Tclin FKBP1A Peptidyl-prolyl cis-trans isomerase FKBP1A

Protein Classes

PANTHER Classes

Protein / Isomerase / Peptidyl-prolyl Cis-trans Isomerase Fkbp1a

Protein / Chaperone / Peptidyl-prolyl Cis-trans Isomerase Fkbp1a

Protein / Calcium-binding Protein / Peptidyl-prolyl Cis-trans Isomerase Fkbp1a

DTO Classes

Protein / Enzyme / Isomerase / Peptidyl-prolyl Cis-trans Isomerase Fkbp1a

Protein Summary

Description

Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed. [provided by RefSeq, Sep 2008]

Uniprot Accession IDs

• P62942
• D3DVW6
• P20071
• Q4VC47
• Q6FGD9
• Q6LEU3
• Q9H103
• Q9H566
• PPIase FKBP1A

Gene Name

• FKBP1A

Ensembl ID

• ENST00000381719
• ENSP00000371138
• ENSG00000088832
• ENST00000400137
• ENSP00000383003

Symbol

• FKBP1
• FKBP12
• FKBP1
• PKC12
• PKCI2
• FKBP12
• PPIASE
• FKBP-12
• FKBP-1A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
disease perturbation	1
transcription factor perturbation	1
kinase perturbation	0.98
molecular function	0.97

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 806.78   (req: < 5)

Gene RIFs: 43   (req: <= 3)

Antibodies: 377   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 806.78   (req: >= 5)

Gene RIFs: 43   (req: > 3)

Antibodies: 377   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 31

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 332

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 5

Approved Drugs (5)

Explore Approved Drugs

1 – 5 of 5

sirolimus

FKBP1ATclin Enzyme

INHIBITOR Kd : 8.96

tacrolimus

FKBP1ATclin Enzyme

INHIBITOR Kd : 9.398

everolimus

FKBP1ATclin Enzyme

INHIBITOR IC50 : 8.25964

temsirolimus

FKBP1ATclin Enzyme

INHIBITOR :

pimecrolimus

FKBP1ATclin Enzyme

INHIBITOR Kd : 9

Active Ligands (332)

Explore Active Ligands

1 – 10 of 332

CHEMBL269732

FKBP1ATclin Enzyme

Ki : 9.39999962

CHEMBL2058794

FKBP1ATclin Enzyme

IC50 : 6.94

CHEMBL3623615

FKBP1ATclin Enzyme

Ki : 6.05

CHEMBL3623613

FKBP1ATclin Enzyme

Ki : 6.22

CHEMBL407550

FKBP1ATclin Enzyme

Kd : 6.46

CHEMBL421507

FKBP1ATclin Enzyme

Kd : 6.5

CHEMBL3623612

FKBP1ATclin Enzyme

Ki : 7.05

CHEMBL2057227

FKBP1ATclin Enzyme

IC50 : 7.22

CHEMBL405917

FKBP1ATclin Enzyme

EC50 : 7.35

CHEMBL412791

FKBP1ATclin Enzyme

EC50 : 7.35

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2	1	2		18.1

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2		18.1

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Orthologs (7)

1 – 5 of 7

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	FK506 binding protein 1A	VGNC:14132	749347
Mouse	FK506 binding protein 1a	MGI:95541	14225
Rat	FK506 binding protein 1a	RGD:2617	25639
Horse	FK506 binding protein 1A		100629541
Cow	FK506 binding protein 1A		614795

Species	Name	OMA	EggNOG	Inparanoid
Chimp	FK506 binding protein 1A
Mouse	FK506 binding protein 1a
Rat	FK506 binding protein 1a
Horse	FK506 binding protein 1A
Cow	FK506 binding protein 1A

Protein Structure (49 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P62942-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 49

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (30)

Reactome (15)

PathwayCommons (11)

WikiPathways (4)

Adaptive Immune System (R-HSA-1280218)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Calcineurin activates NFAT	9 targets	R-HSA-2025928
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of signal transduction	387 targets	R-HSA-5663202
Reactome	Downstream signaling events of B Cell Receptor (BCR)	82 targets	R-HSA-1168372

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Calcineurin activates NFAT	9 targets	R-HSA-2025928
Disease	1105 targets	R-HSA-1643685
Diseases of signal transduction	387 targets	R-HSA-5663202
Downstream signaling events of B Cell Receptor (BCR)	82 targets	R-HSA-1168372

Gene Ontology Terms (40)

Functions (8)

Components (9)

Processes (23)

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Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
FK506 binding	Inferred from Direct Assay (IDA)	BHF-UCL
peptidyl-prolyl cis-trans isomerase activity	Inferred from Direct Assay (IDA)	BHF-UCL
activin binding	Inferred from Physical Interaction (IPI)	BHF-UCL
SMAD binding	Inferred from Physical Interaction (IPI)	BHF-UCL
ion channel binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
transforming growth factor beta receptor binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
type I transforming growth factor beta receptor binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
macrolide binding	Non-traceable Author Statement (NAS)	BHF-UCL

Protein-Protein Interactions (206)

Explore Interacting Targets

1 – 10 of 206

• See Interactions on String-DB

MTOR

Tclin

Family: Kinase

Novelty: 0.00012333

Score: 0.999

Data Source: STRINGDB

TGFBR1

Tchem

Family: Kinase

Novelty: 0.00081645

Score: 0.998

Data Source: Reactome,STRINGDB

PPP3R1

Tbio

Novelty: 0.00263264

Score: 0.997

Data Source: STRINGDB

ACVR1

Tchem

Family: Kinase

Novelty: 0.00284646

Score: 0.992

Data Source: STRINGDB

RYR1

Tclin

Family: IC

Novelty: 0.00077827

Score: 0.985

Data Source: STRINGDB

PPP3CA

Tchem

Family: Enzyme

Novelty: 0.00234189

Score: 0.976

Data Source: STRINGDB

ACVRL1

Tchem

Family: Kinase

Novelty: 0.00310167

Score: 0.961

Data Source: STRINGDB

PIN1

Tchem

Family: Enzyme

Novelty: 0.00957198

Score: 0.955

Data Source: STRINGDB

PPP3CB

Tbio

Family: Enzyme

Novelty: 0.02156713

Score: 0.953

Data Source: STRINGDB

SMAD7

Tbio

Family: TF

Novelty: 0.00116343

Score: 0.947

Data Source: STRINGDB

Publication Statistics

PubMed Score  806.78

PubMed score by year

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PubTator Score  88.76

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Acetylation
Complete proteome
Cytoplasm
Direct protein sequencing
Isomerase
Membrane
Reference proteome
Rotamase
Sarcoplasmic reticulum

GWAS Trait Find Similar Targets

body mass index

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging
muscle phenotype