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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
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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: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. 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
  2. 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
  3. Clinical and molecular spectrum of CHOPS syndrome. Raible SE, et al. Am J Med Genet A, 2019 Jul. PMID 31058441, Free PMC Article
  4. AFF4 globally affects the release of paused RNA polymerase II in HEL cells. Yang ZM, et al. Yi Chuan, 2023 Aug 20. PMID 37609817
  5. Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization. Chen Y, et al. J Biol Chem, 2019 Jul 5. PMID 31147444, Free PMC Article

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

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