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    AFF4 ALF transcription elongation factor 4 [ Homo sapiens (human) ]

    Gene ID: 27125, updated on 10-Dec-2024

    Summary

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    Official Symbol
    AFF4provided by HGNC
    Official Full Name
    ALF transcription elongation factor 4provided by HGNC
    Primary source
    HGNC:HGNC:17869
    See related
    Ensembl:ENSG00000072364 MIM:604417; AllianceGenome:HGNC:17869
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MCEF; CHOPS; AF5Q31
    Summary
    The protein encoded by this gene belongs to the AF4 family of transcription factors involved in leukemia. It is a component of the positive transcription elongation factor b (P-TEFb) complex. A chromosomal translocation involving this gene and MLL gene on chromosome 11 is found in infant acute lymphoblastic leukemia with ins(5;11)(q31;q31q23). [provided by RefSeq, Oct 2011]
    Expression
    Ubiquitous expression in thyroid (RPKM 21.2), adrenal (RPKM 17.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See AFF4 in Genome Data Viewer
    Location:
    5q31.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (132875395..132963634, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (133395153..133483382, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (132211087..132299326, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:132201613-132202812 Neighboring gene growth differentiation factor 9 Neighboring gene ubiquinol-cytochrome c reductase complex III subunit VII Neighboring gene liver enriched antimicrobial peptide 2 Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 50 Neighboring gene ATPase H+ transporting V0 subunit e1 pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:132296353-132296854 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16344 Neighboring gene AFF4 divergent transcript Neighboring gene small nuclear ribonucleoprotein U4/U6.U5 subunit 27 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. AFF4 regulates osteogenic differentiation of human dental follicle cells. Xiao Q, et al. Int J Oral Sci, 2020 Jun 30. PMID 32606293, Free PMC Article
    2. Super Elongation Complex as a Targetable Dependency in Diffuse Midline Glioma. Dahl NA, et al. Cell Rep, 2020 Apr 7. PMID 32268092
    3. The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression. Long Q, et al. Comb Chem High Throughput Screen, 2024. PMID 37815186
    4. Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Izumi K, et al. Nat Genet, 2015 Apr. PMID 25730767, Free PMC Article
    5. AFF4 globally affects the release of paused RNA polymerase II in HEL cells. Yang ZM, et al. Yi Chuan, 2023 Aug 20. PMID 37609817

    See all (111) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. N6-methyladenosine-modified circCDK14 promotes ossification of the ligamentum flavum via epigenetic modulation by targeting AFF4.
      Title: N6-methyladenosine-modified circCDK14 promotes ossification of the ligamentum flavum via epigenetic modulation by targeting AFF4.
    2. Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation.
      Title: Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation.
    3. The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.
      Title: The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.
    4. AFF4 regulates osteogenic potential of human periodontal ligament stem cells via mTOR-ULK1-autophagy axis.
      Title: AFF4 regulates osteogenic potential of human periodontal ligament stem cells via mTOR-ULK1-autophagy axis.
    5. AFF4 globally affects the release of paused RNA polymerase II in HEL cells.
      Title: AFF4 globally affects the release of paused RNA polymerase II in HEL cells.
    6. AFF4 facilitates melanoma cell progression by regulating c-Jun activity.
      Title: AFF4 facilitates melanoma cell progression by regulating c-Jun activity.
    7. Super Elongation Complex as a Targetable Dependency in Diffuse Midline Glioma.
      Title: Super Elongation Complex as a Targetable Dependency in Diffuse Midline Glioma.
    8. AFF4 enhances odontogenic differentiation of human dental pulp cells.
      Title: AFF4 enhances odontogenic differentiation of human dental pulp cells.
    9. AFF4 regulates osteogenic differentiation of human dental follicle cells.
      Title: AFF4 regulates osteogenic differentiation of human dental follicle cells.
    10. Clinical and molecular spectrum of CHOPS syndrome due to AFF4 mutations has been reported.
      Title: Clinical and molecular spectrum of CHOPS syndrome.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 replication requires ELL2, AFF4 and AFF1 for transcriptional elongation as shown through CRISPR/Cas genome editing PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat transactivation is mediated by the AFF4- super elongation complex but does so less than the AFF4-super elongation complex due to a single amino acid that causes a change in affinity of Tat for cyclin T1 PubMed
    tat HIV-1 Tat binds adjacent to AFF4, increases the affinity of AFF4 for P-TEFb, and rescues P-TEFb binding to AFF4 interface mutants. The AFF4 G61A/M62A mutant abolishes this rescue PubMed
    tat The crystal structure demonstrates that Met55Thr substitution in AFF4 forms a hydrogen bond with Glu246 of Cyclin T1, which is not as favorable for HIV-1 Tat docking PubMed
    tat The Tat-AFF4-P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (residues 1-266), human Cdk9 (residues 7-332), and human AFF4 (residues 27-69) is determined by the crystal structure analysis PubMed
    tat Binding of isolated AFF1(1-308) CBS to CDK9/CycT1 prevents HIV-1 Tat from activating HIV transcription and assembling complete SECs (AFF1, AFF4, ELL2, and ENL). The AFF1(1-308) M60A/L61A mutant shows no suppression of Tat transactivation PubMed
    tat HIV-1 Tat forms at least two distinct P-TEFb-containing complexes. Tatcom1 is composed of P-TEFb, AF9, ENL, ELL, AFF1, AFF4, and PAF1, presenting strong CTD-kinase activity, while Tatcom2 consists of 7SK, LARP7, and MEPCE with two molecules of Tat/P-TEFb PubMed
    tat HIV-1 Tat increases the amount of ELL2 bound to P-TEFb without affecting the AFF4-P-TEFb binding. CDK9 is required for the Tat-induced ELL2 accumulation and Tat interaction with ELL2 PubMed
    tat Brd4 inhibits HIV-1 Tat-human super elongation complex (components AFF4, ELL2, CycT1, and CDK9) by competing with HIV-1 Tat for binding to P-TEFb on HIV-1 promoter PubMed
    tat HIV-1 Tat is identified to have a physical interaction with AF4/FMR2 family, member 4 (AFF4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC75036

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in regulation of gene expression IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to endoplasmic reticulum stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in spermatid development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in euchromatin ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in fibrillar center IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    part_of super elongation complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of transcription elongation factor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    AF4/FMR2 family member 4
    Names
    ALL1-fused gene from chromosome 5q31 protein
    major CDK9 elongation factor-associated protein

    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.

    Genomic

    1. NG_030340.1 RefSeqGene

      Range
      5029..93268
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_014423.4 → NP_055238.1  AF4/FMR2 family member 4

      See identical proteins and their annotated locations for NP_055238.1

      Status: REVIEWED

      Source sequence(s)
      AC004500, AF197927, BC100287, DA934874
      Consensus CDS
      CCDS4164.1
      UniProtKB/Swiss-Prot
      B2RP19, B7WPD2, Q498B2, Q59FB3, Q6P592, Q8TDR1, Q9P0E4, Q9UHB7
      Related
      ENSP00000265343.5, ENST00000265343.10
      Conserved Domains (1) summary
      pfam05110
      Location:3 → 1159
      AF-4; AF-4 proto-oncoprotein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      132875395..132963634 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006714587.5 → XP_006714650.1  AF4/FMR2 family member 4 isoform X2

      Conserved Domains (1) summary
      pfam05110
      Location:3 → 1130
      AF-4; AF-4 proto-oncoprotein

    2. XM_047417103.1 → XP_047273059.1  AF4/FMR2 family member 4 isoform X2

    3. XM_005271963.6 → XP_005272020.1  AF4/FMR2 family member 4 isoform X1

      See identical proteins and their annotated locations for XP_005272020.1

      UniProtKB/Swiss-Prot
      B2RP19, B7WPD2, Q498B2, Q59FB3, Q6P592, Q8TDR1, Q9P0E4, Q9UHB7
      Conserved Domains (1) summary
      pfam05110
      Location:3 → 1159
      AF-4; AF-4 proto-oncoprotein

    4. XM_005271964.5 → XP_005272021.1  AF4/FMR2 family member 4 isoform X3

      Conserved Domains (1) summary
      pfam05110
      Location:1 → 781
      AF-4; AF-4 proto-oncoprotein

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      133395153..133483382 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352385.1 → XP_054208360.1  AF4/FMR2 family member 4 isoform X2

    2. XM_054352386.1 → XP_054208361.1  AF4/FMR2 family member 4 isoform X2

    3. XM_054352384.1 → XP_054208359.1  AF4/FMR2 family member 4 isoform X1

      UniProtKB/Swiss-Prot
      B2RP19, B7WPD2, Q498B2, Q59FB3, Q6P592, Q8TDR1, Q9P0E4, Q9UHB7

    4. XM_054352387.1 → XP_054208362.1  AF4/FMR2 family member 4 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UHB7.1 GenPept UniProtKB/Swiss-Prot:Q9UHB7

    Gene LinkOut

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

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