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Protein

Splicing factor U2AF 35 kDa subunit

Gene

U2AF1

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

Functioni

Plays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3'-splice site selection. Recruits U2 snRNP to the branch point. Directly mediates interactions between U2AF2 and proteins bound to the enhancers and thus may function as a bridge between U2AF2 and the enhancer complex to recruit it to the adjacent intron.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri12 – 40C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri149 – 176C3H1-type 2PROSITE-ProRule annotationAdd BLAST28

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • 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
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • RNA export from nucleus Source: Reactome
  • RNA splicing Source: ProtInc
  • termination of RNA polymerase II transcription Source: Reactome

Keywordsi

Molecular functionRNA-binding
Biological processmRNA processing, mRNA splicing
LigandMetal-binding, Zinc

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.
SIGNORiQ01081.

Names & Taxonomyi

Protein namesi
Recommended name:
Splicing factor U2AF 35 kDa subunit
Alternative name(s):
U2 auxiliary factor 35 kDa subunit
U2 small nuclear RNA auxiliary factor 1
U2 snRNP auxiliary factor small subunit
Gene namesi
Name:U2AF1
Synonyms:U2AF35, U2AFBP
ORF Names:FP793
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:12453. U2AF1.

Subcellular locationi

GO - Cellular componenti

  • Cajal body Source: ProtInc
  • catalytic step 2 spliceosome Source: UniProtKB
  • nuclear speck Source: UniProtKB
  • nucleoplasm Source: HPA
  • spliceosomal complex Source: HGNC
  • U2AF Source: GO_Central

Keywords - Cellular componenti

Nucleus, Spliceosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi134W → A: Decreases affinity for UAF2 by 3 orders of magnitude. 1 Publication1

Organism-specific databases

DisGeNETi102724594.
7307.
OpenTargetsiENSG00000160201.
PharmGKBiPA37103.

Polymorphism and mutation databases

BioMutaiU2AF1.
DMDMi267187.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000819942 – 240Splicing factor U2AF 35 kDa subunitAdd BLAST239

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei39N6-methyllysineCombined sources1
Modified residuei61PhosphoserineCombined sources1
Modified residuei145PhosphoserineCombined sources1
Modified residuei165Omega-N-methylarginineCombined sources1
Isoform 2 (identifier: Q01081-2)
Modified residuei39N6-methyllysineCombined sources1
Isoform 3 (identifier: Q01081-3)
Modified residuei39N6-methyllysineCombined sources1

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ01081.
MaxQBiQ01081.
PaxDbiQ01081.
PeptideAtlasiQ01081.
PRIDEiQ01081.

PTM databases

iPTMnetiQ01081.
PhosphoSitePlusiQ01081.
SwissPalmiQ01081.

Expressioni

Gene expression databases

BgeeiENSG00000160201.
CleanExiHS_U2AF1.
ExpressionAtlasiQ01081. baseline and differential.
GenevisibleiQ01081. HS.

Organism-specific databases

HPAiHPA044833.
HPA052083.

Interactioni

Subunit structurei

Interacts (via RS domain) with PHF5A (via N-terminus) (By similarity). Identified in the spliceosome C complex. Heterodimer with U2AF2. Interacts with ZRANB2.By similarity3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi113157. 124 interactors.
3195698. 2 interactors.
DIPiDIP-1108N.
IntActiQ01081. 53 interactors.
MINTiMINT-1468226.
STRINGi9606.ENSP00000291552.

Structurei

Secondary structure

1240
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi45 – 53Combined sources9
Helixi64 – 92Combined sources29
Beta strandi96 – 101Combined sources6
Beta strandi104 – 118Combined sources15
Helixi120 – 130Combined sources11
Beta strandi142 – 144Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JMTX-ray2.20A43-146[»]
ProteinModelPortaliQ01081.
SMRiQ01081.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ01081.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 147RRMPROSITE-ProRule annotationAdd BLAST83

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi178 – 240Arg/Gly/Ser-rich (RS domain)Add BLAST63
Compositional biasi210 – 223Poly-GlyAdd BLAST14

Domaini

The C-terminal SR-rich domain is required for interactions with SR proteins and the splicing regulators TRA and TRA2, and the N-terminal domain is required for formation of the U2AF1/U2AF2 heterodimer.

Sequence similaritiesi

Belongs to the splicing factor SR family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri12 – 40C3H1-type 1PROSITE-ProRule annotationAdd BLAST29
Zinc fingeri149 – 176C3H1-type 2PROSITE-ProRule annotationAdd BLAST28

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG2202. Eukaryota.
ENOG410Z5PX. LUCA.
GeneTreeiENSGT00530000063193.
HOGENOMiHOG000178619.
HOVERGENiHBG054605.
InParanoidiQ01081.
KOiK12836.
OMAiMHLRLAS.
OrthoDBiEOG091G0CUI.
PhylomeDBiQ01081.
TreeFamiTF300143.

Family and domain databases

Gene3Di4.10.1000.10. 1 hit.
InterProiView protein in InterPro
IPR000504. RRM_dom.
IPR003954. RRM_dom_euk.
IPR009145. U2AF_small.
IPR000571. Znf_CCCH.
PANTHERiPTHR12620. PTHR12620. 1 hit.
PfamiView protein in Pfam
PF00076. RRM_1. 1 hit.
PF00642. zf-CCCH. 2 hits.
PRINTSiPR01848. U2AUXFACTOR.
SMARTiView protein in SMART
SM00360. RRM. 1 hit.
SM00361. RRM_1. 1 hit.
SM00356. ZnF_C3H1. 2 hits.
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiView protein in PROSITE
PS50102. RRM. 1 hit.
PS50103. ZF_C3H1. 2 hits.

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q01081-1) [UniParc]FASTAAdd to basket
Also known as: U2AF35a

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
MAEYLASIFG TEKDKVNCSF YFKIGACRHG DRCSRLHNKP TFSQTIALLN
60 70 80 90 100
IYRNPQNSSQ SADGLRCAVS DVEMQEHYDE FFEEVFTEME EKYGEVEEMN
110 120 130 140 150
VCDNLGDHLV GNVYVKFRRE EDAEKAVIDL NNRWFNGQPI HAELSPVTDF
160 170 180 190 200
REACCRQYEM GECTRGGFCN FMHLKPISRE LRRELYGRRR KKHRSRSRSR
210 220 230 240
ERRSRSRDRG RGGGGGGGGG GGGRERDRRR SRDRERSGRF
Length:240
Mass (Da):27,872
Last modified:January 23, 2007 - v3
Checksum:i3DA130DCE0B953F6
GO
Isoform 2 (identifier: Q01081-2) [UniParc]FASTAAdd to basket
Also known as: U2AF35b

The sequence of this isoform differs from the canonical sequence as follows:
     47-66: ALLNIYRNPQNSSQSADGLR → LIQNIYRNPQNSAQTADGSH

Note: Interacts with U2AF2 and stimulates U2AF splicing activity in vitro. Less efficient than isoform 1.Combined sources
Show »
Length:240
Mass (Da):27,882
Checksum:iDDBE62F36F0CDF52
GO
Isoform 3 (identifier: Q01081-3) [UniParc]FASTAAdd to basket
Also known as: U2AF35c

The sequence of this isoform differs from the canonical sequence as follows:
     47-66: ALLNIYRNPQNSSQSADGLR → LIQNIYRNPQNSAQTADGSH
     67-75: CAVSDVEMQ → YHCPLEHLP
     76-240: Missing.

Note: Produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.Combined sources
Show »
Length:75
Mass (Da):8,572
Checksum:i30BF651C83599A9D
GO
Isoform 4 (identifier: Q01081-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.

Show »
Length:167
Mass (Da):19,715
Checksum:i3EBB13A8234C736B
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0426641 – 73Missing in isoform 4. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_04266547 – 66ALLNI…ADGLR → LIQNIYRNPQNSAQTADGSH in isoform 2 and isoform 3. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_04266667 – 75CAVSDVEMQ → YHCPLEHLP in isoform 3. Curated9
Alternative sequenceiVSP_04266776 – 240Missing in isoform 3. CuratedAdd BLAST165

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96982 mRNA. Translation: AAA36619.1.
AJ627978 mRNA. Translation: CAF29556.1.
AF370386 mRNA. Translation: AAQ15222.1.
AP001631 Genomic DNA. No translation available.
AP001748 Genomic DNA. Translation: BAA95534.1.
CH471079 Genomic DNA. Translation: EAX09501.1.
CH471079 Genomic DNA. Translation: EAX09502.1.
CH471079 Genomic DNA. Translation: EAX09504.1.
CH471079 Genomic DNA. Translation: EAX09505.1.
BC001177 mRNA. Translation: AAH01177.1.
BC001923 mRNA. Translation: AAH01923.1.
CCDSiCCDS13694.1. [Q01081-1]
CCDS33574.1. [Q01081-2]
CCDS42948.1. [Q01081-4]
PIRiA46179.
RefSeqiNP_001020374.1. NM_001025203.1. [Q01081-2]
NP_001020375.1. NM_001025204.1. [Q01081-4]
NP_001307575.1. NM_001320646.1. [Q01081-1]
NP_001307577.1. NM_001320648.1. [Q01081-2]
NP_001307580.1. NM_001320651.1. [Q01081-4]
NP_006749.1. NM_006758.2. [Q01081-1]
UniGeneiHs.365116.

Genome annotation databases

EnsembliENST00000291552; ENSP00000291552; ENSG00000160201. [Q01081-1]
ENST00000380276; ENSP00000369629; ENSG00000160201. [Q01081-2]
ENST00000398137; ENSP00000381205; ENSG00000160201. [Q01081-4]
ENST00000459639; ENSP00000418705; ENSG00000160201. [Q01081-4]
ENST00000464750; ENSP00000420672; ENSG00000160201. [Q01081-3]
GeneIDi102724594.
7307.
KEGGihsa:102724594.
hsa:7307.
UCSCiuc002zcy.1. human. [Q01081-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiU2AF1_HUMAN
AccessioniPrimary (citable) accession number: Q01081
Secondary accession number(s): Q701P4, Q71RF1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: July 5, 2017
This is version 196 of the entry and version 3 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

Caution

There is a duplication of the U2AF1 gene on chromosome 21. U2AF1 (AC Q01081) and U2AF1L5 (AC P0DN76) encode identical proteins.Curated

Keywords - Technical termi

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

Documents

  1. Human chromosome 21
    Human chromosome 21: 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