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

    Gene ID: 4299, updated on 27-Nov-2024

    Summary

    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
    NEW
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    Try the new Transcript table

    Genomic context

    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

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    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

    HIV-1 interactions

    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

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    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

    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)

    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_001166693.3NP_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:161211
      AF-4; AF-4 proto-oncoprotein
    2. NM_001313959.2NP_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:91204
      AF-4; AF-4 proto-oncoprotein
    3. NM_001313960.2NP_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:1842
      AF-4; AF-4 proto-oncoprotein
    4. NM_005935.4NP_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:91203
      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_005263007.4XP_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:161211
      AF-4; AF-4 proto-oncoprotein
    2. XM_047415702.1XP_047271658.1  AF4/FMR2 family member 1 isoform X2

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

      UniProtKB/TrEMBL
      Q6LA76
      Conserved Domains (1) summary
      pfam05110
      Location:161210
      AF-4; AF-4 proto-oncoprotein
    4. XM_017008215.3XP_016863704.1  AF4/FMR2 family member 1 isoform X5

      UniProtKB/TrEMBL
      B4DJU9
      Conserved Domains (1) summary
      pfam05110
      Location:1842
      AF-4; AF-4 proto-oncoprotein
    5. XM_011531973.4XP_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:161211
      AF-4; AF-4 proto-oncoprotein
    6. XM_047415703.1XP_047271659.1  AF4/FMR2 family member 1 isoform X2

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

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

      UniProtKB/TrEMBL
      A0A669KBI3
      Related
      ENSP00000501252.1, ENST00000674009.1
      Conserved Domains (1) summary
      pfam05110
      Location:161057
      AF-4; AF-4 proto-oncoprotein
    9. XM_047415704.1XP_047271660.1  AF4/FMR2 family member 1 isoform X3

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

      UniProtKB/TrEMBL
      B4DJU9
      Conserved Domains (1) summary
      pfam05110
      Location:1842
      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_054350053.1XP_054206028.1  AF4/FMR2 family member 1 isoform X1

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

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

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

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

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

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

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

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

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