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FLASH GENE

Symbol

SMARCB1

contributors: mct/pgu - updated : 10-05-2019

HGNC name	SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1
HGNC id	11103

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic thymus       highly Cardiovascular heart       highly Digestive liver       moderately Endocrine pancreas       highly Nervous brain       moderately Reproductive male system prostate     highly Respiratory lung       highly Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two highly conserved imperfect repeats (Rpt1, Rpt2) important for interaction with HIV integrase one with MYC
	a C terminal coiled coil region

HOMOLOGY

interspecies	ortholog to murine Smarcb1 (100.00pc)
	ortholog to rattus Smarcb1 (100.00pc)

Homologene

FAMILY

SNF5 family

CATEGORY

DNA associated , transcription factor , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
	intracellular,nucleus,nucleolus

basic FUNCTION	actin-dependent regulator of chromatin
	involved in cell cycle control pathway
	involved in the oncogenesis of tumors with a completely different histology and prognosis
	required for upregulation of BNIP3L by IGFBP7
	promotes nucleotide excision repair by influencing ATM recruitment and downstream H2AFX phosphorylation
	exerts ploidy control through a pathway that includes CDKN2A, cyclin D, CDK4, RB and E2F
	role in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas
	has a protective role in the DNA damage response
	key mediator of HH signaling and aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of malignant rhabdoid tumors cells
	loss of SMARCB1 drives cancer formation through simultaneous epigenetic perturbation of GLI1 and other key cancer-promoting pathways, several of which may thus constitute viable therapeutic targets
	represses Aurora A transcription in a cell-type-specific manner
	loss dramatically alters SWI/SNF complex composition and prevents formation of complexes required for cellular differentiation
	differential roles for SWI/SNF subunits in muscle differentiation, with SMARCB1 playing a dual role both in the permanent cell cycle exit and in the regulation of muscle-specific genes
	antagonistic roles of the SMARCB1 and MYC transcriptional regulators in mediating cellular and oncogenic functions
	is required for the integrity of SWI/SNF complexes and its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers
	SMARCB1, SMARCD1 and SMARCE1 might act as novel pro-senescence factors in both normal and tumor human skin cells
	SMARCB1 represses bivalent genes in human embryonic stem cells (hESCs) and antagonizes chromatin accessibility at super-enhancers

CELLULAR PROCESS	nucleotide, chromatin organization, remodeling
	nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	component of the chromatin remodeling complex
	component of SWI/SNF chromatin remodeling enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1)
	component of the WINAC complex, at least composed of SMARCA2, SMARCA4, SMARCB1, SMARCC1, SMARCC2, SMARCD1, SMARCE1, ACTL6A, BAZ1B/WSTF, ARID1A, SUPT16H, CHAF1A and TOP2B

INTERACTION

DNA	binding to double-strand DNA

RNA

small molecule

protein	previously shown to interact with HIV integrase
	part of a pathway in which IGFBP7 increases expression of SMARCB1, which in turn leads to increased expression of BNIP3L culminating in apoptosis
	interacting with MYK and MAEL
	interacting with PPP1R15A
	HIV-1 integrase and SMARCB1 bind SAP18 and selectively recruit components of SIN3a-HDAC1 complex into HIV-1 virions
	required for TP53 transcriptional activity, and induction of prosurvival TP53 targets, including CDKN1A and MDM2, may have a role in SMARCB1 prosurvival activity
	interacts with GLI1 (localizes to GLI1-regulated promoters and loss of SMARCB1 leads to activation of the HH-GLI pathway)
	RB1CC1 essentially requires binding with SMARCB1, a chromatin-remodeling factor) to activate the CDKN2A promoter, in order to enhance the RB1 pathway and acts as a tumor suppressor
	CHFR interacts with SMARCA4, SMARCB1, and SMARCD1 of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and SMARCC1 stabilizes these components by blocking their interaction with CHFR
	SMARCA4, SMARCB1, and SMARCD1, but not SMARCC1, are the substrates of CHFR for ubiquitination
	interacts with CHFR through its RPT2 region
	SMARCB1 is indispensable for GADD45GIP1-enhanced TP53 activity and its function in the suppression of cell cycle arrest in human cancer cells
	is a modular domain involved in SMARCB1 interaction, which is functionally distinct from other characterized SWIRM domains that possess DNA binding activity
	BICRA and BICRAL each exclusively associate with BRD9, but not with SMARCB1 (PMID;
	SMARCB1 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity

cell & other

matrix associated

REGULATION

Other

phosphorylated upon DNA damage

ASSOCIATED DISORDERS

corresponding disease(s)

MRBDT , SCWT , CSSSB1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in chromic myeloid leukemia tumoral   LOH     in meningiomas tumoral   deletion     or mutated in malignant rhabdoid tumor or atypical teratoid tumor tumoral somatic mutation       in plexus carcinoma tumoral       loss of function stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation, in infantile malignant rhabdoid tumors, and epithelioid sarcomas tumoral germinal mutation     loss of function mutation loss of functio in familial schwannomatosis tumoral   deletion     predisposing to malignant rhabdoid tumor tumoral   LOH     in schwannomatosis tumoral germinal mutation       associated with somatic NF2 mutations in familial multiple meningiomas constitutional germinal mutation     loss of function ID via EHMT1-associated chromatin modification module tumoral     --low   is associated with poor prognosis in skull base chordoma tumoral germinal mutation       predispose to rhabdoid tumors and schwannomas tumoral         complete absence of SMARCB1 immunoreactivity seen in malignant rhabdoid tumor tumoral     --low   decreased SMARCB1 immunoreactivity with a high specificity (100 p100) for synovial sarcoma and particular sensitivity for poorly differentiated subtypes of synovial sarcoma constitutional   amplification     microduplication in region with SMARCB1 and SNRPD3 genes in patient presented healed cleft lip, mild facial dysmorphism, cognitive deficit, and delayed language development associated with severe behavioral problems including learning difficulties and aggressive behavior

Susceptibility

to familial schwannomatosis to malignant rhabdoid tumor

Variant & Polymorphism insertion/deletion	deletion in malignant rhabdoid tumor

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS