ID U2AF2_HUMAN Reviewed; 474 AA. AC P26368; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 3. DT 28-NOV-2006, entry version 78. 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; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=92168111; PubMed=1538748; DOI=10.1038/355609a0; 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 PROTEIN SEQUENCE OF 1-8; 195-202; 276-285 AND 462-470, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT SER-1, AND MASS SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.; RL Unpublished observations (NOV-2006). RN [3] RP PROTEIN SEQUENCE OF 260-285, MASS SPECTROMETRY, AND INTERACTION WITH RP THE 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 [4] RP INTERACTION WITH SFRS2IP. RX MEDLINE=98107652; PubMed=9447963; RA Zhang W.-J., Wu J.Y.; RT "Sip1, a novel RS domain-containing protein essential for pre-mRNA RT splicing."; RL Mol. Cell. Biol. 18:676-684(1998). RN [5] RP INTERACTION WITH SF1. RX MEDLINE=99380171; PubMed=10449420; DOI=10.1093/emboj/18.16.4549; 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1, AND MASS RP SPECTROMETRY. RX PubMed=16097034; DOI=10.1002/pmic.200401217; RA Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., RA Demol H., Martens L., Goethals M., Vandekerckhove J.; RT "Global phosphoproteome analysis on human HepG2 hepatocytes using RT reversed-phase diagonal LC."; RL Proteomics 5:3589-3599(2005). RN [7] RP STRUCTURE BY NMR OF 147-236. RX MEDLINE=99380169; PubMed=10449418; DOI=10.1093/emboj/18.16.4523; 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 [8] RP STRUCTURE BY NMR OF 371-474 IN COMPLEX WITH SF1, AND MUTAGENESIS OF RP 386-GLU-GLU-387; 390-ASP--GLU-392; 395-GLU-GLU-396 AND PHE-453. RX MEDLINE=22605544; PubMed=12718882; DOI=10.1016/S1097-2765(03)00115-1; 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 [9] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 89-111 IN COMPLEX WITH U2AF1, RP AND MUTAGENESIS OF TRP-91; PRO-95 AND PRO-103. RX MEDLINE=21435806; PubMed=11551507; DOI=10.1016/S0092-8674(01)00480-9; 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 Interacts with SFRS2IP. CC -!- INTERACTION: CC P54253:ATXN1; NbExp=1; IntAct=EBI-946034, EBI-930964; CC Q01081:U2AF1; NbExp=1; IntAct=EBI-946034, EBI-632461; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- SIMILARITY: Belongs to the splicing factor SR family. CC -!- SIMILARITY: Contains 3 RRM (RNA recognition motif) 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; -; mRNA. DR PIR; S20250; S20250. DR UniGene; Hs.528007; -. DR PDB; 1JMT; X-ray; B=84-111. DR PDB; 1O0P; NMR; A=371-474. DR PDB; 1OPI; NMR; A=371-474. DR PDB; 1U2F; NMR; A=147-236. DR PDB; 2U2F; NMR; A=257-341. DR IntAct; P26368; -. DR Ensembl; ENSG00000063244; Homo sapiens. DR KEGG; hsa:11338; -. DR H-InvDB; HIX0015481; -. DR HGNC; HGNC:23156; U2AF2. DR MIM; 191318; gene. DR Reactome; P26368; -. DR ArrayExpress; P26368; -. DR GO; GO:0005681; C:spliceosome complex; IDA:HGNC. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0000398; P:nuclear mRNA splicing, via spliceosome; IC:HGNC. DR InterPro; IPR012677; a_b_plait_nuc_bd. DR InterPro; IPR000504; RNP1_RNA_bd. DR InterPro; IPR006529; U2AF_lg. DR Gene3D; G3DSA:3.30.70.330; a_b_plait_nuc_bd; 3. DR Pfam; PF00076; RRM_1; 3. DR SMART; SM00360; RRM; 3. DR TIGRFAMs; TIGR01642; U2AF_lg; 1. DR PROSITE; PS50102; RRM; 3. KW 3D-structure; Acetylation; Direct protein sequencing; mRNA processing; KW mRNA splicing; Nuclear protein; Phosphorylation; Repeat; RNA-binding; KW Spliceosome. FT INIT_MET 0 0 FT CHAIN 1 474 Splicing factor U2AF 65 kDa subunit. FT /FTId=PRO_0000081988. FT DOMAIN 148 230 RRM 1. FT DOMAIN 258 336 RRM 2. FT DOMAIN 384 465 RRM 3. FT COMPBIAS 26 61 Arg/Ser-rich (RS domain). FT MOD_RES 1 1 N-acetylserine. FT MOD_RES 1 1 Phosphoserine. FT MUTAGEN 91 91 W->A: Decreases affinity for UAF1 by 3 FT orders of magnitude. FT MUTAGEN 95 95 P->G: Decreases affinity for UAF1 by 2 FT orders of magnitude. FT MUTAGEN 103 103 P->G: Decreases affinity for UAF1 by 2 FT orders of magnitude. FT MUTAGEN 386 387 EE->RR: Reduces interaction with SF1. FT MUTAGEN 390 393 DDEE->AAAA: Reduces interaction with SF1. FT MUTAGEN 390 393 DDEE->RRKK: Reduces interaction with SF1. FT MUTAGEN 395 396 EE->AA: No effect. FT MUTAGEN 395 396 EE->GA: Reduces interaction with SF1. FT MUTAGEN 395 396 EE->KK: Reduces interaction with SF1. FT MUTAGEN 453 453 F->A: Reduces interaction with SF1. FT TURN 92 92 FT TURN 96 97 FT TURN 99 100 FT HELIX 103 108 FT TURN 109 109 FT STRAND 149 152 FT TURN 157 158 FT TURN 161 162 FT HELIX 163 172 FT TURN 173 176 FT STRAND 180 182 FT STRAND 184 187 FT TURN 192 195 FT STRAND 196 203 FT TURN 205 209 FT HELIX 210 213 FT STRAND 218 221 FT TURN 228 229 FT STRAND 260 263 FT HELIX 272 278 FT TURN 279 279 FT STRAND 280 282 FT STRAND 284 290 FT STRAND 294 296 FT STRAND 301 309 FT HELIX 310 317 FT TURN 318 318 FT STRAND 319 321 FT STRAND 325 327 FT STRAND 330 333 FT STRAND 375 382 FT TURN 385 389 FT HELIX 391 405 FT TURN 406 408 FT STRAND 411 415 FT TURN 420 421 FT STRAND 422 424 FT TURN 426 427 FT STRAND 430 436 FT HELIX 438 448 FT STRAND 453 456 FT STRAND 459 463 FT HELIX 465 470 FT TURN 471 471 SQ SEQUENCE 474 AA; 53370 MW; 93409B79573D079E CRC64; SDFDEFERQL NENKQERDKE NRHRKRSHSR SRSRDRKRRS RSRDRRNRDQ RSASRDRRRR SKPLTRGAKE EHGGLIRSPR HEKKKKVRKY WDVPPPGFEH ITPMQYKAMQ AAGQIPATAL LPTMTPDGLA VTPTPVPVVG SQMTRQARRL YVGNIPFGIT EEAMMDFFNA QMRLGGLTQA PGNPVLAVQI NQDKNFAFLE FRSVDETTQA MAFDGIIFQG QSLKIRRPHD YQPLPGMSEN PSVYVPGVVS TVVPDSAHKL FIGGLPNYLN DDQVKELLTS FGPLKAFNLV KDSATGLSKG YAFCEYVDIN VTDQAIAGLN GMQLGDKKLL VQRASVGAKN ATLVSPPSTI NQTPVTLQVP GLMSSQVQMG GHPTEVLCLM NMVLPEELLD DEEYEEIVED VRDECSKYGL VKSIEIPRPV DGVEVPGCGK IFVEFTSVFD CQKAMQGLTG RKFANRVVVT KYCDPDSYHR RDFW //