ID U2AF_HUMAN STANDARD; PRT; 475 AA. AC P26368; DT 01-AUG-1992 (Rel. 23, Created) DT 01-APR-1993 (Rel. 25, Last sequence update) DT 01-OCT-2004 (Rel. 45, Last annotation update) DE Splicing factor U2AF 65 kDa subunit (U2 auxiliary factor 65 kDa DE subunit) (U2 snRNP auxiliary factor large subunit) (hU2AF(65)). GN Name=U2AF2; Synonyms=U2AF65; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=92168111; PubMed=1538748; RA Zamore P.D., Patton J.G., Green M.R.; RT "Cloning and domain structure of the mammalian splicing factor U2AF."; RL Nature 355:609-614(1992). RN [2] RP SEQUENCE OF 261-286, MASS SPECTROMETRY, AND INTERACTION WITH THE RP SPLICEOSOME. RX MEDLINE=22166132; PubMed=12176931; DOI=10.1101/gr.473902; RA Rappsilber J., Ryder U., Lamond A.I., Mann M.; RT "Large-scale proteomic analysis of the human spliceosome."; RL Genome Res. 12:1231-1245(2002). RN [3] RP INTERACTION WITH SF1. RX MEDLINE=99380171; PubMed=10449420; RA Wang X., Bruderer S., Rafi Z., Xue J., Milburn P.J., Kraemer A., RA Robinson P.J.; RT "Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent RT protein kinase regulates spliceosome assembly."; RL EMBO J. 18:4549-4559(1999). RN [4] RP STRUCTURE BY NMR OF 148-237. RX MEDLINE=99380169; PubMed=10449418; RA Ito T., Muto Y., Green M.R., Yokoyama S.; RT "Solution structures of the first and second RNA-binding domains of RT human U2 small nuclear ribonucleoprotein particle auxiliary factor RT (U2AF(65))."; RL EMBO J. 18:4523-4534(1999). RN [5] RP STRUCTURE BY NMR OF 372-475 IN COMPLEX WITH SF1, AND MUTAGENESIS OF RP 387-GLU-GLU-388; 391-ASP--GLU-394; 396-GLU-GLU-397 AND PHE-454. RX MEDLINE=22605544; PubMed=12718882; RA Selenko P., Gregorovic G., Sprangers R., Stier G., Rhani Z., RA Kraemer A., Sattler M.; RT "Structural basis for the molecular recognition between human splicing RT factors U2AF65 and SF1/mBBP."; RL Mol. Cell 11:965-976(2003). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 90-112 IN COMPLEX WITH U2AF1, RP AND MUTAGENESIS OF TRP-92; PRO-96 AND PRO-104. RX MEDLINE=21435806; PubMed=11551507; RA Kielkopf C.L., Rodionova N.A., Green M.R., Burley S.K.; RT "A novel peptide recognition mode revealed by the X-ray structure of a RT core U2AF35/U2AF65 heterodimer."; RL Cell 106:595-605(2001). CC -!- FUNCTION: Necessary for the splicing of pre-mRNA. Binds to the CC polypyrimidine tract of introns early during spliceosome assembly. CC Required for the export of mRNA out of the nucleus, even if the CC mRNA is encoded by an intron-less gene. CC -!- SUBUNIT: Heterodimer with U2AF1. Binds unphosphorylated SF1. CC -!- SUBCELLULAR LOCATION: Nuclear. CC -!- SIMILARITY: Belongs to the SR family of splicing factors. CC -!- SIMILARITY: Contains 3 RNA recognition motif (RRM) domains. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X64044; CAA45409.1; -. DR PIR; S20250; S20250. DR PDB; 1JMT; X-ray; B=85-112. DR PDB; 1O0P; NMR; A=372-475. DR PDB; 1OPI; NMR; -. DR PDB; 1U2F; NMR; A=148-236. DR PDB; 2U2F; NMR; A=258-342. DR Genew; HGNC:23156; U2AF2. DR Reactome; P26368; -. DR MIM; 191318; -. DR GO; GO:0008248; F:pre-mRNA splicing factor activity; TAS. DR GO; GO:0006397; P:mRNA processing; TAS. DR InterPro; IPR000504; RNA_rec_mot. DR InterPro; IPR006529; U2AF_lg. DR Pfam; PF00076; RRM_1; 3. DR TIGRFAMs; TIGR01642; U2AF_lg; 1. DR PROSITE; PS50102; RRM; 3. KW 3D-structure; Direct protein sequencing; mRNA processing; KW mRNA splicing; Nuclear protein; Repeat; RNA-binding; Spliceosome. FT DOMAIN 27 62 Arg/Ser-rich (RS domain). FT DOMAIN 149 231 RNA-binding (RRM) 1. FT DOMAIN 259 337 RNA-binding (RRM) 2. FT DOMAIN 385 466 RNA-binding (RRM) 3. FT MUTAGEN 92 92 W->A: Decreases affinity for UAF1 by 3 FT orders of magnitude. FT MUTAGEN 96 96 P->G: Decreases affinity for UAF1 by 2 FT orders of magnitude. FT MUTAGEN 104 104 P->G: Decreases affinity for UAF1 by 2 FT orders of magnitude. FT MUTAGEN 387 388 EE->RR: Reduces interaction with SF1. FT MUTAGEN 391 394 DDEE->AAAA: Reduces interaction with SF1. FT MUTAGEN 391 394 DDEE->RRKK: Reduces interaction with SF1. FT MUTAGEN 396 397 EE->AA: No effect. FT MUTAGEN 396 397 EE->GA: Reduces interaction with SF1. FT MUTAGEN 396 397 EE->KK: Reduces interaction with SF1. FT MUTAGEN 454 454 F->A: Reduces interaction with SF1. FT STRAND 92 92 FT TURN 93 93 FT TURN 97 98 FT TURN 100 101 FT HELIX 104 109 FT TURN 110 110 FT STRAND 150 153 FT TURN 158 159 FT TURN 162 163 FT HELIX 164 173 FT TURN 174 177 FT STRAND 186 188 FT STRAND 191 192 FT TURN 193 196 FT STRAND 197 202 FT TURN 206 210 FT HELIX 211 214 FT STRAND 227 227 FT TURN 229 230 FT STRAND 261 264 FT TURN 265 265 FT HELIX 273 279 FT TURN 280 280 FT STRAND 285 291 FT STRAND 302 307 FT HELIX 311 318 FT TURN 319 319 FT STRAND 331 334 FT STRAND 377 381 FT TURN 386 390 FT HELIX 392 406 FT TURN 407 409 FT STRAND 412 416 FT TURN 421 422 FT TURN 427 428 FT STRAND 431 436 FT HELIX 439 449 FT STRAND 460 464 FT HELIX 466 471 FT TURN 472 472 SQ SEQUENCE 475 AA; 53501 MW; 26AD271CD8FC6211 CRC64; MSDFDEFERQ LNENKQERDK ENRHRKRSHS RSRSRDRKRR SRSRDRRNRD QRSASRDRRR RSKPLTRGAK EEHGGLIRSP RHEKKKKVRK YWDVPPPGFE HITPMQYKAM QAAGQIPATA LLPTMTPDGL AVTPTPVPVV GSQMTRQARR LYVGNIPFGI TEEAMMDFFN AQMRLGGLTQ APGNPVLAVQ INQDKNFAFL EFRSVDETTQ AMAFDGIIFQ GQSLKIRRPH DYQPLPGMSE NPSVYVPGVV STVVPDSAHK LFIGGLPNYL NDDQVKELLT SFGPLKAFNL VKDSATGLSK GYAFCEYVDI NVTDQAIAGL NGMQLGDKKL LVQRASVGAK NATLVSPPST INQTPVTLQV PGLMSSQVQM GGHPTEVLCL MNMVLPEELL DDEEYEEIVE DVRDECSKYG LVKSIEIPRP VDGVEVPGCG KIFVEFTSVF DCQKAMQGLT GRKFANRVVV TKYCDPDSYH RRDFW //