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    ZEB2 zinc finger E-box binding homeobox 2 [ Homo sapiens (human) ]

    Gene ID: 9839, updated on 16-Jun-2013
    Official Symbol
    ZEB2provided by HGNC
    Official Full Name
    zinc finger E-box binding homeobox 2provided by HGNC
    Primary source
    HGNC:14881
    Locus tag
    HRIHFB2411
    See related
    HPRD:05780; MIM:605802
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SIP1; SIP-1; ZFHX1B; HSPC082; SMADIP1
    Summary
    The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]
    Location :
    2q22.3
    Sequence :
    Chromosome: 2; NC_000002.11 (145141942..145277958, complement)
    See ZEB2 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene Rho GTPase activating protein 15 Neighboring gene glycosyltransferase-like domain containing 1 Neighboring gene putative uncharacterized protein encoded by LINC00269-like Neighboring gene ZEB2 antisense RNA 1 Neighboring gene testis expressed 41 (non-protein coding) Neighboring gene sarcoglycan, epsilon, pseudogene Neighboring gene uncharacterized LOC100505498

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Expression of the ZEB2 gene in pancreatic stromal cells in pancreatic ductal adenocarcinoma, pancreatitis, and normal state. Usova EV, et al. Dokl Biol Sci, 2013 Jan-Feb. PMID 23479023.
    2. A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene. Meral C, et al. Turk J Pediatr, 2012 Sep-Oct. PMID 23427518.
    3. Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression. Koopmansch B, et al. Biochem Biophys Res Commun, 2013 Feb 22. PMID 23376074.
    4. BMP and TGF-β pathway mediators are critical upstream regulators of Wnt signaling during midbrain dopamine differentiation in human pluripotent stem cells. Cai J, et al. Dev Biol, 2013 Apr 1. PMID 23352789.
    5. Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons. McKinsey GL, et al. Neuron, 2013 Jan 9. PMID 23312518.

    See all (109) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Expression of the ZEB2 gene in pancreatic stromal cells in pancreatic ductal adenocarcinoma, pancreatitis, and normal state.
      Title: Expression of the ZEB2 gene in pancreatic stromal cells in pancreatic ductal adenocarcinoma, pancreatitis, and normal state.
    2. Increased SIP1 expression is associated with peritoneal carcinomatosis in intestinal type gastric cancer.
      Title: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer.
    3. Generalized epilepsies implicates susceptibility genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32.
      Title: Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32.
    4. levels of ZEB2 expression were low in local lesions but high in metastatic lymph nodes in HNC tissues. Patients with tumors that co-expressed ZEB1(high) and ZEB2(high) had especially poor survival rates.
      Title: Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer.
    5. these results suggest that E-cadherin expression in cancer cells is controlled by a balance between ZEB2 and KLF4 expression levels.
      Title: Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression.
    6. miR-145 inhibits EMT by blocking the expression of Oct4, and downstream transcriptional factors, Snail, ZEB1 and ZEB2
      Title: MiR-145 regulates epithelial to mesenchymal transition of breast cancer cells by targeting Oct4.
    7. The up-regulation in SMAD-interacting protein 1 (SIP1) results in greater repression of the Wnt antagonist, secreted frizzled related protein 1 (Sfrp1) in stem cells.
      Title: BMP and TGF-β pathway mediators are critical upstream regulators of Wnt signaling during midbrain dopamine differentiation in human pluripotent stem cells.
    8. The investigation identified a heterozygous complex rearrangement in exon 8 of ZEB2, specifically a 48-nucleotide deletion and a 44-nucleotide insertion that caused a frameshift.
      Title: A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene.
    9. Overexpression of ZEB2 is associated with glioma.
      Title: ZEB2 mediates multiple pathways regulating cell proliferation, migration, invasion, and apoptosis in glioma.
    10. Zfhx1b zinc finger homeobox gene is required to generate cortical interneurons in the medial ganglionic eminence.
      Title: Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons.
    Submit: New GeneRIF Correction See all (74)

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Mowat-Wilson syndrome

    Summary from GeneReviews: Mowat-Wilson Syndrome Go to GeneReviews

    Disease Characteristics
    Mowat-Wilson syndrome (MWS) is characterized by distinctive facial features; structural anomalies including Hirschsprung disease, genitourinary anomalies (particularly hypospadias in males), congenital heart defects (abnormalities of the pulmonary arteries and/or valves), agenesis or hypogenesis of the corpus callosum, and eye defects (microphthalmia and Axenfeld anomaly); and functional differences including moderate to severe intellectual disability, severe speech impairment with relative preservation of receptive language, seizures, growth retardation with microcephaly, and chronic constipation in those without Hirschsprung disease.
    Diagnosis Testing
    Mutations and deletions in ZEB2 (also known as ZFHX1B or SIP-1) cause MWS. Sequence analysis detects mutations in approximately 81% of individuals; FISH detects large deletions encompassing all or part of ZEB2 in approximately 15% of persons; chromosomal rearrangements that disrupt ZEB2 cause MWS in approximately 2% of individuals; and an additional 2% have intermediate-sized deletions that can be detected by techniques such as quantitative PCR, MLPA or gene-specific array GH.
    Genetic Counseling
    Mowat-Wilson syndrome is typically the result of a de novo dominant mutation. When MWS results from a de novo mutation, the risk to the sibs of a proband is small. No individuals with MWS have been known to reproduce. Although the vast majority of MWS occurs as the result of a de novo mutation, molecular genetic testing can be used to evaluate a pregnancy at theoretically increased risk because of constitutional and/or germline mosaicism for a ZEB2 mutation in a clinically unaffected parent. Parents of an individual with MWS resulting from a structural unbalanced chromosome constitution (e.g., deletion, duplication) are at risk of having a balanced chromosome rearrangement. The risk to sibs of a proband with a structural unbalanced chromosome abnormality depends upon the chromosome findings in the parents. Prenatal diagnosis for pregnancies at increased risk because of parental balanced structural rearrangement is possible by chromosome analysis of fetal cells obtained by amniocentesis or chorionic villus sampling.
    References
    Products Interactant Other Gene Complex Source Pubs Description
    O60315 Q7L5N1 COPS6    HPRD  PubMed  
    O60315 Q13363 CTBP1    HPRD  PubMed  
    O60315 P56545 CTBP2    HPRD  PubMed  
    O60315 Q15797 SMAD1    HPRD  PubMed  
    O60315 Q15796 SMAD2    HPRD  PubMed  
    O60315 P84022 SMAD3    HPRD  PubMed  
    O60315 Q99717 SMAD5    HPRD  PubMed  
    O60315 O15198 SMAD9    HPRD  PubMed  
    BioGRID:115175 BioGRID:106848 APP    BioGRID  PubMed Reconstituted Complex 
    BioGRID:115175 BioGRID:114105 CBX4    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:115175 BioGRID:107479 CEBPA    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115175 BioGRID:116176 COPS6    BioGRID  PubMed Two-hybrid 
    BioGRID:115175 BioGRID:107869 CTBP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:108309 ELAVL1    BioGRID  PubMed Affinity Capture-RNA 
    BioGRID:115175 BioGRID:109315 HDAC1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:109316 HDAC2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:115106 HDAC4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:114562 MTA1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:114652 MTA2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:111863 RBBP4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:111866 RBBP7    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:110261 SMAD1    BioGRID  PubMed Two-hybrid 
    BioGRID:115175 BioGRID:110262 SMAD2    BioGRID  PubMed Two-hybrid 
    BioGRID:115175 BioGRID:110263 SMAD3    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:115175 BioGRID:110268 SMAD9    BioGRID  PubMed Two-hybrid 
    BioGRID:115175 BioGRID:113188 SUMO1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115175 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115175 BioGRID:113177 UBE2I    BioGRID  PubMed Biochemical Activity 
    • TGF Beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TGF Beta Signaling Pathway, organism-specific biosystemThe Transforming growth factor beta (TGFβ) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiat...
    • TGF-beta Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TGF-beta Receptor Signaling Pathway, organism-specific biosystem"The TGF beta receptors TGFBR1 and TGFBR2 belong to a subfamily of membrane-bound serine/threonine kinases which are designated as Type I or II based on their structural and functional properties. Th...

    Markers

    Genotypes

    Homology

    Clone Names

    • FLJ42816, KIAA0569

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    SMAD binding NAS
    Non-traceable Author Statement
    more info
    		  
    phosphatase regulator activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    sequence-specific DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    sequence-specific DNA binding transcription factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    cell proliferation in forebrain IEA
    Inferred from Electronic Annotation
    more info
    		  
    hippocampus development IEA
    Inferred from Electronic Annotation
    more info
    		  
    nervous system development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    neural crest cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    neural tube closure IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of JUN kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of Wnt receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    somitogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    transcription, DNA-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    nucleus IDA
    Inferred from Direct Assay
    more info
    		  
    Preferred Names
    zinc finger E-box-binding homeobox 2
    Names
    zinc finger E-box-binding homeobox 2
    zinc finger homeobox 1b
    SMAD interacting protein 1
    Smad-interacting protein 1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016431.1 RefSeqGene

      Range
      5001..141017
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001171653.1 → NP_001165124.1  zinc finger E-box-binding homeobox 2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is missing an in-frame coding exon compared to variant 1, resulting in a shorter isoform (2) lacking an internal protein segment compared to isoform 1.
      Source sequence(s)
      AB056507, AC010130, AI341193, AK294928, BP218652, DA305985
      Consensus CDS
      CCDS54403.1
      UniProtKB/Swiss-Prot
      O60315
      Conserved Domains (3) summary
      cd00086
      Location:629 – 672
      Blast Score: 91
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
      pfam13465
      Location:272 – 295
      Blast Score: 105
      zf-H2C2_2; Zinc-finger double domain
      cl15478
      Location:259 – 280
      Blast Score: 86
      zf-C2H2; Zinc finger, C2H2 type

    2. NM_014795.3 → NP_055610.1  zinc finger E-box-binding homeobox 2 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AB056507, AC010130, AI341193, BP218652, DA305985
      Consensus CDS
      CCDS2186.1
      UniProtKB/Swiss-Prot
      O60315
      Conserved Domains (3) summary
      cd00086
      Location:653 – 696
      Blast Score: 91
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
      pfam13465
      Location:296 – 319
      Blast Score: 105
      zf-H2C2_2; Zinc-finger double domain
      cl15478
      Location:283 – 304
      Blast Score: 87
      zf-C2H2; Zinc finger, C2H2 type

    RNA

    1. NR_033258.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is missing many exons from the 3' end and contains an alternate 3' terminal exon compared to variant 1. It is represented as non-coding because it has transcript support but lacks a large portion of the coding region.
      Source sequence(s)
      BC025696, BC025730, BP218652, BU688017

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p10 Primary Assembly

      Range
      145141942..145277958, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      137133063..137270287, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018913.1 Alternate CHM1_1.0

      Range
      144641615..144777487, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01028051.1 (8281..78909) None
    genomic ABBA01028052.1 None
    genomic ABBA01028053.1 None
    genomic AC009951.10 AAX93269.1
    genomic AC010130.12 AAX93276.1
    genomic AMYH01011150.1 (51803..187675) None
    genomic AY029472.1 AAK52081.1
    genomic CH471058.2 EAX11575.1
      EAX11576.1
      EAX11577.1
    mRNA AB011141.1 BAA25495.2
    mRNA AB015341.1 BAA34798.1
    mRNA AB056507.1 BAB40819.1
    mRNA AB193095.1 BAD60927.1
    mRNA AB193096.1 BAD60928.1
    mRNA AF085983.1 None
    mRNA AF161345.1 AAF28905.1
    mRNA AI341193.1 None
    mRNA AI858477.1 None
    mRNA AK124806.1 None
    mRNA AK294928.1 BAH11928.1
    mRNA AK308124.1 None
    mRNA AK308445.1 None
    mRNA AL118674.1 None
    mRNA BC025696.1 None
    mRNA BC025730.1 None
    mRNA BC035706.1 None
    mRNA BC037975.1 None
    mRNA BC060819.1 None
    mRNA BC127101.1 AAI27102.1
    mRNA BC127102.1 AAI27103.1
    mRNA BP218652.1 None
    mRNA BU688017.1 None
    mRNA DA305985.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60315.1 GenPept UniProtKB/Swiss-Prot:O60315

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

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        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
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      • EST
        Link to related EST entry
      • Full text in PMC
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        Full text in PubMedCentral identified from shared sequence links
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        Related GEO
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        GTR associated with a gene
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        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • RefSeqGene
        Link to Nucleotide RefSeqGenes
      • SNP
        Related SNP records
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        SNPs linked from GeneView
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        Gene Genotype Report
      • SNP: VarView
        Related Clinical SNP
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

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