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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
Corresponding disease
DTPC2 primary cervical dystonia 2
Location 9q34.11      Physical location : 130.928.344 - 130.966.662
Genatlas name CIP1 (CDKN1A) interacting zinc finger protein 1
Synonym name
  • CIP1-interacting zinc finger protein
  • nuclear protein NP94
  • zinc finger protein 356
  • Synonym symbol(s) LSFR1, NP94, ZNF356
    DNA
    TYPE functioning gene
    STRUCTURE 38.32 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    AK1 9q34.12 adenylate kinase 1 ST6GALNAC6 9q34.13 adenylate kinase 1 SIAT7D 9q34.1 sialyltransferase 7D ((alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3)-N-acetyl galactosaminide alpha-2,6-sialyltransferase) MGC46424 9q34.13 hypothetical protein MGC46424 LOC389790 9 similar to phosphatidylinositol phosphate kinase-like protein DPM2 9q34.13 dolichyl-phosphate mannosyltransferase polypeptide 2, regulatory subunit FLJ10232 9q34.13 hypothetical protein FLJ10232 DKFZp762G199 9q34.13 hypothetical protein DKFZp762G199 MCSC 9q34.13 mitochondrial Ca2+-dependent solute carrier PTGES2 9q34.13 prostaglandin E synthase 2 LOC389791 9 hypothetical gene supported by AK094537 LCN2 9q34 lipocalin 2 (oncogene 24p3) C9orf16 9q34.1 chromosome 9 open reading frame 16 CIZ1 9q34.13 chromosome 9 open reading frame 16 DNM1 9q34 dynamin 1 GOLGA2 9q34.13 golgi autoantigen, golgin subfamily a, 2 LOC375757 9q34.13 hypothetical protein LOC375757 FLJ21673 9q34.13 hypothetical protein FLJ21673 CLONE24922 COQ4 9q34.13 coenzyme Q4 homolog (yeast) TMSL4 9 thymosin-like 4 SLC27A4 9q34.13 solute carrier family 27 (fatty acid transporter), member 4 C9orf74 9q34.13 chromosome 9 open reading frame 74 CEECAM1 9q34.13 cerebral endothelial cell adhesion molecule 1 LOC392394 9 similar to hypothetical protein ODF2 9q34 outer dense fiber of sperm tails 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 splicing 3032 100 898 - 2007 17508423
    18 splicing 2888 - 842 - 2007 17508423
    - 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
  • 18 - 3186 - 954 - 2007 17508423
    16 - 2900 - 797 - 2007 17508423
    17 - 2776 - 818 - 2007 17508423
    18 - 2833 - 837 - 2007 17508423
    17 - 3016 - 898 - 2007 17508423
    - - - - - . 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
  • - - - - - - 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
    - 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)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systemuteruscervix 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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DTPC2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    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