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:FTO

Protein Summary

Gene summary

Gene name: FTO
ASpdb.0 ID: 79068
	Gene
Gene symbol	FTO
Gene ID	79068
Gene name	FTO alpha-ketoglutarate dependent dioxygenase
Synonyms	ALKBH9\|BMIQ14\|GDFD\|IFEX9
Cytomap	16q12.2
Type of gene	protein-coding
Description	alpha-ketoglutarate-dependent dioxygenase FTOAlkB homolog 9U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTOU6 small nuclear RNA N(6)-methyladenosine-demethylase FTOfat mass and obesity associatedfat mass and obesity-associated protei
Modification date	20240416
UniProtAcc	Q9C0B1

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

Partner	Gene	GO ID	GO term	PubMed ID
Gene	FTO	GO:0005634	nucleus	26458103\|28002401\|30197295
Gene	FTO	GO:0005737	cytoplasm	28002401
Gene	FTO	GO:0005829	cytosol	-
Gene	FTO	GO:0005886	plasma membrane	-
Gene	FTO	GO:0006307	DNA alkylation repair	18775698\|20376003
Gene	FTO	GO:0008198	ferrous iron binding	20376003
Gene	FTO	GO:0016607	nuclear speck	22002720
Gene	FTO	GO:0035515	oxidative RNA demethylase activity	18775698\|22002720\|28002401\|30197295
Gene	FTO	GO:0035516	broad specificity oxidative DNA demethylase activity	18775698\|20376003
Gene	FTO	GO:0042245	RNA repair	18775698
Gene	FTO	GO:0043231	intracellular membrane-bounded organelle	-
Gene	FTO	GO:0061157	mRNA destabilization	28002401\|30197295
Gene	FTO	GO:1990931	mRNA N6-methyladenosine dioxygenase activity	25452335\|26457839\|30197295
Gene	FTO	GO:1990984	tRNA demethylase activity	30197295

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
Q9C0B1-1	Q9C0B1-1_4qho_A.pdb	4QHO	X-ray	2.37	A	32	504

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

Q9C0B1

FTO

Q9C0B1-1

Q9C0B1-2

505

127

378

Deletion

none

Q9C0B1

FTO

Q9C0B1-1

Q9C0B1-2

505

127

379

413

Substitution

LRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGV

MEWRKVSECNSVEPCREVKKWPYRCIHHGKNFSRM

Q9C0B1

FTO

Q9C0B1-1

Q9C0B1-3

505

445

Deletion

none

Q9C0B1

FTO

Q9C0B1-1

Q9C0B1-3

505

446

455

Substitution

QNLRREWHAR

MACQGREECW

Q9C0B1

FTO

Q9C0B1-1

Q9C0B1-4

505

106

399

Deletion

none

Multiple sequence alignment of our canonical and alternatively spliced FTO

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

UniProt-id	ENSG	ENST	ENSP
Q9C0B1-1	ENSG00000140718.22	ENST00000471389.6	ENSP00000418823.1
Q9C0B1-2	ENSG00000140718.22	ENST00000463855.1	ENSP00000417843.1
Q9C0B1-4	ENSG00000140718.22	ENST00000431610.6	ENSP00000415636.2
Q9C0B1-4	ENSG00000140718.22	ENST00000460382.5	ENSP00000417422.1

UniProt-id	NM ID	NP ID
Q9C0B1-1	NM_001080432.2	NP_001073901.1

Amino acid sequences of our canonical and alternatively spliced FTO

accession_id	Protein sequence
Q9C0B1-1	MKRTPTAEEREREAKKLRLLEELEDTWLPYLTPKDDEFYQQWQLKYPKLILREASSVSEELHKEVQEAFLTLHKHGCLFRDLVRIQGKDL LTPVSRILIGNPGCTYKYLNTRLFTVPWPVKGSNIKHTEAEIAAACETFLKLNDYLQIETIQALEELAAKEKANEDAVPLCMSADFPRVG MGSSYNGQDEVDIKSRAAYNVTLLNFMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRSAVAVYSYSCEGPEEESEDDSHLEGRDPDIW HVGFKISWDIETPGLAIPLHQGDCYFMLDDLNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFE PAVLKQGEEIHNEVEFEWLRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGVTNAVLHEVKREGLPVEQRNEILTAILASLTARQNLRR
Q9C0B1-2	MEWRKVSECNSVEPCREVKKWPYRCIHHGKNFSRMTNAVLHEVKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQ
Q9C0B1-3
Q9C0B1-4	MAQLEALWKKMEGVTNAVLHEVKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQKPECRPYWEKDDASMPLPFDL

Protein Functional Features

Main function of this protein. (from UniProt)

FTO (go to UniProt):Q9C0B1

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
Q9C0B1	Region	32	327	Note=Fe2OG dioxygenase domain;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20376003;Dbxref=PMID:20376003	Type=Deletion;Start=1;End=378
Q9C0B1	Region	32	327	Note=Fe2OG dioxygenase domain;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20376003;Dbxref=PMID:20376003	Type=Deletion;Start=1;End=445
Q9C0B1	Region	32	327	Note=Fe2OG dioxygenase domain;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20376003;Dbxref=PMID:20376003	Type=Deletion;Start=1;End=399
Q9C0B1	Region	213	224	Note=Loop L1%3B predicted to block binding of double-stranded DNA or RNA;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20376003;Dbxref=PMID:20376003	Type=Deletion;Start=1;End=378
Q9C0B1	Region	213	224	Note=Loop L1%3B predicted to block binding of double-stranded DNA or RNA;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20376003;Dbxref=PMID:20376003	Type=Deletion;Start=1;End=445
Q9C0B1	Region	213	224	Note=Loop L1%3B predicted to block binding of double-stranded DNA or RNA;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:20376003;Dbxref=PMID:20376003	Type=Deletion;Start=1;End=399

Gene Isoform Structures and Expression Levels for FTO

Gene structures of our canonical and alternative spliced genes of FTO
* 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 Q9C0B1-1

3D view using mol* of Q9C0B1-2

3D view using mol* of Q9C0B1-3

3D view using mol* of Q9C0B1-4

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 Q9C0B1-1

pLDDT distribution across the protein length of Q9C0B1-2

pLDDT distribution across the protein length of Q9C0B1-3

pLDDT distribution across the protein length of Q9C0B1-4

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 Q9C0B1-1

Ramachandran plot of Q9C0B1-2

Ramachandran plot of Q9C0B1-3

Ramachandran plot of Q9C0B1-4

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
Q9C0B1-1	1.043	424	1.032	1030.372	0.454	0.763	1.016	0.638	1.122	0.569	0.5	3,5,6,8,9,10,12,13,16,19,80,83,84,85,86,87,90,91,9 2,93,94,96,106,107,108,109,110,203,205,206,207,212 ,214,215,216,217,219,220,226,227,228,229,230,231,2 32,233,234,235,236,237,238,239,240,242,244,270,275 ,278,295,297,298,299,300,301,302,303,306,307,309,3 16,317,318,320,322
Q9C0B1-2	1.087	217	1.14	563.206	0.542	0.748	1.001	1.525	0.764	1.995	0.504	1,2,3,4,5,6,7,21,22,24,25,26,28,29,32,33,35,36,39, 60,63,64,66,67,70,71,73,74,77,92,93,95,96,98,105,1 09
Q9C0B1-3	0.694	44	0.68	135.142	0.785	0.554	0.658	0.343	0.845	0.406	0.836	5,6,7,8,27,28,29,42,43,44,45
Q9C0B1-4	0.697	22	0.7	93.639	0.823	0.635	0.709	1.414	0.373	3.788	0.52	4,8,11,46,49,50,53,75

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 Q9C0B1-1_Q9C0B1-1_4qho_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 Q9C0B1-1_4qho_A_Q9C0B1-2.pdb

3D view using mol* of Q9C0B1-1_4qho_A_Q9C0B1-3.pdb

3D view using mol* of Q9C0B1-1_4qho_A_Q9C0B1-4.pdb

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

3D view using mol* of Q9C0B1-1_Q9C0B1-2.pdb

3D view using mol* of Q9C0B1-1_Q9C0B1-3.pdb

3D view using mol* of Q9C0B1-1_Q9C0B1-4.pdb

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

./stats/secondary_structure/figure/Q9C0B1-1_vs_Q9C0B1-2.png

./stats/secondary_structure/figure/Q9C0B1-1_vs_Q9C0B1-3.png

./stats/secondary_structure/figure/Q9C0B1-1_vs_Q9C0B1-4.png

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

./stats/relative_asa/Q9C0B1-1_vs_Q9C0B1-2.png

./stats/relative_asa/Q9C0B1-1_vs_Q9C0B1-3.png

./stats/relative_asa/Q9C0B1-1_vs_Q9C0B1-4.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 FTO

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
Q9C0B1	FTO	DB11638	Artenimol	approved, experimental, investigational	ligand

Related Diseases to FTO

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

Gene

PMID

Title

Abstract

MeSH ID

MeSH term

Clinically important variants in FTO

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance