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

Summary

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: mouse all

Genomic context

Location:: 19q13.42

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	19	NC_000019.10 (55654050..55674716)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (56165416..56186082)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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.
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.
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.
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.
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.
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.
JMJD6 regulated a large set of alternative splicing events, and importantly, its regulated splicing events were significantly overlapped those controlled by U2AF65.
Title: JMJD6 and U2AF65 co-regulate alternative splicing in both JMJD6 enzymatic activity dependent and independent manner.
This study therefore establishes a structural basis for specific UHM-ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.
Title: UHM-ULM interactions in the RBM39-U2AF65 splicing-factor complex.
The U2AF(65) linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3' terminus and third nucleotide.
Title: An extended U2AF(65)-RNA-binding domain recognizes the 3' splice site signal.
Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65
Title: Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65.

Submit: New GeneRIF Correction See all GeneRIFs (47)

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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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 BioSystems

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Cleavage of Growing Transcript in the Termination Region, organism-specific biosystem (from REACTOME)
Cleavage of Growing Transcript in the Termination Region, organism-specific biosystemThis section includes the cleavage of both polyadenylated and non-polyadenylated transcripts. In the former case polyadenylation has to precede transcript cleavage, while in the latter case there is ...
Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Processing of Capped Intron-Containing Pre-mRNA, organism-specific biosystem (from REACTOME)
Processing of Capped Intron-Containing Pre-mRNA, organism-specific biosystemCo-transcriptional pre-mRNA splicing is not obligatory. Pre-mRNA splicing begins co-transcriptionally and often continues post-transcriptionally. Human genes contain an average of nine introns per ge...
RNA Polymerase II Transcription, organism-specific biosystem (from REACTOME)
RNA Polymerase II Transcription, organism-specific biosystem
RNA Polymerase II Transcription
RNA Polymerase II Transcription Termination, organism-specific biosystem (from REACTOME)
RNA Polymerase II Transcription Termination, organism-specific biosystemThe detailed annotation of this section will be completed in the next release.
Spliceosome, organism-specific biosystem (from KEGG)
Spliceosome, organism-specific biosystemAfter transcription, eukaryotic mRNA precursors contain protein-coding exons and noncoding introns. In the following splicing, introns are excised and exons are joined by a macromolecular complex, th...
Spliceosome, conserved biosystem (from KEGG)
Spliceosome, conserved biosystemAfter transcription, eukaryotic mRNA precursors contain protein-coding exons and noncoding introns. In the following splicing, introns are excised and exons are joined by a macromolecular complex, th...
Transport of Mature Transcript to Cytoplasm, organism-specific biosystem (from REACTOME)
Transport of Mature Transcript to Cytoplasm, organism-specific biosystemTransport of mRNA through the Nuclear Pore Complex (NPC) is a dynamic process involving distinct machinery and receptor subsets. The separation of the two compartments and the regulation of this tran...
Transport of Mature mRNA derived from an Intron-Containing Transcript, organism-specific biosystem (from REACTOME)
Transport of Mature mRNA derived from an Intron-Containing Transcript, organism-specific biosystemTransport of mRNA from the nucleus to the cytoplasm, where it is translated into protein, is highly selective and closely coupled to correct RNA processing. This coupling is achieved by the nuclear p...
mRNA 3'-end processing, organism-specific biosystem (from REACTOME)
mRNA 3'-end processing, organism-specific biosystemThe 3' ends of eukaryotic mRNAs are generated by posttranscriptional processing of an extended primary transcript. For almost all RNAs, 3'-end processing consists of two steps: (i) the mRNA is first ...
mRNA Processing, organism-specific biosystem (from WikiPathways)
mRNA Processing, organism-specific biosystemThis process describes the conversion of precursor messenger RNA into mature messenger RNA (mRNA). The pre-mRNA molecule undergoes three main modifications. These modifications are 5' capping, 3' po...
mRNA Splicing, organism-specific biosystem (from REACTOME)
mRNA Splicing, organism-specific biosystemThe process in which excision of introns from the primary transcript of messenger RNA (mRNA) is followed by ligation of the two exon termini exposed by removal of each intron, is called mRNA splicing...
mRNA Splicing - Major Pathway, organism-specific biosystem (from REACTOME)
mRNA Splicing - Major Pathway, organism-specific biosystemThe splicing of pre-mRNA occurs within a large, very dynamic complex, designated the 'spliceosome'. The 50-60S spliceosomes are estimated to be 40-60 nm in diameter, and have molecular weights in the...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

U2af2 (e-PCR), detects polymorphism
- UniSTS:479300

RH92186 (e-PCR)
- UniSTS:85406

U2AF2_7999 (e-PCR)
- UniSTS:467966

Homology

Homologs of the U2AF2 gene: The U2AF2 gene is conserved in dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, C.elegans, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 175 organisms have orthologs with human gene U2AF2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
C2H2 zinc finger domain binding	IEA Inferred from Electronic Annotation more info
RNA binding	HDA more info	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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
U2AF	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

NG_032904.1 RefSeqGene

Range

5001..25667

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_623

mRNA and Protein(s)

NM_001012478.1 → 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)

BC008740, BC030574, CN364862

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
NM_007279.2 → 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)

BC008740, BC030574, CN364862, X64044

Consensus CDS

CCDS12933.1

UniProtKB/Swiss-Prot

P26368

Related

ENSP00000307863.3, ENST00000308924.8

Conserved Domains (1) summary

cl25887
Location:63 → 474

RRM; RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p12 Primary Assembly

Range

55654050..55674716

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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