Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001749
UniProt IDP50579
Primary gene name(s)METAP2
Synonym gene name(s)MNPEP, P67EIF2
Protein nameMethionine aminopeptidase 2
Protein functionCotranslationally 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.; FUNCTION: 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.
Subcellular locationCytoplasm {ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:21537465}. Note=About 30% of expressed METAP2 associates with polysomes.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P50579
Gene Ontology
(Biological Process)
Complete annatation
N-terminal protein amino acid modification [GO:0031365];
peptidyl-methionine modification [GO:0018206];
protein initiator methionine removal [GO:0070084];
protein processing [GO:0016485];
regulation of rhodopsin mediated signaling pathway [GO:0022400]
Gene Ontology
(Molecular Function)
Complete annatation
aminopeptidase activity [GO:0004177];
metal ion binding [GO:0046872];
metalloaminopeptidase activity [GO:0070006];
metalloexopeptidase activity [GO:0008235];
poly(A RNA binding [GO:0044822]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
plasma membrane [GO:0005886]
Protein-protein interaction116184
Phylogenetic treeP50579
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.821191032293936.60475492075818e-086.63203638678663e-07
AZA vs. DISU-0.013807887230850.9564602777307260.996649735504266
AZA vs. IL70.2525495824087710.1894019863193110.952979086856458
AZA vs. SAHA-0.1771112787558750.4680959965944130.804287694087645
DISU vs. CD3-1.847501165987967.57934080164446e-077.55128772266944e-06
DISU vs. IL70.2574958983762620.3067754864831350.691070002799353
DISU vs. SAHA-0.1626267423186710.5767771408112450.863170120426495
DMSO vs. AZA-0.1034859655191030.5375301088436411
DMSO vs. CD3-1.935871176761834.69680161430119e-095.36446674142892e-08
DMSO vs. DISU-0.09148699716159540.7077660468677380.960763093481455
DMSO vs. IL70.3632246546051450.04378578054487260.422040052246774
DMSO vs. SAHA-0.08102393163380320.7311787178095610.921387247641323
HIV vs. Mock in Activation-0.1952154516418830.7534211181154450.999983755607037
HIV vs. Mock in Latency-0.03212406021261420.8459957986105960.999834320637052
IL7 vs. CD3-1.560006336541091.9985660011379e-061.81910539463476e-05
SAHA vs. CD3-2.023898349496113.26446608633901e-083.8982174263969e-07
SAHA vs. IL7-0.4335196165582890.0755480595293250.241330569674563
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.0207912 0.91686
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.883 1.363 1.281 1.001 1.041
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02310 3,5,6,8-Tetramethyl-N-Methyl Phenanthrolinium experimental unknown unknown
DB02640 Fumagillin experimental unknown ligand
DB02893 D-Methionine experimental unknown unknown
DB03086 N&,39;-(2s,3r)-3-Amino-4-Cyclohexyl-2-Hydroxy-Butano-N-(4-Methylphenyl)Hydrazide experimental unknown unknown
DB03396 (E)-(2r,3r,4s,5r)-3,4,5-Trihydroxy-2-Methoxy-8,8-Dimethyl-Non-6-Enoic Acid ((3s,6r)-6-Hydroxy-2-Oxo-Azepan-3-Yl)-Amide experimental unknown unknown
DB03900 2-Methyl-2-Propanol experimental unknown unknown
DB04108 (2s,3r)-3-Amino-2-Hydroxy-5-(Ethylsulfanyl)Pentanoyl-((S)-(-)-(1-Naphthyl)Ethyl)Amide experimental unknown unknown
DB04324 Ovalicin experimental unknown unknown
DB00134 L-Methionine approved, nutraceutical unknown product of
DB05864 PPI-2458 investigational unknown unknown
DB07309 5-BROMO-2-{[(4-CHLOROPHENYL)SULFONYL]AMINO}BENZOIC ACID experimental unknown unknown
DB07313 5-METHYL-2-[(PHENYLSULFONYL)AMINO]BENZOIC ACID experimental unknown unknown
DB07746 3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-2-METHYLBENZOIC ACID experimental unknown unknown
DB08633 (CHLOROACETYL)CARBAMIC ACID (3R,4S,5S,5R)-5-METHOXY-4-[(2R,3R)-2-METHYL-3-(3-METHYL-2-BUTENYL)OXIRANYL]-1-OXASPIRO[2.5]OCT-6-YL ESTER experimental unknown unknown
DB01422 Nitroxoline approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1B59 X-ray 1.8Å A=109-478.
1B6A X-ray 1.6Å A=1-478.
1BN5 X-ray 1.8Å A=1-478.
1BOA X-ray 1.8Å A=1-478.
1KQ0 X-ray 2.0Å A=1-478.
1KQ9 X-ray 1.9Å A=1-478.
1QZY X-ray 1.6Å A=1-478.
1R58 X-ray 1.9Å A=110-478.
1R5G X-ray 2.0Å A=110-478.
1R5H X-ray 2.4Å A=110-478.
1YW7 X-ray 1.8Å A=110-478.
1YW8 X-ray 2.6Å A=110-478.
1YW9 X-ray 1.6Å A=110-478.
2ADU X-ray 1.9Å A=110-478.
2EA2 X-ray 2.5Å A=110-478.
2EA4 X-ray 2.3Å A=110-478.
2GA2 X-ray 1.9Å A=110-478.
2OAZ X-ray 1.9Å A=110-478.
5CLS X-ray 1.7Å A=108-478.
5D6E X-ray 1.4Å A=108-478.
5D6F X-ray 1.5Å A=108-478.
5JFR X-ray 1.6Å A=110-478.
5JHU X-ray 1.8Å A=110-478.
5JI6 X-ray 2.1Å A=110-478.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found