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

Summary

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

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_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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)

Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (5)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW319193 (e-PCR)
- UniSTS:179214

Aff1 (e-PCR), detects polymorphism
- UniSTS:526962

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
part_of transcription elongation factor complex	ISS Inferred from Sequence or Structural Similarity 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)

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

Status: VALIDATED

Source sequence(s)

AL713989, AL731554
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

NC_000071.7 Reference GRCm39 C57BL/6J

Range

103840307..104003188

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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