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ALKBH4 Gene

protein-coding   GIFtS: 46
GCID: GC07M102096

AlkB, Alkylation Repair Homolog 4 (E. Coli)

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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
AlkB, Alkylation Repair Homolog 4 (E. Coli)1 2
ABH42 3 5
Alkylated DNA Repair Protein AlkB Homolog 42 3
Alpha-Ketoglutarate-Dependent Dioxygenase AlkB Homolog 42
Probable Alpha-Ketoglutarate-Dependent Dioxygenase ABH42
EC 1.14.11.-3

External Ids:    HGNC: 219001   Entrez Gene: 547842   Ensembl: ENSG000001609937   OMIM: 6133025   UniProtKB: Q9NXW93   

Export aliases for ALKBH4 gene to outside databases

Previous GC identifers: GC07M101883 GC07M096686


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for ALKBH4 Gene:
ALKBH4 (alkB, alkylation repair homolog 4 (E. coli)) is a protein-coding gene. GO annotations related to this gene include demethylase activity and actin binding.

UniProtKB/Swiss-Prot: ALKB4_HUMAN, Q9NXW9
Function: Dioxygenase that mediates demethylation of actin monomethylated at 'Lys-84' (K84me1), thereby acting as
a regulator of actomyosin-processes. Demethylation of actin K84me1 is required for maintaining actomyosin
dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. May be involved in
transcription regulation




(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:
NC_000007.14  NT_007933.16  NC_018918.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the ALKBH4 gene promoter:
         SRF   AML1a   SRF (504 AA)   GCNF   Lmo2   GATA-2   HEN1   FAC1   GCNF-1   GCNF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidALKBH4 promoter sequence
   Search Chromatin IP Primers for ALKBH4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ALKBH4


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

Entrez Gene cytogenetic band: 7q22.1   Ensembl cytogenetic band:  7q22.1   HGNC cytogenetic band: 7q22.1

ALKBH4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ALKBH4 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M102096:  view genomic region     (about GC identifiers)

Start:
102,096,667 bp from pter      End:
102,105,323 bp from pter
Size:
8,657 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 101,456,968-101,465,622     

(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: ALKB4_HUMAN, Q9NXW9 (See protein sequence)
Recommended Name: Alpha-ketoglutarate-dependent dioxygenase alkB homolog 4  
Size: 302 amino acids; 33838 Da
Cofactor: Binds 1 Fe(2+) ion per subunit
Subunit: Interacts with ZFHX3, MLLT3, MLLT1, HSF4, EP300, TES, EIF3C, MTMR6 and PSMA6
Miscellaneous: Actin demethylase activity has not been directly confirmed in vitro; however a number of
experiments strongly suggest that ALKBH4 acts as a protein demethylase (PubMed:23673617)
Sequence caution: Sequence=BAB15358.1; Type=Erroneous translation; Note=Wrong choice of CDS;
Secondary accessions: Q53H92 Q9H6A4
Alternative splicing: 2 isoforms:  Q9NXW9-1   Q9NXW9-2   (May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ALKBH4: NX_Q9NXW9

Explore proteomics data for ALKBH4 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See ALKBH4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_060091.1  
    ENSEMBL proteins: 
     ENSP00000292566   ENSP00000420362  

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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:
    ALKB: Alkylation repair homologs

    2 InterPro protein domains:
     IPR027450 AlkB-like
     IPR005123 Oxoglu/Fe-dep_dioxygenase

    Graphical View of Domain Structure for InterPro Entry Q9NXW9

    ProtoNet protein and cluster: Q9NXW9

    UniProtKB/Swiss-Prot: ALKB4_HUMAN, Q9NXW9
    Similarity: Belongs to the alkB family


    Find genes that share domains with ALKBH4           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: ALKB4_HUMAN, Q9NXW9
    Function: Dioxygenase that mediates demethylation of actin monomethylated at 'Lys-84' (K84me1), thereby acting as
    a regulator of actomyosin-processes. Demethylation of actin K84me1 is required for maintaining actomyosin
    dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. May be involved in
    transcription regulation

         Enzyme Number (IUBMB): EC 1.14.11.-1

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003779actin binding IDA--
    GO:0016491oxidoreductase activity ----
    GO:0016706oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors IDA--
    GO:0032451demethylase activity TAS--
    GO:0046872metal ion binding IEA--
         
    Find genes that share ontologies with ALKBH4           About GenesLikeMe


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Alkbh4):
     cellular  mortality/aging 

    Find genes that share phenotypes with ALKBH4           About GenesLikeMe

    Animal Models:
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    (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
    ALKB4_HUMAN, Q9NXW9: Cytoplasm. Nucleus. Midbody. Note=Associates with the contractile ring and midbody
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    mitochondrion4
    cytosol2
    extracellular1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IEA--
    GO:0005739mitochondrion ----
    GO:0030496midbody IDA--
    GO:0070938contractile ring IDA--

    Find genes that share ontologies with ALKBH4           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 ALKBH4
    Interactions:

        Search GeneGlobe Interaction Network for ALKBH4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 6)

    Selected Interacting proteins for ALKBH4 (Q9NXW93 ENSP000002925664) via UniProtKB, MINT, STRING, and/or I2D (see all 8)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DNAJA3Q96EY13I2D: score=4 
    DTX2Q86UW93I2D: score=1 
    RABIFENSP000003562314STRING: ENSP00000356231
    DGAT2ENSP000002280274STRING: ENSP00000228027
    MOGAT1ENSP000004066744STRING: ENSP00000406674
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006351transcription, DNA-templated IEA--
    GO:0006355regulation of transcription, DNA-templated IEA--
    GO:0006482protein demethylation IDA--
    GO:0031032actomyosin structure organization IMP--
    GO:0036090cleavage furrow ingression IMP--

    Find genes that share ontologies with ALKBH4           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 ALKBH4 (ALKB4)



    (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 ALKBH4 gene: 
    NM_017621.3  

    Unigene Cluster for ALKBH4:

    AlkB, alkylation repair homolog 4 (E. coli)
    Hs.658598  [show with all ESTs]
    Unigene Representative Sequence: NM_017621
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000292566(uc003uzl.3 uc003uzm.3) ENST00000490528 ENST00000498283

    miRNA
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    hsa-miR-942
    SwitchGear 3'UTR luciferase reporter plasmidALKBH4 3' UTR sequence
    Inhib. RNA
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    Additional mRNA sequence: 

    AK000020.1 AK026097.1 AK222689.1 BC002820.2 BC017096.1 

    5 DOTS entries:

    DT.422481  DT.95163030  DT.121040393  DT.40260315  DT.101973380 

    Selected AceView cDNA sequences (see all 52):

    AA579919 CA420615 BC017096 BM457449 BQ425330 BC002820 BF725596 BU526881 
    NM_017621 BM764940 AK026097 BP375717 BM083633 AA587078 BX348523 BI871315 
    BF316159 BQ919302 BE384853 BF725595 BQ959688 BP381675 BG499127 AL121411 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for ALKBH4    About this scheme

    ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3a · 3b · 3c · 3d
    SP1:                          -                           
    SP2:                          -                           
    SP3:              -           -                           
    SP4:                                                      
    SP5:              -     -     -                           


    ECgene alternative splicing isoforms for ALKBH4

    (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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    ALKBH4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATCATACCAC
    ALKBH4 Expression
    About this image

    ALKBH4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ALKBH4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.658598

    UniProtKB/Swiss-Prot: ALKB4_HUMAN, Q9NXW9
    Tissue specificity: Widely expressed, with highest expression in pancreas, ovary and spleen

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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 ALKBH4 gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Alkbh41 , 5 alkB, alkylation repair homolog 4 (E. coli)1, 5 81.55(n)1
    83.26(a)1
      5 (75.82 cM)5
    720411  NM_028070.11  NP_082346.11 
     1361361465 
    chicken
    (Gallus gallus)
    Aves ALKBH41 alkB, alkylation repair homolog 4 (E. coli) 65(n)
    65(a)
      417510  XM_004946493.1  XP_004946550.1 
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.39792 Xenopus laevis transcribed sequence with weak similarity more 75.12(n)    CA791123.1 
    zebrafish
    (Danio rerio)
    Actinopterygii alkbh41 alkB, alkylation repair homolog 4 (E. coli) 58.72(n)
    59.62(a)
      553475  XM_681983.3  XP_687075.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG40361 CG4036 50.31(n)
    39.78(a)
      34302  NM_135470.3  NP_609314.1 
    worm
    (Caenorhabditis elegans)
    Secernentea F09F7.71 F09F7.7 47.6(n)
    39.6(a)
      175765  NM_171124.4  NP_741141.1 


    ENSEMBL Gene Tree for ALKBH4 (if available)
    TreeFam Gene Tree for ALKBH4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (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 ALKBH4 (see all 162)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1844626141,2
    C--102097783(+) GCCCTG/TTTCTG 1 -- ut310--------
    rs2009435381,2
    C--102097801(+) CATTTC/TAATCC 1 -- ut310--------
    rs1999137731,2
    --102097837(+) GGAGGC/TGGTTC 1 -- ut310--------
    rs1474344631,2
    F--102097901(+) TCTTGC/TTGCCT 2 Q syn11Minor allele frequency- T:0.00NA 4544
    rs1452306971,2
    C,F--102097966(+) GGCCTC/GGATGT 2 Q E mis12Minor allele frequency- G:0.00NA EU 5097
    rs1476216851,2
    C,F--102097970(+) TCGATG/ATGTCT 2 /H syn12Minor allele frequency- A:0.00NA EU 5041
    rs2018008931,2
    --102097976(+) TGTCTA/GCGGTG 2 R syn10--------
    rs412752271,2,,4
    C,F--102098010(+) GTGCCG/ACCCCG 2 /A /V mis15Minor allele frequency- A:0.10NA EA EU 4646
    rs1504095981,2
    C,F--102098035(+) GGAGCG/AGGCGG 2 /R /C mis11Minor allele frequency- A:0.00NA 3856
    rs1890006311,2
    C--102098147(+) AGGAGC/TAGGCT 2 L syn10--------

    HapMap Linkage Disequilibrium report for ALKBH4 (102096667 - 102105323 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for ALKBH4:    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv7413n71CNV Loss21882294
    nsv888832CNV Loss21882294
    nsv831083CNV Loss17160897
    nsv5879CNV Loss18451855
    nsv464665CNV Loss19166990
    dgv7412n71CNV Loss21882294
    nsv464664CNV Gain19166990
    nsv428182CNV Gain18775914
    nsv824248CNV Gain20364138
    nsv8192CNV Gain18304495

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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: 613302    OMIM disorders: --


    Find genes that share disorders with ALKBH4           About GenesLikeMe


    Export disorders for ALKBH4 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 ALKBH4 gene, integrated from 10 sources (see all 15):
    (articles sorted by number of sources associating them with ALKBH4)
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    1. ALKBH4-dependent demethylation of actin regulates actomyosin dynamics. (PubMed id 23673617)1, 2 Li M.M.... Yang Y.G. (Nat. Commun. 2013)
    2. Human ALKBH4 interacts with proteins associated with transcription. (PubMed id 23145062)1, 2 BjA...Falnes P.A.9. (PLoS ONE 2012)
    3. Spectroscopic and magnetic studies of wild-type and mutant forms of the Fe(II)- and 2-oxoglutarate-dependent decarboxylase ALKBH4. (PubMed id 21166655)1, 2 BjA...Andersson K.K. (Biochem. J. 2011)
    4. Expression and sub-cellular localization of human ABH family molecules. (PubMed id 17979886)1, 2 Tsujikawa K.... Yamamoto H. (J. Cell. Mol. Med. 2007)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    6. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    7. Pathway Analysis of ChIP-Seq-Based NRF1 Target Genes Suggests a Logical Hypothesis of their Involvement in the Pathogenesis of Neurodegenerative Diseases. (PubMed id 24250222)1 Satoh J....Yamamoto Y. (Gene Regul Syst Bio 2013)
    8. Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-I+-acetylation features. (PubMed id 22223895)2 Bienvenut W.V....Giglione C. (amp 2012)
    9. N-terminal acetylome analyses and functional insights of the N- terminal acetyltransferase NatB. (PubMed id 22814378)2 Van Damme P....Aldabe R. (Proc. Natl. Acad. Sci. U.S.A. 2012)
    10. Initial characterization of the human central proteome. (PubMed id 21269460)2 Burkard T.R.... Colinge J. (BMC Syst. Biol. 2011)

    (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: 54784 HGNC: 21900 AceView: FLJ20013 Ensembl:ENSG00000160993 euGenes: HUgn54784
    ECgene: ALKBH4 H-InvDB: ALKBH4

    (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 ALKBH4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ALKBH4 gene:
    Search GeneIP for patents involving ALKBH4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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