P38062 (AMPM2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methionine aminopeptidase 2
Short name=MAP 2
Short name=MetAP 2
EC=3.4.11.18

Alternative name(s):
Initiation factor 2-associated 67 kDa glycoprotein
Peptidase M 2
p67eIF2
Short name=p67

Gene names

Name:	Metap2
Synonyms:	Mnpep, P67eif2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	478 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Removes the amino-terminal methionine from nascent proteins. 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 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 By similarity.
Subunit structure	Binds EIF2S1 at low magnesium concentrations By similarity. Interacts strongly with the eIF-2 gamma-subunit EIF2S3. Ref.5
Subcellular location	Cytoplasm. Note: About 30% of expressed METAP2 associates with polysomes By similarity.
Induction	Heat shock increases expression by more than 36-fold. Ref.3
Post-translational modification	O-glycosylated; contains 12 O-linked GlcNAc. Ref.4 Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding By similarity.
Sequence similarities	Belongs to the peptidase M24A family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Cobalt Metal-binding
Molecular function	Aminopeptidase Hydrolase Protease
PTM	Acetylation Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	N-terminal protein amino acid modification Inferred from sequence or structural similarity. Source: HGNC peptidyl-methionine modification Inferred from sequence or structural similarity. Source: HGNC protein processing Inferred from sequence or structural similarity. Source: HGNC proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: HGNC
Molecular function	aminopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloexopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 478	477	Methionine aminopeptidase 2		PRO_0000148984
Regions
	Compositional bias	36 – 46	11	Arg/Lys-rich (basic)
	Compositional bias	82 – 93	12	Asp/Glu-rich (acidic)
	Compositional bias	98 – 106	9	Poly-Lys
Sites
	Metal binding	251	1	Cobalt 1 By similarity
	Metal binding	262	1	Cobalt 1 By similarity
	Metal binding	262	1	Cobalt 2 By similarity
	Metal binding	331	1	Cobalt 2 By similarity
	Metal binding	364	1	Cobalt 2 By similarity
	Metal binding	459	1	Cobalt 1 By similarity
	Metal binding	459	1	Cobalt 2 By similarity
	Binding site	231	1	Substrate By similarity
	Binding site	339	1	Substrate By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	60	1	Phosphoserine By similarity
	Modified residue	63	1	Phosphoserine By similarity
	Modified residue	427	1	N6-acetyllysine By similarity
	Glycosylation	60	1	O-linked (GlcNAc) Probable
	Glycosylation	63	1	O-linked (GlcNAc) Probable
Experimental info
	Sequence conflict	464 – 478	15	LRPTC…RGDDY → CAQPVKKLSAEEMTIKT in AAA41111. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P38062 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: BE1C0E91E0CB3D74	FASTA	478	53,052
	10 20 30 40 50 60 MAGVEEASSF GGHLNRDLDP DDREEGTSST AEEAAKKKRR KKKKGKGAVS AGQQELDKES 70 80 90 100 110 120 GTSVDEVAKQ LERQALEEKE KDDDDEDGDG DGDGAAGKKK KKKKKKRGPR 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 PKYDILLKAV KDATNTGIKC AGIDVRLCDV 310 320 330 340 350 360 GEAIQEVMES YEVEIDGKTY QVKPIRNLNG HSIGPYRIHA 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

References

[1]	"Cloning and characterization of complementary DNA encoding the eukaryotic initiation factor 2-associated 67-kDa protein (p67)." Wu S., Gupta S., Chatterjee N., Hileman R.E., Kinzy T.G., Denslow N.D., Merrick W.C., Chakrabarti D., Osterman J.C., Gupta N.K. J. Biol. Chem. 268:10796-10801(1993) [PubMed: 8496145] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Reuber H35. Tissue: Liver.
[2]	"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: SEQUENCE REVISION TO C-TERMINUS.
[3]	"Expression and activity of p67 are induced during heat shock." Chatterjee M., Chatterjee N., Datta R., Datta B., Gupta N.K. Biochem. Biophys. Res. Commun. 249:113-117(1998) [PubMed: 9705841] [Abstract] Cited for: INDUCTION BY HEAT SHOCK.
[4]	"A glycosylation site, 60SGTS63, of p67 is required for its ability to regulate the phosphorylation and activity of eukaryotic initiation factor 2alpha." Datta R., Choudhury P., Ghosh A., Datta B. Biochemistry 42:5453-5460(2003) [PubMed: 12731887] [Abstract] Cited for: GLYCOSYLATION AT SER-60 AND SER-63.
[5]	"The N-terminal lysine residue-rich domain II and the 340-430 amino acid segment of eukaryotic initiation factor 2-associated glycoprotein p67 are the binding sites for the gamma-subunit of eIF2." Ghosh A., Datta R., Majumdar A., Bhattacharya M., Datta B. Exp. Cell Res. 312:3184-3203(2006) [PubMed: 16857189] [Abstract] Cited for: INTERACTION WITH EIF2S3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L10652 mRNA. Translation: AAA41111.1.
IPI	IPI00480610.
PIR	A46702.
RefSeq	NP_071984.1. NM_022539.1.
UniGene	Rn.1984.
3D structure databases
ProteinModelPortal	P38062.
SMR	P38062. Positions 110-478.
ModBase	Search...
Protein-protein interaction databases
STRING	P38062.
Protein family/group databases
MEROPS	M24.002.
Proteomic databases
PRIDE	P38062.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	64370.
KEGG	rno:64370.
UCSC	BC091150. rat.
Organism-specific databases
CTD	10988.
RGD	70995. Metap2.
Phylogenomic databases
eggNOG	roNOG14581.
HOVERGEN	HBG050495.
OrthoDB	EOG46T31M.
PhylomeDB	P38062.
Enzyme and pathway databases
BRENDA	3.4.11.18. 5301.
Gene expression databases
Genevestigator	P38062.
GermOnline	ENSRNOG00000021881. Rattus norvegicus.
Family and domain databases
InterPro	IPR001714. Pept_M24_MAP. IPR000994. Pept_M24_structural-domain. IPR002468. Pept_M24A_MAP2. IPR018349. Pept_M24A_MAP2_BS. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.90.230.10. Peptidase_M24_cat_core. 2 hits. G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K01265.
PANTHER	PTHR10804:SF9. Pept_M24A_MAP2. 1 hit.
Pfam	PF00557. Peptidase_M24. 1 hit. [Graphical view]
PRINTS	PR00599. MAPEPTIDASE.
SUPFAM	SSF55920. Peptidase_M24_cat_core. 1 hit.
TIGRFAMs	TIGR00501. Met_pdase_II. 1 hit.
PROSITE	PS01202. MAP_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	613106.

Entry information

Entry name

AMPM2_RAT

Accession

Primary (citable) accession number: P38062

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1996
Last modified:	November 16, 2011
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program