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Protein

Splicing factor U2AF 65 kDa subunit

Gene

U2AF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Necessary for the splicing of pre-mRNA. By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing (PubMed:21536736). Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10.4 Publications

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • nucleotide binding Source: InterPro
  • poly(A) RNA binding Source: UniProtKB
  • poly-pyrimidine tract binding Source: GO_Central
  • pre-mRNA 3'-splice site binding Source: GO_Central

GO - Biological processi

  • mRNA 3'-end processing Source: Reactome
  • mRNA export from nucleus Source: Reactome
  • mRNA processing Source: ProtInc
  • mRNA splicing, via spliceosome Source: GO_Central
  • negative regulation of mRNA splicing, via spliceosome Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • positive regulation of RNA splicing Source: UniProtKB
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • RNA export from nucleus Source: Reactome
  • termination of RNA polymerase II transcription Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

mRNA processing, mRNA splicing

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063244-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
SIGNORiP26368.

Names & Taxonomyi

Protein namesi
Recommended name:
Splicing factor U2AF 65 kDa subunit
Alternative name(s):
U2 auxiliary factor 65 kDa subunit
Short name:
hU2AF(65)
Short name:
hU2AF65
U2 snRNP auxiliary factor large subunit
Gene namesi
Name:U2AF2
Synonyms:U2AF65
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:23156. U2AF2.

Subcellular locationi

GO - Cellular componenti

  • commitment complex Source: GO_Central
  • nuclear speck Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: GO_Central
  • spliceosomal complex Source: HGNC
  • U2AF Source: GO_Central
  • U2-type prespliceosome Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Nucleus, Spliceosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92W → A: Decreases affinity for UAF1 by 3 orders of magnitude. 1 Publication1
Mutagenesisi96P → G: Decreases affinity for UAF1 by 2 orders of magnitude. 1 Publication1
Mutagenesisi104P → G: Decreases affinity for UAF1 by 2 orders of magnitude. 1 Publication1
Mutagenesisi387 – 388EE → RR: Reduces interaction with SF1. 1 Publication2
Mutagenesisi391 – 394DDEE → AAAA: Reduces interaction with SF1. 4
Mutagenesisi391 – 394DDEE → RRKK: Reduces interaction with SF1. 4
Mutagenesisi396 – 397EE → AA: No effect. 1 Publication2
Mutagenesisi396 – 397EE → GA: Reduces interaction with SF1. 1 Publication2
Mutagenesisi396 – 397EE → KK: Reduces interaction with SF1. 1 Publication2
Mutagenesisi454F → A: Reduces interaction with SF1. 1 Publication1

Organism-specific databases

DisGeNETi11338.
OpenTargetsiENSG00000063244.
PharmGKBiPA134908683.

Polymorphism and mutation databases

BioMutaiU2AF2.
DMDMi267188.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000819882 – 475Splicing factor U2AF 65 kDa subunitAdd BLAST474

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei2PhosphoserineCombined sources1
Modified residuei155-hydroxylysine; by JMJD61 Publication1
Modified residuei70N6-acetyllysine; alternateCombined sources1
Cross-linki70Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei79PhosphoserineCombined sources1
Modified residuei2765-hydroxylysine; by JMJD61 Publication1
Modified residuei294PhosphoserineCombined sources1

Post-translational modificationi

Lysyl-hydroxylation at Lys-15 and Lys-276 affects the mRNA splicing activity of the protein, leading to regulate some, but not all, alternative splicing events.1 Publication

Keywords - PTMi

Acetylation, Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP26368.
MaxQBiP26368.
PaxDbiP26368.
PeptideAtlasiP26368.
PRIDEiP26368.
TopDownProteomicsiP26368-1. [P26368-1]
P26368-2. [P26368-2]

PTM databases

iPTMnetiP26368.
PhosphoSitePlusiP26368.
SwissPalmiP26368.

Miscellaneous databases

PMAP-CutDBP26368.

Expressioni

Gene expression databases

BgeeiENSG00000063244.
CleanExiHS_U2AF2.
ExpressionAtlasiP26368. baseline and differential.
GenevisibleiP26368. HS.

Organism-specific databases

HPAiCAB010910.
HPA041943.
HPA043562.

Interactioni

Subunit structurei

Interacts with U2AF1L4 (By similarity). Heterodimer with U2AF1. Binds unphosphorylated SF1. Interacts with SCAF11 and SNW1. Interacts with ZRSR2/U2AF1-RS2. Interacts with RBM17. Interacts with PRPF19; the interaction is direct. Interacts with POLR2A (via the C-terminal domain); recruits PRPF19 and the Prp19 complex to the pre-mRNA.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AESQ081173EBI-742339,EBI-717810
ATXN1P542534EBI-742339,EBI-930964
CHERPQ8IWX82EBI-742339,EBI-2555370
CPSF7Q8N6842EBI-742339,EBI-746909
DACH1Q9UI36-23EBI-742339,EBI-10186082
DDX39BQ138384EBI-11097439,EBI-348622
MUC1P159412EBI-742339,EBI-2804728
PRPF3O433952EBI-742339,EBI-744322
PUF60Q9UHX15EBI-742339,EBI-1053259
RBM10P981752EBI-742339,EBI-721525
RBM5P527562EBI-742339,EBI-714003
SF1Q1563712EBI-742339,EBI-744603
SNRPAP090125EBI-742339,EBI-607085
SNW1Q135735EBI-742339,EBI-632715
SRPK2P783624EBI-742339,EBI-593303
SUGP1Q8IWZ83EBI-742339,EBI-2691671
THAP1Q9NVV94EBI-742339,EBI-741515
U2AF1Q0108111EBI-742339,EBI-632461
U2AF1L5P0DN764EBI-11097439,EBI-11955147

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116466. 181 interactors.
DIPiDIP-2154N.
IntActiP26368. 63 interactors.
MINTiMINT-1192370.
STRINGi9606.ENSP00000307863.

Structurei

Secondary structure

1475
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi104 – 109Combined sources6
Helixi147 – 149Combined sources3
Beta strandi150 – 155Combined sources6
Helixi162 – 175Combined sources14
Beta strandi180 – 183Combined sources4
Beta strandi185 – 191Combined sources7
Beta strandi193 – 204Combined sources12
Helixi205 – 211Combined sources7
Helixi212 – 214Combined sources3
Beta strandi219 – 222Combined sources4
Beta strandi225 – 227Combined sources3
Beta strandi238 – 240Combined sources3
Beta strandi244 – 246Combined sources3
Beta strandi261 – 264Combined sources4
Helixi272 – 280Combined sources9
Beta strandi281 – 283Combined sources3
Beta strandi285 – 292Combined sources8
Turni294 – 296Combined sources3
Beta strandi299 – 309Combined sources11
Helixi312 – 320Combined sources9
Beta strandi326 – 328Combined sources3
Beta strandi331 – 334Combined sources4
Helixi335 – 338Combined sources4
Beta strandi376 – 383Combined sources8
Helixi386 – 389Combined sources4
Helixi392 – 406Combined sources15
Turni407 – 409Combined sources3
Beta strandi414 – 416Combined sources3
Turni422 – 424Combined sources3
Turni427 – 430Combined sources4
Beta strandi431 – 435Combined sources5
Helixi439 – 449Combined sources11
Beta strandi454 – 457Combined sources4
Beta strandi460 – 463Combined sources4
Helixi466 – 470Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JMTX-ray2.20B85-112[»]
1O0PNMR-A372-475[»]
1OPINMR-A372-475[»]
1U2FNMR-A148-237[»]
2G4BX-ray2.50A148-336[»]
2HZCX-ray1.47A148-229[»]
2M0GNMR-B372-475[»]
2U2FNMR-A258-342[»]
2YH0NMR-A148-342[»]
2YH1NMR-A148-342[»]
3VAFX-ray2.49A/B148-336[»]
3VAGX-ray2.19A/B148-336[»]
3VAHX-ray2.50A/B148-336[»]
3VAIX-ray2.20A/B148-336[»]
3VAJX-ray1.90A/B148-336[»]
3VAKX-ray2.17A/B148-336[»]
3VALX-ray2.50A/B/D/I148-336[»]
3VAMX-ray2.40A/B148-336[»]
4FXWX-ray2.29A/C375-475[»]
4TU7X-ray2.09A/B148-336[»]
4TU8X-ray1.92A/B148-336[»]
4TU9X-ray1.99A/B148-336[»]
5EV1X-ray2.04A141-341[»]
5EV2X-ray1.86A141-341[»]
5EV3X-ray1.50A141-341[»]
5EV4X-ray1.57A141-341[»]
ProteinModelPortaliP26368.
SMRiP26368.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26368.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini149 – 231RRM 1PROSITE-ProRule annotationAdd BLAST83
Domaini259 – 337RRM 2PROSITE-ProRule annotationAdd BLAST79
Domaini385 – 466RRM 3PROSITE-ProRule annotationAdd BLAST82

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 93Required for interaction with PRPF191 PublicationAdd BLAST92

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi27 – 62Arg/Ser-rich (RS domain)Add BLAST36

Sequence similaritiesi

Belongs to the splicing factor SR family.Curated
Contains 3 RRM (RNA recognition motif) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0120. Eukaryota.
ENOG410XP92. LUCA.
GeneTreeiENSGT00790000123065.
HOGENOMiHOG000180745.
HOVERGENiHBG062169.
InParanoidiP26368.
KOiK12837.
OMAiERGHADS.
OrthoDBiEOG091G08BA.
PhylomeDBiP26368.
TreeFamiTF314111.

Family and domain databases

Gene3Di3.30.70.330. 3 hits.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
IPR006529. U2AF_lg.
[Graphical view]
PfamiPF00076. RRM_1. 3 hits.
[Graphical view]
SMARTiSM00360. RRM. 3 hits.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 3 hits.
TIGRFAMsiTIGR01642. U2AF_lg. 1 hit.
PROSITEiPS50102. RRM. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P26368-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSDFDEFERQ LNENKQERDK ENRHRKRSHS RSRSRDRKRR SRSRDRRNRD
60 70 80 90 100
QRSASRDRRR RSKPLTRGAK EEHGGLIRSP RHEKKKKVRK YWDVPPPGFE
110 120 130 140 150
HITPMQYKAM QAAGQIPATA LLPTMTPDGL AVTPTPVPVV GSQMTRQARR
160 170 180 190 200
LYVGNIPFGI TEEAMMDFFN AQMRLGGLTQ APGNPVLAVQ INQDKNFAFL
210 220 230 240 250
EFRSVDETTQ AMAFDGIIFQ GQSLKIRRPH DYQPLPGMSE NPSVYVPGVV
260 270 280 290 300
STVVPDSAHK LFIGGLPNYL NDDQVKELLT SFGPLKAFNL VKDSATGLSK
310 320 330 340 350
GYAFCEYVDI NVTDQAIAGL NGMQLGDKKL LVQRASVGAK NATLVSPPST
360 370 380 390 400
INQTPVTLQV PGLMSSQVQM GGHPTEVLCL MNMVLPEELL DDEEYEEIVE
410 420 430 440 450
DVRDECSKYG LVKSIEIPRP VDGVEVPGCG KIFVEFTSVF DCQKAMQGLT
460 470
GRKFANRVVV TKYCDPDSYH RRDFW
Length:475
Mass (Da):53,501
Last modified:January 23, 2007 - v4
Checksum:i26AD271CD8FC6211
GO
Isoform 2 (identifier: P26368-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     345-348: Missing.

Show »
Length:471
Mass (Da):53,121
Checksum:i3F59A02CD2B03F46
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035414345 – 348Missing in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X64044 mRNA. Translation: CAA45409.1.
CH471135 Genomic DNA. Translation: EAW72404.1.
BC008740 mRNA. Translation: AAH08740.1.
BC030574 mRNA. Translation: AAH30574.1.
CCDSiCCDS12933.1. [P26368-1]
CCDS46197.1. [P26368-2]
PIRiS20250.
RefSeqiNP_001012496.1. NM_001012478.1. [P26368-2]
NP_009210.1. NM_007279.2. [P26368-1]
UniGeneiHs.528007.

Genome annotation databases

EnsembliENST00000308924; ENSP00000307863; ENSG00000063244. [P26368-1]
ENST00000450554; ENSP00000388475; ENSG00000063244. [P26368-2]
GeneIDi11338.
KEGGihsa:11338.
UCSCiuc002qlt.4. human. [P26368-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X64044 mRNA. Translation: CAA45409.1.
CH471135 Genomic DNA. Translation: EAW72404.1.
BC008740 mRNA. Translation: AAH08740.1.
BC030574 mRNA. Translation: AAH30574.1.
CCDSiCCDS12933.1. [P26368-1]
CCDS46197.1. [P26368-2]
PIRiS20250.
RefSeqiNP_001012496.1. NM_001012478.1. [P26368-2]
NP_009210.1. NM_007279.2. [P26368-1]
UniGeneiHs.528007.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JMTX-ray2.20B85-112[»]
1O0PNMR-A372-475[»]
1OPINMR-A372-475[»]
1U2FNMR-A148-237[»]
2G4BX-ray2.50A148-336[»]
2HZCX-ray1.47A148-229[»]
2M0GNMR-B372-475[»]
2U2FNMR-A258-342[»]
2YH0NMR-A148-342[»]
2YH1NMR-A148-342[»]
3VAFX-ray2.49A/B148-336[»]
3VAGX-ray2.19A/B148-336[»]
3VAHX-ray2.50A/B148-336[»]
3VAIX-ray2.20A/B148-336[»]
3VAJX-ray1.90A/B148-336[»]
3VAKX-ray2.17A/B148-336[»]
3VALX-ray2.50A/B/D/I148-336[»]
3VAMX-ray2.40A/B148-336[»]
4FXWX-ray2.29A/C375-475[»]
4TU7X-ray2.09A/B148-336[»]
4TU8X-ray1.92A/B148-336[»]
4TU9X-ray1.99A/B148-336[»]
5EV1X-ray2.04A141-341[»]
5EV2X-ray1.86A141-341[»]
5EV3X-ray1.50A141-341[»]
5EV4X-ray1.57A141-341[»]
ProteinModelPortaliP26368.
SMRiP26368.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116466. 181 interactors.
DIPiDIP-2154N.
IntActiP26368. 63 interactors.
MINTiMINT-1192370.
STRINGi9606.ENSP00000307863.

PTM databases

iPTMnetiP26368.
PhosphoSitePlusiP26368.
SwissPalmiP26368.

Polymorphism and mutation databases

BioMutaiU2AF2.
DMDMi267188.

Proteomic databases

EPDiP26368.
MaxQBiP26368.
PaxDbiP26368.
PeptideAtlasiP26368.
PRIDEiP26368.
TopDownProteomicsiP26368-1. [P26368-1]
P26368-2. [P26368-2]

Protocols and materials databases

DNASUi11338.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308924; ENSP00000307863; ENSG00000063244. [P26368-1]
ENST00000450554; ENSP00000388475; ENSG00000063244. [P26368-2]
GeneIDi11338.
KEGGihsa:11338.
UCSCiuc002qlt.4. human. [P26368-1]

Organism-specific databases

CTDi11338.
DisGeNETi11338.
GeneCardsiU2AF2.
HGNCiHGNC:23156. U2AF2.
HPAiCAB010910.
HPA041943.
HPA043562.
MIMi191318. gene.
neXtProtiNX_P26368.
OpenTargetsiENSG00000063244.
PharmGKBiPA134908683.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0120. Eukaryota.
ENOG410XP92. LUCA.
GeneTreeiENSGT00790000123065.
HOGENOMiHOG000180745.
HOVERGENiHBG062169.
InParanoidiP26368.
KOiK12837.
OMAiERGHADS.
OrthoDBiEOG091G08BA.
PhylomeDBiP26368.
TreeFamiTF314111.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063244-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
SIGNORiP26368.

Miscellaneous databases

ChiTaRSiU2AF2. human.
EvolutionaryTraceiP26368.
GeneWikiiU2AF2.
GenomeRNAii11338.
PMAP-CutDBP26368.
PROiP26368.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000063244.
CleanExiHS_U2AF2.
ExpressionAtlasiP26368. baseline and differential.
GenevisibleiP26368. HS.

Family and domain databases

Gene3Di3.30.70.330. 3 hits.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
IPR006529. U2AF_lg.
[Graphical view]
PfamiPF00076. RRM_1. 3 hits.
[Graphical view]
SMARTiSM00360. RRM. 3 hits.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 3 hits.
TIGRFAMsiTIGR01642. U2AF_lg. 1 hit.
PROSITEiPS50102. RRM. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiU2AF2_HUMAN
AccessioniPrimary (citable) accession number: P26368
Secondary accession number(s): Q96HC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 192 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.