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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.
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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

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