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FLASH GENE

Symbol

CUX1

contributors: mct/npt/pgu - updated : 06-02-2016

HGNC name	cut-like homeobox 1
HGNC id	2557

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	7q22.1      Physical location : 101.459.291 - 101.927.249
Synonym name	gp91-phox (CYBB) regulator
	cut homeobox
	Drosophila cut-like 1 homolog, homeo domain encoding gene
	cut-like 1, CCAAT displacement protein (Drosophila)
	CCAAT displacement protein
	golgi integral membrane protein 6
Synonym symbol(s)	CDP, CUX, EVI71, CASP, CUT1, P110CUX1, COY1, Nbla10317, CUTL1, CDP1, Clox, GOLIM6

DNA

TYPE	functioning gene
STRUCTURE	468.07 kb     24 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	at least three isoforms produced by alternative splicing

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_181552 24 splicing 5578 NP_853530 164.18 1505 - 1997 9332351 NM_001913 23 - 3039 NP_001904 77.4 678 - 2011 21037323 P110 an activator of FTO and RPGRIP1L NM_181500 23 splicing 3033 NP_852477 164.18 1505 - 1997 9332351 NM_001202543 24 - 13882 164.18 1505 - 2011 21037323 isoform p200 function exclusively as a transcriptional repressor NM_001202545 22 - 2901 72.03 632 - 1997 9332351 NM_001202544 22 - 2991 75.68 662 - 1997 9332351 NM_001202546 22 - 2818 72.84 639 - 1997 9332351

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 mouth       highly Lymphoid/Immune thymus       highly Nervous brain forebrain cerebral cortex     Homo sapiens   brain forebrain cerebral cortex   highly Homo sapiens Reproductive female system uterus cervix   highly Respiratory respiratory tract larynx     highly Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular exocrine

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte Homo sapiens Nervous pyramidal cell Homo sapiens

cell lineage	myeloid cells
cell lines
fluid/secretion

at STAGE

physiological period

embryo

Text	highly expressed in the nephrogenic zone of the developing kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminus containing the sequence FALNSLL that is similar to the Eh1 (Engrailed like homeodomain1 sequence) motif designated by the consensus sequence FXIXXIL
	three Drosophila cut DNA binding domains (CUX class) with PKPW motifs
	four potential DNA binding domains: three 60 amino acid repeats, termed cut repeats, and the homeodomain
	a consensus binding motif, ATCRAT
	a conserved GZMB cleavage site that could modify its intracellular localization and interaction with sorting nexin 27

secondary structure

helix-turn-helix

HOMOLOGY

interspecies	homolog to Drosophila cut-like 1
	homolog to murine Cutl1

Homologene

FAMILY	CUT homeobox family
	homeodomain family of DNA binding proteins

CATEGORY

regulatory , DNA associated , transcription factor , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	binding selectively to nuclear matrix/scaffold associated regions of DNA,i.e. MARbeta, upstream of the T cell receptor beta gene
	able, like CUX2, to perform the CCAAT-displacement activity
	proteolytic processing of CUX1 generates p110 isoform that accelerates entry into S phase, inducing replication genes during cell cycle progression
	transcription factor implicated primarily in the control of cell-autonomous functions, such as cell cycle progression and mobility
	important mediator of cell migration and tumor invasion downstream of transforming growth factor beta (TGFbeta)
	stimulate cell proliferation by accelerating entry into S phase and cooperate with E2F1 in the regulation of many cell cycle genes
	with CUX2, have redundant roles in specifying Reelin expressing cortical interneurons
	with E2F1 regulate coordinated expression of the mitotic complex genes ECT2, RACGAP1, and MKLP1 in S phase
	plays a role in at least two distinct processes with relevance to cancer: cell cycle progression and cell motility
	important modulator of invasion and resistance to apoptosis
	causes chromosomal instability by activating a transcriptional program that prevents multipolar divisions and enables the survival of tetraploid cells that evolve to become genetically unstable and tumorigenic
	contributes to the establishment of a transcriptional program that enables tetraploid cells to undergo bipolar mitosis in the presence of multiple centrosomes
	acts as a negative regulator of TGFB and potent inhibitor of type I collagen transcription
	CUX1 and NFIB contribute to autism spectrum disorder susceptibility
	as a conserved, haploinsufficient tumor suppressor frequently deleted in myeloid neoplasms
	not only was able to regulate the next adjacent gene, but also regulated the gene located beyond this one as well as the gene located further away in the opposite direction
	is an adaptor molecule uniquely expressed in lymphocytes that forms complexes with both vesicle-initiating and sorting proteins, and has roles in NK cell migration, cytotoxicity, and cytokine secretion
	CUX1 is required for intestinal epithelial wound healing and targets the VAV2-RAC1 signalling complex

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

part of a complex bound to the CDKN1B promoter in the native chromatin configuration in the developing kidney

INTERACTION

DNA

RNA

small molecule

protein	CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes ECT2, RACGAP1, and KIF23 in S phase
	directly interacts with the co-repressor TLE4 (Groucho 4), a known effector of Notch signaling (interacting partner for CUX1, involved in repression of CDKN1B during kidney development)
	GRIA3 could be confirmed as a downstream effector of CUX1 and was expressed in pancreatic cancer tissues
	ZBTB16 is a transcriptional target for the CUX1 repressor (the novel genetic relationship between CUX1 and PLZF could be of relevance to human diseases, such as leukemia)
	FTO and RPGRIP1L are regulated by isoforms P200 and P110 of the transcription factor, CUX1
	may bind to a single enhancer that regulates the expression of both FTO and RPGRIP1L
	downregulates several NFKB-regulated chemokines such as CXCL10
	interacts with NFKB RELA, leading to reduced binding of NFKB RELA to the chemokine promoters
	guanine nucleotide exchange factor VAV2 gene is a direct target for CUX1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in uterine leiomyoma tumoral     --over   in various human tumors and associated with poor prognosis tumoral     --over   is inversely correlates with patient survival in breast cancers tumoral       loss of function in drug-resistant gastric cancer cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive stomach is an attractive therapeutic target to modulate multidrug resistance in gastric cancer

ANIMAL & CELL MODELS