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FLASH GENE

Symbol

FBXW11

contributors: mct - updated : 01-10-2019

HGNC name	F-box and WD-40 domain protein 11
HGNC id	13607

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	145.32 kb     14 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_033644 13 splicing 4536 NP_387448 60.7 529 not in spleen 2000 10694485 lacking exon 2 isoform b NM_033645 12 splicing 4473 NP_387449 58.2 508 ubiquitous, not in spleen 2000 10694485 lacking exon 2-3 isoform a NM_012300 13 splicing 4575 NP_036432 61.9 542 ubiquitous, not in spleen 2000 10694485 lacking exon 3 isoform c

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 stomach       highly Nervous brain       highly Homo sapiens Fetal Reproductive male system prostate     highly Visual eye         Homo sapiens Fetal

cell lineage
cell lines	primary gastric cancer cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text

lung

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a 40AA F-box motif
	seven WD40 repeats

HOMOLOGY

interspecies

homolog to murine Fbxw11(99.6pc)

intraspecies

homolog to BTRC

Homologene

FAMILY

F-box protein family, fbws class

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus
text	BTRC and FBXW11 localise to both nucleus and cytosol

basic FUNCTION	promoting ubiquitination and degradation of proteins by proteasome
	substrate recognition subunit of SCF ubiquitin protein ligase complex
	BTRC and FBXW11 were involved in the cell autonomous circadian rhythm generation in culture cells
	regulates various signal transduction pathways, and it may have pathological roles in tumorigenesis
	BTRC and FBXW11 regulates the transition from mitosis to meiosis in male germ cells by targeting DMRT1 for degradation
	F-box protein, part of the Skp1-cullin-F-box (SCF) ubiquitin ligase complex, involved in ubiquitination and proteasomal degradation and thus fundamental to many protein regulatory processes
	role of FBXW11 in multiple developmental processes, including those involving the brain, eye, digits, and jaw
	role for FBXW11 in the development of the eye, jaw, limbs, and brain

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

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

INTERACTION

DNA

RNA

small molecule

protein	CTNNB1, HIV-V-pu
	binds HIV1-Vpu and is able to induce CD4 down-modulation as efficiently as BTRC
	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
	FBXW11 bound, polyubiquitylated, and destabilized RAPGEF2, a guanine nucleotide exchange factor that activates the small GTPase TERF2IP
	CDKN2A was recognized by the F-box protein FBXW11 and degraded by the proteasome
	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
	involved in HH signaling by regulating the ubiquitination of GLI transcription factors

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

NDEDJ

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   aberrantly upregulated in patients with lymphocytic leukemia

Susceptibility

Variant & Polymorphism

Candidate gene	for holoprosencephaly-preaxial polydactyly syndrome associated with a unique case of dup5q35.1
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   may serve as a potential molecular target for the treatment of lymphocytic leukemia

ANIMAL & CELL MODELS

	over-expressed in chemically induced mouse skin tumors
	deletion of the genes for both beta-TrCP1 and beta-TrCP2 paralogs in germ cells of male mice resulted in accumulation of the transcription factor DMRT1 and spermatogenic failure