Methionine aminopeptidase 2 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P50579 (AMPM2_HUMAN)

Last modified June 16, 2009. Version 95. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Methionine aminopeptidase 2
      Short name=MetAP 2
      Short name=MAP 2
    EC=3.4.11.18
Alternative name(s):
    Peptidase M 2
    Initiation factor 2-associated 67 kDa glycoprotein
    p67eIF2
      Short name=p67

Gene names

Name:	METAP2
Synonyms:	MNPEP, P67EIF2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	478 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Removes the amino-terminal methionine from nascent proteins. Ref.7 Ref.12
Catalytic activity	Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
Cofactor	Binds 2 cobalt ions per subunit. The true nature of the physiological cofactor is under debate. The enzyme is also active with zinc, manganese or divalent iron ions. Ref.12 Ref.6
Sequence similarities	Belongs to the peptidase M24A family.

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Ontologies

Keywords
Ligand	Cobalt Metal-binding
Molecular function	Aminopeptidase Hydrolase Protease
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	N-terminal protein amino acid modification Inferred from direct assay. Source: HGNC peptidyl-methionine modification Inferred from direct assay. Source: HGNC protein processing Inferred from direct assay. Source: HGNC proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HGNC
Molecular function	aminopeptidase activity Inferred from direct assay. Source: UniProtKB cobalt ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloexopeptidase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 478

478

Methionine aminopeptidase 2

PRO_0000148982

Regions

Compositional bias

36 – 46

Arg/Lys-rich (basic)

Compositional bias

82 – 93

Asp/Glu-rich (acidic)

Compositional bias

98 – 106

Poly-Lys

Sites

Metal binding

251

Cobalt 1

Metal binding

262

Cobalt 1

Metal binding

262

Cobalt 2

Metal binding

331

Cobalt 2

Metal binding

364

Cobalt 2

Metal binding

459

Cobalt 1

Metal binding

459

Cobalt 2

Binding site

231

Substrate

Binding site

339

Substrate

Amino acid modifications

Modified residue

Phosphoserine Ref.4

Modified residue

Phosphoserine Ref.4

Modified residue

Phosphoserine Ref.4

Modified residue

Phosphoserine Ref.4

Secondary structure

478

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P50579-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 5788E4BB83E48F9A
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FASTA

478

52,892

        10         20         30         40         50         60 
MAGVEEVAAS GSHLNGDLDP DDREEGAAST AEEAAKKKRR KKKKSKGPSA AGEQEPDKES 

        70         80         90        100        110        120 
GASVDEVARQ LERSALEDKE RDEDDEDGDG DGDGATGKKK KKKKKKRGPK VQTDPPSVPI 

       130        140        150        160        170        180 
CDLYPNGVFP KGQECEYPPT QDGRTAAWRT TSEEKKALDQ ASEEIWNDFR EAAEAHRQVR 

       190        200        210        220        230        240 
KYVMSWIKPG MTMIEICEKL EDCSRKLIKE NGLNAGLAFP TGCSLNNCAA HYTPNAGDTT 

       250        260        270        280        290        300 
VLQYDDICKI DFGTHISGRI IDCAFTVTFN PKYDTLLKAV KDATNTGIKC AGIDVRLCDV 

       310        320        330        340        350        360 
GEAIQEVMES YEVEIDGKTY QVKPIRNLNG HSIGQYRIHA GKTVPIVKGG EATRMEEGEV 

       370        380        390        400        410        420 
YAIETFGSTG KGVVHDDMEC SHYMKNFDVG HVPIRLPRTK HLLNVINENF GTLAFCRRWL 

       430        440        450        460        470 
DRLGESKYLM ALKNLCDLGI VDPYPPLCDI KGSYTAQFEH TILLRPTCKE VVSRGDDY

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes." Arfin S.M., Kendall R.L., Hall L., Weaver L.H., Stewart A.E., Matthews B.W., Bradshaw R.A. Proc. Natl. Acad. Sci. U.S.A. 92:7714-7718(1995) [PubMed: 7644482] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Molecular cloning of a human complementary DNA encoding an initiation factor 2-associated protein (p67)." Li X., Chang Y. Biochim. Biophys. Acta 1260:333-336(1995) [PubMed: 7873610] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[4]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-60; SER-63 AND SER-74, MASS SPECTROMETRY.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"Structure of human methionine aminopeptidase-2 complexed with fumagillin." Liu S., Widom J., Kemp C.W., Crews C.M., Clardy J. Science 282:1324-1327(1998) [PubMed: 9812898] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH FUMAGILLIN, COFACTOR.
[7]	"Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors." Towbin H., Bair K.W., DeCaprio J.A., Eck M.J., Kim S., Kinder F.R., Morollo A., Mueller D.R., Schindler P., Song H.K., van Oostrum J., Versace R.W., Voshol H., Wood J., Zabludoff S., Phillips P.E. J. Biol. Chem. 278:52964-52971(2003) [PubMed: 14534293] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH COBALT IONS AND BENGAMIDE, FUNCTION.
[8]	"3-amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2." Sheppard G.S., Wang J., Kawai M., BaMaung N.Y., Craig R.A., Erickson S.A., Lynch L., Patel J., Yang F., Searle X.B., Lou P., Park C., Kim K.H., Henkin J., Lesniewski R. Bioorg. Med. Chem. Lett. 14:865-868(2004) [PubMed: 15012983] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 110-478 IN COMPLEX WITH INHIBITOR A-357300.
[9]	"4-aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo." Kallander L.S., Lu Q., Chen W., Tomaszek T., Yang G., Tew D., Meek T.D., Hofmann G.A., Schulz-Pritchard C.K., Smith W.W., Janson C.A., Ryan M.D., Zhang G.-F., Johanson K.O., Kirkpatrick R.B., Ho T.F., Fisher P.W., Mattern M.R. Thompson S.K. J. Med. Chem. 48:5644-5647(2005) [PubMed: 16134930] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 110-478 IN COMPLEX WITH 4-ARYL-1,2,3-TRIAZOLE AND COBALT IONS.
[10]	"Human methionine aminopeptidase type 2 in complex with L- and D-methionine." Nonato M.C., Widom J., Clardy J. Bioorg. Med. Chem. Lett. 16:2580-2583(2006) [PubMed: 16540317] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH ZINC IONS AND METHIONINE, PARTIAL PROTEIN SEQUENCE.
[11]	"Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids." Wang G.T., Mantei R.A., Kawai M., Tedrow J.S., Barnes D.M., Wang J., Zhang Q., Lou P., Garcia L.A., Bouska J., Yates M., Park C., Judge R.A., Lesniewski R., Sheppard G.S., Bell R.L. Bioorg. Med. Chem. Lett. 17:2817-2822(2007) [PubMed: 17350258] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 110-478 IN COMPLEX WITH MANGANESE AND INHIBITOR.
[12]	"Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore." Marino J.P. Jr., Fisher P.W., Hofmann G.A., Kirkpatrick R.B., Janson C.A., Johnson R.K., Ma C., Mattern M., Meek T.D., Ryan M.D., Schulz C., Smith W.W., Tew D.G., Tomazek T.A. Jr., Veber D.F., Xiong W.C., Yamamoto Y., Yamashita K., Yang G., Thompson S.K. J. Med. Chem. 50:3777-3785(2007) [PubMed: 17636946] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 110-478 IN COMPLEX WITH COBALT IONS AND INHIBITOR, COFACTOR, FUNCTION.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

U29607 mRNA. Translation: AAA82930.1.
U13261 mRNA. Translation: AAC63402.1.
BC013782 mRNA. Translation: AAH13782.1.

IPI

IPI00033036.

PIR

DPHUM2. S52112.

RefSeq

NP_006829.1.

UniGene

Hs.591005

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B59	X-ray	1.80	A	109-478	[»]
1B6A	X-ray	1.60	A	1-478	[»]
1BN5	X-ray	1.80	A	1-478	[»]
1BOA	X-ray	1.80	A	1-478	[»]
1KQ0	X-ray	2.00	A	1-478	[»]
1KQ9	X-ray	1.90	A	1-478	[»]
1QZY	X-ray	1.60	A	1-478	[»]
1R58	X-ray	1.90	A	110-478	[»]
1R5G	X-ray	2.00	A	110-478	[»]
1R5H	X-ray	2.40	A	110-478	[»]
1YW7	X-ray	1.85	A	110-478	[»]
1YW8	X-ray	2.65	A	110-478	[»]
1YW9	X-ray	1.64	A	110-478	[»]
2ADU	X-ray	1.90	A	110-478	[»]
2EA2	X-ray	2.50	A	110-478	[»]
2EA4	X-ray	2.35	A	110-478	[»]
2GA2	X-ray	1.95	A	110-478	[»]
2OAZ	X-ray	1.90	A	110-478	[»]

ModBase

Search...

Protein family/group databases

MEROPS

M24.002.

PTM databases

PhosphoSite

P50579.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00033036.

Proteomic databases

PeptideAtlas

P50579.

PRIDE

P50579.

Genome annotation databases

Ensembl

ENSG00000111142. Homo sapiens. [Contig view]

GeneID

10988.

KEGG

hsa:10988.

Organism-specific databases

GeneCards

GC12P094370.

H-InvDB

HIX0010896.

HGNC

HGNC:16672. METAP2.

HPA

CAB013025.

MIM

601870. gene.

PharmGKB

PA30765.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P50579.

HOVERGEN

P50579.

OMA

P50579. TPNAGDK.

Enzyme and pathway databases

BRENDA

3.4.11.18. 247.

Gene expression databases

ArrayExpress

P50579.

Bgee

P50579.

CleanEx

HS_METAP2.

GermOnline

ENSG00000111142. Homo sapiens.

Family and domain databases

InterPro

IPR001714. Pept_M24_MAP.
IPR000994. Pept_M24_structural-domain.
IPR002468. Pept_M24A_MAP2.
IPR018349. Pept_M24A_MAP2_BS.
[Graphical view]

Gene3D

G3DSA:3.90.230.10. Peptidase_M24_cat_core. 1 hit.

PANTHER

PTHR10804:SF9. Pept_M24A_MAP2. 1 hit.
PTHR10804. Peptidase_M24_cat_core. 1 hit.

Pfam

PF00557. Peptidase_M24. 1 hit.
[Graphical view]

PRINTS

PR00599. MAPEPTIDASE.

TIGRFAMs

TIGR00501. met_pdase_II. 1 hit.

PROSITE

PS01202. MAP_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00134. L-Methionine.

NextBio

41747.

SOURCE

Search...

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Entry information

Entry name

AMPM2_HUMAN

Accession

Primary (citable) accession number: P50579

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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