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SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4

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Target not currently curated in GtoImmuPdb

Target id: 2740

Nomenclature: SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4

Abbreviated Name: SMARCA4

Family: Non-enzymatic BRD containing proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1647 19p13.2 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
Mouse - 1613 9 7.84 cM Smarca4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
Rat - 1613 8q13 Smarca4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
Previous and Unofficial Names Click here for help
BAF190 | SNF2-BETA | SWI2 | SWI/SNF related
Database Links Click here for help
Alphafold P51532 (Hs), Q3TKT4 (Mm)
CATH/Gene3D 1.20.920.10
ChEMBL Target CHEMBL3085620 (Hs)
Ensembl Gene ENSG00000127616 (Hs), ENSMUSG00000032187 (Mm), ENSRNOG00000009271 (Rn)
Entrez Gene 6597 (Hs), 20586 (Mm), 171379 (Rn)
Human Protein Atlas ENSG00000127616 (Hs)
KEGG Gene hsa:6597 (Hs), mmu:20586 (Mm), rno:171379 (Rn)
OMIM 603254 (Hs)
Pharos P51532 (Hs)
RefSeq Nucleotide NM_001128849 (Hs), NM_001174078 (Mm), NM_134368 (Rn)
RefSeq Protein NP_001122321 (Hs), NP_001167549 (Mm), NP_599195 (Rn)
SynPHARM 80802 (in complex with PFI-3)
UniProtKB P51532 (Hs), Q3TKT4 (Mm)
Wikipedia SMARCA4 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PFI-3 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Binding 7.1 pKd 2
⤷ pKd 7.1 (Kd 8.9x10-8 M) [2]
GNE-064 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 – 8.0 pIC50 3
⤷ pIC50 8.0 (IC50 1x10-8 M) [3]
Description: Potency determined by BromoScan assay
pIC50 7.5 (IC50 3.5x10-8 M) [3]
Description: Potency determined by TR-FRET assay
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SMD-3040 Small molecule or natural product Click here for species-specific activity table Hs Binding 7.9 pKd 4
⤷ pKd 7.9 (Kd 1.28x10-8 M) [4]
Description: Binding affinity of SMARCA2/4 ligand 3 moiety
A947 Small molecule or natural product Click here for species-specific activity table Hs Binding 7.2 pKd 1
⤷ pKd 7.2 (Kd 6.5x10-8 M) [1]
Description: Binding affinity for SMARCA4 bromodomain.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Coffin-Siris syndrome
Disease Ontology: DOID:1925
OMIM: 135900
Orphanet: ORPHA1465
Disease:  Mental retardation, autosomal dominant 16; MRD16
Synonyms: Autosomal dominant non-syndromic intellectual disability [Disease Ontology: DOID:0060307]
Disease Ontology: DOID:0060307
OMIM: 614609
Disease:  Rhabdoid tumor predisposition syndrome 2
Synonyms: Familial rhabdoid tumor [Orphanet: ORPHA231108]
OMIM: 613325
Orphanet: ORPHA231108

References

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1. Cantley J, Ye X, Rousseau E, Januario T, Hamman BD, Rose CM, Cheung TK, Hinkle T, Soto L, Quinn C et al.. (2022) Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers. Nat Commun, 13 (1): 6814. [PMID:36357397]

2. SGC. PFI-3 A Selective chemical probe for SMARCA bromodomains. Accessed on 10/11/2014. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/PFI-3

3. Taylor AM, Bailey C, Belmont LD, Campbell R, Cantone N, Côté A, Crawford TD, Cummings R, DeMent K, Duplessis M et al.. (2022) GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1. J Med Chem, 65 (16): 11177-11186. [PMID:35930799]

4. Yang L, Tu W, Huang L, Miao B, Kaneshige A, Jiang W, Leng L, Wang M, Wen B, Sun D et al.. (2023) Discovery of SMD-3040 as a Potent and Selective SMARCA2 PROTAC Degrader with Strong in vivo Antitumor Activity. J Med Chem, 66 (15): 10761-10781. [PMID:37523716]

How to cite this page

Non-enzymatic BRD containing proteins: SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4. Last modified on 01/08/2023. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2740.