METAP2

Summary

METAP2 (methionyl aminopeptidase 2, HGNC:16672) is a protein-coding gene on chromosome 12q22, encoding Methionine aminopeptidase 2 (P50579). Cotranslationally removes the N-terminal methionine from nascent proteins. It is a selective cancer dependency (DepMap: 68.1% of cell lines).

The protein encoded by this gene is a member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10988 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 50 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 68.1% of screened cell lines
• MANE Select transcript: NM_006838

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16672
Approved symbol	METAP2
Name	methionyl aminopeptidase 2
Location	12q22
Locus type	gene with protein product
Status	Approved
Aliases	MNPEP, p67, MAP2
Ensembl gene	ENSG00000111142
Ensembl biotype	protein_coding
OMIM	601870
Entrez	10988

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000261220, ENST00000323666, ENST00000535095, ENST00000546478, ENST00000546753, ENST00000549136, ENST00000549502, ENST00000549808, ENST00000550777, ENST00000551840, ENST00000553151, ENST00000878866, ENST00000878867, ENST00000934960, ENST00000934961, ENST00000934962, ENST00000934963, ENST00000934964, ENST00000934965, ENST00000947084, ENST00000947085, ENST00000947086, ENST00000947087

RefSeq mRNA: 4 — MANE Select: NM_006838 NM_001317182, NM_001317183, NM_001330246, NM_006838

CCDS: CCDS81723, CCDS81724, CCDS81725, CCDS9052

Canonical transcript exons

ENST00000323666 — 11 exons

Exon	Start	End
ENSE00000753404	95483215	95483280
ENSE00000753405	95485879	95485981
ENSE00000753406	95494056	95494217
ENSE00000753407	95494957	95495138
ENSE00000753408	95496004	95496098
ENSE00000922696	95504065	95504161
ENSE00000922697	95511895	95511998
ENSE00001295819	95513652	95515839
ENSE00002357869	95474152	95474330
ENSE00003575452	95476071	95476178
ENSE00003635249	95512801	95512916

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 118.8213 / max 2644.2238, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127441	104.0800	1827
127440	10.3354	1749
127439	4.4059	1531

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.10	gold quality
seminal vesicle	UBERON:0000998	98.42	gold quality
calcaneal tendon	UBERON:0003701	98.42	gold quality
tendon	UBERON:0000043	97.74	gold quality
tendon of biceps brachii	UBERON:0008188	97.71	gold quality
trabecular bone tissue	UBERON:0002483	97.64	gold quality
oral cavity	UBERON:0000167	97.25	gold quality
secondary oocyte	CL:0000655	97.10	gold quality
ganglionic eminence	UBERON:0004023	97.10	gold quality
embryo	UBERON:0000922	97.02	gold quality
endometrium	UBERON:0001295	97.02	gold quality
colonic epithelium	UBERON:0000397	97.00	gold quality
adrenal tissue	UBERON:0018303	96.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.97	gold quality
cauda epididymis	UBERON:0004360	96.92	gold quality
ventricular zone	UBERON:0003053	96.83	gold quality
medial globus pallidus	UBERON:0002477	96.80	gold quality
biceps brachii	UBERON:0001507	96.77	gold quality
descending thoracic aorta	UBERON:0002345	96.74	gold quality
parotid gland	UBERON:0001831	96.69	gold quality
mammalian vulva	UBERON:0000997	96.68	gold quality
tonsil	UBERON:0002372	96.64	gold quality
corpus epididymis	UBERON:0004359	96.57	gold quality
globus pallidus	UBERON:0001875	96.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.44	gold quality
cortical plate	UBERON:0005343	96.33	gold quality
stromal cell of endometrium	CL:0002255	96.24	gold quality
superficial temporal artery	UBERON:0001614	96.22	gold quality
cartilage tissue	UBERON:0002418	96.17	gold quality
gastrocnemius	UBERON:0001388	96.09	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	142.38
E-CURD-122	yes	19.98
E-GEOD-111727	no	1208.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, PLAGL2

miRNA regulators (miRDB)

105 targeting METAP2, 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-4262	100.00	73.26	3931
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-1323	99.83	69.89	2471

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 24)

• the functional role of S100A4 in regulating endothelial cell growth and tumor metastasis involves interaction with the N-terminal half of Methionine Aminopeptidase 2. (PMID:11994292)
• High expression in germinal center B cells and their neoplastic counterparts. (PMID:12118091)
• Divalent metal cofactors are physiologically relevant for activity of this enzyme. (PMID:12718546)
• MetAP protein has a role in colorectal adenocarcinoma progression (PMID:15102683)
• Expressed in colon cancer cells (PMID:15336565)
• MetAP-1 and MetAP-2 have essential functions in the control of mammalian cell proliferation (PMID:15962312)
• A comparison of the structual differences between Type I and Type II methionine aminopeptidases. (PMID:16274222)
• Data suggest that methionine aminopeptidase 2 plays a role in the proliferation of fibroblasts and myofibroblasts in fibrotic lung diseases and may serve as a novel pharmacologic target in idiopathic pulmonary fibrosis. (PMID:17446530)
• MetAP2 plays an important role in tumor cell growth and may contribute to tumorigenesis (PMID:18264137)
• Discovery, identification, and characterization of candidate pharmacodynamic markers of METAP2 inhibition are reported. (PMID:18828628)
• Data indicate that MetAP2 expression and pp60c-src phosphorylation were decreased in NC2213 treated cells. (PMID:19703310)
• the substrate specificities of Escherichia coli MetAP1, human MetAP1, and human MetAP2 were systematically profiled (PMID:20521764)
• This study demonstrated a hitherto-undescribed role of MetAP2 in definitive hematopoiesis and a possible link to noncanonical Wnt and ERK signaling. (PMID:21937698)
• Increased expression of METAP2 is associated with pilocytic astrocytoma. (PMID:23161775)
• The activity of unmodified, nitrated and oxidised METAP2 was assessed and it was found that nitration significantly reduced its ability to cleave a chromogenic substrate. Mass spectrometry analysis identified Tyr336 as a nitrated residue in METAP2. (PMID:24041691)
• Data indicate that methionine aminopeptidase 2 (MetAP2) contains a single disulfide bond that exists in oxidized and reduced states and influences enzyme function. (PMID:24700462)
• Nt-acetylation prevents the excision of the initiator methionine by MetAP2. (PMID:25886145)
• Suggest MetAP2 as important regulator of proliferation/apoptosis in non-small cell lung cancers. (PMID:26935506)
• MetAP1 and MetAP2 have roles in driving cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state (PMID:27542228)
• Results show that methionine aminopeptidase-2 (MetAP2) regulates angiogenesis in glioblastoma and identify MetAP2-specific substrates that may serve as candidates for clinical assay development. (PMID:29116484)
• CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2. (PMID:32922205)
• In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification. (PMID:33637565)
• Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons. (PMID:38335281)
• Using bovine cell extract, fumagillin was found to be bound by methionine aminopeptidase (MetAP-2). (PMID:9177176)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	metap2b	ENSDARG00000102571
mus_musculus	Metap2	ENSMUSG00000036112
rattus_norvegicus	Metap2-ps1	ENSRNOG00000015772
rattus_norvegicus	Metap2	ENSRNOG00000021881
caenorhabditis_elegans	F53B6.5	WBGENE00009960
caenorhabditis_elegans		WBGENE00012075

Paralogs (7): XPNPEP1 (ENSG00000108039), XPNPEP2 (ENSG00000122121), PEPD (ENSG00000124299), METAP1 (ENSG00000164024), PA2G4 (ENSG00000170515), METAP1D (ENSG00000172878), XPNPEP3 (ENSG00000196236)

Protein

Protein identifiers

Methionine aminopeptidase 2 — P50579 (reviewed: P50579)

Alternative names: Initiation factor 2-associated 67 kDa glycoprotein, Peptidase M

All UniProt accessions (8): P50579, A0A140VJE3, F8VQZ7, F8VRR3, F8VSC4, F8VY03, F8VZX9, G3V1U3

UniProt curated annotations — full annotation on UniProt →

Function. Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.

Subunit / interactions. Interacts strongly with the eIF-2 gamma-subunit EIF2S3. Binds EIF2S1 at low magnesium concentrations.

Subcellular location. Cytoplasm.

Post-translational modifications. Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.

Cofactor. Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site. Also manganese has been proposed to be the physiological cofactor for human METAP2.

Similarity. Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P50579-1	1	yes
P50579-2	2
P50579-3	3

RefSeq proteins (4): NP_001304111, NP_001304112, NP_001317175, NP_006829* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000994	Pept_M24	Domain
IPR001714	Pept_M24_MAP	Family
IPR002468	Pept_M24A_MAP2	Family
IPR018349	Pept_M24A_MAP2_BS	Binding_site
IPR036005	Creatinase/aminopeptidase-like	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR050247	Met_Aminopeptidase_Type2	Family

Pfam: PF00557

Enzyme classification (BRENDA):

• EC 3.4.11.18 — methionyl aminopeptidase (BRENDA: 45 organisms, 219 substrates, 968 inhibitors, 153 Km, 147 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
MET-GLY-MET-MET	0.058–18.3	20
L-MET-7-AMIDO-4-METHYLCOUMARIN	0.0309–0.5467	16
MET-ALA-SER	0.018–4.54	11
L-MET-GLY-L-MET-L-MET	0.6–3.2	10
L-MET 4-NITROANILIDE	0.154–2.77	9
L-MET-PSI[C(O)S]GLY-L-PHE	0.35–16	8
MET-4-METHYLCOUMARYL-7-AMIDE	0.111–0.168	8
MET-PRO-4-NITROANILIDE	0.06–3.26	7
L-ALANINE-4-METHYLCOUMARIN-7-AMIDE	0.125–0.284	6
L-LEU-7-AMIDO-4-METHYLCOUMARIN	0.0345–0.9795	6
L-METHIONINE 4-NITROANILIDE	0.0002–0.543	4
L-METHIONINE-4-METHYLCOUMARIN-7-AMIDE	0.011–0.17	4
MET-7-AMIDO-4-METHYLCOUMARIN	0.12–6.27	4
L-MET-L-ALA-L-SER	3–15	3
MET-ALA-ALA	1.5–5.2	3

UniProt features (58 total): strand 17, helix 12, binding site 9, modified residue 5, compositionally biased region 4, splice variant 3, glycosylation site 2, turn 2, initiator methionine 1, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

40 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5D6E	X-RAY DIFFRACTION	1.49
5D6F	X-RAY DIFFRACTION	1.55
1B6A	X-RAY DIFFRACTION	1.6
1QZY	X-RAY DIFFRACTION	1.6
5JFR	X-RAY DIFFRACTION	1.6
6QEJ	X-RAY DIFFRACTION	1.62
1YW9	X-RAY DIFFRACTION	1.64
5LYW	X-RAY DIFFRACTION	1.69
8OXG	X-RAY DIFFRACTION	1.73
5CLS	X-RAY DIFFRACTION	1.75
6QEF	X-RAY DIFFRACTION	1.79
1B59	X-RAY DIFFRACTION	1.8
1BN5	X-RAY DIFFRACTION	1.8
1BOA	X-RAY DIFFRACTION	1.8
5JHU	X-RAY DIFFRACTION	1.8
6QED	X-RAY DIFFRACTION	1.8
6QEI	X-RAY DIFFRACTION	1.8
1YW7	X-RAY DIFFRACTION	1.85
1KQ9	X-RAY DIFFRACTION	1.9
1R58	X-RAY DIFFRACTION	1.9
2ADU	X-RAY DIFFRACTION	1.9
2OAZ	X-RAY DIFFRACTION	1.9
5LYX	X-RAY DIFFRACTION	1.9
7A16	X-RAY DIFFRACTION	1.9
2GA2	X-RAY DIFFRACTION	1.95
1KQ0	X-RAY DIFFRACTION	2
1R5G	X-RAY DIFFRACTION	2
7A12	X-RAY DIFFRACTION	2
7A13	X-RAY DIFFRACTION	2.04
6QEG	X-RAY DIFFRACTION	2.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50579-F1	86.07	0.78

Functional residue map

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

Ligand- & substrate-binding residues (9): 262; 331; 339; 364; 459; 459; 231; 251; 262

Post-translational modifications (5): 2, 45, 60, 63, 74

Glycosylation sites (2): 60, 63

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-2187338	Visual phototransduction
R-HSA-2514856	The phototransduction cascade
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 201 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, PEREZ_TP63_TARGETS, GOBP_TRANSLATIONAL_INITIATION, GNF2_RRM1, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CTAGGAA_MIR384, GOBP_PROTEIN_MATURATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GNF2_SMC4L1, HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP, AAAGACA_MIR511, GARY_CD5_TARGETS_DN

GO Biological Process (3): regulation of translational initiation (GO:0006446), protein processing (GO:0016485), proteolysis (GO:0006508)

GO Molecular Function (9): RNA binding (GO:0003723), aminopeptidase activity (GO:0004177), initiator methionyl aminopeptidase activity (GO:0004239), metalloexopeptidase activity (GO:0008235), metal ion binding (GO:0046872), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
The phototransduction cascade	1
Sensory Perception	1
Visual phototransduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exopeptidase activity	2
aminopeptidase activity	2
cellular anatomical structure	2
translational initiation	1
regulation of translation	1
proteolysis	1
protein maturation	1
protein metabolic process	1
nucleic acid binding	1
metallopeptidase activity	1
cation binding	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

4589 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METAP2	METAP1	P53582	970
METAP2	SKP1	P34991	698
METAP2	CRBN	Q96SW2	614
METAP2	BTRC	Q9Y297	597
METAP2	S100A4	P26447	595
METAP2	DDX18	Q9NVP1	516
METAP2	ESR1	P03372	507
METAP2	ODC1	P11926	498
METAP2	ZBTB17	Q13105	494
METAP2	RTL10	Q7L3V2	490
METAP2	S100A6	P06703	468
METAP2	METAP1D	Q6UB28	467
METAP2	NPRL2	Q8WTW4	446
METAP2	WDR24	Q96S15	444
METAP2	NPRL3	Q12980	440
METAP2	LIN28A	Q9H9Z2	440

IntAct

127 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
CUL5	SOCS7	psi-mi:“MI:0914”(association)	0.640
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
CCT2	PPP6C	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
FCRL2	METAP2	psi-mi:“MI:0915”(physical association)	0.590
DRD4	METAP2	psi-mi:“MI:0915”(physical association)	0.560
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SUN2	POTEF	psi-mi:“MI:0914”(association)	0.530
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
PLIN5	INPPL1	psi-mi:“MI:0914”(association)	0.530
ASB6	POLR2D	psi-mi:“MI:0914”(association)	0.530
DDX28	PTCD1	psi-mi:“MI:0914”(association)	0.530
GNAS	CPT2	psi-mi:“MI:0914”(association)	0.530
TMEM213	METAP2	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530

BioGRID (329): METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Co-fractionation), METAP2 (Affinity Capture-MS), METAP2 (Synthetic Lethality), METAP2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), METAP2 (Reconstituted Complex)

ESM2 similar proteins: A1CH02, A1CXT5, A2QHX0, A4RDI6, A6QLA4, A6ZKL2, A8QBZ2, B3LNM2, B5VDQ0, B6HTQ4, B6Q1N3, B8LUH2, B8NA06, C4JF09, C5DE35, C7GSF3, C8Z3V4, C9SB49, D1ZEN1, D8PR70, E3QW41, E5R4J3, O08663, O59730, O60085, P38062, P38174, P50579, P53582, Q01662, Q0CL94, Q0UTI9, Q2GSJ7, Q3ZC89, Q4QRK0, Q4VBS4, Q54WU3, Q56Y85, Q5I0A0, Q5RBF3

Diamond homologs: A1CCP2, A1CH02, A1CXT5, A1CYM1, A1DA84, A2QAF9, A2QHX0, A4RDI6, A5DR89, A5E5I9, A6RGC8, A6RTU0, A6ZKL2, A7EZ86, A8QBZ2, B0CRL4, B0XTJ7, B0Y5N4, B0YAX5, B2B738, B2VW14, B2W1N6, B3LNM2, B5VDQ0, B6H5L5, B6HTQ4, B6Q1N3, B6QD96, B8LUH2, B8M990, B8NA06, B8NLL0, B9WJA2, C0NIQ4, C0NX86, C0SIM8, C1GLM4, C1HAB2, C4JSX6, C4R2P3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
Formation of tubulin folding intermediates by CCT/TriC	5	23.2×	5e-04
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	22.4×	5e-04
Chaperonin-mediated protein folding	5	16.5×	1e-03
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	5	16.5×	1e-03
Association of TriC/CCT with target proteins during biosynthesis	5	16.1×	1e-03
Protein folding	5	14.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
adult locomotory behavior	6	13.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5488 predictions. Top by Δscore:

Variant	Effect	Δscore
12:95474329:AGG:A	donor_loss	1.0000
12:95474331:GTA:G	donor_loss	1.0000
12:95476066:ATCAG:A	acceptor_loss	1.0000
12:95476067:TCAGC:T	acceptor_loss	1.0000
12:95476068:CAGC:C	acceptor_loss	1.0000
12:95476069:A:AG	acceptor_gain	1.0000
12:95476069:A:C	acceptor_loss	1.0000
12:95476069:AGCAG:A	acceptor_gain	1.0000
12:95476070:G:GA	acceptor_gain	1.0000
12:95476070:G:T	acceptor_loss	1.0000
12:95476070:GC:G	acceptor_gain	1.0000
12:95476070:GCA:G	acceptor_gain	1.0000
12:95476070:GCAGG:G	acceptor_gain	1.0000
12:95476072:AGGG:A	acceptor_gain	1.0000
12:95476073:GGGG:G	acceptor_gain	1.0000
12:95476177:AGG:A	donor_loss	1.0000
12:95476179:GTAA:G	donor_loss	1.0000
12:95483277:GGAC:G	donor_gain	1.0000
12:95483278:G:GT	donor_gain	1.0000
12:95483278:GAC:G	donor_gain	1.0000
12:95483281:G:GG	donor_gain	1.0000
12:95483290:T:G	donor_gain	1.0000
12:95483290:T:TG	donor_gain	1.0000
12:95483295:T:G	donor_gain	1.0000
12:95494225:G:GT	donor_gain	1.0000
12:95494237:G:GG	donor_gain	1.0000
12:95494263:T:TG	donor_gain	1.0000
12:95494955:A:AG	acceptor_gain	1.0000
12:95494956:G:GA	acceptor_gain	1.0000
12:95495095:G:GG	donor_gain	1.0000

AlphaMissense

3140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:95494157:G:C	R177P	1.000
12:95494217:G:A	C197Y	1.000
12:95494957:T:G	C197W	1.000
12:95494980:G:C	R205P	1.000
12:95495019:C:A	A218E	1.000
12:95495021:T:A	F219I	1.000
12:95495021:T:C	F219L	1.000
12:95495021:T:G	F219V	1.000
12:95495022:T:C	F219S	1.000
12:95495022:T:G	F219C	1.000
12:95495023:T:A	F219L	1.000
12:95495023:T:G	F219L	1.000
12:95495025:C:A	P220H	1.000
12:95495030:G:A	G222R	1.000
12:95495030:G:C	G222R	1.000
12:95495031:G:A	G222E	1.000
12:95495033:T:C	C223R	1.000
12:95495052:C:A	A229D	1.000
12:95495055:C:A	A230D	1.000
12:95495057:C:G	H231D	1.000
12:95495059:T:A	H231Q	1.000
12:95495059:T:G	H231Q	1.000
12:95495118:A:C	D251A	1.000
12:95495118:A:T	D251V	1.000
12:95495119:C:A	D251E	1.000
12:95495119:C:G	D251E	1.000
12:95495124:G:A	G253E	1.000
12:95496004:G:A	G258D	1.000
12:95496004:G:T	G258V	1.000
12:95496017:C:A	D262E	1.000

dbSNP variants (sampled 300 via entrez): RS1000034352 (12:95492352 G>A), RS1000056014 (12:95478811 A>G), RS1000142329 (12:95502381 G>A), RS1000183117 (12:95507617 C>T), RS1000195120 (12:95475147 C>G), RS1000299654 (12:95510904 A>G), RS1000395023 (12:95511147 A>G), RS1000516033 (12:95487261 G>A,T), RS1000548404 (12:95487570 A>G,T), RS1000554201 (12:95492605 G>A,C,T), RS1000624003 (12:95497269 C>A,G), RS1000727875 (12:95481205 C>A,G,T), RS1000892386 (12:95500628 T>C), RS1000927110 (12:95504034 A>C,T), RS1000942871 (12:95500891 A>T)

Disease associations

OMIM: gene MIM:601870 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004628_51	Immature fraction of reticulocytes	4.000000e-17
GCST006585_2591	Blood protein levels	5.000000e-08
GCST007614_56	C-reactive protein levels	5.000000e-14
GCST009391_1231	Metabolite levels	3.000000e-07
GCST90002385_236	High light scatter reticulocyte count	1.000000e-51
GCST90002386_330	High light scatter reticulocyte percentage of red cells	3.000000e-53
GCST90002405_237	Reticulocyte count	3.000000e-32
GCST90013407_138	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-24

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004458	C-reactive protein measurement
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831223 (PROTEIN FAMILY), CHEMBL3922 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 104,042 (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
CHEMBL1454910	NITROXOLINE	4	1,860
CHEMBL497	CLIOQUINOL	4	12,977
CHEMBL625	THIABENDAZOLE	4	58,476
CHEMBL4297504	BELORANIB	3	430
CHEMBL51085	EBSELEN	3	13,237
CHEMBL1170610	BENZOXIQUINE	2	511
CHEMBL225164	CLOXYQUIN	2	3,892
CHEMBL32838	FUMAGILLIN	2	10,089
CHEMBL424278	O-CHLOROACETYLCARBAMOYLFUMAGILLOL	2	2,307
CHEMBL3527358	PPI-2458	1	263

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M24: Methionyl aminopeptidase

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

Ligand	Action	Affinity	Parameter
BAY-277	Inhibition	8.24	pIC50
XMT-1191	Inhibition	8.0	pIC50
M8891	Inhibition	7.27	pIC50
nitroxoline	Inhibition	7.26	pIC50

Binding affinities (BindingDB)

674 measured of 752 human assays (752 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-(benzylsulfanyl)-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.04 nM
N-[5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]pyridin-3-amine	KI	0.04 nM
5-(benzylsulfanyl)-N-(4-methoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	0.05 nM
5-(benzylsulfanyl)-N-(4-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.07 nM
FOS-69	IC50	0.1 nM
5-{[(2-fluorophenyl)methyl]sulfanyl}-N-(4-methoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	0.13 nM
5-[(3-methylbut-2-en-1-yl)sulfanyl]-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.15 nM
N-(4-methoxyphenyl)-5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.16 nM
5-{[(2-fluorophenyl)methyl]sulfanyl}-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.23 nM
N-(5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	0.3 nM
Ovalicin	IC50	0.4 nM
methyl 4-[(5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)amino]benzoate	KI	0.41 nM
5-(benzylsulfanyl)-N-(4-chlorophenyl)-4H-1,2,4-triazol-3-amine	KI	0.43 nM
5-(benzylsulfanyl)-N-phenyl-4H-1,2,4-triazol-3-amine	KI	0.5 nM
methyl 4-({5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	0.5 nM
N-(5-{[(3,4-difluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	0.5 nM
N-(4-chlorophenyl)-5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.52 nM
N-(4-chlorophenyl)-5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	0.61 nM
5-{[(2-fluorophenyl)methyl]sulfanyl}-N-(4-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	0.65 nM
methyl 4-{[5-(benzylsulfanyl)-4H-1,2,4-triazol-3-yl]amino}benzoate	KI	0.7 nM
N-phenyl-5-[(thiophen-2-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.75 nM
methyl 4-[(5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)amino]benzoate	KI	0.8 nM
N-(3,4-dimethoxyphenyl)-5-[(3-methylbut-2-en-1-yl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	0.9 nM
methyl 4-({5-[(pyridin-2-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	0.9 nM
methyl 4-({5-[(pyridin-4-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	0.9 nM
5-[(3-methylbut-2-en-1-yl)sulfanyl]-N-phenyl-4H-1,2,4-triazol-3-amine	KI	1 nM
(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl N-(2-chloroacetyl)carbamate	KI	1 nM
5-(4-iodophenyl)-1H-1,2,3-triazole	KI	1 nM
5-(3,4-dibromophenyl)-1H-1,2,3-triazole	KI	1 nM
AGM-1470	IC50	1 nM
5-[(3-methylbut-2-en-1-yl)sulfanyl]-N-(4-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	1.2 nM
N-(3,4-dimethoxyphenyl)-5-{[(2-fluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.3 nM
methyl 4-[(5-{[(3,4-difluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)amino]benzoate	KI	1.3 nM
7-[2-(3-hydroxypyrrolidin-1-yl)-3-pyridinyl]-5-(2,2,2-trifluoroethyl)-2,3,3a,5a,6,7,8,9,9a,9b-decahydro-1H-pyrazolo[4,3-c]quinolin-4-one	IC50	1.46 nM	US-9169246: Pyrazoloquinolinone derivatives, preparation thereof and therapeutic use thereof
N-(4-chlorophenyl)-5-{[(3,4-difluorophenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.5 nM
N-(5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	1.5 nM
N-(4-methoxyphenyl)-5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.6 nM
5-(benzylsulfanyl)-N-(3,4-dimethoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	1.7 nM
N-(5-{[(2-methylphenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-yl)pyridin-3-amine	KI	1.7 nM
N-(4-chlorophenyl)-5-{[(5-methyl-1,2-oxazol-3-yl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	1.8 nM
1,2,4-Triazole Compound, 102	KI	2 nM
FOS-68	IC50	2 nM
5-{[(3,4-difluorophenyl)methyl]sulfanyl}-N-(4-methoxyphenyl)-4H-1,2,4-triazol-3-amine	KI	2.1 nM
7-(4-piperazin-1-ylphenyl)-5-(2,2,2-trifluoroethyl)-2,3,3a,5a,6,7,8,9,9a,9b-decahydro-1H-pyrazolo[4,3-c]quinolin-4-one	IC50	2.13 nM	US-9169246: Pyrazoloquinolinone derivatives, preparation thereof and therapeutic use thereof
5-{[(3,4-difluorophenyl)methyl]sulfanyl}-N-(2-methylphenyl)-4H-1,2,4-triazol-3-amine	KI	2.4 nM
N-(2-methylphenyl)-5-{[(2-methylphenyl)methyl]sulfanyl}-4H-1,2,4-triazol-3-amine	KI	2.5 nM
N-(4-chlorophenyl)-5-[(pyridin-4-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-amine	KI	2.5 nM
methyl 4-({5-[(cyclohexylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}amino)benzoate	KI	2.7 nM
N-{5-[(pyridin-4-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyridin-3-amine	KI	3 nM
5-[(furan-2-ylmethyl)sulfanyl]-N-[2-(propan-2-yl)phenyl]-4H-1,2,4-triazol-3-amine	KI	3 nM

ChEMBL bioactivities

1342 potent at pChembl≥5 of 1426 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Ki	0.04	nM	CHEMBL241829
10.40	Ki	0.04	nM	CHEMBL243306
10.30	Ki	0.05	nM	CHEMBL397477
10.15	Ki	0.07079	nM	CHEMBL243111
10.15	Ki	0.07	nM	CHEMBL243111
10.02	EC50	0.095	nM	PPI-2458
9.89	Ki	0.13	nM	CHEMBL242435
9.82	Ki	0.15	nM	CHEMBL245022
9.80	Ki	0.16	nM	CHEMBL245226
9.80	Ki	0.16	nM	CHEMBL4475680
9.64	Ki	0.23	nM	CHEMBL389087
9.52	EC50	0.3	nM	CHEMBL3527591
9.52	Ki	0.3	nM	CHEMBL242050
9.41	IC50	0.39	nM	CHEMBL176975
9.40	IC50	0.4	nM	OVALICIN
9.39	Ki	0.41	nM	CHEMBL242875
9.37	Ki	0.43	nM	CHEMBL242028
9.37	IC50	0.43	nM	CHEMBL368349
9.30	Ki	0.5	nM	CHEMBL243303
9.30	Ki	0.5	nM	CHEMBL242051
9.30	Ki	0.5	nM	CHEMBL243101
9.29	IC50	0.51	nM	CHEMBL172123
9.28	Ki	0.52	nM	CHEMBL242891
9.21	Ki	0.61	nM	CHEMBL242462
9.20	IC50	0.63	nM	FUMAGILLIN
9.19	Ki	0.65	nM	CHEMBL243320
9.15	Ki	0.7	nM	CHEMBL242663
9.12	Ki	0.75	nM	CHEMBL243305
9.10	Ki	0.8	nM	CHEMBL396988
9.10	Ki	0.8	nM	CHEMBL243305
9.10	IC50	0.8	nM	CHEMBL367938
9.06	Kd	0.88	nM	CHEMBL4451402
9.05	Ki	0.9	nM	CHEMBL430001
9.05	Ki	0.9	nM	CHEMBL242876
9.05	Ki	0.9	nM	CHEMBL242447
9.05	Ki	0.9	nM	CHEMBL4451402
9.02	IC50	0.96	nM	CHEMBL137766
9.00	Ki	1	nM	CHEMBL364051
9.00	Ki	1	nM	CHEMBL195915
9.00	IC50	1	nM	O-CHLOROACETYLCARBAMOYLFUMAGILLOL
9.00	Ki	1	nM	O-CHLOROACETYLCARBAMOYLFUMAGILLOL
9.00	Ki	1	nM	CHEMBL230640
9.00	IC50	1	nM	FUMAGILLIN
8.94	Kd	1.14	nM	CHEMBL4448724
8.92	IC50	1.2	nM	FUMAGILLIN
8.92	Ki	1.202	nM	CHEMBL398002
8.92	Ki	1.2	nM	CHEMBL398002
8.92	IC50	1.2	nM	CHEMBL172883
8.92	IC50	1.2	nM	CHEMBL174250
8.89	EC50	1.3	nM	CHEMBL3526173

PubChem BioAssay actives

1155 with measured affinity, of 1673 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
N-(3-benzylsulfanyl-1H-1,2,4-triazol-5-yl)pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	<0.0001	uM
3-benzylsulfanyl-N-(2-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	<0.0001	uM
3-(3-methylbut-2-enylsulfanyl)-N-(2-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
[(3S,4R,5R,6R)-4-hydroxy-5-methoxy-4-[(2R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] 4-chlorobutanoate	1799439: Enzymatic Assay from Article 10.1016/s1074-5521(97)90198-8: “Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.”	ic50	0.0001	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate	1223628: Inhibition of MetAP2 activity in HUVEC assessed as inhibition of cell proliferation by MTT assay	ec50	0.0001	uM
3-benzylsulfanyl-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
3-[(2-fluorophenyl)methylsulfanyl]-N-(4-methoxyphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
3-benzylsulfanyl-N-(4-methoxyphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0001	uM
3-[(2-fluorophenyl)methylsulfanyl]-N-(2-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0002	uM
N-(4-methoxyphenyl)-3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0002	uM
(3S)-N-[(3-chloro-5-fluorophenyl)methyl]-3-hydroxy-2-oxo-1-(2-oxo-3,4-dihydro-1H-quinolin-6-yl)pyrrolidine-3-carboxamide	1617491: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by Cheng-Prusoff equation analysis	ki	0.0002	uM
N-[3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0003	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-hydroxy-3-methyl-1-oxobutan-2-yl]carbamate	1223628: Inhibition of MetAP2 activity in HUVEC assessed as inhibition of cell proliferation by MTT assay	ec50	0.0003	uM
(3S,4R,5S)-4-hydroxy-5-methoxy-4-[(2S,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-one	424804: Inhibition of methionine aminopeptidase 2	ic50	0.0004	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] carbamate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0004	uM
methyl 4-[[3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0004	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-carbonochloridoylcarbamate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0004	uM
(3S,4R,5S)-4-hydroxy-5-methoxy-4-[(2R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-one	1799439: Enzymatic Assay from Article 10.1016/s1074-5521(97)90198-8: “Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.”	ic50	0.0004	uM
3-benzylsulfanyl-N-(4-chlorophenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0004	uM
N-[3-[(3,4-difluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
methyl 4-[[3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
N-(4-chlorophenyl)-3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] acetate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0005	uM
3-benzylsulfanyl-N-phenyl-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0005	uM
3-[(2-fluorophenyl)methylsulfanyl]-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0006	uM
Fumagillin	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0006	uM
N-(4-chlorophenyl)-3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0006	uM
methyl 4-[(3-benzylsulfanyl-1H-1,2,4-triazol-5-yl)amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0007	uM
N-phenyl-3-(thiophen-2-ylmethylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0008	uM
methyl 4-[[3-[(5-methyl-1,2-oxazol-3-yl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0008	uM
[(3R,4S,5S,6R)-4-[(E)-N-(cyclohexylmethoxy)-C-methylcarbonimidoyl]-5-methoxy-1-oxaspiro[2.5]octan-6-yl] 4-ethylpiperazine-1-carboxylate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0008	uM
(3S)-N-[(3,5-difluorophenyl)methyl]-3-hydroxy-2-oxo-1-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolidine-3-carboxamide	1617491: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by Cheng-Prusoff equation analysis	ki	0.0009	uM
N-(3,4-dimethoxyphenyl)-3-(3-methylbut-2-enylsulfanyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0009	uM
methyl 4-[[3-(pyridin-2-ylmethylsulfanyl)-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0009	uM
methyl 4-[[3-(pyridin-4-ylmethylsulfanyl)-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0009	uM
3-(3-methylbut-2-enylsulfanyl)-N-phenyl-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0010	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-(2-chloroacetyl)carbamate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0010	uM
[(3R,5S,6R)-5-methoxy-4-[(2S)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] N-(2-chloroacetyl)carbamate	1799439: Enzymatic Assay from Article 10.1016/s1074-5521(97)90198-8: “Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.”	ic50	0.0010	uM
4-(4-iodophenyl)-2H-triazole	1797630: Enzyme Inhibition Assay from Article 10.1021/jm050408c: “4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.”	ki	0.0010	uM
4-(3,4-dibromophenyl)-2H-triazole	1797630: Enzyme Inhibition Assay from Article 10.1021/jm050408c: “4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo.”	ki	0.0010	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl] (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate	1551719: Inhibition of human MetAP2	ic50	0.0010	uM
(3S)-N-[(3-chloro-5-fluorophenyl)methyl]-3-hydroxy-2-oxo-1-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolidine-3-carboxamide	1617492: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by FCCS analysis	kd	0.0011	uM
3-(3-methylbut-2-enylsulfanyl)-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0012	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(E)-C-methyl-N-phenylmethoxycarbonimidoyl]-1-oxaspiro[2.5]octan-6-yl] acetate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0012	uM
[(3R,4S,5S,6R)-5-methoxy-4-[(E)-C-methyl-N-phenylmethoxycarbonimidoyl]-1-oxaspiro[2.5]octan-6-yl] carbamate	107928: Inhibitory activity against Methionine aminopeptidase 2	ic50	0.0012	uM
[(3R,4S,5S,6R)-4-[(2R,3R)-3-[[(2R)-3,3-dimethyloxiran-2-yl]methyl]-2-methyloxiran-2-yl]-5-methoxy-1-oxaspiro[2.5]octan-6-yl] N-[(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate	1223628: Inhibition of MetAP2 activity in HUVEC assessed as inhibition of cell proliferation by MTT assay	ec50	0.0013	uM
methyl 4-[[3-[(3,4-difluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]amino]benzoate	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0013	uM
N-(3,4-dimethoxyphenyl)-3-[(2-fluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0013	uM
N-[3-[(5-methyl-1,2-oxazol-3-yl)methylsulfanyl]-1H-1,2,4-triazol-5-yl]pyridin-3-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0015	uM
N-(4-chlorophenyl)-3-[(3,4-difluorophenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine	1797624: Enzyme Inhibition Assay from Article 10.1021/jm061182w: “Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore.”	ki	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
fumagillin	decreases activity, decreases metabolic processing, affects cotreatment	2
Cobalt	increases activity, affects binding	2
Gold	decreases expression	2
Triazoles	decreases activity, decreases reaction	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
nitroxoline	decreases activity	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
tetrahydropalmatine	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases activity	1
manganese chloride	decreases activity, decreases reaction, increases activity	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
pinosylvin	decreases expression	1
glycidamide	increases expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
3,4,5-trihydroxy-2–methoxy-8,8-dimethyl-N-(hexahydro-2-oxo-6-(cyclohexylcarbonyl)oxy-2H-azepin-3-yl)non-6-enamide	affects metabolic processing, affects cotreatment, decreases activity, decreases metabolic processing, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

111 unique, capped per target: 105 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — J Nat Prod
CHEMBL1027137	Binding	Inhibition of methionine aminopeptidase 2	A selective account of effective paradigms and significant outcomes in the discovery of inspirational marine natural products. — J Nat Prod
CHEMBL5464009	Functional	Degradation in HT1080 cells (CE) (Capillary electrophoresis (CE))	Data for DCP probe BAY-277

Clinical trials (associated diseases)

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