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FLASH GENE

Symbol

RBCK1

contributors: mct/npt/pgu - updated : 27-06-2017

HGNC name	RanBP-type and C3HC4-type zinc finger containing 1
HGNC id	15864

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	24.09 kb     12 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006462 11 splicing initiation site codon stop 2633 52.9 468 highly in brain, placenta, pancreas, moderately in heart, skeletal muscle, lowly in lung, liver, kidney 2015 26525107 lacking exon 2 which contains a translation start codon used by variant 2 using an in-frame start codon in exon 1 E3 activity of RBCK1 is controlled by two distinct manners, interaction with RBCK2 and phosphorylation by PKCâ having a distinct N-terminus compared to that of isoform 2 NM_031229 or RBCK2 12 splicing initiation site codon stop 2778 56.4 500 bone marrow, spleen, thymus, brain, heart, skeletal muscle, liver, pancreas, prostate, kidney, lung 2015 26525107 containing exon 2 with a translation start codon used by variant 2 no transcriptional activity and instead it represses the transcriptional activity of RBCK1 present usually in the cytoplasm containing two Leu-rich regions that presumably serve as a nuclear export signal (NES) lacking the C-terminal half including the RING-IBR domain NM_001323956 11 - 3802 NP_001310885 - 340 - 2015 26525107 NM_001323958 10 - 3657 NP_001310887 - 340 - 2015 26525107 NM_001323960 3 - 1274 NP_001310889 - 105 - 2015 26525107

EXPRESSION

Type	ubiquitous

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 intestine large intestine colon   highly   pancreas exocrine         Lymphoid/Immune lymph node           thymus         Nervous nerve cranial nerve     highly Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal region containing Leu-142 and Leu-145 serving as the nuclear export
	an ubiquitin like domain, required for the binding to RNF31 to assemble LUBAC, and interacting with the Phe4-centered patch of the proximal UBC
	two coiled-coil regions
	a RING finger
	a B-box, and a B-box-like motif
	a Npl4 zinc finger (NZF) domain specifically binds linear polyubiquitin chains and determined the crystal structure of the RBCK1 NZF domain in complex with linear diubiquitin
	a C-terminal one containing the RING-IBR domain, serving as localization signals

conjugated

PhosphoP , MetalloP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to rattus Pkcbpb15
	ortholog to murine AL033326

Homologene

FAMILY

RING finger proteins family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm,nuclear bodies
text	shuttle between the nucleus and cytoplasm

basic FUNCTION	acting as a E3 ubiquitin protein ligase
	involved in transcriptional machinery in the nuclear bodies, and its transcriptional activity is regulated by nucleocytoplasmic shuttling
	function as a transcriptional activator whose nuclear translocation is prevented by interaction with the cytoplasmic RBCK2
	possessed a transcriptional activity, shuttling between the cytoplasm and nucleus, has also been found to exhibit a significant ubiquinating activity, which is inhibited by interaction with its splice variant RBCK2 or phosphorylation by PKC beta
	is not required for iron-dependent degradation of IREB2 in most cell types
	function as a transcriptional activator whose nuclear translocation is prevented by interaction with the cytoplasmic RBCK2
	regulates cell cycle progression and proliferation of ERalpha-positive breast cancer cells by supporting transcription of ERalpha and cyclin B1
	may be unique in its mechanism of interaction with linear chains
	is likely important for the ubiquitination of NR1I2 and may play a role in its proteasomal degradation

CELLULAR PROCESS	nucleotide, transcription, regulation
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	binding to PRKCB1, PRKCZ, UBE2L3, X protein of hepatite B virus, IRP2
	interact with nuclear body proteins, CREB-binding protein (CBP), and promyelocytic leukemia protein (PML)
	binds to a unique 73-AAs domain in IREB2 in an iron-dependent manner to regulate IREB2 polyubiquitylation and degradation
	protein kinase C (PKC) beta- and zeta-interacting protein
	with SHARPIN are novel interaction partners of EYA1, and are coexpressed with EYA1 in several organs during craniofacial embryogenesis
	SHARPIN activates NFKB1 signaling by forming a linear ubiquitin chain assembly complex with RNF31 (HOIP) and RBCK1 (HOIL1)
	specific interaction between the RBCK1L NZF domain and linear chains is important for NFKB1 activation
	ESR1 regulation of its own mRNA expression is facilitated by RBCK1 recruitment, suggesting an ESR1 coactivator function of RBCK1
	RBCK1 ubiquitinates NR1I2, and this may target NR1I2 for degradation by the ubiquitin-proteasome pathway
	co operates with the E3 ubiquitin ligase RNF31 to modify specific NFKB1 signaling proteins with linear M1-linked polyubiquitin chains
	MALT1-mediated RBCK1 cleavage provides a gain-of-function mechanism that is involved in the negative feedback regulation of NFKB1 signaling
	is a negative regulator of lymphocyte activation cleaved by MALT1
	HOXA1 binds RBCK1 and TRAF2 and modulates the TNF/NFKB1 pathway in a transcription-independent manner

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

PGBM1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   mediates the development of myocyte hypertrophy, and promotes cardiac myocyte hypertrophy tumoral         silencing of RBCK1 impairs lung tumor growth

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular aquired heart failure PRKCB1-RBCK1 interaction would serve as a potential therapeutic target to treat pathological cardiac hypertrophy cancer     is likely an attractive target for cancer therapy

ANIMAL & CELL MODELS

Hoil-1-deficient mice exhibit amylopectin-like deposits in the myocardium, pathogen-specific immunodeficiency, but minimal signs of hyper-inflammation