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AFF1 AF4/FMR2 family member 1 [ Homo sapiens (human) ]

Gene ID: 4299, updated on 22-Jan-2020

Summary

Official Symbol
AFF1provided by HGNC
Official Full Name
AF4/FMR2 family member 1provided by HGNC
Primary source
HGNC:HGNC:7135
See related
Ensembl:ENSG00000172493 MIM:159557
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; 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

Genomic context

See AFF1 in Genome Data Viewer
Location:
4q21.3-q22.1
Exon count:
25
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 4 NC_000004.12 (86934606..87141054)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (87855758..88062206)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene chromosome 4 open reading frame 36 Neighboring gene actin related protein 2/3 complex subunit 1A pseudogene Neighboring gene AFF1 antisense RNA 1 Neighboring gene trans-2,3-enoyl-CoA reductase pseudogene 1 Neighboring gene uncharacterized LOC105377320 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

NHGRI GWAS Catalog

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

Homology

Clone Names

  • MGC134969

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA-binding transcription factor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
double-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
regulation of transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
ELL-EAF complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription elongation factor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
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)

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_001166693.2NP_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, AI638134, AK300364, BC114930, DC340279, L13773
    Consensus CDS
    CCDS54775.1
    UniProtKB/Swiss-Prot
    P51825
    UniProtKB/TrEMBL
    Q14C88
    Related
    ENSP00000378578.4, ENST00000395146.8
    Conserved Domains (1) summary
    pfam05110
    Location:161211
    AF-4; AF-4 proto-oncoprotein
  2. NM_001313959.1NP_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, AI638134, BC114930, L13773
    UniProtKB/Swiss-Prot
    P51825
    UniProtKB/TrEMBL
    Q14C88
    Related
    ENSP00000440843.2, ENST00000544085.5
    Conserved Domains (1) summary
    pfam05110
    Location:91204
    AF-4; AF-4 proto-oncoprotein
  3. NM_001313960.1NP_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, AI638134, AK296243, BC114930, L13773
    UniProtKB/Swiss-Prot
    P51825
    UniProtKB/TrEMBL
    B4DJU9, Q14C88
    Conserved Domains (1) summary
    pfam05110
    Location:1842
    AF-4; AF-4 proto-oncoprotein
  4. NM_005935.3NP_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, AI638134, BC114930, L13773
    Consensus CDS
    CCDS3616.1
    UniProtKB/Swiss-Prot
    P51825
    UniProtKB/TrEMBL
    Q14C88
    Related
    ENSP00000305689.6, ENST00000307808.10
    Conserved Domains (1) summary
    pfam05110
    Location:91203
    AF-4; AF-4 proto-oncoprotein

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

    Range
    86934606..87141054
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005263009.4XP_005263066.1  AF4/FMR2 family member 1 isoform X2

    Conserved Domains (1) summary
    pfam05110
    Location:161210
    AF-4; AF-4 proto-oncoprotein
  2. XM_017008215.2XP_016863704.1  AF4/FMR2 family member 1 isoform X5

    Conserved Domains (1) summary
    pfam05110
    Location:1842
    AF-4; AF-4 proto-oncoprotein
  3. XM_005263013.4XP_005263070.1  AF4/FMR2 family member 1 isoform X4

    Related
    ENSP00000501252.1, ENST00000674009.1
    Conserved Domains (1) summary
    pfam05110
    Location:161057
    AF-4; AF-4 proto-oncoprotein
  4. XM_011531973.3XP_011530275.1  AF4/FMR2 family member 1 isoform X1

    See identical proteins and their annotated locations for XP_011530275.1

    UniProtKB/Swiss-Prot
    P51825
    Conserved Domains (1) summary
    pfam05110
    Location:161211
    AF-4; AF-4 proto-oncoprotein
  5. XM_005263007.3XP_005263064.1  AF4/FMR2 family member 1 isoform X1

    See identical proteins and their annotated locations for XP_005263064.1

    UniProtKB/Swiss-Prot
    P51825
    Conserved Domains (1) summary
    pfam05110
    Location:161211
    AF-4; AF-4 proto-oncoprotein
  6. XM_005263011.3XP_005263068.1  AF4/FMR2 family member 1 isoform X3

    Conserved Domains (1) summary
    pfam05110
    Location:141209
    AF-4; AF-4 proto-oncoprotein
  7. XM_017008216.1XP_016863705.1  AF4/FMR2 family member 1 isoform X5

    Conserved Domains (1) summary
    pfam05110
    Location:1842
    AF-4; AF-4 proto-oncoprotein
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