ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:METAP2

Protein Summary

Gene summary

Gene name: METAP2
ASpdb.0 ID: 10988
	Gene
Gene symbol	METAP2
Gene ID	10988
Gene name	methionyl aminopeptidase 2
Synonyms	MAP2\|MNPEP\|p67eIF2
Cytomap	12q22
Type of gene	protein-coding
Description	methionine aminopeptidase 2eIF-2-associated p67 homologinitiation factor 2-associated 67 kDa glycoproteinpeptidase M 2testicular tissue protein Li 17
Modification date	20240305
UniProtAcc	P50579

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	METAP2	GO:0004177	aminopeptidase activity	8858118
Gene	METAP2	GO:0005737	cytoplasm	15102683
Gene	METAP2	GO:0005829	cytosol	-
Gene	METAP2	GO:0005886	plasma membrane	-
Gene	METAP2	GO:0008235	metalloexopeptidase activity	8858118
Gene	METAP2	GO:0016485	protein processing	8858118
Gene	METAP2	GO:0018206	peptidyl-methionine modification	8858118
Gene	METAP2	GO:0031365	N-terminal protein amino acid modification	8858118

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P50579-1	P50579-1_5d6e_A.pdb	5D6E	X-ray	1.49	A	109	478

ASpdb's canonical and alternatively spliced isoform information.

accession_id

gene_name

canonical_id

alternative_id

canonical_length

alternative_length

canonical_start

canonical_end

type

originalSEQ

variationSEQ

alternative_start

alternative_end

P50579

METAP2

P50579-1

P50579-2

478

455

Deletion

none

P50579

METAP2

P50579-1

P50579-2

478

455

109

Substitution

DGDGDGDGATGKKKKKKKKKRGP

P50579

METAP2

P50579-1

P50579-3

478

455

109

132

Substitution

PKVQTDPPSVPICDLYPNGVFPKG

109

Multiple sequence alignment of our canonical and alternatively spliced METAP2

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of METAP2

UniProt-id	ENSG	ENST	ENSP
P50579-1	ENSG00000111142.14	ENST00000323666.10	ENSP00000325312.5
P50579-2	ENSG00000111142.14	ENST00000261220.13	ENSP00000261220.9
P50579-3	ENSG00000111142.14	ENST00000546753.5	ENSP00000448169.1

UniProt-id	NM ID	NP ID
P50579-1	NM_006838.3	NP_006829.1
P50579-2	NM_001317183.1	NP_001304112.1
P50579-3	NM_001317182.1	NP_001304111.1

Amino acid sequences of our canonical and alternatively spliced METAP2

accession_id	Protein sequence
P50579-1	MAGVEEVAASGSHLNGDLDPDDREEGAASTAEEAAKKKRRKKKKSKGPSAAGEQEPDKESGASVDEVARQLERSALEDKERDEDDEDGDG DGDGATGKKKKKKKKKRGPKVQTDPPSVPICDLYPNGVFPKGQECEYPPTQDGRTAAWRTTSEEKKALDQASEEIWNDFREAAEAHRQVR KYVMSWIKPGMTMIEICEKLEDCSRKLIKENGLNAGLAFPTGCSLNNCAAHYTPNAGDTTVLQYDDICKIDFGTHISGRIIDCAFTVTFN PKYDTLLKAVKDATNTGIKCAGIDVRLCDVGEAIQEVMESYEVEIDGKTYQVKPIRNLNGHSIGQYRIHAGKTVPIVKGGEATRMEEGEV YAIETFGSTGKGVVHDDMECSHYMKNFDVGHVPIRLPRTKHLLNVINENFGTLAFCRRWLDRLGESKYLMALKNLCDLGIVDPYPPLCDI
P50579-2	MAGVEEVAASGSHLNGDLDPDDREEGAASTAEEAAKKKRRKKKKSKGPSAGEQEPDKESGASVDEVARQLERSALEDKERDEDDEAKVQT DPPSVPICDLYPNGVFPKGQECEYPPTQDGRTAAWRTTSEEKKALDQASEEIWNDFREAAEAHRQVRKYVMSWIKPGMTMIEICEKLEDC SRKLIKENGLNAGLAFPTGCSLNNCAAHYTPNAGDTTVLQYDDICKIDFGTHISGRIIDCAFTVTFNPKYDTLLKAVKDATNTGIKCAGI DVRLCDVGEAIQEVMESYEVEIDGKTYQVKPIRNLNGHSIGQYRIHAGKTVPIVKGGEATRMEEGEVYAIETFGSTGKGVVHDDMECSHY MKNFDVGHVPIRLPRTKHLLNVINENFGTLAFCRRWLDRLGESKYLMALKNLCDLGIVDPYPPLCDIKGSYTAQFEHTILLRPTCKEVVS
P50579-3	MAGVEEVAASGSHLNGDLDPDDREEGAASTAEEAAKKKRRKKKKSKGPSAAGEQEPDKESGASVDEVARQLERSALEDKERDEDDEDGDG DGDGATGKKKKKKKKKRGRQECEYPPTQDGRTAAWRTTSEEKKALDQASEEIWNDFREAAEAHRQVRKYVMSWIKPGMTMIEICEKLEDC SRKLIKENGLNAGLAFPTGCSLNNCAAHYTPNAGDTTVLQYDDICKIDFGTHISGRIIDCAFTVTFNPKYDTLLKAVKDATNTGIKCAGI DVRLCDVGEAIQEVMESYEVEIDGKTYQVKPIRNLNGHSIGQYRIHAGKTVPIVKGGEATRMEEGEVYAIETFGSTGKGVVHDDMECSHY MKNFDVGHVPIRLPRTKHLLNVINENFGTLAFCRRWLDRLGESKYLMALKNLCDLGIVDPYPPLCDIKGSYTAQFEHTILLRPTCKEVVS

Protein Functional Features

Main function of this protein. (from UniProt)

METAP2 (go to UniProt):P50579

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P50579	Region	1	123	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=50;End=50
P50579	Region	1	123	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=87;End=109
P50579	Region	1	123	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=109;End=132
P50579	Compositional bias	47	78	Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=50;End=50

Gene Isoform Structures and Expression Levels for METAP2

Gene structures of our canonical and alternative spliced genes of METAP2
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P50579-1

3D view using mol* of P50579-2

3D view using mol* of P50579-3

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P50579-1

pLDDT distribution across the protein length of P50579-2

pLDDT distribution across the protein length of P50579-3

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P50579-1

Ramachandran plot of P50579-2

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P50579-1	1.048	285	1.031	530.278	0.494	0.77	0.943	0.633	1.139	0.555	1.308	11,12,13,14,15,16,17,18,218,219,220,222,224,229,23 0,231,249,251,262,297,326,327,328,329,331,338,339, 341,342,343,345,346,347,350,351,353,364,366,374,37 5,376,382,384,413,414,443,444,445,447,457,459
P50579-2	1.187	106	0.987	169.442	0.329	0.977	1.238	0.818	1.654	0.495	1.586	15,196,197,199,201,206,207,208,209,226,228,239,305 ,306,308,315,316,341,343,359,360,361,391,421,424,4 34
P50579-3	1.053	296	1.06	812.567	0.461	0.777	1.001	0.557	1.062	0.525	0.825	12,13,14,15,16,196,197,199,200,201,206,207,208,209 ,226,228,229,239,240,241,303,304,305,306,307,308,3 09,313,314,315,316,317,318,319,320,339,341,343,350 ,351,352,353,359,361,362,363,364,365,389,390,391,4 19,420,421,422,424,434,436

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P50579-1_P50579-1_5d6e_A.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P50579-1_5d6e_A_P50579-2.pdb

3D view using mol* of P50579-1_5d6e_A_P50579-3.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P50579-1_P50579-2.pdb

3D view using mol* of P50579-1_P50579-3.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P50579-1_vs_P50579-2.png

./stats/secondary_structure/figure/P50579-1_vs_P50579-3.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P50579-1_vs_P50579-2.png

./stats/relative_asa/P50579-1_vs_P50579-3.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to METAP2

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
P50579	METAP2	DB04108	(2s,3r)-3-Amino-2-Hydroxy-5-(Ethylsulfanyl)Pentanoyl-((S)-(-)-(1-Naphthyl)Ethyl)Amide	experimental
P50579	METAP2	DB03900	tert-butanol	experimental
P50579	METAP2	DB02310	3,5,6,8-Tetramethyl-N-Methyl Phenanthrolinium	experimental
P50579	METAP2	DB07377	N'-((2S,3R)-3-AMINO-2-HYDROXY-5-(ISOPROPYLSULFANYL)PENTANOYL)-N-3-CHLOROBENZOYL HYDRAZIDE	experimental
P50579	METAP2	DB03396	(2R,3R,4S,5R,6E)-3,4,5-Trihydroxy-N-[(3S,6R)-6-hydroxy-2-oxo-3-azepanyl]-2-methoxy-8,8-dimethyl-6-nonenamide	experimental
P50579	METAP2	DB05864	PPI-2458	investigational
P50579	METAP2	DB07322	2-[(PHENYLSULFONYL)AMINO]-5,6,7,8-TETRAHYDRONAPHTHALENE-1-CARBOXYLIC ACID	experimental
P50579	METAP2	DB04324	Ovalicin	experimental
P50579	METAP2	DB02640	Fumagillin	experimental	ligand
P50579	METAP2	DB07313	5-METHYL-2-[(PHENYLSULFONYL)AMINO]BENZOIC ACID	experimental
P50579	METAP2	DB08633	TNP-470	investigational
P50579	METAP2	DB07323	2-[({2-[(1Z)-3-(DIMETHYLAMINO)PROP-1-ENYL]-4-FLUOROPHENYL}SULFONYL)AMINO]-5,6,7,8-TETRAHYDRONAPHTHALENE-1-CARBOXYLIC ACID	experimental
P50579	METAP2	DB07746	3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-2-METHYLBENZOIC ACID	experimental
P50579	METAP2	DB01422	Nitroxoline	experimental	inhibitor
P50579	METAP2	DB07309	5-BROMO-2-{[(4-CHLOROPHENYL)SULFONYL]AMINO}BENZOIC ACID	experimental
P50579	METAP2	DB02893	D-Methionine	approved, experimental, investigational
P50579	METAP2	DB00134	Methionine	approved, nutraceutical	product of
P50579	METAP2	DB03086	N'-(2s,3r)-3-Amino-4-Cyclohexyl-2-Hydroxy-Butano-N-(4-Methylphenyl)Hydrazide	experimental

Related Diseases to METAP2

Previous studies relating to the alternative splicing of METAP2 and disease information from the MeSH term (PubMed)

Gene

PMID

Title

Abstract

MeSH ID

MeSH term

Clinically important variants in METAP2

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance