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FLASH GENE

Symbol

CIZ1

contributors: mct - updated : 05-03-2019

HGNC name	CDKN1A interacting zinc finger protein 1
HGNC id	16744

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_012127 17 splicing 3032 NP_036259 100 898 - 2007 17508423 NM_001131015 18 splicing 2888 NP_001124487 - 842 - 2007 17508423 CIZ1 delta E4 - splicing - - - misexpressed as a consequence of intronic mutation in Ewing tumor (ET) cell lines 2007 17508423 lacking exon 4 influences the spatial distribution of the protein within the nucleus, and raise the possibility that CIZ1 alternative splicing could influence organized patterns of DNA replication and contributes to the development of cancer cells lineages NM_001257975 18 - 3186 NP_001244904 - 954 - 2007 17508423 NM_001257976 16 - 2900 NP_001244905 - 797 - 2007 17508423 NM_001131018 17 - 2776 NP_001124490 - 818 - 2007 17508423 NM_001131017 18 - 2833 NP_001124489 - 837 - 2007 17508423 NM_001131016 17 - 3016 NP_001124488 - 898 - 2007 17508423 CIZ1 delta 8-12 - - - - - . is over-expressed in common solid tumors including colon and breast, pronounced in early stage but not highly-proliferative late stage tumors . expressed in proliferating cells in an unusual cell cycle-dependent manner 2018 30280956 CIZ1-F restricted to cancer cells, and may therefore be a useful novel biomarker is sensitive to RNase identifying it as part of the RNA-fraction of the nuclear matrix (NM) may have potential as a tumor biomarker CIZ1ex8 - - - - - - 2008 18583151 lacking a glutamine-rich region, due to alternative splicing in exon 8, is upregulated in Alzheimer brains relative to the full-length CIZ1 protein b-variant CIZ1 - splicing - - - detected in plasma from patients with small cell lung cancers (SCLC) and non-SCLC patients 2012 23074256 alternative-splicing event at the exon 14/15 junction

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 salivary gland       highly Nervous brain         Homo sapiens Reproductive female system uterus cervix   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	polyglutamine repeats and glutamine-rich region in the N terminus, and N-terminal replication domain
	three zinc finger motifs and one MH3 (matrin 3 homologous domain 3) in the C terminal region, with C-terminal nuclear matrix anchor , and this nuclear matrix anchor domain is responsible for its interaction with YAP1

HOMOLOGY

interspecies

homolog to Fugu rubripes 1,linked to surfeit gene

Homologene

FAMILY

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	regulating the subcellular localization of CIP/WAP1
	functions to promote DNA replication after replication complex formation, suggesting that CIZ1 splicing contributes to the regulation of DNA replication during development
	stimulates initiation of mammalian DNA replication and is normally tethered to the nuclear matrix within DNA replication foci
	participates in the regulation of the cell cycle in estrogen-stimulated breast cancer cells
	DNA-binding factor, coregulating ESR1 by enhancing ESR1 transactivation activity by promoting the recruitment of the ESR1 complex to the target gene chromatin
	stimulates DNA replication and is required for mammalian cells to enter S phase
	CIZ1 functions as a tumor suppressor
	CIZ1 may be involved in colon cancer progression by regulating cell proliferation, cell cycle, apoptosis and colony formation
	numerous biological functions of CIZ1 in DNA replication, cell proliferation, and differentiation
	is a positive regulator of YAP1 signaling
	CIZ1 may be involved in the post-mitotic differentiation of neurons in response to external signals
	may contribute to oncogenesis by induction of DNA replication stress and CIZ1 may be a multifaceted target in cancer therapy
	promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers
	plays a critical role in DNA replication and cell-cycle progression at the G1/S checkpoint
	promotes cyclin-dependent DNA replication and resides in sub-nuclear foci that are part of the protein nuclear matrix (NM), and in RNA assemblies that are enriched at the inactive X chromosome (Xi) in female cells
	possible positive role of CIZ1 in endothelial cell proliferation and migration

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	cell cycle control

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	zinc Zn2+

protein	CIP1 (CDKN1A) interacting
	estrogen-responsive gene
	interactor of ERH, is also a nuclear zinc finger protein interacting with CDKN1A, a universal inhibitor of cyclin-dependent kinases, and is a DNA replication factor (interaction with ERH could block the binding of CDKN1A by CIZ1 in the cell)
	nuclear matrix protein that cooperates with cyclin A2 (encoded by CCNA2) and CDK2 to promote mammalian DNA replication
	CIZ1 enhanced the interaction between YAP1 and TEAD1
	has likely an essential role in anchoring XIST to the nuclear matrix in specific somatic lineages
	DHX9 shares common functions with CIZ1, including interaction with XIST long-non-coding RNA, epigenetic maintenance and regulation of DNA replication
	DHX9-CIZ1 are required for efficient cell cycle progression at the G1/S transition and that nucleolar recruitment is integral to their mechanism of action

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DTPC2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         aberrantly expressed in Ewing sarcoma constitutional     --over   more highly expressed in Alzheimer tissue than in healthy brains constitutional     --over   in hemangioma of the tongue while its expression is minimal in the normal tongue tissues

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	variant CIZ1 is a strong candidate for a cancer-specific single marker capable of identifying early-stage lung cancer within at-risk groups without resort to invasive procedures
	overexpression of CIZ1 may contribute to the growth and angiogenesis of lung squamous cell carcinoma (LSCC), thus CIZ1 could represent a biomarker for diagnosis and a target for therapeutic intervention
Therapy target
	System Type Disorder Pubmed cancer digestive liver CIZ1 might be a therapeutic target for HCC

ANIMAL & CELL MODELS

	germline knockout of Ciz1 is associated with motor and hematological abnormalities in young adult mice
	Ciz1(-/-) mice did not manifest dystonia, but exhibited mild motoric abnormalities on balance, open-field activity, and gait