Target Information

Target General Information

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Target ID

T74066 (Former ID: TTDI02553)

Target Name

Polycomb complex protein BMI-1 (BMI1)

Synonyms

RNF51; RING finger protein 51; Polycomb group RING finger protein 4; PCGF4

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Gene Name

BMI1

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Leiomyosarcoma [ICD-11: 2B58]

Function

PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A. In the PRC1-like complex, regulates the E3 ubiquitin-protein ligase activity of RNF2/RING2. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.

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BioChemical Class

Zinc-finger

UniProt ID

BMI1_HUMAN

Sequence

MHRTTRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQV
HKTRPLLNIRSDKTLQDIVYKLVPGLFKNEMKRRRDFYAAHPSADAANGSNEDRGEVADE
DKRIITDDEIISLSIEFFDQNRLDRKVNKDKEKSKEEVNDKRYLRCPAAMTVMHLRKFLR
SKMDIPNTFQIDVMYEEEPLKDYYTLMDIAYIYTWRRNGPLPLKYRVRPTCKRMKISHQR
DGLTNAGELESDSGSDKANSPAGGIPSTSSCLPSPSTPVQSPHPQFPHISSTMNGTSNSP
SGNHQSSFANRPRKSSVNGSSATSSG

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3D Structure

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AlphaFold

HIT2.0 ID

T95Z7B

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
E3 ubiquitin-protein ligase RNF8 (RNF8)	PF00498 ; PF13920	36.471 (31/85)	1.28E-07
RING finger protein 24 (RNF24)	PF13639	38.182 (21/55)	1.19E-05
E3 ubiquitin-protein ligase TRIM35 (TRIM35)	PF13765 ; PF00622 ; PF00643 ; PF13920 More >>	34.286 (24/70)	1.08E-04
RING finger protein 10 (RNF10)	PF13639	31.579 (30/95)	8.40E-04
E3 ubiquitin-protein ligase TRAIP (TRAIP)	PF13639	33.929 (19/56)	8.88E-04
Tripartite motif-containing protein 64C (TRIM64C)	PF00622	40.909 (18/44)	1.00E-03
Tripartite motif-containing protein 10 (TRIM10)	PF13765 ; PF00622 ; PF00643 ; PF15227 More >>	36.364 (20/55)	1.00E-03
E3 ubiquitin-protein ligase TRIM39 (TRIM39)	PF13765 ; PF00622 ; PF00643 ; PF15227 More >>	36.923 (24/65)	1.00E-03
RING finger protein 39 (RNF39)	PF13765 ; PF00097	31.169 (24/77)	1.00E-03
E3 ubiquitin-protein ligase TRIM69 (TRIM69)	PF13765 ; PF00622 ; PF15227 More >>	21.939 (43/196)	2.00E-03
E3 ubiquitin-protein ligase TRIM50 (TRIM50)	PF13765 ; PF00622 ; PF00643 ; PF13445 More >>	26.316 (20/76)	2.00E-03
Tripartite motif-containing protein 43B (TRIM43B)	PF00622 ; PF15227	31.343 (21/67)	3.00E-03
Tripartite motif-containing protein 43 (TRIM43)	PF00622 ; PF15227	31.343 (21/67)	3.00E-03
E3 ubiquitin-protein ligase TRIM31 (TRIM31)	PF00643 ; PF15227	30.000 (27/90)	3.00E-03
Tripartite motif-containing protein 64 (TRIM64)	PF00622 ; PF00097	43.182 (19/44)	3.00E-03
Putative tripartite motif-containing protein 64B (TRIM64B)	PF00622 ; PF00097	43.182 (19/44)	3.00E-03
E3 ubiquitin-protein ligase RNF165 (RNF165)	PF13639	33.333 (15/45)	3.00E-03
RING finger protein 141 (RNF141)	PF13920	32.075 (17/53)	3.00E-03
Tripartite motif-containing protein 74 (TRIM74)	PF00643 ; PF13445	31.343 (21/67)	3.00E-03
Tripartite motif-containing protein 73 (TRIM73)	PF00643 ; PF13445	31.343 (21/67)	4.00E-03
E3 ubiquitin-protein ligase TRIM21 (TRIM21)	PF13765 ; PF00622 ; PF00643 ; PF00097 More >>	31.169 (24/77)	5.00E-03
E3 ubiquitin-protein ligase Topors (TOPORS)	PF13920	28.261 (13/46)	5.00E-03
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KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Signaling pathways regulating pluripotency of stem cells	hsa04550	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy

Degree	19	Degree centrality	2.04E-03	Betweenness centrality	2.68E-05
Closeness centrality	2.11E-01	Radiality	1.37E+01	Clustering coefficient	6.43E-01
Neighborhood connectivity	2.49E+01	Topological coefficient	1.77E-01	Eccentricity	12
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Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 1

The expression and prognostic value of stem cell markers Bmi-1, HESC5:3, and HES77 in human papillomavirus-positive and -negative oropharyngeal squ... Tumour Biol. 2019 Mar;41(3):1010428319840473.

REF 2

ClinicalTrials.gov (NCT05269355) A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma. U.S.National Institutes of Health.

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