TGM2, clone1	Embryonic stem cell	Male
CVCL_A7K3	SEES3-1V human TGM2, clone2	Embryonic stem cell	Male
CVCL_A7K4	SEES3-1V human TGM2, clone3	Embryonic stem cell	Male
CVCL_B1I0	Abcam A-549 TGM2 KO 1	Cancer cell line	Male
CVCL_B2IG	Abcam HeLa TGM2 KO	Cancer cell line	Female
CVCL_B2QJ	Abcam A-549 TGM2 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus