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ONECUT2 Gene

protein-coding   GIFtS: 49
GCID: GC18P055102

One Cut Homeobox 2

(Previous names: one cut domain, family member 2)
  See ONECUT2-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
One Cut Homeobox 21 2 3     OC22 5
One Cut Domain, Family Member 21 2     One Cut Domain Family Member 22
Hepatocyte Nuclear Factor 6-Beta2 3     Onecut 22
Transcription Factor ONECUT-22 3     ONECUT-2 Homeodomain Transcription Factor2
HNF-6-beta2 3     HNF6B3
OC-22 3     

External Ids:    HGNC: 81391   Entrez Gene: 94802   Ensembl: ENSG000001195477   OMIM: 6048945   UniProtKB: O959483   

Export aliases for ONECUT2 gene to outside databases

Previous GC identifers: GC18P055133 GC18P054887 GC18P053251 GC18P053253 GC18P051813


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ONECUT2 Gene:
This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain
and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target
genes, including genes involved in melanocyte and hepatocyte differentiation. (provided by RefSeq, Jul 2008)

GeneCards Summary for ONECUT2 Gene:
ONECUT2 (one cut homeobox 2) is a protein-coding gene. Diseases associated with ONECUT2 include hemophilia b. GO annotations related to this gene include sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is CUX2.

UniProtKB/Swiss-Prot: ONEC2_HUMAN, O95948
Function: Transcriptional activator. Activates the transcription of a number of liver genes such as HNF3B




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000018.9  NC_018929.2  NT_010966.15  
Regulatory elements:
   Regulatory transcription factor binding sites in the ONECUT2 gene promoter:
         GR   Elk-1   CUTL1   Cdc5   GATA-1   FOXL1   AREB6   MEF-2A   GR-alpha   aMEF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidONECUT2 promoter sequence
   Search Chromatin IP Primers for ONECUT2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ONECUT2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 18q21.31   Ensembl cytogenetic band:  18q21.31   HGNC cytogenetic band: 18q21.31

ONECUT2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ONECUT2 gene location

GeneLoc information about chromosome 18         GeneLoc Exon Structure

GeneLoc location for GC18P055102:  view genomic region     (about GC identifiers)

Start:
55,102,917 bp from pter      End:
55,158,530 bp from pter
Size:
55,614 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ONEC2_HUMAN, O95948 (See protein sequence)
Recommended Name: One cut domain family member 2  
Size: 504 amino acids; 54303 Da
Caution: It is uncertain whether Met-1 or Met-20 is the initiator
Sequence caution: Sequence=CAB38253.1; Type=Frameshift; Positions=18;

Explore the universe of human proteins at neXtProt for ONECUT2: NX_O95948

Explore proteomics data for ONECUT2 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See ONECUT2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004843.2  
    ENSEMBL proteins: 
     ENSP00000419185   ENSP00000419741  

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    Browse Sino Biological Cell Lysates
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    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for ONECUT2 

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CUT: Homeoboxes / CUT class

    4 InterPro protein domains:
     IPR010982 Lambda_DNA-bd_dom
     IPR003350 Hmoeo_CUT
     IPR001356 Homeobox_dom
     IPR009057 Homeodomain-like

    Graphical View of Domain Structure for InterPro Entry O95948

    ProtoNet protein and cluster: O95948

    1 Blocks protein domain: IPB003350 Homeodomain protein CUT

    UniProtKB/Swiss-Prot: ONEC2_HUMAN, O95948
    Similarity: Belongs to the CUT homeobox family
    Similarity: Contains 1 CUT DNA-binding domain
    Similarity: Contains 1 homeobox DNA-binding domain


    Find genes that share domains with ONECUT2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ONEC2_HUMAN, O95948
    Function: Transcriptional activator. Activates the transcription of a number of liver genes such as HNF3B

         Genatlas biochemistry entry for ONECUT2:
    one cut domain, family member 2

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity IEA--
    GO:0043565sequence-specific DNA binding IEA--
         
    Find genes that share ontologies with ONECUT2           About GenesLikeMe


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 1 allele(MGI details for Onecut2):
     endocrine/exocrine gland  liver/biliary system 

    Find genes that share phenotypes with ONECUT2           About GenesLikeMe

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ONECUT2
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    miRTarBase miRNAs that target ONECUT2:
    hsa-mir-16-5p (MIRT031575), hsa-let-7d-5p (MIRT032175), hsa-mir-9-5p (MIRT005390)

    Block miRNA regulation of human, mouse, rat ONECUT2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate ONECUT2 (see all 303):
    hsa-miR-124* hsa-miR-579 hsa-miR-502-3p hsa-miR-3170 hsa-miR-200b hsa-miR-3622a-5p hsa-miR-374b* hsa-miR-34c-5p
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ONECUT2


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ONEC2_HUMAN, O95948: Nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol2

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--

    Find genes that share ontologies with ONECUT2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for ONECUT2
    Interactions:

        Search GeneGlobe Interaction Network for ONECUT2

    1 Interacting protein for ONECUT2 (O959483) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    KDM5BQ9UGL13I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001889liver development IEA--
    GO:0001952regulation of cell-matrix adhesion IEA--
    GO:0002064epithelial cell development IEA--
    GO:0006351transcription, DNA-templated IEA--
    GO:0006355regulation of transcription, DNA-templated ----

    Find genes that share ontologies with ONECUT2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ONECUT2 (ONEC2)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for ONECUT2 gene: 
    NM_004852.2  

    Unigene Cluster for ONECUT2:

    One cut homeobox 2
    Hs.194725  [show with all ESTs]
    Unigene Representative Sequence: NM_004852
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000491143(uc002lgo.3) ENST00000481727
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate ONECUT2 (see all 303):
    hsa-miR-124* hsa-miR-579 hsa-miR-502-3p hsa-miR-3170 hsa-miR-200b hsa-miR-3622a-5p hsa-miR-374b* hsa-miR-34c-5p
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      QuantiTect SYBR Green Assays in human, mouse, rat ONECUT2
      QuantiFast Probe-based Assays in human, mouse, rat ONECUT2

    Additional mRNA sequence: 

    AK021717.1 AK124558.1 BC013134.1 BC108926.1 Y18198.1 

    3 DOTS entries:

    DT.40207491  DT.121101711  DT.95156900 

    5 AceView cDNA sequences:

    NM_004852 BU186994 BV197222 Y18198 AA121824 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ONECUT2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTAAGTCAGA
    ONECUT2 Expression
    About this image


    ONECUT2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Epithelial Cells
             Immature Biliary Epithelial Cells Intrahepatic Biliary Tree
     
     Liver (Hepatobiliary System)    fully expand to see all 3 entries
             Immature Biliary Epithelial Cells Intrahepatic Biliary Tree
     
     Ovary (Reproductive System)
             Granulosa Cells Primary Follicle
     
     Pancreas (Endocrine System)
             Pancreatic endoderm/endocrine precursor-like cells
     
     Gut Tube (Gastrointestinal Tract)
             Hepatic Endoderm Cells Ventral Foregut Endoderm
    ONECUT2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ONECUT2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.194725
        Custom PCR Arrays for ONECUT2
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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for ONECUT2 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Onecut21 , 5 one cut domain, family member 21, 5 91.65(n)1
    98.81(a)1
      18 (37.33 cM)5
    2256311  NM_194268.21  NP_919244.21 
     643403645 
    chicken
    (Gallus gallus)
    Aves ONECUT21 one cut homeobox 2 79.02(n)
    77.46(a)
      100857974  XM_003642903.2  XP_003642951.1 
    lizard
    (Anolis carolinensis)
    Reptilia ONECUT26
    one cut homeobox 2
    75(a)
    1 ↔ 1
    GL343213.1(2025117-2092535)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia onecut21 one cut homeobox 2 80.54(n)
    86.93(a)
      100485320  XM_002934443.2  XP_002934489.2 
    zebrafish
    (Danio rerio)
    Actinopterygii si:ch1073-41k10.11 si:ch1073-41k10.1 78.34(n)
    81.82(a)
      100000073  XM_001920273.4  XP_001920308.3 
    fruit fly
    (Drosophila melanogaster)
    Insecta onecut3 regulation of transcription,
    DNA-dependent RNA more
    59(a)   102C2   --
    worm
    (Caenorhabditis elegans)
    Secernentea C17H12.93 homeobox protein 80(a)
    (best of 2)
      IV(6812313-6815318)   --


    ENSEMBL Gene Tree for ONECUT2 (if available)
    TreeFam Gene Tree for ONECUT2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ONECUT2 gene
    CUX22  ONECUT12  ONECUT32  CUX12  
    2 SIMAP similar genes for ONECUT2 using alignment to 2 protein entries:     ONEC2_HUMAN (see all proteins):
    ONECUT1    ONECUT3

    Find genes that share paralogs with ONECUT2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ONECUT2 (see all 1234)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 18 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs37606161,2
    C,F,H--55100927(-) CCCACC/TCCCAC 1 -- us2k113Minor allele frequency- T:0.24EA NS NA 2832
    rs1398466661,2
    --55101135(+) CTGCTC/GTTCTT 1 -- us2k10--------
    rs1893987531,2
    --55101321(+) TGCCGC/GGTGTT 1 -- us2k10--------
    rs80904811,2
    C,F,A,H--55101359(+) ACCCCG/CACTCG 1 -- us2k17Minor allele frequency- C:0.24NS NA CSA WA EA 602
    rs1816827651,2
    --55101413(+) ACCTCC/TAGACC 1 -- us2k10--------
    rs1457100651,2
    C--55101542(+) TGCAGA/GTGTCA 1 -- us2k10--------
    rs1860716851,2
    --55101578(+) CCGCCG/TTTTCT 1 -- us2k10--------
    rs1128653171,2
    C--55101608(+) CGGGA-/GT    
       
    /GTGT
    GTGTG
    1 -- us2k11CSA 2
    rs105629241,2
    C--55101609(+) CGGGA-/GTgtgtg 1 -- us2k10--------
    rs1473226081,2
    --55101631(+) TGTGTC/GTGTGT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for ONECUT2 (55102917 - 55158530 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for ONECUT2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv995991CNV Insertion20482838
    esv1478795CNV Insertion17803354
    nsv828250CNV Gain20364138

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604894    OMIM disorders: --

    1 disease for ONECUT2:    
    About MalaCards
    hemophilia b


    Find genes that share disorders with ONECUT2           About GenesLikeMe

    Genetic Association Database (GAD): ONECUT2

    Export disorders for ONECUT2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ONECUT2 gene, integrated from 10 sources (see all 15):
    (articles sorted by number of sources associating them with ONECUT2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. OC-2, a novel mammalian member of the ONECUT class of homeodomain transcription factors whose function in liver partially overlaps with that of hepatocyte nuclear factor-6. (PubMed id 9915796)1, 2, 3, 9 Jacquemin P.... Lemaigre F.P. (J. Biol. Chem. 1999)
    2. The transcription factor onecut-2 controls the microphthalmia-associated transcription factor gene. (PubMed id 11478782)1, 9 Jacquemin P....Rousseau G.G. (Biochem. Biophys. Res. Commun. 2001)
    3. A CpG mutational hotspot in a ONECUT binding site accounts for the prevalent variant of hemophilia B Leyden. (PubMed id 23472758)1 Funnell A.P....Crossley M. (Am. J. Hum. Genet. 2013)
    4. The PcG protein hPc2 interacts with the N-terminus of histone demethylase JARID1B and acts as a transcriptional co-repressor. (PubMed id 19336002)1 Zhou W....Zhang L. (BMB Rep 2009)
    5. Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells. (PubMed id 18418398)1 Furuno K....Yamamoto K. (Genes Immun. 2008)
    6. DNA methylation profiles in diffuse large B-cell lymphoma and their relationship to gene expression status. (PubMed id 18288132)1 Pike B.L....Hacia J.G. (Leukemia 2008)
    7. Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. (PubMed id 17903306)4 Newton-Cheh C....Larson M.G. (BMC Med. Genet. 2007)
    8. Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project. (PubMed id 17903300)4 Fox C.S....Atwood L.D. (BMC Med. Genet. 2007)
    9. MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells. (PubMed id 16912168)1 Rauch T....Pfeifer G.P. (Cancer Res. 2006)
    10. DNA sequence and analysis of human chromosome 18. (PubMed id 16177791)2 Nusbaum C.... Lander E.S. (Nature 2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 9480 HGNC: 8139 AceView: ONECUT2 Ensembl:ENSG00000119547 euGenes: HUgn9480
    ECgene: ONECUT2 H-InvDB: ONECUT2

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for ONECUT2 Pharmacogenomics, SNPs, Pathways
    Wikipedia http://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ONECUT2 gene:
    Search GeneIP for patents involving ONECUT2

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