Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

METAP2 (P50579) - Overview - Molecular Target Synopsis

Protein


METAP2, Methionine aminopeptidase 2
Enzyme Classification 3.4.11.18
UniProt P50579

Also Known as MAP2_HUMAN, METAP2, MNPEP, P67EIF2

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. Interacts strongly with the eIF-2 gamma-subunit EIF2S3 (By similarity). Binds EIF2S1 at low magnesium concentrations.

5LYX
CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX; WITH AN INHIBITOR 5-((R)-1-[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL- PYRROLIDIN-2-YLMETHOXY)-ISOQUINOLINE
RCSB/PDB
Inspect Structure
See all 3D Structures for METAP2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: METAP2 is active in the following subcellular-locations: cytoplasm.
GO terms: METAP2 is active in the following subcellular-locations: cytoplasm, cytosol, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project METAP2 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, UO_31, 786_0

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HT, KARPAS-422, SU-DHL-5

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, HMEC

(see details)

3D Structures


For METAP2 there are:
26 structures (26 chains) solved
25 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

METAP2 is solved in complex with the approved drug(s):

MET/METHIONINE (1KQ9_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


METAP2 has been screened with 874 compounds (1468 bioactivities), 539 compounds have bioactivities that show binding affinity of <= 500nM (945 bioactivities). (see details)