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    AFF1 ALF transcription elongation factor 1 [ Homo sapiens (human) ]

    Gene ID: 4299, updated on 28-Oct-2024

    Summary

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    Official Symbol
    AFF1provided by HGNC
    Official Full Name
    ALF transcription elongation factor 1provided by HGNC
    Primary source
    HGNC:HGNC:7135
    See related
    Ensembl:ENSG00000172493 MIM:159557; AllianceGenome:HGNC:7135
    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
    AF4; FEL; PBM1; MLLT2
    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. The protein functions as a regulator of RNA polymerase II-mediated transcription through elongation and chromatin remodeling functions. Through RNA interference screens, this gene has been shown to promote the expression of CD133, a plasma membrane glycoprotein required for leukemia cell survival. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
    Expression
    Ubiquitous expression in thyroid (RPKM 30.6), fat (RPKM 17.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See AFF1 in Genome Data Viewer
    Location:
    4q21.3-q22.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (86935011..87141039)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (90264015..90470100)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (87856163..88062191)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene chromosome 4 open reading frame 36 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:87836141-87836640 Neighboring gene Sharpr-MPRA regulatory region 3757 Neighboring gene ARPC1A pseudogene 4 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:87856539-87857080 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:87857081-87857622 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:87861204-87861704 Neighboring gene AFF1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21697 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:87879079-87879662 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:87880372-87881044 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:87881045-87881716 Neighboring gene Sharpr-MPRA regulatory region 10323 Neighboring gene Sharpr-MPRA regulatory region 12874 Neighboring gene Sharpr-MPRA regulatory region 10097/5096 Neighboring gene trans-2,3-enoyl-CoA reductase pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21698 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21699 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21700 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15552 Neighboring gene Sharpr-MPRA regulatory region 119 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15553 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:87934257-87934756 Neighboring gene NANOG hESC enhancer GRCh37_chr4:87955092-87955593 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:87958100-87958600 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:87958601-87959101 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15554 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr4:87960255-87961006 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21701 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21702 Neighboring gene uncharacterized LOC105377320 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21703 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21704 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:88041283-88041858 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15555 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:88073576-88074076 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:88074077-88074577 Neighboring gene uracil DNA glycosylase pseudogene Neighboring gene kelch like family member 8 Neighboring gene glyceraldehyde-3-phosphate dehydrogenase pseudogene 60

    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 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. Association Study of an AFF1 Gene Polymorphism (rs340630) with Iranian Systemic Lupus Erythematosus Patients. Arabi E, et al. Acta Reumatol Port, 2016 Jan-Mar. PMID 27115110
    2. Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation between AF4-MLL and MLL-AF4 fusions. Bueno C, et al. Haematologica, 2019 Jun. PMID 30679325, Free PMC Article
    3. The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia. Chen CS, et al. Blood, 1993 Aug 15. PMID 8353274
    4. A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias. Morrissey J, et al. Blood, 1993 Mar 1. PMID 8443374
    5. Combined effects of the two reciprocal t(4;11) fusion proteins MLL.AF4 and AF4.MLL confer resistance to apoptosis, cell cycling capacity and growth transformation. Gaussmann A, et al. Oncogene, 2007 May 17. PMID 17130830

    See all (118) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion.
      Title: Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion.
    3. [AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].
      Title: [AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].
    4. The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(4;11).
      Title: The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(4;11).
    5. miR-130b and miR-128a are essential lineage-specific codrivers of t(4;11) MLL-AF4 acute leukemia.
      Title: miR-130b and miR-128a are essential lineage-specific codrivers of t(4;11) MLL-AF4 acute leukemia.
    6. Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair.
      Title: Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair.
    7. Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996.
      Title: Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996.
    8. Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells.
      Title: Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells.
    9. Nuclear FGFR2 Interacts with the MLL-AF4 Oncogenic Chimera and Positively Regulates HOXA9 Gene Expression in t(4;11) Leukemia Cells.
      Title: Nuclear FGFR2 Interacts with the MLL-AF4 Oncogenic Chimera and Positively Regulates HOXA9 Gene Expression in t(4;11) Leukemia Cells.
    10. HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.
      Title: HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.
    Submit: New GeneRIF Correction See all GeneRIFs (49)

    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

    EBI GWAS Catalog

    Description
    A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.
    EBI GWAS Catalog
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genetic variants associated with disordered eating.
    EBI GWAS Catalog
    Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
    EBI GWAS Catalog
    Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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 AFF1- super elongation complex and does so more than the AFF4-super elongation complex due to a single amino acid that causes enhancement of Tat for cyclin T1 PubMed
    tat HIV-1 Tat(C22G) fails to bind to P-TEFb, but this lack of binding is rescued by co-expressing AFF1 wild-type but not three mutants V67A, F70A, and V67A/F70A PubMed
    tat CDK9-CycT1-AFF1 is stimulated by HIV-1 Tat and transferred as a single complex unit to BRD4 upon stress-induced disruption of AFF1-containing 7SK snRNP (HEMX1, MEPCE, LARP7, 7SK RNA, CDK9, CycT1, and AFF1) 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 AFF1 enhances the affinity of HIV-1 Tat for CycT1, which competitively dissociates HEXIM1 and is responsible for AFF1's promotion of Tat's extraction of CDK9/CycT1 from 7SK snRNP 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 is identified to have a physical interaction with AF4/FMR2 family, member 1 (AFF1) 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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC134969

    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
    		  
    Component Evidence Code Pubs
    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 1
    Names
    ALL1-fused gene from chromosome 4 protein
    KMT2A/AFF1 fusion protein
    myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 2
    pre-B-cell monocytic leukemia partner 1
    proto-oncogene AF4

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001166693.3 → NP_001160165.1  AF4/FMR2 family member 1 isoform 1

      See identical proteins and their annotated locations for NP_001160165.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC092658, AC093779, AC093827
      Consensus CDS
      CCDS54775.1
      UniProtKB/TrEMBL
      Q6LA76
      Related
      ENSP00000378578.4, ENST00000395146.9
      Conserved Domains (1) summary
      pfam05110
      Location:16 → 1211
      AF-4; AF-4 proto-oncoprotein

    2. NM_001313959.2 → NP_001300888.1  AF4/FMR2 family member 1 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains a distinct 5' UTR and uses an alternate translation start site compared to variant 1. It encodes isoform 2, which has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AC092658, AC093779, AC093827
      Consensus CDS
      CCDS93557.1
      UniProtKB/TrEMBL
      Q14C88, Q6LA76
      Related
      ENSP00000440843.3, ENST00000544085.6
      Conserved Domains (1) summary
      pfam05110
      Location:9 → 1204
      AF-4; AF-4 proto-oncoprotein

    3. NM_001313960.2 → NP_001300889.1  AF4/FMR2 family member 1 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains a distinct 5' UTR, uses an alternate translation start site, and lacks two alternate, in-frame exons compared to variant 1. It encodes isoform 4, which is shorter than and has a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AC092658, AC093779, AC093827
      UniProtKB/TrEMBL
      B4DJU9
      Conserved Domains (1) summary
      pfam05110
      Location:1 → 842
      AF-4; AF-4 proto-oncoprotein

    4. NM_005935.4 → NP_005926.1  AF4/FMR2 family member 1 isoform 2

      See identical proteins and their annotated locations for NP_005926.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains a distinct 5' UTR, uses an alternate translation start site, and uses an alternate in-frame splice site in the 3' coding region compared to variant 1. It encodes isoform 2, which has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AC092658, AC093779, AC093827
      Consensus CDS
      CCDS3616.1
      UniProtKB/Swiss-Prot
      B4DTU1, E9PBM3, P51825
      UniProtKB/TrEMBL
      Q6LA76
      Related
      ENSP00000305689.6, ENST00000307808.10
      Conserved Domains (1) summary
      pfam05110
      Location:9 → 1203
      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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      86935011..87141039
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005263007.4 → XP_005263064.1  AF4/FMR2 family member 1 isoform X1

      See identical proteins and their annotated locations for XP_005263064.1

      UniProtKB/TrEMBL
      Q6LA76
      Conserved Domains (1) summary
      pfam05110
      Location:16 → 1211
      AF-4; AF-4 proto-oncoprotein

    2. XM_047415702.1 → XP_047271658.1  AF4/FMR2 family member 1 isoform X2

    3. XM_005263009.5 → XP_005263066.1  AF4/FMR2 family member 1 isoform X2

      UniProtKB/TrEMBL
      Q6LA76
      Conserved Domains (1) summary
      pfam05110
      Location:16 → 1210
      AF-4; AF-4 proto-oncoprotein

    4. XM_017008215.3 → XP_016863704.1  AF4/FMR2 family member 1 isoform X5

      UniProtKB/TrEMBL
      B4DJU9
      Conserved Domains (1) summary
      pfam05110
      Location:1 → 842
      AF-4; AF-4 proto-oncoprotein

    5. XM_011531973.4 → XP_011530275.1  AF4/FMR2 family member 1 isoform X1

      See identical proteins and their annotated locations for XP_011530275.1

      UniProtKB/TrEMBL
      Q6LA76
      Conserved Domains (1) summary
      pfam05110
      Location:16 → 1211
      AF-4; AF-4 proto-oncoprotein

    6. XM_047415703.1 → XP_047271659.1  AF4/FMR2 family member 1 isoform X2

    7. XM_047415705.1 → XP_047271661.1  AF4/FMR2 family member 1 isoform X5

    8. XM_005263013.5 → XP_005263070.1  AF4/FMR2 family member 1 isoform X4

      UniProtKB/TrEMBL
      A0A669KBI3
      Related
      ENSP00000501252.1, ENST00000674009.1
      Conserved Domains (1) summary
      pfam05110
      Location:16 → 1057
      AF-4; AF-4 proto-oncoprotein

    9. XM_047415704.1 → XP_047271660.1  AF4/FMR2 family member 1 isoform X3

    10. XM_017008216.2 → XP_016863705.1  AF4/FMR2 family member 1 isoform X5

      UniProtKB/TrEMBL
      B4DJU9
      Conserved Domains (1) summary
      pfam05110
      Location:1 → 842
      AF-4; AF-4 proto-oncoprotein

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      90264015..90470100
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054350053.1 → XP_054206028.1  AF4/FMR2 family member 1 isoform X1

    2. XM_054350056.1 → XP_054206031.1  AF4/FMR2 family member 1 isoform X2

    3. XM_054350059.1 → XP_054206034.1  AF4/FMR2 family member 1 isoform X5

    4. XM_054350054.1 → XP_054206029.1  AF4/FMR2 family member 1 isoform X2

    5. XM_054350060.1 → XP_054206035.1  AF4/FMR2 family member 1 isoform X5

    6. XM_054350058.1 → XP_054206033.1  AF4/FMR2 family member 1 isoform X4

    7. XM_054350052.1 → XP_054206027.1  AF4/FMR2 family member 1 isoform X1

    8. XM_054350055.1 → XP_054206030.1  AF4/FMR2 family member 1 isoform X2

    9. XM_054350057.1 → XP_054206032.1  AF4/FMR2 family member 1 isoform X3

    10. XM_054350061.1 → XP_054206036.1  AF4/FMR2 family member 1 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51825.1 GenPept UniProtKB/Swiss-Prot:P51825

    Gene LinkOut

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