METAP2 methionyl aminopeptidase 2 [Homo sapiens (human)] - Gene

Summary

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

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC31600 (e-PCR)
- UniSTS:22290

D12S1806 (e-PCR)
- UniSTS:36630

RH39871 (e-PCR)
- UniSTS:92743

WI-21736 (e-PCR)
- UniSTS:29785

D12S1183E (e-PCR)
- UniSTS:62578

D12S1199E (e-PCR)
- UniSTS:151462

STS-N33173 (e-PCR)
- UniSTS:80830

RH46408 (e-PCR)
- UniSTS:79830

RH92290 (e-PCR)
- UniSTS:90328

SHGC-64320 (e-PCR)
- UniSTS:32217

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	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

EC 3.4.11.18

NP_001304112.1

EC 3.4.11.18

NP_001317175.1

EC 3.4.11.18

NP_006829.1

EC 3.4.11.18

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)

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
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
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
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

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