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FLASH GENE

Symbol

CUL3

contributors: mct/pgu - updated : 15-03-2016

HGNC name	cullin 3
HGNC id	2553

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	a newly bio-informatically identified transcript variant (PMID: 15897978)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003590 16 - 6784 NP_003581 89 768 - 2005 15897978 NM_001257197 15 - 6592 NP_001244126 - 702 - 2005 15897978 NM_001257198 16 - 6473 NP_001244127 - 774 - 2005 15897978

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 Cardiovascular vessel       highly Digestive esophagus       highly   pharynx       highly Endocrine parathyroid       predominantly Lymphoid/Immune lymph node       highly Reproductive male system testis     highly Urinary kidney       highly

tissue

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

cell lineage

cell lines

fluid/secretion

at STAGE

cell cycle

cell cycle, checkpoint, G1S

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

PhosphoP , Other

mono polymer

dimer

HOMOLOGY

interspecies	homolog to rattus Cul3 (99.6 pc)
	homolog to murine Cul3 (99.5 pc)

Homologene

FAMILY

cullin family

CATEGORY

regulatory , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus,chromatin/chromosome
text	KLHL7 and CUL3 co-localized in punctate structures in the cytoplasm
	in the absence of Retinoic acid (RA), present in the cytoplasm, and migrates to nuclei in response to RA
	ZBTB16 transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex

basic FUNCTION	likely involved in cell proliferation control
	may target other proteins for ubiquitin-dependent proteolysis
	negative regulator of the cell cycle
	playing a role in the induction of apoptosis by intracellular signals
	SPOP/CUL3-ubiquitin ligase plays an essential role in the control of DAXX level and, thus, in the regulation of DAXX-mediated cellular processes, including transcriptional regulation and apoptosis
	crucial role of CUL3 in regulating late steps in the endolysosomal trafficking pathway
	potentially required but not limiting for efficient EGF and EGFR trafficking and degradation
	fundamental role for KLHL3 and CUL3 in blood pressure, K+ and pH homeostasis
	CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats
	specific role of CUL3 and KLHL3 in electrolyte homeostasis, providing a molecular explanation for the effects of disease-causing mutations in both KLHL3 and WNK4

CELLULAR PROCESS	cell cycle, checkpoint
	cell life, proliferation/growth
	cell life, cell death/apoptosis
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

text	mitotic G1/S transition
	third step of ubiquitin conjugation
	positive regulation of cell proliferation

PATHWAY

metabolism

signaling

a component	part of a complex consisting of PCGF4, CUL3 and SPOP
	part of a complex consisting of H2AFY, CUL3 and SPOP
	neddylated (deneddylated via its interaction with the COP9 signalosome (CSN) complex)
	dimeric SPOP-CUL3 assembly involving a conserved helical structure C-terminal of BTB domains
	NFE2L2 serves as a substrate adaptor to link NFE2L2 to CUL3 and RBX1 (NFE2L2 regulates CUL3-RBX1 by controlling regulation of expression and induction of CUL3-RBX1, and the induction of CUL3-RBX1 control NFE2Lf2 by increasing degradation)
	forms a dimer, assembles with CUL3 through its BTB and BACK domains, and exerts E3 activity
	KBTBD13 is able to form a complex with CUL3 and RBX1 to reconstitute a functional ubiquitin ligase capable of conjugating ubiquitin onto KBTBD13
	BCL6-CUL3 complexes also provide essential negative feedback regulation during both thymocyte development and T cell activation to restrain excessive T follicular helper (Tfh) responses

INTERACTION

DNA

RNA

small molecule

protein	interacting with RBX1, RNF7, CYCE and TIP120A/CAND1
	interacting specifically with Keap1
	KLHL20-CUL3-RBX1 E3 ligase complex promotes DAPK1 polyubiquitination, thereby inducing the proteasomal degradation of DAPK1, and controling interferon response
	KLHL7 co-localizes with CUL3, and all of the domains are necessary for the punctate subcellular localization
	CUL3, a component of E3 ubiquitin ligase, is a new binding partner of BRMS1 and the interaction between BRMS1 and CUL3 is mediated by the SPOP adaptor protein
	responsible for joining the ligase activity-bearing subunit RBX1 with a BTB-containing protein
	KBTBD13 interacts with Cullin 3 (CUL3) and the BTB domain mediates this interaction
	CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-centre B cell and follicular T-helper cell programs
	WNK4 is a substrate for KLHL3-CUL3 E3 ubiquitin ligase complexes
	CUL3 has the ability to bind to Kelch-like 3 protein (KLHL3) and therefore mediating the degradation of some members of the WNK kinases
	CUL3-KLHL20 ubiquitin E3 ligase catalyzes a nondegradable, K33-linked polyubiquitination on CORO7, which facilitates CORO7 targeting to TGN through a ubiquitin-dependent interaction with EPS15
	KCTD6(BTB) and KCTD11(BTB) bind CUL3 with high affinity forming stable complexes with 4:4 stoichiometries
	KCTD5 or Cullin3 overexpression increased ZNF711 protein stability
	ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of the CUL3-KLHL20 ubiquitin ligase
	CUL3 also interacts with both ARRB1, ARRB2 but has no influence on their ubiquitination
	CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells
	the effects of DCUN1D1 on spermatogenesis likely involve its regulation of cullin-RING-ligase (CRL)-type ubiquitin E3 activity during spermiogenesis through its role in promoting CUL3 neddylation

cell & other

REGULATION

induced by

phorbol 12-myristate 13-acetate (PMA)

inhibited by

salicylate

ASSOCIATED DISORDERS

corresponding disease(s)

PHA2E

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in colon carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS