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    Aff1 AF4/FMR2 family, member 1 [ Mus musculus (house mouse) ]

    Gene ID: 17355, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Aff1provided by MGI
    Official Full Name
    AF4/FMR2 family, member 1provided by MGI
    Primary source
    MGI:MGI:1100819
    See related
    Ensembl:ENSMUSG00000029313 AllianceGenome:MGI:1100819
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Af4; Rob; Mllt2h; 9630032B01Rik
    Summary
    This gene encodes a member of the AF4/ lymphoid nuclear protein related to the Fragile X E syndrome (FRAXE) family of proteins, which have been implicated in human childhood lymphoblastic leukemia, fragile chromosome X intellectual disability, and ataxia. It is the prevalent mixed-lineage leukemia fusion gene associated with spontaneous acute lymphoblastic leukemia. Members of this family have three conserved domains: an N-terminal homology domain, an AF4/ lymphoid nuclear protein domain, and a C-terminal homology domain. Knockout of the mouse gene by homologous recombination severely affects early events in lymphopoiesis, including precursor proliferation or recruitment, but is dispensable for terminal differentiation. In addition, an autosomal dominant missense mutation results in several phenotypes including ataxia and adult-onset Purkinje cell loss in the cerebellum, indicating a role in Purkinje cell maintenance and function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
    Expression
    Ubiquitous expression in thymus adult (RPKM 11.6), lung adult (RPKM 6.6) and 25 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    5 E5; 5 50.45 cM
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (103840307..104003188)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (103692362..103855322)

    Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene RIKEN cDNA 1700016H13 gene Neighboring gene STARR-seq mESC enhancer starr_13780 Neighboring gene predicted gene, 42138 Neighboring gene predicted gene, 25721 Neighboring gene STARR-positive B cell enhancer ABC_E3590 Neighboring gene STARR-positive B cell enhancer mm9_chr5:104121192-104121493 Neighboring gene STARR-positive B cell enhancer ABC_E3591 Neighboring gene STARR-seq mESC enhancer starr_13785 Neighboring gene STARR-seq mESC enhancer starr_13786 Neighboring gene STARR-positive B cell enhancer ABC_E10335 Neighboring gene STARR-positive B cell enhancer ABC_E8066 Neighboring gene STARR-seq mESC enhancer starr_13791 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:104155653-104155892 Neighboring gene STARR-seq mESC enhancer starr_13794 Neighboring gene STARR-positive B cell enhancer ABC_E2755 Neighboring gene STARR-positive B cell enhancer ABC_E9258 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:104185304-104185591 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:104189527-104189796 Neighboring gene STARR-seq mESC enhancer starr_13808 Neighboring gene kelch-like 8 Neighboring gene predicted gene, 42139 Neighboring gene predicted gene, 24897

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. The robotic mouse: understanding the role of AF4, a cofactor of transcriptional elongation and chromatin remodelling, in purkinje cell function. Bitoun E, et al. Cerebellum, 2009 Sep. PMID 19340490
    2. Behavioural characterisation of the robotic mouse mutant. Oliver PL, et al. Behav Brain Res, 2007 Aug 6. PMID 17532061
    3. Altered lymphoid development in mice deficient for the mAF4 proto-oncogene. Isnard P, et al. Blood, 2000 Jul 15. PMID 10887138
    4. Amlexanox Downregulates S100A6 to Sensitize KMT2A/AFF1-Positive Acute Lymphoblastic Leukemia to TNFα Treatment. Tamai H, et al. Cancer Res, 2017 Aug 15. PMID 28646023
    5. AF4 is a critical regulator of the IGF-1 signaling pathway during Purkinje cell development. Bitoun E, et al. J Neurosci, 2009 Dec 9. PMID 20007461, Free PMC Article

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia.
      Title: Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia.
    2. define a specific pairing of two amino acids that creates a salt bridge between MLLT1/3 and AFF proteins that is critically important for MLL-mediated transformation of HPCs
      Title: Importance of a specific amino acid pairing for murine MLL leukemias driven by MLLT1/3 or AFF1/4.
    3. Data show that the minimal 90-amino acid AF9 fragment in MLL-AF9 retains an ability to form higher order complexes with AF4*P-TEFb and with DOT1.
      Title: Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes.
    4. small changes in the levels of a single transcriptional cofactor AF4 can deleteriously affect normal cerebellum function and opens new avenues of research for the manipulation of the IGF-1 pathway in the treatment of cerebellar ataxia in humans.
      Title: AF4 is a critical regulator of the IGF-1 signaling pathway during Purkinje cell development.
    5. Af4 functions as part of a large multiprotein complex that stimulates RNA polymerase II elongation and mediates chromatin remodelling during transcription.
      Title: The robotic mouse: understanding the role of AF4, a cofactor of transcriptional elongation and chromatin remodelling, in purkinje cell function.
    6. enhancement of S100A6 expression plays an important role in MLL-AF4-associated leukemogenesis
      Title: Multistep pathogenesis of leukemia via the MLL-AF4 chimeric gene/Flt3 gene tyrosine kinase domain (TKD) mutation-related enhancement of S100A6 expression.
    7. Overlapping expression of Af9 with Af4/Aff1 and Fmr2/Aff2, two genes that are also related to neurodevelopmental diseases, as well as with the highly homologous Enl.
      Title: Expression of Leukaemia associated transcription factor Af9/Mllt3 in the cerebral cortex of the mouse.
    8. demonstrated that Af4 is specifically expressed in Purkinje cells; hypothesize that the expression of mutant Af4 leads to neurodegeneration
      Title: A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse.
    9. Robotic mutants are significantly impaired on the rotarod and static rod tests of coordination and their performance declined during aging; however, spontaneous alternation testing in a T-maze was not significantly affected in robotic mice.
      Title: Behavioural characterisation of the robotic mouse mutant.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables DNA-binding transcription factor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within DNA-templated transcription TAS
    Traceable Author Statement
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of gene expression IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of super elongation complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of transcription elongation factor complex ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    AF4/FMR2 family member 1
    Names
    homolog of human MLLT2 unidentified
    myeloid/lymphoid or mixed-lineage leukemia translocated to 2 homolog
    protein AF-4
    proto-oncogene AF4
    robotic

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_001080798.3 → NP_001074267.1  AF4/FMR2 family member 1 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AL713989, AL731554
      Consensus CDS
      CCDS39189.1
      UniProtKB/TrEMBL
      E9Q921, Q5XM34
      Related
      ENSMUSP00000031256.6, ENSMUST00000031256.6
      Conserved Domains (1) summary
      pfam05110
      Location:17 → 1221
      AF-4; AF-4 proto-oncoprotein

    2. NM_001408251.1 → NP_001395180.1  AF4/FMR2 family member 1 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AL713989, AL731554

    3. NM_133919.5 → NP_598680.3  AF4/FMR2 family member 1 isoform 2

      See identical proteins and their annotated locations for NP_598680.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate 5'-terminal exon, which results in a different 5' UTR and use of an alternate start codon. It encodes isoform 2, which has a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AL713989, AL731554
      Consensus CDS
      CCDS39188.1
      UniProtKB/TrEMBL
      A3KMF4, Q5XM34
      Related
      ENSMUSP00000059744.4, ENSMUST00000054979.10
      Conserved Domains (1) summary
      pfam05110
      Location:9 → 1213
      AF-4; AF-4 proto-oncoprotein

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000071.7 Reference GRCm39 C57BL/6J

      Range
      103840307..104003188
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_036164846.1 → XP_036020739.1  AF4/FMR2 family member 1 isoform X2

      UniProtKB/TrEMBL
      Q5XM34
      Conserved Domains (3) summary
      PHA03247
      Location:350 → 687
      PHA03247; large tegument protein UL36; Provisional
      pfam05110
      Location:4 → 503
      AF-4; AF-4 proto-oncoprotein
      pfam18876
      Location:953 → 1214
      AF-4_C; AF-4 proto-oncoprotein C-terminal region
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O88573.2 GenPept UniProtKB/Swiss-Prot:O88573

    Gene LinkOut

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

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