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U2AF2 U2 small nuclear RNA auxiliary factor 2 [ Homo sapiens (human) ]

Gene ID: 11338, updated on 3-Jan-2021

Summary

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Official Symbol
U2AF2provided by HGNC
Official Full Name
U2 small nuclear RNA auxiliary factor 2provided by HGNC
Primary source
HGNC:HGNC:23156
See related
Ensembl:ENSG00000063244 MIM:191318
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
U2AF65
Summary
U2 auxiliary factor (U2AF), comprised of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in spleen (RPKM 33.5), appendix (RPKM 33.2) and 25 other tissues See more
Orthologs
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Genomic context

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See U2AF2 in Genome Data Viewer
Location:
19q13.42
Exon count:
14
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 19 NC_000019.10 (55654132..55674716)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (56165416..56186082)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene zinc finger protein 581 Neighboring gene zinc finger protein 580 Neighboring gene coiled-coil domain containing 106 Neighboring gene epsin 1 Neighboring gene vomeronasal 1 receptor 106 pseudogene Neighboring gene NLR family pyrin domain containing 9 Neighboring gene RN7SK pseudogene 109

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. An autoinhibitory intramolecular interaction proof-reads RNA recognition by the essential splicing factor U2AF2. Kang HS, et al. Proc Natl Acad Sci U S A, 2020 Mar 31. PMID 32188783, Free PMC Article
  2. In vitro iCLIP-based modeling uncovers how the splicing factor U2AF2 relies on regulation by cofactors. Sutandy FXR, et al. Genome Res, 2018 May. PMID 29643205, Free PMC Article
  3. Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs. Melé M, et al. Genome Res, 2017 Jan. PMID 27927715, Free PMC Article
  4. An extended U2AF(65)-RNA-binding domain recognizes the 3' splice site signal. Agrawal AA, et al. Nat Commun, 2016 Mar 8. PMID 26952537, Free PMC Article
  5. Circulating U2 small nuclear RNA fragments as a diagnostic and prognostic biomarker in lung cancer patients. Köhler J, et al. J Cancer Res Clin Oncol, 2016 Apr. PMID 26687686

See all (205) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. intrinsically disordered linker region connecting the two RNA recognition motif domains of U2AF2 mediates autoinhibitory intramolecular interactions to reduce nonproductive binding to weak Py-tract RNAs
    Title: An autoinhibitory intramolecular interaction proof-reads RNA recognition by the essential splicing factor U2AF2.
  2. The splicing factors U2AF65 and CAPERalpha engage multivalent interactions through their low complexity RS domains. The resulting assemblies can bridge the U2snRNP component SF3b155 with repeated polypyrimidine tracts in introns, to promote alternative splicing.
    Title: U2AF<sup>65</sup> assemblies drive sequence-specific splice site recognition.
  3. Taken together, the present study provides the first evidence that OTUB2 acts as a pivotal driver in non-small cell lung cancer tumorigenesis by stabilizing U2AF2 and activating the AKT/mTOR pathway and the Warburg effect.
    Title: OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer.
  4. The highly conserved Trp45 in the Rev ULM is crucial for UHM binding in vitro, for Rev co-precipitation with U2AF65 in human cells and for proper processing of HIV transcripts
    Title: Modulation of HIV-1 gene expression by binding of a ULM motif in the Rev protein to UHM-containing splicing factors.
  5. Data show that trans-acting RNA-binding proteins (RBPs) extensively regulate U2 (RNU2) small nuclear RNA auxiliary factor 2 protein (U2AF2) binding in vivo, including enhanced recruitment to 3' splice sites and clearance of introns
    Title: In vitro iCLIP-based modeling uncovers how the splicing factor U2AF2 relies on regulation by cofactors.
  6. Data suggest that one way heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) regulates exon definition is to modulate the interaction of U2 small nuclear RNA auxiliary factor 2 (U2AF2) with decoy or bona fide 3' splice site (3'ss).
    Title: HNRNPA1 promotes recognition of splice site decoys by U2AF2 in vivo.
  7. In summary, we provide insight into the underlying molecular mechanism of U2AF binding to 3' splice sites.
    Title: Recognition of the 3' splice site RNA by the U2AF heterodimer involves a dynamic population shift.
  8. the most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers but may be partially attributed to lower U2AF65 binding and weaker splicing-related motifs.
    Title: Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs.
  9. RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.
    Title: Global regulation of alternative RNA splicing by the SR-rich protein RBM39.
  10. These findings uncovered a hitherto unappreciated function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative splicing and cancer aggressiveness, with potential prognostic and therapeutic implications in melanoma
    Title: CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation.
Submit: New GeneRIF Correction See all GeneRIFs (51)

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)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Expression of HIV-1 Tat upregulates the abundance of U2 small nuclear RNA auxiliary factor 2 (U2AF2) in the nucleoli of Jurkat T-cells 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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
C2H2 zinc finger domain binding IEA
Inferred from Electronic Annotation
more info
  
RNA binding HDA PubMed 
enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
poly-pyrimidine tract binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
pre-mRNA 3'-splice site binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
pre-mRNA 3'-splice site binding IDA
Inferred from Direct Assay
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
RNA export from nucleus TAS
Traceable Author Statement
more info
  
mRNA 3'-end processing TAS
Traceable Author Statement
more info
  
mRNA export from nucleus TAS
Traceable Author Statement
more info
  
mRNA processing TAS
Traceable Author Statement
more info
 PubMed 
mRNA splicing, via spliceosome IC
Inferred by Curator
more info
 PubMed 
mRNA splicing, via spliceosome IDA
Inferred from Direct Assay
more info
 PubMed 
mRNA splicing, via spliceosome TAS
Traceable Author Statement
more info
  
negative regulation of mRNA splicing, via spliceosome IDA
Inferred from Direct Assay
more info
 PubMed 
negative regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
negative regulation of protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of RNA splicing IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
colocalizes_with Prp19 complex IDA
Inferred from Direct Assay
more info
 PubMed 
U2-type prespliceosome IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
U2-type prespliceosome IDA
Inferred from Direct Assay
more info
 PubMed 
U2AF complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
U2AF complex IDA
Inferred from Direct Assay
more info
 PubMed 
commitment complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nuclear speck IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nuclear speck IDA
Inferred from Direct Assay
more info
 PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
  
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
spliceosomal complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
splicing factor U2AF 65 kDa subunit
Names
U2 (RNU2) small nuclear RNA auxiliary factor 2
U2 auxiliary factor 65 kDa subunit
U2 small nuclear ribonucleoprotein auxiliary factor (65kD)
U2 snRNP auxiliary factor large subunit
hU2AF65

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_032904.1 RefSeqGene

    Range
    5001..25667
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_623

mRNA and Protein(s)

  1. NM_001012478.2 → NP_001012496.1  splicing factor U2AF 65 kDa subunit isoform b

    See identical proteins and their annotated locations for NP_001012496.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AC008735, BC008740, BC030574
    Consensus CDS
    CCDS46197.1
    UniProtKB/Swiss-Prot
    P26368
    Related
    ENSP00000388475.1, ENST00000450554.6
    Conserved Domains (1) summary
    TIGR01642
    Location:63 → 470
    U2AF_lg; U2 snRNP auxilliary factor, large subunit, splicing factor

  2. NM_007279.3 → NP_009210.1  splicing factor U2AF 65 kDa subunit isoform a

    See identical proteins and their annotated locations for NP_009210.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AC008735, BC008740, BC030574, X64044
    Consensus CDS
    CCDS12933.1
    UniProtKB/Swiss-Prot
    P26368
    Related
    ENSP00000307863.3, ENST00000308924.8
    Conserved Domains (1) summary
    TIGR01642
    Location:63 → 474
    U2AF_lg; U2 snRNP auxilliary factor, large subunit, splicing factor

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p13 Primary Assembly

    Range
    55654132..55674716
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006722994.2 → XP_006723057.1  splicing factor U2AF 65 kDa subunit isoform X2

    Related
    ENSP00000466935.1, ENST00000590551.1
    Conserved Domains (3) summary
    cd12230
    Location:1 → 65
    RRM1_U2AF65; RNA recognition motif 1 found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins
    cd12231
    Location:95 → 171
    RRM2_U2AF65; RNA recognition motif 2 found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins
    cd12232
    Location:211 → 297
    RRM3_U2AF65; RNA recognition motif 3 found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins

  2. XM_011526410.1 → XP_011524712.1  splicing factor U2AF 65 kDa subunit isoform X1

    Conserved Domains (3) summary
    cd12230
    Location:44 → 125
    RRM1_U2AF65; RNA recognition motif 1 found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins
    cd12231
    Location:155 → 231
    RRM2_U2AF65; RNA recognition motif 2 found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins
    cd12232
    Location:271 → 357
    RRM3_U2AF65; RNA recognition motif 3 found in U2 large nuclear ribonucleoprotein auxiliary factor U2AF 65 kDa subunit (U2AF65) and similar proteins
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P26368.4 GenPept UniProtKB/Swiss-Prot:P26368

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