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

Gene ID: 4299, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (86935011..87141039)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (90264015..90470100)
105.20220307 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
  • 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. 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
  2. Association study of AFF1 rs340630 polymorphism with genetic susceptibility to rheumatoid arthritis in Chinese population. Sun QQ, et al. Braz J Med Biol Res, 2018. PMID 29791587, Free PMC Article
  3. 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
  4. Age-related differences in leukemia biology and prognosis: the paradigm of MLL-AF4-positive acute lymphoblastic leukemia. Pui CH, et al. Leukemia, 2007 Apr. PMID 17301807
  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 (114) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. [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].
  3. 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).
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Osteopontin-c is overexpressed in KMT2A-AFF1 positive pediatric B-cell lymphoblastic leukemia when compared to those with ETV6-RUNX1"".
    Title: Osteopontin-c is overexpressed in KMT2A-AFF1 positive pediatric B-cell lymphoblastic leukemia when compared to those with ETV6-RUNX1".
Submit: New GeneRIF Correction See all GeneRIFs (48)

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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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_2023_10

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

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