Q01081 (U2AF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	U2AF1
Synonyms:	U2AF35, U2AFBP
ORF Names:	FP793

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	240 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.8
Subunit structure	Interacts (via RS domain) with PHF5A (via N-terminus) By similarity. Identified in the spliceosome C complex. Heterodimer with U2AF2. Interacts with ZRANB2. Ref.9 Ref.10
Subcellular location	Nucleus. Nucleus speckle Ref.2.
Domain	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 similarities	Belongs to the splicing factor SR family. Contains 2 C3H1-type zinc fingers. Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	mRNA 3'-end processing Traceable author statement. Source: Reactome mRNA export from nucleus Traceable author statement. Source: Reactome mRNA splicing, via spliceosome Inferred by curator Ref.10. Source: UniProtKB termination of RNA polymerase II transcription Traceable author statement. Source: Reactome
Cellular_component	Cajal body Traceable author statement Ref.1. Source: ProtInc catalytic step 2 spliceosome Inferred from direct assay Ref.10. Source: UniProtKB nuclear speck Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CIR1	Q86X95	4	EBI-632461,EBI-627102
U2AF2	P26368	6	EBI-632461,EBI-742339

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q01081-1)

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.

Isoform 2 (identifier: Q01081-2)

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.

Isoform 3 (identifier: Q01081-3)

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.

Isoform 4 (identifier: Q01081-4)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Chain

2 – 240

239

Splicing factor U2AF 35 kDa subunit

PRO_0000081994

Regions

Domain

65 – 147

83

RRM

Zinc finger

12 – 40

29

C3H1-type 1

Zinc finger

149 – 176

28

C3H1-type 2

Compositional bias

178 – 240

63

Arg/Gly/Ser-rich (RS domain)

Compositional bias

210 – 223

14

Poly-Gly

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.7

Modified residue

61

1

Phosphoserine Ref.14

Natural variations

Alternative sequence

1 – 73

73

Missing in isoform 4.

VSP_042664

Alternative sequence

47 – 66

20

ALLNI…ADGLR → LIQNIYRNPQNSAQTADGSH in isoform 2 and isoform 3.

VSP_042665

Alternative sequence

67 – 75

9

CAVSDVEMQ → YHCPLEHLP in isoform 3.

VSP_042666

Alternative sequence

76 – 240

165

Missing in isoform 3.

VSP_042667

Experimental info

Mutagenesis

134

1

W → A: Decreases affinity for UAF2 by 3 orders of magnitude. Ref.15

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

240

Helix Strand Turn

Details...

Beta strand

45 – 53

9

Helix

64 – 92

29

Beta strand

96 – 101

6

Beta strand

104 – 118

15

Helix

120 – 130

11

Beta strand

142 – 144

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (U2AF35a) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3DA130DCE0B953F6	FASTA	240	27,872
	10 20 30 40 50 60 MAEYLASIFG TEKDKVNCSF YFKIGACRHG DRCSRLHNKP TFSQTIALLN IYRNPQNSSQ 70 80 90 100 110 120 SADGLRCAVS DVEMQEHYDE FFEEVFTEME EKYGEVEEMN VCDNLGDHLV GNVYVKFRRE 130 140 150 160 170 180 EDAEKAVIDL NNRWFNGQPI HAELSPVTDF REACCRQYEM GECTRGGFCN FMHLKPISRE 190 200 210 220 230 240 LRRELYGRRR KKHRSRSRSR ERRSRSRDRG RGGGGGGGGG GGGRERDRRR SRDRERSGRF
	Isoform 2 (U2AF35b) [UniParc]. Checksum: DDBE62F36F0CDF52	FASTA	240	27,882
	10 20 30 40 50 60 MAEYLASIFG TEKDKVNCSF YFKIGACRHG DRCSRLHNKP TFSQTILIQN IYRNPQNSAQ 70 80 90 100 110 120 TADGSHCAVS DVEMQEHYDE FFEEVFTEME EKYGEVEEMN VCDNLGDHLV GNVYVKFRRE 130 140 150 160 170 180 EDAEKAVIDL NNRWFNGQPI HAELSPVTDF REACCRQYEM GECTRGGFCN FMHLKPISRE 190 200 210 220 230 240 LRRELYGRRR KKHRSRSRSR ERRSRSRDRG RGGGGGGGGG GGGRERDRRR SRDRERSGRF
	Isoform 3 (U2AF35c) [UniParc]. Checksum: 30BF651C83599A9D	FASTA	75	8,572
	10 20 30 40 50 60 MAEYLASIFG TEKDKVNCSF YFKIGACRHG DRCSRLHNKP TFSQTILIQN IYRNPQNSAQ 70 TADGSHYHCP LEHLP
	Isoform 4 [UniParc]. Checksum: 3EBB13A8234C736B	FASTA	167	19,715
	10 20 30 40 50 60 MQEHYDEFFE EVFTEMEEKY GEVEEMNVCD NLGDHLVGNV YVKFRREEDA EKAVIDLNNR 70 80 90 100 110 120 WFNGQPIHAE LSPVTDFREA CCRQYEMGEC TRGGFCNFMH LKPISRELRR ELYGRRRKKH 130 140 150 160 RSRSRSRERR SRSRDRGRGG GGGGGGGGGG RERDRRRSRD RERSGRF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit." Zhang M., Zamore P.D., Carmo-Fonseca M., Lamond A.I., Green M.R. Proc. Natl. Acad. Sci. U.S.A. 89:8769-8773(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 68-89 AND 126-151. Tissue: Fetal brain.
[2]	"Diversity of vertebrate splicing factor U2AF35: identification of alternatively spliced U2AF1 mRNAs." Pacheco T.R.D., Gomes N.L., Benes V., Ansorge W., Wollerton M., Smith C.W., Valcarcel J., Carmo-Fonseca M. J. Biol. Chem. 279:27039-27049(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION. Tissue: Spleen.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[4]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[7]	Bienvenut W.V. Submitted (JUL-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[8]	"The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing." Zuo P., Maniatis T. Genes Dev. 10:1356-1368(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"ZNF265 -- a novel spliceosomal protein able to induce alternative splicing." Adams D.J., van der Weyden L., Mayeda A., Stamm S., Morris B.J., Rasko J.E.J. J. Cell Biol. 154:25-32(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZRANB2.
[10]	"Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis." Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J. RNA 8:426-439(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPLICEOSOMAL C COMPLEX.
[11]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61, MASS SPECTROMETRY.
[15]	"A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35/U2AF65 heterodimer." Kielkopf C.L., Rodionova N.A., Green M.R., Burley S.K. Cell 106:595-605(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 43-146 IN COMPLEX WITH U2AF2, MUTAGENESIS OF TRP-134.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00005613.

PIR

A46179.

RefSeq

NP_001020374.1. NM_001025203.1.
NP_001020375.1. NM_001025204.1.
NP_006749.1. NM_006758.2.

UniGene

Hs.365116.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JMT	X-ray	2.20	A	43-146	[»]

ProteinModelPortal

Q01081.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1108N.

IntAct

Q01081. 10 interactions.

MINT

MINT-3024108.

STRING

9606.ENSP00000291552.

PTM databases

PhosphoSite

Q01081.

Polymorphism databases

DMDM

267187.

Proteomic databases

PaxDb

Q01081.

PeptideAtlas

Q01081.

PRIDE

Q01081.

Protocols and materials databases

DNASU

7307.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000291552; ENSP00000291552; ENSG00000160201.
ENST00000380276; ENSP00000369629; ENSG00000160201.
ENST00000398137; ENSP00000381205; ENSG00000160201.
ENST00000459639; ENSP00000418705; ENSG00000160201.
ENST00000464750; ENSP00000420672; ENSG00000160201.

GeneID

7307.

KEGG

hsa:7307.

UCSC

uc002zcy.1. human.

Organism-specific databases

CTD

7307.

GeneCards

GC21M044513.

HGNC

HGNC:12453. U2AF1.

HPA

HPA044833.

MIM

191317. gene.

neXtProt

NX_Q01081.

PharmGKB

PA37103.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG323920.

HOGENOM

HOG000178619.

HOVERGEN

HBG054605.

KO

K12836.

OMA

DRGGNND.

OrthoDB

EOG4MSD07.

PhylomeDB

Q01081.

Enzyme and pathway databases

Reactome

REACT_1675. mRNA Processing.
REACT_1788. Transcription.
REACT_71. Gene Expression.
REACT_78. Post-Elongation Processing of the Transcript.

Gene expression databases

ArrayExpress

Q01081.

Bgee

Q01081.

CleanEx

HS_U2AF1.

Genevestigator

Q01081.

GermOnline

ENSG00000160201. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
IPR009145. U2_small.
IPR000571. Znf_CCCH.
[Graphical view]

PANTHER

PTHR12620. PTHR12620. 1 hit.

Pfam

PF00642. zf-CCCH. 2 hits.
[Graphical view]

PRINTS

PR01848. U2AUXFACTOR.

SMART

SM00360. RRM. 1 hit.
SM00356. ZnF_C3H1. 2 hits.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
PS50103. ZF_C3H1. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

U2AF1. human.

EvolutionaryTrace

Q01081.

GenomeRNAi

7307.

NextBio

28572.

SOURCE

Search...

Entry information

Entry name

U2AF1_HUMAN

Accession

Primary (citable) accession number: Q01081
Secondary accession number(s): Q701P4, Q71RF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 153 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.