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FLASH GENE

Symbol

CXXC5

contributors: shn/mct - updated : 03-03-2020

HGNC name	CXXC finger 5
HGNC id	26943

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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         Digestive mouth tongue (see gustatory)       Lymphoid/Immune thymus         Nervous brain         Reproductive female system ovary       Urinary kidney

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	in the developing kidney, Wid and Wt1 are coexpressed in podocytes of maturing nephrons.

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

C-terminal CXXC zinc finger and Dishevelled binding domains (Kim 2010)

HOMOLOGY

interspecies	homolog to CXXC4, Homo sapiens
	ortholog to Cxxc5, Mus musculus
	ortholog to Cxxc5, rattus norvegicus
	ortholog to CXXC5, Pan troglodytes

Homologene

FAMILY

CXXC-type zinc-finger protein family

CATEGORY

DNA associated , receptor nuclear

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	may participate in activation of the NF- kappa-B and MAPK pathways
	is a BMP4-regulated modulator of Wnt signaling essential for proper response of telencephalic stem cells to canonical Wnt3a signaling
	a possible functional role for CXXC5 in forebrain development
	having regulatory function in both normal and tumoral myelopoiesis (Pendino 2009)
	physiological function of CXXC5 in nephrogenesis might be conserved in mammals (Kim 2010)
	plays a crucial role in ATM-p53 signaling in response to DNA damage (Kim 2010)
	is a negative regulator of the Wnt/CTNNB1 pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled
	may act as a tumor suppressor by promoting TGFbeta signaling via a positive feedback loop
	function of CXXC5 in hepatocellular carcinoma development
	CXXC5 plays an important role in embryonic development and adult tissue homeostasis by regulating cell proliferation, differentiation and apoptosis
	important role for CXXC5 as a suppressor of longitudinal bone growth involving growth plate activity
	is a regulator of the pluripotency network genes and TET enzymes in ESCs
	CXXC-type zinc finger epigenetic regulator, playing
	a role in monocyte development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

a component

CXXC5 forms a complex with NANOG, POU5F1, TET1, and TET2 and facilitates their proper recruitment to regulatory regions of pluripotency and TET genes in ESCs to positively regulate their transcription

INTERACTION

DNA	DNA binding

RNA

small molecule

protein	Axin2 and Wnt3a
	physically interacts with ATM and is required for DNA damage-induced ATM phosphorylation but not its recruitment to chromatin (Kim 2010)
	interacts with Dishevelled via its C-terminal CXXC zinc finger and Dishevelled binding domains and potently inhibits WNT/beta-catenin signaling (Kim 2010)
	NUDT21 inhibits hepatocellular carcinoma proliferation, metastasis and tumorigenesis, at least in part, by suppressing PSMB2 and CXXC5
	is able to bind to DNA and act as a transcription factor and epigenetic factor through protein-protein interactions
	CXXC5 binds to the chromatin and is enriched at promoters and enhancers of TET1, TET2, and pluripotency genes

cell & other

REGULATION

activated by	BONE MORPHOGENETIC PROTEIN 4; BMP4
	WT1 (activates CXXC5 transcription through the upstream enhancer region) (Kim 2010)

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed dermatology hair   CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss dermatology skin   potential target for future therapies aimed at improving wound healing

ANIMAL & CELL MODELS

Cxxc5(-/-) mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis