Reviewed, UniProtKB/Swiss-Prot P26368 (U2AF2_HUMAN)

Names and origin

Protein names

Recommended name:
    Splicing factor U2AF 65 kDa subunit
Alternative name(s):
    U2 auxiliary factor 65 kDa subunit
      Short name=hU2AF65
      Short name=hU2AF(65)
    U2 snRNP auxiliary factor large subunit

Gene names

Name:	U2AF2
Synonyms:	U2AF65

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	475 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	Necessary for the splicing of pre-mRNA. Binds to the polypyrimidine tract of introns early during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene.
Subunit structure	Interacts with U2AF1L4 By similarity. Heterodimer with U2AF1. Binds unphosphorylated SF1. Interacts with SFRS2IP.
Subcellular location	Nucleus.
Sequence similarities	Belongs to the splicing factor SR family. Contains 3 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Nucleus Spliceosome
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	nuclear mRNA splicing, via spliceosome Inferred by curator. Source: HGNC
Cellular component	spliceosome Inferred from direct assay. Source: HGNC
Molecular function	RNA binding Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.6 Ref.16 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P26368-1)

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: P26368-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 475

474

Splicing factor U2AF 65 kDa subunit

PRO_0000081988

Regions

Domain

149 – 231

83

RRM 1

Domain

259 – 337

79

RRM 2

Domain

385 – 466

82

RRM 3

Compositional bias

27 – 62

36

Arg/Ser-rich (RS domain)

Amino acid modifications

Modified residue

2

1

N-acetylserine

Modified residue

2

1

Phosphoserine

Modified residue

53

1

Phosphoserine

Modified residue

55

1

Phosphoserine

Modified residue

79

1

Phosphoserine

Natural variations

Alternative sequence

345 – 348

4

Missing in isoform 2.

VSP_035414

Experimental info

Mutagenesis

92

1

W → A: Decreases affinity for UAF1 by 3 orders of magnitude

Mutagenesis

96

1

P → G: Decreases affinity for UAF1 by 2 orders of magnitude

Mutagenesis

104

1

P → G: Decreases affinity for UAF1 by 2 orders of magnitude

Mutagenesis

387 – 388

2

EE → RR: Reduces interaction with SF1

Mutagenesis

391 – 394

4

DDEE → AAAA: Reduces interaction with SF1

Mutagenesis

391 – 394

4

DDEE → RRKK: Reduces interaction with SF1

Mutagenesis

396 – 397

2

EE → AA: No effect

Mutagenesis

396 – 397

2

EE → GA: Reduces interaction with SF1

Mutagenesis

396 – 397

2

EE → KK: Reduces interaction with SF1

Mutagenesis

454

1

F → A: Reduces interaction with SF1

Secondary structure

1

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475

Helix Strand Turn

Details...

Helix

104 – 109

6

Beta strand

150 – 155

6

Helix

162 – 175

14

Beta strand

180 – 183

4

Beta strand

185 – 191

7

Beta strand

193 – 204

12

Helix

205 – 211

7

Helix

212 – 214

3

Beta strand

225 – 227

3

Turn

236 – 259

24

Beta strand

261 – 264

4

Helix

272 – 280

9

Beta strand

285 – 292

8

Turn

294 – 296

3

Beta strand

298 – 309

12

Helix

312 – 320

9

Beta strand

331 – 334

4

Beta strand

376 – 383

8

Turn

386 – 390

5

Helix

392 – 406

15

Turn

407 – 409

3

Beta strand

412 – 416

5

Beta strand

421 – 425

5

Beta strand

430 – 437

8

Helix

439 – 449

11

Beta strand

454 – 457

4

Beta strand

460 – 464

5

Helix

466 – 470

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 26AD271CD8FC6211	FASTA	475	53,501
	10 20 30 40 50 60 MSDFDEFERQ LNENKQERDK ENRHRKRSHS RSRSRDRKRR SRSRDRRNRD QRSASRDRRR 70 80 90 100 110 120 RSKPLTRGAK EEHGGLIRSP RHEKKKKVRK YWDVPPPGFE HITPMQYKAM QAAGQIPATA 130 140 150 160 170 180 LLPTMTPDGL AVTPTPVPVV GSQMTRQARR LYVGNIPFGI TEEAMMDFFN AQMRLGGLTQ 190 200 210 220 230 240 APGNPVLAVQ INQDKNFAFL EFRSVDETTQ AMAFDGIIFQ GQSLKIRRPH DYQPLPGMSE 250 260 270 280 290 300 NPSVYVPGVV STVVPDSAHK LFIGGLPNYL NDDQVKELLT SFGPLKAFNL VKDSATGLSK 310 320 330 340 350 360 GYAFCEYVDI NVTDQAIAGL NGMQLGDKKL LVQRASVGAK NATLVSPPST INQTPVTLQV 370 380 390 400 410 420 PGLMSSQVQM GGHPTEVLCL MNMVLPEELL DDEEYEEIVE DVRDECSKYG LVKSIEIPRP 430 440 450 460 470 VDGVEVPGCG KIFVEFTSVF DCQKAMQGLT GRKFANRVVV TKYCDPDSYH RRDFW
	Isoform 2 [UniParc]. Checksum: 3F59A02CD2B03F46		471	53,121
	10 20 30 40 50 60 MSDFDEFERQ LNENKQERDK ENRHRKRSHS RSRSRDRKRR SRSRDRRNRD QRSASRDRRR 70 80 90 100 110 120 RSKPLTRGAK EEHGGLIRSP RHEKKKKVRK YWDVPPPGFE HITPMQYKAM QAAGQIPATA 130 140 150 160 170 180 LLPTMTPDGL AVTPTPVPVV GSQMTRQARR LYVGNIPFGI TEEAMMDFFN AQMRLGGLTQ 190 200 210 220 230 240 APGNPVLAVQ INQDKNFAFL EFRSVDETTQ AMAFDGIIFQ GQSLKIRRPH DYQPLPGMSE 250 260 270 280 290 300 NPSVYVPGVV STVVPDSAHK LFIGGLPNYL NDDQVKELLT SFGPLKAFNL VKDSATGLSK 310 320 330 340 350 360 GYAFCEYVDI NVTDQAIAGL NGMQLGDKKL LVQRASVGAK NATLSTINQT PVTLQVPGLM 370 380 390 400 410 420 SSQVQMGGHP TEVLCLMNMV LPEELLDDEE YEEIVEDVRD ECSKYGLVKS IEIPRPVDGV 430 440 450 460 470 EVPGCGKIFV EFTSVFDCQK AMQGLTGRKF ANRVVVTKYC DPDSYHRRDF W

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and domain structure of the mammalian splicing factor U2AF." Zamore P.D., Patton J.G., Green M.R. Nature 355:609-614(1992) [PubMed: 1538748] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases 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] (ISOFORM 2). Tissue: Lymph and Skin.
[4]	Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E. Submitted (NOV-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-9; 196-203; 277-286 AND 463-471, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[5]	"Large-scale proteomic analysis of the human spliceosome." Rappsilber J., Ryder U., Lamond A.I., Mann M. Genome Res. 12:1231-1245(2002) [PubMed: 12176931] [Abstract] Cited for: PROTEIN SEQUENCE OF 261-286, MASS SPECTROMETRY, INTERACTION WITH THE SPLICEOSOME.
[6]	"Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing." Zhang W.-J., Wu J.Y. Mol. Cell. Biol. 18:676-684(1998) [PubMed: 9447963] [Abstract] Cited for: INTERACTION WITH SFRS2IP.
[7]	"Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly." Wang X., Bruderer S., Rafi Z., Xue J., Milburn P.J., Kraemer A., Robinson P.J. EMBO J. 18:4549-4559(1999) [PubMed: 10449420] [Abstract] Cited for: INTERACTION WITH SF1.
[8]	"Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC." Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., Demol H., Martens L., Goethals M., Vandekerckhove J. Proteomics 5:3589-3599(2005) [PubMed: 16097034] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY. Tissue: Hepatocyte.
[9]	"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-2; SER-53; SER-55 AND SER-79, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, MASS SPECTROMETRY.
[12]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, MASS SPECTROMETRY.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79, MASS SPECTROMETRY.
[14]	"Solution structures of the first and second RNA-binding domains of human U2 small nuclear ribonucleoprotein particle auxiliary factor (U2AF(65))." Ito T., Muto Y., Green M.R., Yokoyama S. EMBO J. 18:4523-4534(1999) [PubMed: 10449418] [Abstract] Cited for: STRUCTURE BY NMR OF 148-237.
[15]	"Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP." Selenko P., Gregorovic G., Sprangers R., Stier G., Rhani Z., Kraemer A., Sattler M. Mol. Cell 11:965-976(2003) [PubMed: 12718882] [Abstract] Cited for: STRUCTURE BY NMR OF 372-475 IN COMPLEX WITH SF1, MUTAGENESIS OF 387-GLU-GLU-388; 391-ASP--GLU-393; 396-GLU-GLU-397 AND PHE-454.
[16]	"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 90-112 IN COMPLEX WITH U2AF1, MUTAGENESIS OF TRP-92; PRO-96 AND PRO-104.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X64044 mRNA. Translation: CAA45409.1.
CH471135 Genomic DNA. Translation: EAW72404.1.
BC008740 mRNA. Translation: AAH08740.1.
BC030574 mRNA. Translation: AAH30574.1.

PIR

S20250.

RefSeq

NP_001012496.1.
NP_009210.1.

UniGene

Hs.528007

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JMT	X-ray	2.20	B	85-112	[»]
1O0P	NMR	-	A	372-475	[»]
1OPI	NMR	-	A	372-475	[»]
1U2F	NMR	-	A	148-237	[»]
2G4B	X-ray	2.50	A	148-336	[»]
2HZC	X-ray	1.47	A	148-229	[»]
2U2F	NMR	-	A	258-342	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:2154N.

PTM databases

PhosphoSite

P26368.

Genome annotation databases

Ensembl

ENSG00000063244. Homo sapiens. [Contig view]

GeneID

11338.