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 snRNP auxiliary factor small subunit

Gene names

Name:	U2AF1
Synonyms:	U2AF35, U2AFBP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.5
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.6
Subcellular location	Nucleus. Nucleus speckle By similarity.
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.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.8 Ref.9
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
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 nuclear mRNA splicing, via spliceosome Inferred by curator Ref.7. Source: UniProtKB termination of RNA polymerase II transcription Traceable author statement. Source: Reactome
Cellular component	Cajal body Traceable author statement. Source: ProtInc catalytic step 2 spliceosome Inferred from direct assay Ref.7. 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 protein binding Inferred from physical interaction. Source: UniProtKB 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	3	EBI-632461,EBI-742339

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

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.4 Ref.10

Modified residue

59

1

Phosphoserine Ref.9

Modified residue

195

1

Phosphoserine Ref.8

Modified residue

197

1

Phosphoserine Ref.8

Experimental info

Mutagenesis

134

1

W → A: Decreases affinity for UAF2 by 3 orders of magnitude. Ref.12

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)
	Q01081 [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

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: 1388271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 68-89 AND 126-151. Tissue: Fetal brain.
[2]	"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: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[4]	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.
[5]	"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: 8647433] [Abstract] Cited for: FUNCTION.
[6]	"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: 11448987] [Abstract] Cited for: INTERACTION WITH ZRANB2.
[7]	"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: 11991638] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SPLICEOSOMAL C COMPLEX.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-195 AND SER-197, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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: 11551507] [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.
AP001748 Genomic DNA. Translation: BAA95534.1.
BC001177 mRNA. Translation: AAH01177.1.
BC001923 mRNA. Translation: AAH01923.1.

IPI

IPI00005613.

PIR

A46179.

RefSeq

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.

SMR

Q01081. Positions 43-146.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1108N.

IntAct

Q01081. 7 interactions.

MINT

MINT-3024108.

STRING

Q01081.

PTM databases

PhosphoSite

Q01081.

Polymorphism databases

DMDM

267187.

Proteomic databases

PeptideAtlas

Q01081.

PRIDE

Q01081.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000291552; ENSP00000291552; ENSG00000160201.

GeneID

7307.

KEGG

hsa:7307.

UCSC

uc002zdb.1. human.

Organism-specific databases

CTD

7307.

GeneCards

GC21M044513.

H-InvDB

HIX0203123.

HGNC

HGNC:12453. U2AF1.

HPA

HPA044833.

MIM

191317. gene.

neXtProt

NX_Q01081.

PharmGKB

PA37103.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12328.

HOVERGEN

HBG054605.

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

InterPro

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

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 1 hit.

KO

K12836.

PANTHER

PTHR12620. U2_small. 1 hit.

Pfam

PF00076. RRM_1. 1 hit.
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

NextBio

28572.

SOURCE

Search...

Entry information

Entry name

U2AF1_HUMAN

Accession

Primary (citable) accession number: Q01081

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 139 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.