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Protein

Methionine aminopeptidase 2

Gene

METAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Catalytic activityi

Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.UniRule annotation1 Publication

Cofactori

Co2+UniRule annotation3 Publications, Zn2+UniRule annotation3 Publications, Mn2+UniRule annotation3 Publications, Fe2+UniRule annotation3 PublicationsNote: 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 Fe2+-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.UniRule annotation3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei231SubstrateUniRule annotation1 Publication1
Metal bindingi251Divalent metal cation 1UniRule annotation5 Publications1
Metal bindingi262Divalent metal cation 1UniRule annotation5 Publications1
Metal bindingi262Divalent metal cation 2; catalyticUniRule annotation5 Publications1
Metal bindingi331Divalent metal cation 2; catalytic; via tele nitrogenUniRule annotation5 Publications1
Binding sitei339SubstrateUniRule annotation1 Publication1
Metal bindingi364Divalent metal cation 2; catalyticUniRule annotation5 Publications1
Metal bindingi459Divalent metal cation 1UniRule annotation5 Publications1
Metal bindingi459Divalent metal cation 2; catalyticUniRule annotation5 Publications1

GO - Molecular functioni

  • aminopeptidase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • metalloexopeptidase activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • N-terminal protein amino acid modification Source: HGNC
  • peptidyl-methionine modification Source: HGNC
  • protein processing Source: HGNC
  • regulation of rhodopsin mediated signaling pathway Source: Reactome

Keywordsi

Molecular functionAminopeptidase, Hydrolase, Protease
LigandMetal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03371-MONOMER
BRENDAi3.4.11.18 2681
ReactomeiR-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade

Protein family/group databases

MEROPSiM24.002

Names & Taxonomyi

Protein namesi
Recommended name:
Methionine aminopeptidase 2UniRule annotation (EC:3.4.11.18UniRule annotation)
Short name:
MAP 2UniRule annotation
Short name:
MetAP 2UniRule annotation
Alternative name(s):
Initiation factor 2-associated 67 kDa glycoproteinUniRule annotation
Short name:
p67UniRule annotation
Short name:
p67eIF2UniRule annotation
Peptidase MUniRule annotation
Gene namesi
Name:METAP2UniRule annotation
Synonyms:MNPEP, P67EIF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111142.13
HGNCiHGNC:16672 METAP2
MIMi601870 gene
neXtProtiNX_P50579

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi10988
OpenTargetsiENSG00000111142
PharmGKBiPA30765

Chemistry databases

ChEMBLiCHEMBL3922
DrugBankiDB03900 2-Methyl-2-Propanol
DB07746 3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-2-METHYLBENZOIC ACID
DB07309 5-BROMO-2-{[(4-CHLOROPHENYL)SULFONYL]AMINO}BENZOIC ACID
DB07313 5-METHYL-2-[(PHENYLSULFONYL)AMINO]BENZOIC ACID
DB02893 D-Methionine
DB02640 Fumagillin
DB00134 L-Methionine
DB01422 Nitroxoline
DB04324 Ovalicin
DB05864 PPI-2458
GuidetoPHARMACOLOGYi1573

Polymorphism and mutation databases

BioMutaiMETAP2
DMDMi1703273

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001489822 – 478Methionine aminopeptidase 2Add BLAST477

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei45PhosphoserineCombined sources1
Modified residuei60Phosphoserine; alternateCombined sources1
Glycosylationi60O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei63Phosphoserine; alternateCombined sources1
Glycosylationi63O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei74PhosphoserineCombined sources1

Post-translational modificationi

Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.UniRule annotation1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP50579
MaxQBiP50579
PaxDbiP50579
PeptideAtlasiP50579
PRIDEiP50579
TopDownProteomicsiP50579-1 [P50579-1]

2D gel databases

REPRODUCTION-2DPAGEiIPI00033036

PTM databases

iPTMnetiP50579
PhosphoSitePlusiP50579
SwissPalmiP50579

Expressioni

Gene expression databases

BgeeiENSG00000111142
CleanExiHS_METAP2
ExpressionAtlasiP50579 baseline and differential
GenevisibleiP50579 HS

Organism-specific databases

HPAiCAB013025
HPA019095

Interactioni

Subunit structurei

Interacts strongly with the eIF-2 gamma-subunit EIF2S3 (By similarity). Binds EIF2S1 at low magnesium concentrations.By similarity6 Publications

Protein-protein interaction databases

BioGridi116184, 55 interactors
IntActiP50579, 6 interactors
MINTiP50579
STRINGi9606.ENSP00000325312

Chemistry databases

BindingDBiP50579

Structurei

Secondary structure

1478
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi120 – 123Combined sources4
Beta strandi133 – 135Combined sources3
Beta strandi141 – 143Combined sources3
Helixi147 – 151Combined sources5
Helixi153 – 160Combined sources8
Helixi163 – 186Combined sources24
Helixi193 – 208Combined sources16
Helixi212 – 214Combined sources3
Beta strandi215 – 225Combined sources11
Beta strandi228 – 231Combined sources4
Beta strandi248 – 256Combined sources9
Beta strandi259 – 267Combined sources9
Helixi271 – 273Combined sources3
Helixi274 – 290Combined sources17
Helixi297 – 309Combined sources13
Beta strandi312 – 315Combined sources4
Beta strandi318 – 321Combined sources4
Beta strandi330 – 334Combined sources5
Beta strandi337 – 339Combined sources3
Beta strandi346 – 349Combined sources4
Beta strandi360 – 370Combined sources11
Beta strandi382 – 385Combined sources4
Helixi397 – 409Combined sources13
Turni410 – 412Combined sources3
Helixi417 – 421Combined sources5
Turni422 – 424Combined sources3
Helixi429 – 437Combined sources9
Beta strandi440 – 444Combined sources5
Beta strandi455 – 464Combined sources10
Beta strandi469 – 471Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B59X-ray1.80A109-478[»]
1B6AX-ray1.60A1-478[»]
1BN5X-ray1.80A1-478[»]
1BOAX-ray1.80A1-478[»]
1KQ0X-ray2.00A1-478[»]
1KQ9X-ray1.90A1-478[»]
1QZYX-ray1.60A1-478[»]
1R58X-ray1.90A110-478[»]
1R5GX-ray2.00A110-478[»]
1R5HX-ray2.40A110-478[»]
1YW7X-ray1.85A110-478[»]
1YW8X-ray2.65A110-478[»]
1YW9X-ray1.64A110-478[»]
2ADUX-ray1.90A110-478[»]
2EA2X-ray2.50A110-478[»]
2EA4X-ray2.35A110-478[»]
2GA2X-ray1.95A110-478[»]
2OAZX-ray1.90A110-478[»]
5CLSX-ray1.75A108-478[»]
5D6EX-ray1.49A108-478[»]
5D6FX-ray1.55A108-478[»]
5JFRX-ray1.60A110-478[»]
5JHUX-ray1.80A110-478[»]
5JI6X-ray2.15A110-478[»]
5LYWX-ray1.69A108-478[»]
5LYXX-ray1.90A108-478[»]
ProteinModelPortaliP50579
SMRiP50579
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50579

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi41 – 46Poly-Lys6
Compositional biasi98 – 106Poly-Lys9

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2775 Eukaryota
COG0024 LUCA
GeneTreeiENSGT00530000063220
HOGENOMiHOG000226278
HOVERGENiHBG050495
InParanoidiP50579
KOiK01265
OMAiTINKHFG
OrthoDBiEOG091G07WE
PhylomeDBiP50579
TreeFamiTF300426

Family and domain databases

CDDicd01088 MetAP2, 1 hit
Gene3Di1.10.10.10, 1 hit
HAMAPiMF_03175 MetAP_2_euk, 1 hit
InterProiView protein in InterPro
IPR036005 Creatinase/aminopeptidase-like
IPR000994 Pept_M24
IPR001714 Pept_M24_MAP
IPR002468 Pept_M24A_MAP2
IPR018349 Pept_M24A_MAP2_BS
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00557 Peptidase_M24, 1 hit
PRINTSiPR00599 MAPEPTIDASE
SUPFAMiSSF46785 SSF46785, 1 hit
SSF55920 SSF55920, 2 hits
TIGRFAMsiTIGR00501 met_pdase_II, 1 hit
PROSITEiView protein in PROSITE
PS01202 MAP_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P50579-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGVEEVAAS GSHLNGDLDP DDREEGAAST AEEAAKKKRR KKKKSKGPSA
60 70 80 90 100
AGEQEPDKES GASVDEVARQ LERSALEDKE RDEDDEDGDG DGDGATGKKK
110 120 130 140 150
KKKKKKRGPK VQTDPPSVPI CDLYPNGVFP KGQECEYPPT QDGRTAAWRT
160 170 180 190 200
TSEEKKALDQ ASEEIWNDFR EAAEAHRQVR KYVMSWIKPG MTMIEICEKL
210 220 230 240 250
EDCSRKLIKE NGLNAGLAFP TGCSLNNCAA HYTPNAGDTT VLQYDDICKI
260 270 280 290 300
DFGTHISGRI IDCAFTVTFN PKYDTLLKAV KDATNTGIKC AGIDVRLCDV
310 320 330 340 350
GEAIQEVMES YEVEIDGKTY QVKPIRNLNG HSIGQYRIHA GKTVPIVKGG
360 370 380 390 400
EATRMEEGEV YAIETFGSTG KGVVHDDMEC SHYMKNFDVG HVPIRLPRTK
410 420 430 440 450
HLLNVINENF GTLAFCRRWL DRLGESKYLM ALKNLCDLGI VDPYPPLCDI
460 470
KGSYTAQFEH TILLRPTCKE VVSRGDDY
Length:478
Mass (Da):52,892
Last modified:October 1, 1996 - v1
Checksum:i5788E4BB83E48F9A
GO
Isoform 2 (identifier: P50579-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     50-50: Missing.
     87-109: DGDGDGDGATGKKKKKKKKKRGP → A

Note: No experimental confirmation available.
Show »
Length:455
Mass (Da):50,510
Checksum:i6B2C99F5B40B951F
GO
Isoform 3 (identifier: P50579-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     109-132: PKVQTDPPSVPICDLYPNGVFPKG → R

Note: No experimental confirmation available.
Show »
Length:455
Mass (Da):50,497
Checksum:i7370E721E31AAD64
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti434N → D in BAC03733 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05546750Missing in isoform 2. 1 Publication1
Alternative sequenceiVSP_05546887 – 109DGDGD…KKRGP → A in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_057353109 – 132PKVQT…VFPKG → R in isoform 3. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U29607 mRNA Translation: AAA82930.1
U13261 mRNA Translation: AAC63402.1
AK091730 mRNA Translation: BAC03733.1
AK300836 mRNA Translation: BAG62487.1
AK315559 mRNA Translation: BAG37935.1
AC018475 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97537.1
CH471054 Genomic DNA Translation: EAW97538.1
BC013782 mRNA Translation: AAH13782.1
CCDSiCCDS81723.1 [P50579-3]
CCDS81725.1 [P50579-2]
CCDS9052.1 [P50579-1]
PIRiS52112 DPHUM2
RefSeqiNP_001304111.1, NM_001317182.1 [P50579-3]
NP_001304112.1, NM_001317183.1 [P50579-2]
NP_001317175.1, NM_001330246.1
NP_006829.1, NM_006838.3 [P50579-1]
UniGeneiHs.444986

Genome annotation databases

EnsembliENST00000261220; ENSP00000261220; ENSG00000111142 [P50579-2]
ENST00000323666; ENSP00000325312; ENSG00000111142 [P50579-1]
ENST00000546753; ENSP00000448169; ENSG00000111142 [P50579-3]
GeneIDi10988
KEGGihsa:10988
UCSCiuc001tec.4 human [P50579-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMAP2_HUMAN
AccessioniPrimary (citable) accession number: P50579
Secondary accession number(s): B2RDI8
, B4DUX5, G3XA91, Q8NB11
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 183 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

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