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Protein

Splicing factor U2AF 65 kDa subunit

Gene

U2AF2

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

Functioni

Plays a role in pre-mRNA splicing and 3'-end processing (PubMed:17024186). 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. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186).5 Publications

GO - Molecular functioni

  • C2H2 zinc finger domain binding Source: Ensembl
  • enzyme binding Source: UniProtKB
  • poly-pyrimidine tract binding Source: GO_Central
  • pre-mRNA 3'-splice site binding Source: GO_Central
  • RNA binding Source: UniProtKB

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
  • negative regulation of protein ubiquitination Source: BHF-UCL
  • positive regulation of RNA splicing Source: UniProtKB
  • RNA export from nucleus Source: Reactome

Keywordsi

Molecular functionRepressor, RNA-binding
Biological processmRNA processing, mRNA splicing

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000063244.12
HGNCiHGNC:23156 U2AF2
MIMi191318 gene
neXtProtiNX_P26368

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 JMJD6; alternate1 Publication1
Cross-linki15Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
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-CutDBiP26368

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 (PubMed:11551507). Binds unphosphorylated SF1 (PubMed:10449420, PubMed:12718882). Interacts with SCAF11 and SNW1 (PubMed:9447963, PubMed:21460037). Interacts with ZRSR2/U2AF1-RS2. Interacts with RBM17 (PubMed:17589525). 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 (PubMed:21536736). Interacts with KHDC4 (Isoform 2) (PubMed:19641227). Interacts with ZRSR2 (PubMed:9237760). Interacts with the SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A (PubMed:27720643). Interacts (via N-terminus) with CPSF7 (via C-terminus); this interaction stimulates pre-mRNA 3'-end processing by promoting the recruitment of the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186).By similarity12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • C2H2 zinc finger domain binding Source: Ensembl
  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116466, 381 interactors
CORUMiP26368
DIPiDIP-2154N
IntActiP26368, 69 interactors
MINTiP26368
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[»]
5W0GX-ray1.07A148-229[»]
5W0HX-ray1.11A258-336[»]
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
Regioni17 – 47Necessary and sufficient to stimulate pre-mRNAs 3'-end cleavage in a CFIm complex-dependent manner1 PublicationAdd BLAST31

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

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.70.330, 5 hits
InterProiView protein in InterPro
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
IPR006529 U2AF_lg
PfamiView protein in Pfam
PF00076 RRM_1, 3 hits
SMARTiView protein in SMART
SM00360 RRM, 3 hits
SUPFAMiSSF54928 SSF54928, 3 hits
TIGRFAMsiTIGR01642 U2AF_lg, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 3 hits

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

Similar proteinsi

Entry informationi

Entry nameiU2AF2_HUMAN
AccessioniPrimary (citable) accession number: P26368
Secondary accession number(s): Q96HC5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 205 of the entry and version 4 of the sequence. See 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
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