Tchem CYP26B1 Cytochrome P450 26B1

Protein Summary

Description

Involved in the metabolism of retinoic acid (RA), rendering this classical morphogen inactive through oxidation. Involved in the specific inactivation of all-trans-retinoic acid (all-trans-RA), with a preference for the following substrates: all-trans-RA > 9-cis-RA > 13-cis-RA. Generates several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA, and 18-OH-RA. Essential for postnatal survival. Plays a central role in germ cell development: acts by degrading RA in the developing testis, preventing STRA8 expression, thereby leading to delay of meiosis. Required for the maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells, inducing arrest in G0 phase of the cell cycle and preventing meiotic entry. Plays a role in skeletal development, both at the level of patterning and in the ossification of bone and the establishment of some synovial joints. Has also a significant activity in oxidation of tazarotenic acid and may therefore metabolize that xenobiotic in vivo. This gene encodes a member of the cytochrome P450 superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein is localized to the endoplasmic reticulum, and functions as a critical regulator of all-trans retinoic acid levels by the specific inactivation of all-trans retinoic acid to hydroxylated forms. Mutations in this gene are associated with radiohumeral fusions and other skeletal and craniofacial anomalies, and increased levels of the encoded protein are associated with atherosclerotic lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

Uniprot Accession IDs

• Q9NR63
• B2R8M7
• B7Z2K6
• B7Z2P4
• B7Z3B8
• E4W5W7
• Q32MC0
• Q53TW1
• Q9NP41

Gene Name

• CYP26B1

Ensembl ID

• ENST00000001146
• ENSP00000001146
• ENSG00000003137
• ENST00000546307
• ENSP00000443304

Symbol

• CYP26A2
• P450RAI2
• RHFCA
• CYP26A2
• P450RAI2
• P450RAI-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.97
biological process	0.93
molecular function	0.84
pathway	0.83
PubMedID	0.73

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Oxygenase / Cytochrome P450 26b1

DTO Classes

Protein / Enzyme / Oxidoreductase / Oxygenase / Cytochrome P450 26b1

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: 108.99   (req: < 5)

Gene RIFs: 25   (req: <= 3)

Antibodies: 252   (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: 108.99   (req: >= 5)

Gene RIFs: 25   (req: > 3)

Antibodies: 252   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

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

Active Ligands: 5

Tclin

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

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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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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Approved Drugs (0)

No approved drugs found

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

Liarozole

CYP26B1Tchem

pIC50 : 8.64

CHEMBL309282

CYP26B1Tchem

pKd : 8.92

Talarozole

CYP26B1Tchem

pIC50 : 9.34

CHEMBL3787323

CYP26B1Tchem

pIC50 : 6.57

CHEMBL3787564

CYP26B1Tchem

pIC50 : 6.03

Protein-Protein Interactions (87)

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1 – 10 of 87

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ECSIT

Tbio

Novelty:  0.04690184

p_int:  0.975701584

p_ni:  0.024298416

p_wrong:  1e-9

Data Source:  BioPlex

SCARB2

Tbio

Novelty:  0.0044075

p_int:  0.97151014

p_ni:  0.028489859

p_wrong:  1e-9

Data Source:  BioPlex

CRELD1

Tbio

Novelty:  0.04938248

p_int:  0.946470026

p_ni:  0.053529888

p_wrong:  8.6e-8

Data Source:  BioPlex

NDUFAF1

Tclin

Novelty:  0.05630549

p_int:  0.939325185

p_ni:  0.060673197

p_wrong:  0.000001618

Data Source:  BioPlex

PCYOX1

Tbio

Family:  Enzyme

Novelty:  0.18505748

p_int:  0.928030248

p_ni:  0.071969752

Data Source:  BioPlex

MGST2

Tbio

Family:  Enzyme

Novelty:  0.04976733

p_int:  0.864742985

p_ni:  0.000009198

p_wrong:  0.135247817

Data Source:  BioPlex

ALDH1A2

Tchem

Family:  Enzyme

Novelty:  0.00461371

Score:  0.978

Data Source:  STRINGDB

ALDH1A1

Tchem

Family:  Enzyme

Novelty:  0.0012292

Score:  0.958

Data Source:  STRINGDB

CRABP1

Tbio

Novelty:  0.00284292

Score:  0.956

Data Source:  Reactome,STRINGDB

CYP2S1

Tbio

Novelty:  0.02967417

Score:  0.93

Data Source:  STRINGDB

Nearest Tclin Targets (6)

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Upstream (3)

Downstream (3)

1 – 3 of 3

CYP3A5

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Retinol metabolism

2: Metabolic pathways

CYP3A7

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Retinol metabolism

2: Metabolic pathways

CYP3A4

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Retinol metabolism

2: Metabolic pathways

Pathways (54)

Reactome (13)

KEGG (2)

WikiPathways (39)

Biological oxidations (R-HSA-211859)

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5

1 – 5 of 13

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Biological oxidations	221 targets	R-HSA-211859
Reactome	Cytochrome P450 - arranged by substrate type	65 targets	R-HSA-211897
Reactome	Defective CYP26B1 causes Radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA)	1 targets	R-HSA-5579015
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of metabolism	103 targets	R-HSA-5668914

Name	Explore in Pharos	Explore in Source
Biological oxidations	221 targets	R-HSA-211859
Cytochrome P450 - arranged by substrate type	65 targets	R-HSA-211897
Defective CYP26B1 causes Radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA)	1 targets	R-HSA-5579015
Disease	1105 targets	R-HSA-1643685
Diseases of metabolism	103 targets	R-HSA-5668914

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (32)

Functions (5)

Components (3)

Processes (24)

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Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	Inferred from Direct Assay (IDA)	UniProtKB
retinoic acid 4-hydroxylase activity	Inferred from Direct Assay (IDA)	BHF-UCL
retinoic acid binding	Inferred from Direct Assay (IDA)	BHF-UCL
heme binding	Non-traceable Author Statement (NAS)	BHF-UCL
iron ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations (null)

No disease associations found

GWAS Traits (4)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body height	EFO_0004339	1	2	2		72.8
schizophrenia	EFO_0000692	1	1	0	1.1	27.3
heel bone mineral density	EFO_0009270	2	1	2		13.7
mitochondrial heteroplasmy measurement	EFO_0600008	1	1	1		0

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body height	EFO_0004339	2		72.8
schizophrenia	EFO_0000692	0	1.1	27.3
heel bone mineral density	EFO_0009270	2		13.7
mitochondrial heteroplasmy measurement	EFO_0600008	1		0

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UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Complete proteome
Craniosynostosis
Disease mutation
Endoplasmic reticulum
Heme
Iron
Membrane
Metal-binding
Microsome

GWAS Trait Find Similar Targets

No Header	No Header
body height
heel bone mineral density
mitochondrial heteroplasmy measurement
schizophrenia

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
endocrine/exocrine gland phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
limbs/digits/tail phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450 26B1		738157
Mouse	cytochrome P450, family 26, subfamily b, polypeptide 1	MGI:2176159	232174
Rat	cytochrome P450, family 26, subfamily b, polypeptide 1	RGD:631379	312495
Dog	cytochrome P450 family 26 subfamily B member 1	VGNC:50344	483120
Horse	cytochrome P450 family 26 subfamily B member 1	VGNC:50561	100059609

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cytochrome P450 26B1
Mouse	cytochrome P450, family 26, subfamily b, polypeptide 1
Rat	cytochrome P450, family 26, subfamily b, polypeptide 1
Dog	cytochrome P450 family 26 subfamily B member 1
Horse	cytochrome P450 family 26 subfamily B member 1

Publication Statistics

PubMed Score 108.99

PubMed score by year

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PubTator Score 40.03

PubTator score by year

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Related Publications

Text Mined References (44)

GeneRif Annotations (25)

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10

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PMID	Year	Title