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FLASH GENE

Symbol

BTRC

contributors: mct - updated : 24-04-2018

HGNC name	beta-transducin repeat containing
HGNC id	1144

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	10q24.32      Physical location : 103.113.824 - 103.317.068
Genatlas name	F-box and WD40 domain protein 1A
Synonym name	F-box protein W1A
	supernumerary limbs homolog
Synonym symbol(s)	FWD1, FBW1A, BTRCP1, FBXW1A, BETATRCP, TRCP1, SLIMB, FWD-40, Scf

DNA

TYPE	functioning gene
STRUCTURE	203.51 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

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_033637 15 splicing 6146 NP_378663 68.9 605 - 2011 21138764 NM_003939 14 splicing 6013 NP_003930 64.8 569 - 2011 21138764 lacking 108nt in the coding region compared to variant 1 36AA shorter isoform NM_001256856 - - 6102 NP_001243785 - 579 - 2011 21138764

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 Cardiovascular heart       highly Digestive intestine small intestine       Urinary kidney       highly

tissue

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

cell lineage
cell lines	gastric cancer cell lines
fluid/secretion

at STAGE

physiological period

embryo

cell cycle

cell cycle, checkpoint, G1S

Text

widely

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	F-box near the N terminus
	seven WD-40 repeats (beta transducin repeats) at the C terminus

conjugated

FlavoP

HOMOLOGY

interspecies	homolog to Xenopus btrcp1
	homolog to yeast S.cerevisiae met30
	homolog to Drosophila slimb
	homolog to murine Btrc
	homolog to Xenopus bTrCP1

intraspecies

homolog to FBXW11

Homologene

FAMILY

F-box protein family,FBWS class/beta catenin ubiquitin ligase complex

CATEGORY

adaptor , receptor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	interacting with HIV1 Vpu to trigger the destruction of CD4 in the endoplasmic reticulum
	functioning in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway,specific determinant for the signal-induced ubiquitination of I kappa B (NFKBIA)
	ubiquitin conjugating enzyme and substrate recognition subunit of SCF ubiquitin protein ligase complex
	specificity determinant for the signal-induced ubiquitanation of CHUK (IkappaB kinase-alpha)
	HIV-1 Vpu protein interacts with CD4 within the endoplasmic reticula of infected cells and targets CD4 for degradation through interaction with BTRC
	dispensable for the central clock in the suprachiasmatic nucleus
	BTRC and FBXW11 were involved in the cell autonomous circadian rhythm generation in culture cells
	potential role in regulating the eventual ratio of resulting differentiated retinal cell types
	E3 ligase that targets various substrates essential for many aspects of tumorigenesis
	may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer
	is required for internalisation of the growth hormone receptor (GHR) and acts via a direct interaction with the ubiquitin-dependent endocytosis motif
	controls GH receptor degradation via two different motifs, the UbE motif in the cytoplasmic tail of the GHR and a downstream degron, DSGRTS
	directs the conjugation of ubiquitin to a variety of substrate proteins, leading to the destruction of the substrate by the proteasome
	BTRC, FBXW7, FBXL14, FBXO45, FBXL5, FBXO11 play in controlling EMT during development and cancer progression, a process dependent on post-translational modifications that govern their interaction with target proteins
	BTRC and FBXW11 regulates the transition from mitosis to meiosis in male germ cells by targeting DMRT1 for degradation

CELLULAR PROCESS	protein, degradation
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

text	ubiquitin-dependent protein degradation

PATHWAY

metabolism

signaling

signal transduction

NFKB, WNT and hedgehog signaling pathway

a component

one of the four subunits of the E3 ubiquitin protein ligase complex:(SCF) with SKP1/CDC53,CUL1,RBX1,F-box protein (BTRC) bringing ubiquitin conjugating enzymes to substrates recruited by F-box

INTERACTION

DNA

RNA

small molecule

protein	HIV1Vpu (NFKBIA)
	phosphorylated I kappa B alpha
	pro-caspase-3 appears to be a substrate of SAG/ROC-SCF(BTRC) E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3
	both BTRC and FBXW11 bind specifically to USP47, and point mutations in the TRCP WD-repeat region completely abolished USP47 binding, indicating an E3-substrate-type interaction
	wild-type BMI1 but not the mutant BMI1 interacts with BTRC
	interacting with PHLPP1 (cellular localization of BTRC is altered in glioblastoma, resulting in dysregulation of PHLPP1 and other substrates such as beta-catenin)
	in the nucleus, BTRC promotes the degradation of NRF1 by catalyzing its polyubiquitination
	both BTRC- and SYVN1-dependent degradation mechanisms regulate the transcriptional activity of NRF1 to maintain cellular homeostasis
	BTRC regulates cell growth and autophagy by controlling the ubiquitination and destruction of DEPTOR, an endogenous mammalian target of rapamycin inhibitor, in a phosphorylation-dependent manner
	E3 ligase subunit BTRC interacts with CTTN, and its overexpression reduced cortactin protein levels, an effect attenuated by MAPK1 inhibition
	BTRC is a novel TERF1-associating protein
	interacts directly via its WD40 domain with the UbE (ubiquitin-dependent endocytosis) motif in GHR, promoting GHR ubiquitination
	BTRC-mediated regulation of OIP5 stability is a mechanism to restrict centromere function of OIP5 complex from late mitosis to early G1 phase
	during the G2 phase of the cell division cycle, TFAP4 is targeted for proteasome-dependent degradation by the BTRC ubiquitin ligase
	BHLHE40 is a highly unstable protein that is targeted for proteasome-dependent degradation by the BTRC ubiquitin ligase in cooperation with CSNK1A1
	TRIB2 associated-BTRC, RFWD2 and SMURF1 reduced TCF4/CTNNB1 expression, and these effects could be enhanced by TRIB2
	PPP1R15B is a BTRC substrate, and a Protein Phosphatase 1 (PP1) specificity subunit that targets the translation initiation factor EIF2S1 to promote the removal of a stress-induced inhibitory phosphorylation and increase cap-dependent translation
	BTRC-mediated ubiquitination and degradation of liver-enriched transcription factor CREB3L3
	BTRC interacted with USP33 independently of the classic binding motif for BTRC, and mediated USP33 degradation via the ubiquitin proteasome pathway
	BTRC and FBXW11 is capable of suppressing oxidative stress-induced CASP3-dependent apoptosis through suppression of MAP3K5, assisting in the organism's ability to maintain homeostasis in an unstable environment
	TIAM1 regulates PLK4 levels through promoting BTRC-mediated degradation independently of RAC1 activation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function of BTRC results in accumulation of MDM2 and decreased TP53 activity, and resistance to apoptosis induced by DNA damaging agents tumoral     --low   suppresses prostate cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate combining BTRC inhibition with androgen ablation could benefit advanced prostate cancer patients

ANIMAL & CELL MODELS