Full text data of KHSRP
KHSRP
(FUBP2)
[Confidence: low (only semi-automatic identification from reviews)]
Far upstream element-binding protein 2; FUSE-binding protein 2 (KH type-splicing regulatory protein; KSRP; p75)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Far upstream element-binding protein 2; FUSE-binding protein 2 (KH type-splicing regulatory protein; KSRP; p75)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q92945
ID FUBP2_HUMAN Reviewed; 711 AA.
AC Q92945; O00301; Q59EZ9; Q5U4P6; Q9UNT5; Q9UQH5;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 4.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Far upstream element-binding protein 2;
DE Short=FUSE-binding protein 2;
DE AltName: Full=KH type-splicing regulatory protein;
DE Short=KSRP;
DE AltName: Full=p75;
GN Name=KHSRP; Synonyms=FUBP2;
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], PROTEIN SEQUENCE OF 72-85; 123-128;
RP 267-281; 283-291; 348-359; 474-488; 489-494; 621-627; 629-646 AND
RP 647-653, AND FUNCTION.
RC TISSUE=Neuroblastoma, and Retinoblastoma;
RX PubMed=9136930;
RA Min H., Turck C.W., Nikolic J.M., Black D.L.;
RT "A new regulatory protein, KSRP, mediates exon inclusion through an
RT intronic splicing enhancer.";
RL Genes Dev. 11:1023-1036(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115 AND 573-711.
RX PubMed=10087204; DOI=10.1006/geno.1998.5725;
RA Ring H.Z., Vameghi-Meyers V., Nikolic J.M., Min H., Black D.L.,
RA Francke U.;
RT "Mapping of the KHSRP gene to a region of conserved synteny on human
RT chromosome 19p13.3 and mouse chromosome 17.";
RL Genomics 56:350-352(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-711, AND FUNCTION.
RC TISSUE=B-cell lymphoma, and Skeletal muscle;
RX PubMed=8940189; DOI=10.1074/jbc.271.49.31679;
RA Davis-Smyth T., Duncan R.C., Zheng T., Michelotti G., Levens D.;
RT "The far upstream element-binding proteins comprise an ancient family
RT of single-strand DNA-binding transactivators.";
RL J. Biol. Chem. 271:31679-31687(1996).
RN [6]
RP PROTEIN SEQUENCE OF 151-162; 321-331 AND 385-394, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 183-566.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AND INTERACTION WITH PTBP1; PTBP2 AND HNRPH1.
RX PubMed=11003644; DOI=10.1128/MCB.20.20.7463-7479.2000;
RA Markovtsov V., Nikolic J.M., Goldman J.A., Turck C.W., Chou M.-Y.,
RA Black D.L.;
RT "Cooperative assembly of an hnRNP complex induced by a tissue-specific
RT homolog of polypyrimidine tract binding protein.";
RL Mol. Cell. Biol. 20:7463-7479(2000).
RN [9]
RP INTERACTION WITH PARN.
RX PubMed=15175153; DOI=10.1016/j.molcel.2004.05.002;
RA Gherzi R., Lee K.-Y., Briata P., Wegmueller D., Moroni C., Karin M.,
RA Chen C.-Y.;
RT "A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA
RT turnover by recruiting the degradation machinery.";
RL Mol. Cell 14:571-583(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-100; SER-181 AND
RP SER-274, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-480, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181; SER-274 AND
RP SER-480, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP STRUCTURE BY NMR OF 218-418 AND 423-525.
RX PubMed=17437720; DOI=10.1016/j.str.2007.03.006;
RA Garcia-Mayoral M.F., Hollingworth D., Masino L., Diaz-Moreno I.,
RA Kelly G., Gherzi R., Chou C.F., Chen C.Y., Ramos A.;
RT "The structure of the C-terminal KH domains of KSRP reveals a
RT noncanonical motif important for mRNA degradation.";
RL Structure 15:485-498(2007).
RN [23]
RP STRUCTURE BY NMR OF 130-218 AND 221-305, PHOSPHORYLATION AT SER-193,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19198587; DOI=10.1038/nsmb.1558;
RA Diaz-Moreno I., Hollingworth D., Frenkiel T.A., Kelly G., Martin S.,
RA Howell S., Garcia-Mayoral M., Gherzi R., Briata P., Ramos A.;
RT "Phosphorylation-mediated unfolding of a KH domain regulates KSRP
RT localization via 14-3-3 binding.";
RL Nat. Struct. Mol. Biol. 16:238-246(2009).
CC -!- FUNCTION: Binds to the dendritic targeting element and may play a
CC role in mRNA trafficking (By similarity). Part of a ternary
CC complex that binds to the downstream control sequence (DCS) of the
CC pre-mRNA. Mediates exon inclusion in transcripts that are subject
CC to tissue-specific alternative splicing. May interact with single-
CC stranded DNA from the far-upstream element (FUSE). May activate
CC gene expression. Also involved in degradation of inherently
CC unstable mRNAs that contain AU-rich elements (AREs) in their 3'-
CC UTR, possibly by recruiting degradation machinery to ARE-
CC containing mRNAs.
CC -!- SUBUNIT: Part of a ternary complex containing FUBP2, PTBP1, PTBP2
CC and HNRPH1. Interacts with PARN.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=A small proportion
CC is also found in the cytoplasm of neuronal cell bodies and
CC dendrites (By similarity).
CC -!- TISSUE SPECIFICITY: Detected in neural and non-neural cell lines.
CC -!- DOMAIN: KH domains KH 3 and KH 4 behave as independent binding
CC modules and can interact with different regions of the AU-rich RNA
CC targets of degradation.
CC -!- PTM: Phosphorylation at Ser-193 leads to the unfolding of the
CC unstable KH domain 1, creating a site for 14-3-3 YWHAZ binding,
CC which promotes nuclear localization and impairs the RNA
CC degradation function.
CC -!- SIMILARITY: Belongs to the KHSRP family.
CC -!- SIMILARITY: Contains 4 KH domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50892.1; Type=Frameshift; Positions=304, 309, 466, 473;
CC Sequence=AAH85004.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
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DR EMBL; U94832; AAB53222.1; -; mRNA.
DR EMBL; AC011491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC085004; AAH85004.1; ALT_SEQ; mRNA.
DR EMBL; AF093747; AAD29861.1; -; Genomic_DNA.
DR EMBL; AF093745; AAD29861.1; JOINED; Genomic_DNA.
DR EMBL; AF093748; AAD29862.1; -; Genomic_DNA.
DR EMBL; U69126; AAC50892.1; ALT_FRAME; mRNA.
DR EMBL; AB209662; BAD92899.1; -; mRNA.
DR RefSeq; NP_003676.2; NM_003685.2.
DR UniGene; Hs.727344; -.
DR PDB; 2HH2; NMR; -; A=423-525.
DR PDB; 2HH3; NMR; -; A=318-418.
DR PDB; 2JVZ; NMR; -; A=233-396.
DR PDB; 2OPU; NMR; -; A=130-218.
DR PDB; 2OPV; NMR; -; A=221-305.
DR PDB; 4B8T; NMR; -; A=317-418.
DR PDBsum; 2HH2; -.
DR PDBsum; 2HH3; -.
DR PDBsum; 2JVZ; -.
DR PDBsum; 2OPU; -.
DR PDBsum; 2OPV; -.
DR PDBsum; 4B8T; -.
DR ProteinModelPortal; Q92945; -.
DR SMR; Q92945; 130-503.
DR DIP; DIP-48484N; -.
DR IntAct; Q92945; 13.
DR MINT; MINT-2813544; -.
DR STRING; 9606.ENSP00000381216; -.
DR ChEMBL; CHEMBL1795105; -.
DR PhosphoSite; Q92945; -.
DR DMDM; 160380711; -.
DR REPRODUCTION-2DPAGE; Q92945; -.
DR PaxDb; Q92945; -.
DR PRIDE; Q92945; -.
DR Ensembl; ENST00000398148; ENSP00000381216; ENSG00000088247.
DR GeneID; 8570; -.
DR KEGG; hsa:8570; -.
DR UCSC; uc002mer.4; human.
DR CTD; 8570; -.
DR GeneCards; GC19M006413; -.
DR H-InvDB; HIX0040083; -.
DR HGNC; HGNC:6316; KHSRP.
DR HPA; HPA034739; -.
DR MIM; 603445; gene.
DR neXtProt; NX_Q92945; -.
DR PharmGKB; PA30097; -.
DR eggNOG; NOG300923; -.
DR HOGENOM; HOG000231552; -.
DR HOVERGEN; HBG000625; -.
DR InParanoid; Q92945; -.
DR KO; K13210; -.
DR OMA; GPMGPFN; -.
DR OrthoDB; EOG77Q4WB; -.
DR PhylomeDB; Q92945; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; KHSRP; human.
DR EvolutionaryTrace; Q92945; -.
DR GeneWiki; KHSRP; -.
DR GenomeRNAi; 8570; -.
DR NextBio; 32149; -.
DR PMAP-CutDB; Q92945; -.
DR PRO; PR:Q92945; -.
DR ArrayExpress; Q92945; -.
DR Bgee; Q92945; -.
DR CleanEx; HS_KHSRP; -.
DR Genevestigator; Q92945; -.
DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006397; P:mRNA processing; TAS:ProtInc.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; TAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR015096; DUF1897.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR Pfam; PF09005; DUF1897; 2.
DR Pfam; PF00013; KH_1; 4.
DR SMART; SM00322; KH; 4.
DR PROSITE; PS50084; KH_TYPE_1; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; mRNA processing;
KW mRNA splicing; mRNA transport; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Transcription;
KW Transcription regulation; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 711 Far upstream element-binding protein 2.
FT /FTId=PRO_0000050137.
FT DOMAIN 144 208 KH 1.
FT DOMAIN 233 299 KH 2.
FT DOMAIN 322 386 KH 3.
FT DOMAIN 424 491 KH 4.
FT REPEAT 571 582 1.
FT REPEAT 617 628 2.
FT REPEAT 643 654 3.
FT REPEAT 673 684 4.
FT REGION 571 684 4 X 12 AA imperfect repeats.
FT COMPBIAS 7 67 Gly/Pro-rich.
FT COMPBIAS 68 496 Gly-rich.
FT COMPBIAS 498 612 Ala/Gly/Pro-rich.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 100 100 Phosphothreonine.
FT MOD_RES 181 181 Phosphoserine.
FT MOD_RES 184 184 Phosphoserine (By similarity).
FT MOD_RES 193 193 Phosphoserine.
FT MOD_RES 274 274 Phosphoserine.
FT MOD_RES 480 480 Phosphoserine.
FT CONFLICT 46 46 G -> C (in Ref. 1; AAB53222 and 4;
FT AAD29861).
FT CONFLICT 96 96 V -> G (in Ref. 5; AAC50892).
FT CONFLICT 406 407 MP -> I (in Ref. 5; AAC50892).
FT CONFLICT 422 422 Missing (in Ref. 5; AAC50892).
FT CONFLICT 487 488 AK -> CR (in Ref. 5; AAC50892).
FT CONFLICT 694 696 GPG -> VP (in Ref. 5; AAC50892).
FT STRAND 132 134
FT HELIX 141 144
FT STRAND 146 151
FT HELIX 153 159
FT TURN 161 163
FT HELIX 165 174
FT STRAND 179 183
FT STRAND 188 194
FT HELIX 198 216
FT STRAND 234 240
FT TURN 242 244
FT TURN 245 249
FT TURN 251 253
FT HELIX 254 261
FT STRAND 265 269
FT STRAND 271 273
FT STRAND 275 279
FT STRAND 281 287
FT HELIX 289 302
FT STRAND 306 308
FT TURN 317 319
FT STRAND 325 330
FT TURN 331 333
FT HELIX 334 338
FT STRAND 340 342
FT HELIX 343 352
FT STRAND 355 358
FT STRAND 363 375
FT HELIX 376 393
FT STRAND 400 405
FT TURN 413 415
FT STRAND 427 432
FT HELIX 433 435
FT TURN 436 438
FT TURN 441 444
FT HELIX 446 453
FT STRAND 454 460
FT STRAND 472 479
FT HELIX 481 494
SQ SEQUENCE 711 AA; 73115 MW; AB0B7C0B5B938114 CRC64;
MSDYSTGGPP PGPPPPAGGG GGAGGAGGGP PPGPPGAGDR GGGGPGGGGP GGGSAGGPSQ
PPGGGGPGIR KDAFADAVQR ARQIAAKIGG DAATTVNNST PDFGFGGQKR QLEDGDQPES
KKLASQGDSI SSQLGPIHPP PRTSMTEEYR VPDGMVGLII GRGGEQINKI QQDSGCKVQI
SPDSGGLPER SVSLTGAPES VQKAKMMLDD IVSRGRGGPP GQFHDNANGG QNGTVQEIMI
PAGKAGLVIG KGGETIKQLQ ERAGVKMILI QDGSQNTNVD KPLRIIGDPY KVQQACEMVM
DILRERDQGG FGDRNEYGSR IGGGIDVPVP RHSVGVVIGR SGEMIKKIQN DAGVRIQFKQ
DDGTGPEKIA HIMGPPDRCE HAARIINDLL QSLRSGPPGP PGGPGMPPGG RGRGRGQGNW
GPPGGEMTFS IPTHKCGLVI GRGGENVKAI NQQTGAFVEI SRQLPPNGDP NFKLFIIRGS
PQQIDHAKQL IEEKIEGPLC PVGPGPGGPG PAGPMGPFNP GPFNQGPPGA PPHAGGPPPH
QYPPQGWGNT YPQWQPPAPH DPSKAAAAAA DPNAAWAAYY SHYYQQPPGP VPGPAPAPAA
PPAQGEPPQP PPTGQSDYTK AWEEYYKKIG QQPQQPGAPP QQDYTKAWEE YYKKQAQVAT
GGGPGAPPGS QPDYSAAWAE YYRQQAAYYG QTPGPGGPQP PPTQQGQQQA Q
//
ID FUBP2_HUMAN Reviewed; 711 AA.
AC Q92945; O00301; Q59EZ9; Q5U4P6; Q9UNT5; Q9UQH5;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 4.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Far upstream element-binding protein 2;
DE Short=FUSE-binding protein 2;
DE AltName: Full=KH type-splicing regulatory protein;
DE Short=KSRP;
DE AltName: Full=p75;
GN Name=KHSRP; Synonyms=FUBP2;
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], PROTEIN SEQUENCE OF 72-85; 123-128;
RP 267-281; 283-291; 348-359; 474-488; 489-494; 621-627; 629-646 AND
RP 647-653, AND FUNCTION.
RC TISSUE=Neuroblastoma, and Retinoblastoma;
RX PubMed=9136930;
RA Min H., Turck C.W., Nikolic J.M., Black D.L.;
RT "A new regulatory protein, KSRP, mediates exon inclusion through an
RT intronic splicing enhancer.";
RL Genes Dev. 11:1023-1036(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-115 AND 573-711.
RX PubMed=10087204; DOI=10.1006/geno.1998.5725;
RA Ring H.Z., Vameghi-Meyers V., Nikolic J.M., Min H., Black D.L.,
RA Francke U.;
RT "Mapping of the KHSRP gene to a region of conserved synteny on human
RT chromosome 19p13.3 and mouse chromosome 17.";
RL Genomics 56:350-352(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-711, AND FUNCTION.
RC TISSUE=B-cell lymphoma, and Skeletal muscle;
RX PubMed=8940189; DOI=10.1074/jbc.271.49.31679;
RA Davis-Smyth T., Duncan R.C., Zheng T., Michelotti G., Levens D.;
RT "The far upstream element-binding proteins comprise an ancient family
RT of single-strand DNA-binding transactivators.";
RL J. Biol. Chem. 271:31679-31687(1996).
RN [6]
RP PROTEIN SEQUENCE OF 151-162; 321-331 AND 385-394, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 183-566.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AND INTERACTION WITH PTBP1; PTBP2 AND HNRPH1.
RX PubMed=11003644; DOI=10.1128/MCB.20.20.7463-7479.2000;
RA Markovtsov V., Nikolic J.M., Goldman J.A., Turck C.W., Chou M.-Y.,
RA Black D.L.;
RT "Cooperative assembly of an hnRNP complex induced by a tissue-specific
RT homolog of polypyrimidine tract binding protein.";
RL Mol. Cell. Biol. 20:7463-7479(2000).
RN [9]
RP INTERACTION WITH PARN.
RX PubMed=15175153; DOI=10.1016/j.molcel.2004.05.002;
RA Gherzi R., Lee K.-Y., Briata P., Wegmueller D., Moroni C., Karin M.,
RA Chen C.-Y.;
RT "A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA
RT turnover by recruiting the degradation machinery.";
RL Mol. Cell 14:571-583(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-100; SER-181 AND
RP SER-274, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-480, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181; SER-274 AND
RP SER-480, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP STRUCTURE BY NMR OF 218-418 AND 423-525.
RX PubMed=17437720; DOI=10.1016/j.str.2007.03.006;
RA Garcia-Mayoral M.F., Hollingworth D., Masino L., Diaz-Moreno I.,
RA Kelly G., Gherzi R., Chou C.F., Chen C.Y., Ramos A.;
RT "The structure of the C-terminal KH domains of KSRP reveals a
RT noncanonical motif important for mRNA degradation.";
RL Structure 15:485-498(2007).
RN [23]
RP STRUCTURE BY NMR OF 130-218 AND 221-305, PHOSPHORYLATION AT SER-193,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19198587; DOI=10.1038/nsmb.1558;
RA Diaz-Moreno I., Hollingworth D., Frenkiel T.A., Kelly G., Martin S.,
RA Howell S., Garcia-Mayoral M., Gherzi R., Briata P., Ramos A.;
RT "Phosphorylation-mediated unfolding of a KH domain regulates KSRP
RT localization via 14-3-3 binding.";
RL Nat. Struct. Mol. Biol. 16:238-246(2009).
CC -!- FUNCTION: Binds to the dendritic targeting element and may play a
CC role in mRNA trafficking (By similarity). Part of a ternary
CC complex that binds to the downstream control sequence (DCS) of the
CC pre-mRNA. Mediates exon inclusion in transcripts that are subject
CC to tissue-specific alternative splicing. May interact with single-
CC stranded DNA from the far-upstream element (FUSE). May activate
CC gene expression. Also involved in degradation of inherently
CC unstable mRNAs that contain AU-rich elements (AREs) in their 3'-
CC UTR, possibly by recruiting degradation machinery to ARE-
CC containing mRNAs.
CC -!- SUBUNIT: Part of a ternary complex containing FUBP2, PTBP1, PTBP2
CC and HNRPH1. Interacts with PARN.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=A small proportion
CC is also found in the cytoplasm of neuronal cell bodies and
CC dendrites (By similarity).
CC -!- TISSUE SPECIFICITY: Detected in neural and non-neural cell lines.
CC -!- DOMAIN: KH domains KH 3 and KH 4 behave as independent binding
CC modules and can interact with different regions of the AU-rich RNA
CC targets of degradation.
CC -!- PTM: Phosphorylation at Ser-193 leads to the unfolding of the
CC unstable KH domain 1, creating a site for 14-3-3 YWHAZ binding,
CC which promotes nuclear localization and impairs the RNA
CC degradation function.
CC -!- SIMILARITY: Belongs to the KHSRP family.
CC -!- SIMILARITY: Contains 4 KH domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50892.1; Type=Frameshift; Positions=304, 309, 466, 473;
CC Sequence=AAH85004.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
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DR EMBL; U94832; AAB53222.1; -; mRNA.
DR EMBL; AC011491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC085004; AAH85004.1; ALT_SEQ; mRNA.
DR EMBL; AF093747; AAD29861.1; -; Genomic_DNA.
DR EMBL; AF093745; AAD29861.1; JOINED; Genomic_DNA.
DR EMBL; AF093748; AAD29862.1; -; Genomic_DNA.
DR EMBL; U69126; AAC50892.1; ALT_FRAME; mRNA.
DR EMBL; AB209662; BAD92899.1; -; mRNA.
DR RefSeq; NP_003676.2; NM_003685.2.
DR UniGene; Hs.727344; -.
DR PDB; 2HH2; NMR; -; A=423-525.
DR PDB; 2HH3; NMR; -; A=318-418.
DR PDB; 2JVZ; NMR; -; A=233-396.
DR PDB; 2OPU; NMR; -; A=130-218.
DR PDB; 2OPV; NMR; -; A=221-305.
DR PDB; 4B8T; NMR; -; A=317-418.
DR PDBsum; 2HH2; -.
DR PDBsum; 2HH3; -.
DR PDBsum; 2JVZ; -.
DR PDBsum; 2OPU; -.
DR PDBsum; 2OPV; -.
DR PDBsum; 4B8T; -.
DR ProteinModelPortal; Q92945; -.
DR SMR; Q92945; 130-503.
DR DIP; DIP-48484N; -.
DR IntAct; Q92945; 13.
DR MINT; MINT-2813544; -.
DR STRING; 9606.ENSP00000381216; -.
DR ChEMBL; CHEMBL1795105; -.
DR PhosphoSite; Q92945; -.
DR DMDM; 160380711; -.
DR REPRODUCTION-2DPAGE; Q92945; -.
DR PaxDb; Q92945; -.
DR PRIDE; Q92945; -.
DR Ensembl; ENST00000398148; ENSP00000381216; ENSG00000088247.
DR GeneID; 8570; -.
DR KEGG; hsa:8570; -.
DR UCSC; uc002mer.4; human.
DR CTD; 8570; -.
DR GeneCards; GC19M006413; -.
DR H-InvDB; HIX0040083; -.
DR HGNC; HGNC:6316; KHSRP.
DR HPA; HPA034739; -.
DR MIM; 603445; gene.
DR neXtProt; NX_Q92945; -.
DR PharmGKB; PA30097; -.
DR eggNOG; NOG300923; -.
DR HOGENOM; HOG000231552; -.
DR HOVERGEN; HBG000625; -.
DR InParanoid; Q92945; -.
DR KO; K13210; -.
DR OMA; GPMGPFN; -.
DR OrthoDB; EOG77Q4WB; -.
DR PhylomeDB; Q92945; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; KHSRP; human.
DR EvolutionaryTrace; Q92945; -.
DR GeneWiki; KHSRP; -.
DR GenomeRNAi; 8570; -.
DR NextBio; 32149; -.
DR PMAP-CutDB; Q92945; -.
DR PRO; PR:Q92945; -.
DR ArrayExpress; Q92945; -.
DR Bgee; Q92945; -.
DR CleanEx; HS_KHSRP; -.
DR Genevestigator; Q92945; -.
DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006397; P:mRNA processing; TAS:ProtInc.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; TAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR015096; DUF1897.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR Pfam; PF09005; DUF1897; 2.
DR Pfam; PF00013; KH_1; 4.
DR SMART; SM00322; KH; 4.
DR PROSITE; PS50084; KH_TYPE_1; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; mRNA processing;
KW mRNA splicing; mRNA transport; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Transcription;
KW Transcription regulation; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 711 Far upstream element-binding protein 2.
FT /FTId=PRO_0000050137.
FT DOMAIN 144 208 KH 1.
FT DOMAIN 233 299 KH 2.
FT DOMAIN 322 386 KH 3.
FT DOMAIN 424 491 KH 4.
FT REPEAT 571 582 1.
FT REPEAT 617 628 2.
FT REPEAT 643 654 3.
FT REPEAT 673 684 4.
FT REGION 571 684 4 X 12 AA imperfect repeats.
FT COMPBIAS 7 67 Gly/Pro-rich.
FT COMPBIAS 68 496 Gly-rich.
FT COMPBIAS 498 612 Ala/Gly/Pro-rich.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 100 100 Phosphothreonine.
FT MOD_RES 181 181 Phosphoserine.
FT MOD_RES 184 184 Phosphoserine (By similarity).
FT MOD_RES 193 193 Phosphoserine.
FT MOD_RES 274 274 Phosphoserine.
FT MOD_RES 480 480 Phosphoserine.
FT CONFLICT 46 46 G -> C (in Ref. 1; AAB53222 and 4;
FT AAD29861).
FT CONFLICT 96 96 V -> G (in Ref. 5; AAC50892).
FT CONFLICT 406 407 MP -> I (in Ref. 5; AAC50892).
FT CONFLICT 422 422 Missing (in Ref. 5; AAC50892).
FT CONFLICT 487 488 AK -> CR (in Ref. 5; AAC50892).
FT CONFLICT 694 696 GPG -> VP (in Ref. 5; AAC50892).
FT STRAND 132 134
FT HELIX 141 144
FT STRAND 146 151
FT HELIX 153 159
FT TURN 161 163
FT HELIX 165 174
FT STRAND 179 183
FT STRAND 188 194
FT HELIX 198 216
FT STRAND 234 240
FT TURN 242 244
FT TURN 245 249
FT TURN 251 253
FT HELIX 254 261
FT STRAND 265 269
FT STRAND 271 273
FT STRAND 275 279
FT STRAND 281 287
FT HELIX 289 302
FT STRAND 306 308
FT TURN 317 319
FT STRAND 325 330
FT TURN 331 333
FT HELIX 334 338
FT STRAND 340 342
FT HELIX 343 352
FT STRAND 355 358
FT STRAND 363 375
FT HELIX 376 393
FT STRAND 400 405
FT TURN 413 415
FT STRAND 427 432
FT HELIX 433 435
FT TURN 436 438
FT TURN 441 444
FT HELIX 446 453
FT STRAND 454 460
FT STRAND 472 479
FT HELIX 481 494
SQ SEQUENCE 711 AA; 73115 MW; AB0B7C0B5B938114 CRC64;
MSDYSTGGPP PGPPPPAGGG GGAGGAGGGP PPGPPGAGDR GGGGPGGGGP GGGSAGGPSQ
PPGGGGPGIR KDAFADAVQR ARQIAAKIGG DAATTVNNST PDFGFGGQKR QLEDGDQPES
KKLASQGDSI SSQLGPIHPP PRTSMTEEYR VPDGMVGLII GRGGEQINKI QQDSGCKVQI
SPDSGGLPER SVSLTGAPES VQKAKMMLDD IVSRGRGGPP GQFHDNANGG QNGTVQEIMI
PAGKAGLVIG KGGETIKQLQ ERAGVKMILI QDGSQNTNVD KPLRIIGDPY KVQQACEMVM
DILRERDQGG FGDRNEYGSR IGGGIDVPVP RHSVGVVIGR SGEMIKKIQN DAGVRIQFKQ
DDGTGPEKIA HIMGPPDRCE HAARIINDLL QSLRSGPPGP PGGPGMPPGG RGRGRGQGNW
GPPGGEMTFS IPTHKCGLVI GRGGENVKAI NQQTGAFVEI SRQLPPNGDP NFKLFIIRGS
PQQIDHAKQL IEEKIEGPLC PVGPGPGGPG PAGPMGPFNP GPFNQGPPGA PPHAGGPPPH
QYPPQGWGNT YPQWQPPAPH DPSKAAAAAA DPNAAWAAYY SHYYQQPPGP VPGPAPAPAA
PPAQGEPPQP PPTGQSDYTK AWEEYYKKIG QQPQQPGAPP QQDYTKAWEE YYKKQAQVAT
GGGPGAPPGS QPDYSAAWAE YYRQQAAYYG QTPGPGGPQP PPTQQGQQQA Q
//
MIM
603445
*RECORD*
*FIELD* NO
603445
*FIELD* TI
*603445 KH-TYPE SPLICING REGULATORY PROTEIN; KHSRP
;;KSRP;;
FAR UPSTREAM ELEMENT-BINDING PROTEIN 2; FUBP2;;
read moreFUSE-BINDING PROTEIN 2; FBP2
*FIELD* TX
DESCRIPTION
The KHSRP gene encodes a multifunctional RNA-binding protein implicated
in a variety of cellular processes, including transcription, alternative
pre-mRNA splicing, and mRNA localization (Min et al., 1997; Gherzi et
al., 2004).
CLONING
The pre-mRNA of the protooncogene SRC (190090) contains an 18-nucleotide
exon, N1, that is spliced into the mRNA in neuronal cells but is
excluded in nonneuronal cells. N1 exon inclusion in neurons is under the
positive control of an intronic regulatory sequence called the
downstream control sequence (DCS). Using neuronal cell extracts, Min et
al. (1995) isolated a complex that assembles specifically onto DCS RNA
and that is required for N1 exon splicing in vitro. UV-crosslinking
experiments identified HNRNPF (601037), a neuron-specific 75-kD protein
(p75) doublet, and 4 non-cell-type-specific proteins as components of
the DCS complex. By PCR of cDNA from a neuronal cell line using
degenerate primers based on a partial p75 protein sequence, Min et al.
(1997) isolated a partial p75 cDNA. They screened cDNA and genomic
libraries and identified additional clones corresponding to the entire
p75 coding region. The predicted 711-amino acid protein contains a
proline/glycine-rich N terminus and a C-terminal domain that is rich in
proline, glycine, alanine, and glutamine. The central region contains 4
tandemly repeated KH domains (see 602449), leading the authors to rename
the protein 'KH-type splicing regulatory protein' (KSRP). Using Northern
and Western blot analysis, Min et al. (1997) demonstrated that KSRP is
expressed in both neuronal and nonneuronal cells, although it is
approximately 3-fold more abundant in neuronal cells. They stated that
the neuronal cell-specific crosslinking observed must arise from factors
other than the relative levels of KSRP in various cell types.
Davis-Smyth et al. (1996) identified KSRP (which they called FBP2) and
FBP3 (FUBP3; 603536) as proteins related to the far upstream
element-binding protein FBP1 (FUBP1; 603444). All 3 proteins had the
same general architecture, with 3 distinct domains including a central
nucleic acid-binding region containing KH motifs.
GENE FUNCTION
Min et al. (1997) identified KSRP as part of a complex that assembles
onto DCS RNA and is required for splicing of the N1 exon of SRC in
vitro. Antibodies against KSRP inhibited both the assembly of the DCS
complex and the in vitro splicing of the N1 exon. The KSRP antibodies
did not bind to complexes already assembled onto the DCS. Instead, they
blocked the complexes from assembling.
Davis-Smyth et al. (1996) found that the FBPs, including FBP2, each
bound specifically to 1 strand of the far upstream element (FUSE)
originally identified upstream of MYC (190080), and each possessed a
potent C-terminal activation domain.
AU-rich elements (AREs) in the 3-prime UTR of inherently unstable mRNAs
act as instability determinants by interacting with ARE-binding proteins
that promote mRNA decay. Using human cell lines, Gherzi et al. (2004)
demonstrated that KSRP is an essential factor for ARE-directed mRNA
decay. Some of the KH motifs of KSRP directly mediated RNA binding, mRNA
decay, and interactions with the exosome and poly(A) ribonuclease (PARN;
604212). The ability of KH domains to promote mRNA decay correlated with
their ability to bind ARE and associate with RNA-degrading enzymes.
Gherzi et al. (2004) concluded that the KH domains of KSRP promote rapid
mRNA decay by recruiting degradation machinery to ARE-containing mRNAs.
Briata et al. (2005) found that Ksrp underwent p38 (MAPK14;
600289)-dependent phosphorylation during differentiation in a mouse
myogenic cell line. Phosphorylated Ksrp displayed compromised ability to
bind ARE-containing transcripts and failed to promote their rapid decay,
although it retained the ability to interact with the mRNA degradation
machinery. Overexpression of Ksrp selectively impaired induction of
ARE-containing early myogenic transcripts, but it did not affect
p38-mediated transcriptional responses. Briata et al. (2005) concluded
that KSRP provides a biochemical link between differentiation-activated
p38 signaling and turnover of myogenic mRNAs.
In studies in mouse neuroblastoma cells (N2a), Tadesse et al. (2008)
found that KSRP is an arginine-methylated protein and interacts directly
with the tudor domain of SMN (600354). The binding was abolished by
mutations in the tudor domain of SMN found in patients with severe
spinal muscular atrophy (SMA; 253300). In normal cells, KSRP and SMN
colocalized in differentiating neuronal processes, but not in the
nucleus. KSRP was found to be arginine methylated by CARM1 (603934), and
this methylation was necessary for the interaction with SMN and for
normal localization of KSRP. The absence of SMN resulted in
misregulation of KSRP and concomitant increased mRNA stability of the
target protein CDKN1A (116899) in mouse spinal cord. The findings
indicated that SMN can act as a molecular chaperone for methylated
proteins involved in RNA metabolism, and suggested that defects in RNA
metabolism may be involved in the pathophysiology of SMA.
Trabucchi et al. (2009) showed in mammalian cells that KSRP serves as a
component of both Drosha and Dicer complexes and regulates the
biogenesis of a subset of miRNAs. KSRP binds with high affinity to the
terminal loop of the target miRNA precursors and promotes their
maturation. This mechanism is required for specific changes in target
mRNA expression that affect specific biologic programs, including
proliferation, apoptosis, and differentiation. Trabucchi et al. (2009)
concluded that their findings revealed an unexpected mechanism that
links KSRP to the machinery regulating maturation of a cohort of miRNAs
that, in addition to its role in promoting mRNA decay, independently
serves to integrate specific regulatory programs of protein expression.
Sundaram et al. (2013) found that the FLTS1 (605547) transcript could
function either as an mRNA that was translated into the FLTS1 protein or
as a primary miRNA that was processed into miRNA-198. KSRP was required
for the switch between FLTS1 mRNA translation and MIR198 processing.
MAPPING
By radiation hybrid analysis, Ring et al. (1999) mapped the KHSRP gene
to chromosome 19p13.3. They mapped the mouse Khsrp gene to a region of
chromosome 17 that shares homology of synteny with human chromosome
19p13.3.
*FIELD* RF
1. Briata, P.; Forcales, S. V.; Ponassi, M.; Corte, G.; Chen, C.-Y.;
Karin, M.; Puri, P. L.; Gherzi, R.: p38-dependent phosphorylation
of the mRNA decay-promoting factor KSRP controls the stability of
select myogenic transcripts. Molec. Cell 20: 891-903, 2005.
2. Davis-Smyth, T.; Duncan, R. C.; Zheng, T.; Michelotti, G.; Levens,
D.: The far upstream element-binding proteins comprise an ancient
family of single-strand DNA-binding transactivators. J. Biol. Chem. 271:
31679-31687, 1996.
3. Gherzi, R.; Lee, K.-Y.; Briata, P.; Wegmuller, D.; Moroni, C.;
Karin, M.; Chen, C.-Y.: A KH domain RNA binding protein, KSRP, promotes
ARE-directed mRNA turnover by recruiting the degradation machinery. Molec.
Cell 14: 571-583, 2004.
4. Min, H.; Chan, R. C.; Black, D. L.: The generally expressed hnRNP
F is involved in a neural-specific pre-mRNA splicing event. Genes
Dev. 9: 2659-2671, 1995.
5. Min, H.; Turck, C. W.; Nikolic, J. M.; Black, D. L.: A new regulatory
protein, KSRP, mediates exon inclusion through an intronic splicing
enhancer. Genes Dev. 11: 1023-1036, 1997.
6. Ring, H. Z.; Vameghi-Meyers, V.; Nikolic, J. M.; Min, H.; Black,
D. L.; Francke, U.: Mapping of the KHSRP gene to a region of conserved
synteny on human chromosome 19p13.3 and mouse chromosome 17. Genomics 56:
350-352, 1999.
7. Sundaram, G. M.; Common, J. E. A.; Gopal, F. E.; Srikanta, S.;
Lakshman, K.; Lunny, D. P.; Lim, T. C.; Tanavde, V.; Lane, E. B.;
Sampath, P.: 'See-saw' expression of microRNA-198 and FSTL1 from
a single transcript in wound healing. Nature 495: 103-106, 2013.
8. Tadesse, H,; Deschenes-Furry, J.; Boisvenue, S.; Cote, J: KH-type
splicing regulatory protein interacts with survival motor neuron protein
and is misregulated in spinal muscular atrophy. Hum. Molec. Genet. 17:
506-524, 2008. .
9. Trabucchi, M.; Briata, P.; Garcia-Mayoral, M.; Haase, A. D.; Filipowicz,
W.; Ramos, A.; Gherzi, R.; Rosenfeld, M. G.: The RNA-binding protein
KSRP promotes the biogenesis of a subset of microRNAs. Nature 459:
1010-1014, 2009.
*FIELD* CN
Patricia A. Hartz - updated: 05/02/2013
Cassandra L. Kniffin - updated: 3/1/2010
Ada Hamosh - updated: 8/14/2009
Patricia A. Hartz - updated: 1/20/2006
*FIELD* CD
Rebekah S. Rasooly: 1/19/1999
*FIELD* ED
mgross: 05/02/2013
wwang: 4/9/2010
ckniffin: 3/1/2010
alopez: 8/20/2009
terry: 8/14/2009
wwang: 8/27/2008
mgross: 1/20/2006
psherman: 7/22/1999
psherman: 7/21/1999
alopez: 1/19/1999
*RECORD*
*FIELD* NO
603445
*FIELD* TI
*603445 KH-TYPE SPLICING REGULATORY PROTEIN; KHSRP
;;KSRP;;
FAR UPSTREAM ELEMENT-BINDING PROTEIN 2; FUBP2;;
read moreFUSE-BINDING PROTEIN 2; FBP2
*FIELD* TX
DESCRIPTION
The KHSRP gene encodes a multifunctional RNA-binding protein implicated
in a variety of cellular processes, including transcription, alternative
pre-mRNA splicing, and mRNA localization (Min et al., 1997; Gherzi et
al., 2004).
CLONING
The pre-mRNA of the protooncogene SRC (190090) contains an 18-nucleotide
exon, N1, that is spliced into the mRNA in neuronal cells but is
excluded in nonneuronal cells. N1 exon inclusion in neurons is under the
positive control of an intronic regulatory sequence called the
downstream control sequence (DCS). Using neuronal cell extracts, Min et
al. (1995) isolated a complex that assembles specifically onto DCS RNA
and that is required for N1 exon splicing in vitro. UV-crosslinking
experiments identified HNRNPF (601037), a neuron-specific 75-kD protein
(p75) doublet, and 4 non-cell-type-specific proteins as components of
the DCS complex. By PCR of cDNA from a neuronal cell line using
degenerate primers based on a partial p75 protein sequence, Min et al.
(1997) isolated a partial p75 cDNA. They screened cDNA and genomic
libraries and identified additional clones corresponding to the entire
p75 coding region. The predicted 711-amino acid protein contains a
proline/glycine-rich N terminus and a C-terminal domain that is rich in
proline, glycine, alanine, and glutamine. The central region contains 4
tandemly repeated KH domains (see 602449), leading the authors to rename
the protein 'KH-type splicing regulatory protein' (KSRP). Using Northern
and Western blot analysis, Min et al. (1997) demonstrated that KSRP is
expressed in both neuronal and nonneuronal cells, although it is
approximately 3-fold more abundant in neuronal cells. They stated that
the neuronal cell-specific crosslinking observed must arise from factors
other than the relative levels of KSRP in various cell types.
Davis-Smyth et al. (1996) identified KSRP (which they called FBP2) and
FBP3 (FUBP3; 603536) as proteins related to the far upstream
element-binding protein FBP1 (FUBP1; 603444). All 3 proteins had the
same general architecture, with 3 distinct domains including a central
nucleic acid-binding region containing KH motifs.
GENE FUNCTION
Min et al. (1997) identified KSRP as part of a complex that assembles
onto DCS RNA and is required for splicing of the N1 exon of SRC in
vitro. Antibodies against KSRP inhibited both the assembly of the DCS
complex and the in vitro splicing of the N1 exon. The KSRP antibodies
did not bind to complexes already assembled onto the DCS. Instead, they
blocked the complexes from assembling.
Davis-Smyth et al. (1996) found that the FBPs, including FBP2, each
bound specifically to 1 strand of the far upstream element (FUSE)
originally identified upstream of MYC (190080), and each possessed a
potent C-terminal activation domain.
AU-rich elements (AREs) in the 3-prime UTR of inherently unstable mRNAs
act as instability determinants by interacting with ARE-binding proteins
that promote mRNA decay. Using human cell lines, Gherzi et al. (2004)
demonstrated that KSRP is an essential factor for ARE-directed mRNA
decay. Some of the KH motifs of KSRP directly mediated RNA binding, mRNA
decay, and interactions with the exosome and poly(A) ribonuclease (PARN;
604212). The ability of KH domains to promote mRNA decay correlated with
their ability to bind ARE and associate with RNA-degrading enzymes.
Gherzi et al. (2004) concluded that the KH domains of KSRP promote rapid
mRNA decay by recruiting degradation machinery to ARE-containing mRNAs.
Briata et al. (2005) found that Ksrp underwent p38 (MAPK14;
600289)-dependent phosphorylation during differentiation in a mouse
myogenic cell line. Phosphorylated Ksrp displayed compromised ability to
bind ARE-containing transcripts and failed to promote their rapid decay,
although it retained the ability to interact with the mRNA degradation
machinery. Overexpression of Ksrp selectively impaired induction of
ARE-containing early myogenic transcripts, but it did not affect
p38-mediated transcriptional responses. Briata et al. (2005) concluded
that KSRP provides a biochemical link between differentiation-activated
p38 signaling and turnover of myogenic mRNAs.
In studies in mouse neuroblastoma cells (N2a), Tadesse et al. (2008)
found that KSRP is an arginine-methylated protein and interacts directly
with the tudor domain of SMN (600354). The binding was abolished by
mutations in the tudor domain of SMN found in patients with severe
spinal muscular atrophy (SMA; 253300). In normal cells, KSRP and SMN
colocalized in differentiating neuronal processes, but not in the
nucleus. KSRP was found to be arginine methylated by CARM1 (603934), and
this methylation was necessary for the interaction with SMN and for
normal localization of KSRP. The absence of SMN resulted in
misregulation of KSRP and concomitant increased mRNA stability of the
target protein CDKN1A (116899) in mouse spinal cord. The findings
indicated that SMN can act as a molecular chaperone for methylated
proteins involved in RNA metabolism, and suggested that defects in RNA
metabolism may be involved in the pathophysiology of SMA.
Trabucchi et al. (2009) showed in mammalian cells that KSRP serves as a
component of both Drosha and Dicer complexes and regulates the
biogenesis of a subset of miRNAs. KSRP binds with high affinity to the
terminal loop of the target miRNA precursors and promotes their
maturation. This mechanism is required for specific changes in target
mRNA expression that affect specific biologic programs, including
proliferation, apoptosis, and differentiation. Trabucchi et al. (2009)
concluded that their findings revealed an unexpected mechanism that
links KSRP to the machinery regulating maturation of a cohort of miRNAs
that, in addition to its role in promoting mRNA decay, independently
serves to integrate specific regulatory programs of protein expression.
Sundaram et al. (2013) found that the FLTS1 (605547) transcript could
function either as an mRNA that was translated into the FLTS1 protein or
as a primary miRNA that was processed into miRNA-198. KSRP was required
for the switch between FLTS1 mRNA translation and MIR198 processing.
MAPPING
By radiation hybrid analysis, Ring et al. (1999) mapped the KHSRP gene
to chromosome 19p13.3. They mapped the mouse Khsrp gene to a region of
chromosome 17 that shares homology of synteny with human chromosome
19p13.3.
*FIELD* RF
1. Briata, P.; Forcales, S. V.; Ponassi, M.; Corte, G.; Chen, C.-Y.;
Karin, M.; Puri, P. L.; Gherzi, R.: p38-dependent phosphorylation
of the mRNA decay-promoting factor KSRP controls the stability of
select myogenic transcripts. Molec. Cell 20: 891-903, 2005.
2. Davis-Smyth, T.; Duncan, R. C.; Zheng, T.; Michelotti, G.; Levens,
D.: The far upstream element-binding proteins comprise an ancient
family of single-strand DNA-binding transactivators. J. Biol. Chem. 271:
31679-31687, 1996.
3. Gherzi, R.; Lee, K.-Y.; Briata, P.; Wegmuller, D.; Moroni, C.;
Karin, M.; Chen, C.-Y.: A KH domain RNA binding protein, KSRP, promotes
ARE-directed mRNA turnover by recruiting the degradation machinery. Molec.
Cell 14: 571-583, 2004.
4. Min, H.; Chan, R. C.; Black, D. L.: The generally expressed hnRNP
F is involved in a neural-specific pre-mRNA splicing event. Genes
Dev. 9: 2659-2671, 1995.
5. Min, H.; Turck, C. W.; Nikolic, J. M.; Black, D. L.: A new regulatory
protein, KSRP, mediates exon inclusion through an intronic splicing
enhancer. Genes Dev. 11: 1023-1036, 1997.
6. Ring, H. Z.; Vameghi-Meyers, V.; Nikolic, J. M.; Min, H.; Black,
D. L.; Francke, U.: Mapping of the KHSRP gene to a region of conserved
synteny on human chromosome 19p13.3 and mouse chromosome 17. Genomics 56:
350-352, 1999.
7. Sundaram, G. M.; Common, J. E. A.; Gopal, F. E.; Srikanta, S.;
Lakshman, K.; Lunny, D. P.; Lim, T. C.; Tanavde, V.; Lane, E. B.;
Sampath, P.: 'See-saw' expression of microRNA-198 and FSTL1 from
a single transcript in wound healing. Nature 495: 103-106, 2013.
8. Tadesse, H,; Deschenes-Furry, J.; Boisvenue, S.; Cote, J: KH-type
splicing regulatory protein interacts with survival motor neuron protein
and is misregulated in spinal muscular atrophy. Hum. Molec. Genet. 17:
506-524, 2008. .
9. Trabucchi, M.; Briata, P.; Garcia-Mayoral, M.; Haase, A. D.; Filipowicz,
W.; Ramos, A.; Gherzi, R.; Rosenfeld, M. G.: The RNA-binding protein
KSRP promotes the biogenesis of a subset of microRNAs. Nature 459:
1010-1014, 2009.
*FIELD* CN
Patricia A. Hartz - updated: 05/02/2013
Cassandra L. Kniffin - updated: 3/1/2010
Ada Hamosh - updated: 8/14/2009
Patricia A. Hartz - updated: 1/20/2006
*FIELD* CD
Rebekah S. Rasooly: 1/19/1999
*FIELD* ED
mgross: 05/02/2013
wwang: 4/9/2010
ckniffin: 3/1/2010
alopez: 8/20/2009
terry: 8/14/2009
wwang: 8/27/2008
mgross: 1/20/2006
psherman: 7/22/1999
psherman: 7/21/1999
alopez: 1/19/1999