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    METAP2 methionyl aminopeptidase 2 [ Homo sapiens (human) ]

    Gene ID: 10988, updated on 2-Nov-2024

    Summary

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    Official Symbol
    METAP2provided by HGNC
    Official Full Name
    methionyl aminopeptidase 2provided by HGNC
    Primary source
    HGNC:HGNC:16672
    See related
    Ensembl:ENSG00000111142 MIM:601870; AllianceGenome:HGNC:16672
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MAP2; MNPEP; p67eIF2
    Summary
    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. [provided by RefSeq, Nov 2015]
    Expression
    Ubiquitous expression in testis (RPKM 26.5), lymph node (RPKM 23.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See METAP2 in Genome Data Viewer
    Location:
    12q22
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (95474152..95515839)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (95455178..95496879)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (95867928..95909615)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984545 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:95846624-95846848 Neighboring gene RNA, U6 small nuclear 735, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6810 Neighboring gene ribosomal protein L29 pseudogene 26 Neighboring gene MPRA-validated peak1899 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:95916458-95916958 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:95936387-95936886 Neighboring gene ubiquitin specific peptidase 44 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6811 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:96004940-96005508 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:96005509-96006077 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:96008766-96009393 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:96016523-96017477 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4739 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:96026735-96027934 Neighboring gene Sharpr-MPRA regulatory region 15569 Neighboring gene phosphoglycerate mutase 1 pseudogene 5 Neighboring gene netrin 4

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Methionine Aminopeptidase 2 as a Potential Therapeutic Target for Human Non-Small-Cell Lung Cancers. Shimizu H, et al. Adv Clin Exp Med, 2016 Jan-Feb. PMID 26935506
    2. Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties. Kawai M, et al. Bioorg Med Chem Lett, 2006 Jul 1. PMID 16632353
    3. Molecular analysis of a constitutional complex genome rearrangement with 11 breakpoints involving chromosomes 3, 11, 12, and 21 and a approximately 0.5-Mb submicroscopic deletion in a patient with mild mental retardation. Borg K, et al. Hum Genet, 2005 Nov. PMID 16160854
    4. Methionine aminopeptidases type I and type II are essential to control cell proliferation. Bernier SG, et al. J Cell Biochem, 2005 Aug 15. PMID 15962312
    5. Methionine aminopeptidase 2 inhibition is an effective treatment strategy for neuroblastoma in preclinical models. Morowitz MJ, et al. Clin Cancer Res, 2005 Apr 1. PMID 15814649

    See all (105) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons.
      Title: Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons.
    2. In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.
      Title: In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.
    3. CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2.
      Title: CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2.
    4. 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.
      Title: Suppression of glioblastoma growth and angiogenesis through molecular targeting of methionine aminopeptidase-2.
    5. MetAP1 and MetAP2 have roles in driving cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state
      Title: MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state.
    6. Suggest MetAP2 as important regulator of proliferation/apoptosis in non-small cell lung cancers.
      Title: Methionine Aminopeptidase 2 as a Potential Therapeutic Target for Human Non-Small-Cell Lung Cancers.
    7. Nt-acetylation prevents the excision of the initiator methionine by MetAP2.
      Title: N-terminal acetylome analysis reveals the specificity of Naa50 (Nat5) and suggests a kinetic competition between N-terminal acetyltransferases and methionine aminopeptidases.
    8. Data indicate that methionine aminopeptidase 2 (MetAP2) contains a single disulfide bond that exists in oxidized and reduced states and influences enzyme function.
      Title: Redox regulation of methionine aminopeptidase 2 activity.
    9. 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.
      Title: Tyrosine nitration moderates the peptidase activity of human methionyl aminopeptidase 2.
    10. Increased expression of METAP2 is associated with pilocytic astrocytoma.
      Title: MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables aminopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables aminopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables initiator methionyl aminopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloaminopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloexopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloexopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in N-terminal protein amino acid modification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-methionine modification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    methionine aminopeptidase 2
    Names
    eIF-2-associated p67 homolog
    initiation factor 2-associated 67 kDa glycoprotein
    peptidase M 2
    testicular tissue protein Li 17
    NP_001304111.1
    NP_001304112.1
    NP_001317175.1
    NP_006829.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001317182.2 → NP_001304111.1  methionine aminopeptidase 2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC018475, AK300836
      Consensus CDS
      CCDS81723.1
      UniProtKB/Swiss-Prot
      P50579
      Related
      ENSP00000448169.1, ENST00000546753.5
      Conserved Domains (1) summary
      PTZ00053
      Location:110 → 455
      PTZ00053; methionine aminopeptidase 2; Provisional

    2. NM_001317183.2 → NP_001304112.1  methionine aminopeptidase 2 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice junction and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC018475, AK091730, DW409106
      Consensus CDS
      CCDS81725.1
      UniProtKB/TrEMBL
      F8VRR3
      Related
      ENSP00000261220.9, ENST00000261220.13
      Conserved Domains (1) summary
      PTZ00053
      Location:89 → 455
      PTZ00053; methionine aminopeptidase 2; Provisional

    3. NM_001330246.2 → NP_001317175.1  methionine aminopeptidase 2 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate in-frame splice junction in the 5' coding region compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is one amino acid shorter compared to isoform 1.
      Source sequence(s)
      AC018475, AK091730, CA450598, U13261
      Consensus CDS
      CCDS81724.1
      UniProtKB/TrEMBL
      F8VQZ7, F8VRR3
      Related
      ENSP00000450063.1, ENST00000551840.5
      Conserved Domains (1) summary
      PTZ00053
      Location:106 → 477
      PTZ00053; methionine aminopeptidase 2; Provisional

    4. NM_006838.4 → NP_006829.1  methionine aminopeptidase 2 isoform 1

      See identical proteins and their annotated locations for NP_006829.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC018475, U13261
      Consensus CDS
      CCDS9052.1
      UniProtKB/Swiss-Prot
      B2RDI8, B4DUX5, G3XA91, P50579, Q8NB11
      UniProtKB/TrEMBL
      A0A140VJE3, F8VRR3
      Related
      ENSP00000325312.5, ENST00000323666.10
      Conserved Domains (1) summary
      PTZ00053
      Location:107 → 478
      PTZ00053; methionine aminopeptidase 2; Provisional

    RNA

    1. NR_133673.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate exon in the 3' end compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC018475, AK125296

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      95474152..95515839
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      95455178..95496879
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P50579.1 GenPept UniProtKB/Swiss-Prot:P50579

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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