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FLASH GENE

Symbol

RBPJ

contributors: mct - updated : 04-04-2018

HGNC name	recombination signal binding protein for immunoglobulin kappa J region
HGNC id	5724

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	271.64 kb     12 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	three alternative splicing isoforms APCR-1, APCR-2, APCR-3

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005349 12 splicing 2388 NP_005340 55 500 - 2017 28487372 NM_015874 11 splicing 2316 NP_056958 54 487 - 2017 28487372 NM_203283 11 splicing 2272 NP_976028 54 485 - 2017 28487372 NM_203284 12 splicing 2499 NP_976029 54 486 - 2017 28487372

EXPRESSION

Type

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 Digestive liver       moderately   mouth       highly   pharynx       predominantly   stomach       highly Endocrine adrenal gland       moderately   neuroendocrine pituitary     highly Lymphoid/Immune thymus       moderately Nervous nerve       moderately Reproductive female system uterus cervix   highly Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Muscular       highly

cell lineage
cell lines
fluid/secretion	moderately in blood, highly in lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

one IPT/TIG domain

HOMOLOGY

interspecies	homolog to murine Rbpsuh (97.8 pc)
	homolog to Drosophila Su(H) (77.8 pc)

Homologene

FAMILY	phage-integrase family
	Su(H) family

CATEGORY

DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,nucleolus
text	major transcriptional effector of NOTCH1 signaling, RBPJ, is retained on mitotic chromatin, and this mitotic chromatin association is mediated through the direct association of RBPJ with DNA

basic FUNCTION	involved in the V-(D)-J recombination as a recombinase
	playing a central role in Notch signaling
	acting as a transcriptional repressor when it is not associated with Notch proteins
	acting as a transcriptional activator for Notch target genes, when associated with some Notch protein
	probably involved in repression or activation of transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively
	important roles for RBPJ and NOTCH signaling in multiple aspects of inner ear development including prosensory cell maturation, cellular differentiation and survival
	having a novel function that promotes INP (intermediate neural progenitors) differentiation
	MAML1 and RBPJ, which are components of the Notch transcription complex, enhance Notch acetylation and we suggest that MAML1 increases Notch acetylation by potentiating EP300 autoacetylation
	evolutionarily conserved protein that coordinates transcriptional activation of Notch-target genes through the assembly of protein complexes containing coactivators
	negatively role of RBPJ in the differentiation of osteoclasts, suggesting that NOTCH1 pathway may be a new therapeutic target for bone diseases related to increased osteoclastogenesis
	RBPJ can function as a mitotic bookmark, marking genes for efficient transcriptional activation or repression upon mitotic exit
	likely by collaborating with CTCF, RBPJ may participate in establishing chromatin domains and/or long-range chromatin interactions that could be propagated through cell division to maintain gene expression programs
	uterine RBPJ is essential for normal embryo development via instructing the initial embryonic-uterine orientation and ensuring normal decidual patterning in a stage-specific manner
	temporal requirement for RBPJ in postnatal endothelial cell (EC) to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and Arteriovenous malformations (AVMs) pathogenesis
	environmental cues that regulate RBPJ expression/function potentially modulate the requirement for costimulatory signaling for osteoclast differentiation and bone remodeling
	is a key transcription factor downstream of Notch receptor activation
	role of RBPJ-dependent and independent NOTCH1 signaling pathways in cell apoptosis
	is a key transcriptional repressor and mediator of Notch signaling

CELLULAR PROCESS	cell life, differentiation
	nucleotide, recombination
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development , immunity/defense , angiogenesis

text	B cell differentiation; defense response to bacterium; heart development

PATHWAY

metabolism

signaling

signal transduction

	Notch signaling pathway
	NOTCH1/RBPJ signaling regulates the generation and differentiation of arcuate nucleus (Arc) neurons, which contribute to homeostatic regulation of body size neurons
	RBPJ-dependent NOTCH1 pathway is a novel pathway involved in joint maintenance and articular cartilage homeostasis, a critical regulator of articular cartilage ECM-related molecules
	NOTCH1/RBPJ signaling regulates dopamine responsiveness in the striatum, which may explain the mechanism whereby NOTCH1/RBPJ signaling affects an individual susceptibility to neuropsychiatric disease

a component	immunoglobulin Kappa-type J segment recombination signal sequence / RBPSUH complex with NOTCH in nucleus
	SPEN forms a high affinity complex with RBPJ

INTERACTION

DNA	binding specifically to the immunoglobulin kappa-type J segment recombination signal sequence

RNA

small molecule

protein	interacting with activated NOTCH1, NOTCH2 or NOTCH3
	interacting with MINT/SHARP (which may mediate the recruitment of large corepressor complexes containing proteins such as HDAC1, HDAC2, NCOR2, SAP30, FHL1/KYOT2 and CIR)
	interacting with EP300
	NOTCH1 in concert with NOTCH2 contributes to the morphogenesis of renal vesicles into S-shaped bodies in a RBPJ-dependent manner
	interacting with MAPK8IP1 (RBPJ inhibits MAPK8IP1-mediated activation of the MAPK8 signaling cascade and cell death)
	principal DNA-binding partner of the Notch intracellular domain
	WNT5A inhibited the physical association between RBPJ and NCOR2 suggesting that WNT5A induced CAMK2A activation plays a critical role in the endogenous RBPJ-NCOR2 binding
	KDM1A functions as a corepressor when associated with RBPJ-repressor complex and as a NOTCH1 coactivator upon NOTCH1 activation
	FHL1 binds RBPJ with high affinity and competes with coactivators, such as NOTCH1, for binding RBPJ
	TP53, a key effector of the DNA damage response, negatively controls RBPJ gene transcription, through suppression of RBPJ promoter activity and, indirectly, by increased CDKN1A expression
	RBPJ binds and trans-activates the IL23R promoter and induces IL23R expression and represses anti-inflammatory IL10 production in Th17 cells
	RITA1 is a RBPJ (mammalian CSL ortholog)-interacting protein
	in the absence of NOTCH intracellular domain (NOTCH ICD), RBPJ recruits L3MBTL3 and the histone demethylase KDM1A (also known as LSD1) to the enhancers of Notch target genes, leading to H3K4me2 demethylation and to transcriptional repression
	SNW1 interacts with RBPJ to regulate the NOTCH signaling pathway

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

AOS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function RBPJ deficient Dendritic cells exhibited attenuated cytoskeleton reorganization when contacting T cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate short hairpin interfering RNA (shRNA) intervention of RBPJ expression could be a promising therapeutic approach for treating human prostate cancer immunology inflammatory   potentially important therapeutic target for Osteoarthritis (OA) -like joint disease

ANIMAL & CELL MODELS