Full text data of PTBP1
PTBP1
(PTB)
[Confidence: high (present in two of the MS resources)]
Polypyrimidine tract-binding protein 1; PTB (57 kDa RNA-binding protein PPTB-1; Heterogeneous nuclear ribonucleoprotein I; hnRNP I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Polypyrimidine tract-binding protein 1; PTB (57 kDa RNA-binding protein PPTB-1; Heterogeneous nuclear ribonucleoprotein I; hnRNP I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00179964
IPI00179964 Splice isoform 1 of P26599 Polypyrimidine tract-binding protein 1 Splice isoform 1 of P26599 Polypyrimidine tract-binding protein 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 3 n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a nuclear n/a expected molecular weight found in band 14 kDa
IPI00179964 Splice isoform 1 of P26599 Polypyrimidine tract-binding protein 1 Splice isoform 1 of P26599 Polypyrimidine tract-binding protein 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 3 n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a nuclear n/a expected molecular weight found in band 14 kDa
UniProt
P26599
ID PTBP1_HUMAN Reviewed; 531 AA.
AC P26599; Q9BUQ0;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1992, sequence version 1.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=Polypyrimidine tract-binding protein 1;
DE Short=PTB;
DE AltName: Full=57 kDa RNA-binding protein PPTB-1;
DE AltName: Full=Heterogeneous nuclear ribonucleoprotein I;
DE Short=hnRNP I;
GN Name=PTBP1; Synonyms=PTB;
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], AND PROTEIN SEQUENCE OF 123-130 AND
RP 219-238.
RC TISSUE=Placenta;
RX PubMed=1906035;
RA Gil A., Sharp P.A., Jamison S.F., Garcia-Blanco M.A.;
RT "Characterization of cDNAs encoding the polypyrimidine tract-binding
RT protein.";
RL Genes Dev. 5:1224-1236(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1906036;
RA Patton J.G., Mayer S.A., Tempst P., Nadal-Ginard B.;
RT "Characterization and molecular cloning of polypyrimidine tract-
RT binding protein: a component of a complex necessary for pre-mRNA
RT splicing.";
RL Genes Dev. 5:1237-1251(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1641332; DOI=10.1093/nar/20.14.3671;
RA Ghetti A., Pinol-Roma S., Michael W., Morandi C., Dreyfuss G.;
RT "hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear
RT localization and association with hnRNAs.";
RL Nucleic Acids Res. 20:3671-3678(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung, Ovary, and Skin;
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 [8]
RP PROTEIN SEQUENCE OF 1-13; 65-92; 123-134; 219-238; 326-348; 411-418;
RP 429-437 AND 472-482, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, Hepatoma, and Mammary carcinoma;
RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.,
RA Matallanas D., Cooper W.N., Boldt K., von Kriegsheim A.F., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 123-129; 399-405; 411-426 AND 429-437.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [10]
RP INTERACTION WITH SFPQ.
RX PubMed=10653975;
RX DOI=10.1002/(SICI)1097-4644(20000315)76:4<559::AID-JCB4>3.3.CO;2-L;
RA Meissner M., Dechat T., Gerner C., Grimm R., Foisner R., Sauermann G.;
RT "Differential nuclear localization and nuclear matrix association of
RT the splicing factors PSF and PTB.";
RL J. Cell. Biochem. 76:559-566(2000).
RN [11]
RP FUNCTION, AND INTERACTION WITH HNRPH1; PTBP2 AND KHSRP.
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 [12]
RP FUNCTION.
RX PubMed=15009664; DOI=10.1046/j.1471-4159.2003.02232.x;
RA Wang J., Gao Q.S., Wang Y., Lafyatis R., Stamm S., Andreadis A.;
RT "Tau exon 10, whose missplicing causes frontotemporal dementia, is
RT regulated by an intricate interplay of cis elements and trans
RT factors.";
RL J. Neurochem. 88:1078-1090(2004).
RN [13]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=16260624; DOI=10.1128/MCB.25.22.10111-10121.2005;
RA Lin J.C., Tarn W.Y.;
RT "Exon selection in alpha-tropomyosin mRNA is regulated by the
RT antagonistic action of RBM4 and PTB.";
RL Mol. Cell. Biol. 25:10111-10121(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-141, AND MASS
RP 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-141, 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 FUNCTION.
RX PubMed=21518792; DOI=10.1083/jcb.201007131;
RA Lin J.C., Tarn W.Y.;
RT "RBM4 down-regulates PTB and antagonizes its activity in muscle cell-
RT specific alternative splicing.";
RL J. Cell Biol. 193:509-520(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-433, AND
RP 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 [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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 [23]
RP STRUCTURE BY NMR OF 335-531, AND RNA-BINDING.
RX PubMed=10856256; DOI=10.1093/emboj/19.12.3132;
RA Conte M.R., Gruene T., Ghuman J., Kelly G., Ladas A., Matthews S.,
RA Curry S.;
RT "Structure of tandem RNA recognition motifs from polypyrimidine tract
RT binding protein reveals novel features of the RRM fold.";
RL EMBO J. 19:3132-3141(2000).
RN [24]
RP STRUCTURE BY NMR OF 55-301, SUBUNIT, AND RNA-BINDING.
RX PubMed=15341728; DOI=10.1016/j.str.2004.07.008;
RA Simpson P.J., Monie T.P., Szendroei A., Davydova N., Tyzack J.K.,
RA Conte M.R., Read C.M., Cary P.D., Svergun D.I., Konarev P.V.,
RA Curry S., Matthews S.;
RT "Structure and RNA interactions of the N-terminal RRM domains of
RT PTB.";
RL Structure 12:1631-1643(2004).
RN [25]
RP STRUCTURE BY NMR OF 49-531 IN COMPLEXES WITH RNA, AND FUNCTION.
RX PubMed=16179478; DOI=10.1126/science.1114066;
RA Oberstrass F.C., Auweter S.D., Erat M., Hargous Y., Henning A.,
RA Wenter P., Reymond L., Amir-Ahmady B., Pitsch S., Black D.L.,
RA Allain F.H.;
RT "Structure of PTB bound to RNA: specific binding and implications for
RT splicing regulation.";
RL Science 309:2054-2057(2005).
RN [26]
RP STRUCTURE BY NMR OF 324-531.
RX PubMed=16362043; DOI=10.1038/sj.emboj.7600911;
RA Vitali F., Henning A., Oberstrass F.C., Hargous Y., Auweter S.D.,
RA Erat M., Allain F.H.;
RT "Structure of the two most C-terminal RNA recognition motifs of PTB
RT using segmental isotope labeling.";
RL EMBO J. 25:150-162(2006).
CC -!- FUNCTION: Plays a role in pre-mRNA splicing and in the regulation
CC of alternative splicing events. Activates exon skipping of its own
CC pre-mRNA during muscle cell differentiation. Binds to the
CC polypyrimidine tract of introns. May promote RNA looping when
CC bound to two separate polypyrimidine tracts in the same pre-mRNA.
CC May promote the binding of U2 snRNP to pre-mRNA. Cooperates with
CC RAVER1 to modulate switching between mutually exclusive exons
CC during maturation of the TPM1 pre-mRNA. Represses the splicing of
CC MAPT/Tau exon 10.
CC -!- SUBUNIT: Monomer. Part of a ternary complex containing KHSRP,
CC PTBP1, PTBP2 and HNRPH1. Interacts with RAVER1 and SFPQ.
CC -!- INTERACTION:
CC P29991:- (xeno); NbExp=5; IntAct=EBI-350540, EBI-8826689;
CC Q7ZYE9:hnrnpab (xeno); NbExp=4; IntAct=EBI-350540, EBI-1086317;
CC Q15365:PCBP1; NbExp=2; IntAct=EBI-350540, EBI-946095;
CC Q96PU8:QKI; NbExp=3; IntAct=EBI-350540, EBI-945792;
CC P23246:SFPQ; NbExp=2; IntAct=EBI-350540, EBI-355453;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=1;
CC IsoId=P26599-1; Sequence=Displayed;
CC Name=2; Synonyms=PTB2;
CC IsoId=P26599-2; Sequence=VSP_005802;
CC Name=3;
CC IsoId=P26599-3; Sequence=VSP_043649;
CC -!- SIMILARITY: Contains 4 RRM (RNA recognition motif) domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PTBP1ID46504ch19p13.html";
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DR EMBL; X62006; CAA43973.1; -; mRNA.
DR EMBL; X65371; CAA46443.1; -; mRNA.
DR EMBL; X65372; CAA46444.1; -; mRNA.
DR EMBL; X60648; CAA43056.1; -; mRNA.
DR EMBL; X66975; CAA47386.1; -; mRNA.
DR EMBL; BT006819; AAP35465.1; -; mRNA.
DR EMBL; AC006273; AAC99798.1; -; Genomic_DNA.
DR EMBL; CH471242; EAW61154.1; -; Genomic_DNA.
DR EMBL; BC002397; AAH02397.1; -; mRNA.
DR EMBL; BC004383; AAH04383.1; -; mRNA.
DR EMBL; BC013694; AAH13694.1; -; mRNA.
DR PIR; S23016; S23016.
DR RefSeq; NP_002810.1; NM_002819.4.
DR RefSeq; NP_114367.1; NM_031990.3.
DR RefSeq; NP_114368.1; NM_031991.3.
DR UniGene; Hs.172550; -.
DR PDB; 1QM9; NMR; -; A=335-531.
DR PDB; 1SJQ; NMR; -; A=55-147.
DR PDB; 1SJR; NMR; -; A=147-301.
DR PDB; 2AD9; NMR; -; A=49-146.
DR PDB; 2ADB; NMR; -; A=172-298.
DR PDB; 2ADC; NMR; -; A=324-531.
DR PDB; 2EVZ; NMR; -; A=324-531.
DR PDB; 3ZZY; X-ray; 1.40 A; A/B=156-285.
DR PDB; 3ZZZ; X-ray; 1.55 A; A/B=156-285.
DR PDBsum; 1QM9; -.
DR PDBsum; 1SJQ; -.
DR PDBsum; 1SJR; -.
DR PDBsum; 2AD9; -.
DR PDBsum; 2ADB; -.
DR PDBsum; 2ADC; -.
DR PDBsum; 2EVZ; -.
DR PDBsum; 3ZZY; -.
DR PDBsum; 3ZZZ; -.
DR ProteinModelPortal; P26599; -.
DR SMR; P26599; 49-146, 172-298, 324-531.
DR IntAct; P26599; 41.
DR MINT; MINT-1348690; -.
DR STRING; 9606.ENSP00000349428; -.
DR ChEMBL; CHEMBL1293230; -.
DR PhosphoSite; P26599; -.
DR DMDM; 131528; -.
DR SWISS-2DPAGE; P26599; -.
DR PaxDb; P26599; -.
DR PRIDE; P26599; -.
DR DNASU; 5725; -.
DR Ensembl; ENST00000349038; ENSP00000014112; ENSG00000011304.
DR Ensembl; ENST00000356948; ENSP00000349428; ENSG00000011304.
DR Ensembl; ENST00000394601; ENSP00000408096; ENSG00000011304.
DR GeneID; 5725; -.
DR KEGG; hsa:5725; -.
DR UCSC; uc002lpr.2; human.
DR CTD; 5725; -.
DR GeneCards; GC19P000797; -.
DR H-InvDB; HIX0137476; -.
DR HGNC; HGNC:9583; PTBP1.
DR HPA; CAB013507; -.
DR MIM; 600693; gene.
DR neXtProt; NX_P26599; -.
DR PharmGKB; PA33934; -.
DR eggNOG; NOG263741; -.
DR HOGENOM; HOG000231699; -.
DR HOVERGEN; HBG069548; -.
DR KO; K13218; -.
DR OMA; SEECAQT; -.
DR OrthoDB; EOG7V7691; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR EvolutionaryTrace; P26599; -.
DR GeneWiki; PTBP1; -.
DR GenomeRNAi; 5725; -.
DR NextBio; 22252; -.
DR PMAP-CutDB; P26599; -.
DR PRO; PR:P26599; -.
DR ArrayExpress; P26599; -.
DR Bgee; P26599; -.
DR CleanEx; HS_PTBP1; -.
DR Genevestigator; P26599; -.
DR GO; GO:0005730; C:nucleolus; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0008187; F:poly-pyrimidine tract binding; TAS:ProtInc.
DR GO; GO:0036002; F:pre-mRNA binding; IDA:UniProtKB.
DR GO; GO:0000380; P:alternative mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IDA:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR Gene3D; 3.30.70.330; -; 4.
DR InterPro; IPR006536; HnRNP-L_PTB.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 4.
DR TIGRFAMs; TIGR01649; hnRNP-L_PTB; 1.
DR PROSITE; PS50102; RRM; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Complete proteome; Direct protein sequencing; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; RNA-binding.
FT CHAIN 1 531 Polypyrimidine tract-binding protein 1.
FT /FTId=PRO_0000081737.
FT DOMAIN 59 143 RRM 1.
FT DOMAIN 184 260 RRM 2.
FT DOMAIN 337 411 RRM 3.
FT DOMAIN 454 529 RRM 4.
FT COMPBIAS 316 323 Poly-Ala.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 16 16 Phosphoserine.
FT MOD_RES 138 138 Phosphothreonine.
FT MOD_RES 141 141 Phosphoserine.
FT MOD_RES 433 433 Phosphoserine.
FT VAR_SEQ 297 297 F -> FASPYAGAGFPPTFAIPQAA (in isoform 2).
FT /FTId=VSP_005802.
FT VAR_SEQ 297 297 F -> FGAPGIISASPYAGAGFPPTFAIPQAA (in
FT isoform 3).
FT /FTId=VSP_043649.
FT STRAND 60 63
FT HELIX 72 82
FT STRAND 85 91
FT TURN 92 95
FT STRAND 96 103
FT HELIX 104 114
FT STRAND 127 130
FT STRAND 132 135
FT TURN 142 145
FT STRAND 182 190
FT HELIX 197 204
FT HELIX 205 207
FT STRAND 210 218
FT STRAND 221 229
FT HELIX 231 241
FT STRAND 245 247
FT STRAND 250 257
FT STRAND 259 262
FT STRAND 269 274
FT TURN 289 291
FT TURN 294 296
FT HELIX 329 332
FT STRAND 339 342
FT STRAND 346 348
FT HELIX 351 359
FT STRAND 365 368
FT TURN 371 373
FT STRAND 378 380
FT TURN 382 384
FT HELIX 385 394
FT STRAND 400 403
FT STRAND 405 408
FT STRAND 417 425
FT STRAND 427 431
FT STRAND 437 440
FT HELIX 444 446
FT STRAND 455 458
FT HELIX 467 476
FT STRAND 483 488
FT STRAND 494 497
FT HELIX 501 511
FT STRAND 515 519
FT STRAND 524 527
SQ SEQUENCE 531 AA; 57221 MW; BE12D5EA21537BED CRC64;
MDGIVPDIAV GTKRGSDELF STCVTNGPFI MSSNSASAAN GNDSKKFKGD SRSAGVPSRV
IHIRKLPIDV TEGEVISLGL PFGKVTNLLM LKGKNQAFIE MNTEEAANTM VNYYTSVTPV
LRGQPIYIQF SNHKELKTDS SPNQARAQAA LQAVNSVQSG NLALAASAAA VDAGMAMAGQ
SPVLRIIVEN LFYPVTLDVL HQIFSKFGTV LKIITFTKNN QFQALLQYAD PVSAQHAKLS
LDGQNIYNAC CTLRIDFSKL TSLNVKYNND KSRDYTRPDL PSGDSQPSLD QTMAAAFGLS
VPNVHGALAP LAIPSAAAAA AAAGRIAIPG LAGAGNSVLL VSNLNPERVT PQSLFILFGV
YGDVQRVKIL FNKKENALVQ MADGNQAQLA MSHLNGHKLH GKPIRITLSK HQNVQLPREG
QEDQGLTKDY GNSPLHRFKK PGSKNFQNIF PPSATLHLSN IPPSVSEEDL KVLFSSNGGV
VKGFKFFQKD RKMALIQMGS VEEAVQALID LHNHDLGENH HLRVSFSKST I
//
ID PTBP1_HUMAN Reviewed; 531 AA.
AC P26599; Q9BUQ0;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1992, sequence version 1.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=Polypyrimidine tract-binding protein 1;
DE Short=PTB;
DE AltName: Full=57 kDa RNA-binding protein PPTB-1;
DE AltName: Full=Heterogeneous nuclear ribonucleoprotein I;
DE Short=hnRNP I;
GN Name=PTBP1; Synonyms=PTB;
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], AND PROTEIN SEQUENCE OF 123-130 AND
RP 219-238.
RC TISSUE=Placenta;
RX PubMed=1906035;
RA Gil A., Sharp P.A., Jamison S.F., Garcia-Blanco M.A.;
RT "Characterization of cDNAs encoding the polypyrimidine tract-binding
RT protein.";
RL Genes Dev. 5:1224-1236(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1906036;
RA Patton J.G., Mayer S.A., Tempst P., Nadal-Ginard B.;
RT "Characterization and molecular cloning of polypyrimidine tract-
RT binding protein: a component of a complex necessary for pre-mRNA
RT splicing.";
RL Genes Dev. 5:1237-1251(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1641332; DOI=10.1093/nar/20.14.3671;
RA Ghetti A., Pinol-Roma S., Michael W., Morandi C., Dreyfuss G.;
RT "hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear
RT localization and association with hnRNAs.";
RL Nucleic Acids Res. 20:3671-3678(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung, Ovary, and Skin;
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 [8]
RP PROTEIN SEQUENCE OF 1-13; 65-92; 123-134; 219-238; 326-348; 411-418;
RP 429-437 AND 472-482, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, Hepatoma, and Mammary carcinoma;
RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.,
RA Matallanas D., Cooper W.N., Boldt K., von Kriegsheim A.F., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 123-129; 399-405; 411-426 AND 429-437.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [10]
RP INTERACTION WITH SFPQ.
RX PubMed=10653975;
RX DOI=10.1002/(SICI)1097-4644(20000315)76:4<559::AID-JCB4>3.3.CO;2-L;
RA Meissner M., Dechat T., Gerner C., Grimm R., Foisner R., Sauermann G.;
RT "Differential nuclear localization and nuclear matrix association of
RT the splicing factors PSF and PTB.";
RL J. Cell. Biochem. 76:559-566(2000).
RN [11]
RP FUNCTION, AND INTERACTION WITH HNRPH1; PTBP2 AND KHSRP.
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 [12]
RP FUNCTION.
RX PubMed=15009664; DOI=10.1046/j.1471-4159.2003.02232.x;
RA Wang J., Gao Q.S., Wang Y., Lafyatis R., Stamm S., Andreadis A.;
RT "Tau exon 10, whose missplicing causes frontotemporal dementia, is
RT regulated by an intricate interplay of cis elements and trans
RT factors.";
RL J. Neurochem. 88:1078-1090(2004).
RN [13]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=16260624; DOI=10.1128/MCB.25.22.10111-10121.2005;
RA Lin J.C., Tarn W.Y.;
RT "Exon selection in alpha-tropomyosin mRNA is regulated by the
RT antagonistic action of RBM4 and PTB.";
RL Mol. Cell. Biol. 25:10111-10121(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-141, AND MASS
RP 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-141, 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 FUNCTION.
RX PubMed=21518792; DOI=10.1083/jcb.201007131;
RA Lin J.C., Tarn W.Y.;
RT "RBM4 down-regulates PTB and antagonizes its activity in muscle cell-
RT specific alternative splicing.";
RL J. Cell Biol. 193:509-520(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-433, AND
RP 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 [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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 [23]
RP STRUCTURE BY NMR OF 335-531, AND RNA-BINDING.
RX PubMed=10856256; DOI=10.1093/emboj/19.12.3132;
RA Conte M.R., Gruene T., Ghuman J., Kelly G., Ladas A., Matthews S.,
RA Curry S.;
RT "Structure of tandem RNA recognition motifs from polypyrimidine tract
RT binding protein reveals novel features of the RRM fold.";
RL EMBO J. 19:3132-3141(2000).
RN [24]
RP STRUCTURE BY NMR OF 55-301, SUBUNIT, AND RNA-BINDING.
RX PubMed=15341728; DOI=10.1016/j.str.2004.07.008;
RA Simpson P.J., Monie T.P., Szendroei A., Davydova N., Tyzack J.K.,
RA Conte M.R., Read C.M., Cary P.D., Svergun D.I., Konarev P.V.,
RA Curry S., Matthews S.;
RT "Structure and RNA interactions of the N-terminal RRM domains of
RT PTB.";
RL Structure 12:1631-1643(2004).
RN [25]
RP STRUCTURE BY NMR OF 49-531 IN COMPLEXES WITH RNA, AND FUNCTION.
RX PubMed=16179478; DOI=10.1126/science.1114066;
RA Oberstrass F.C., Auweter S.D., Erat M., Hargous Y., Henning A.,
RA Wenter P., Reymond L., Amir-Ahmady B., Pitsch S., Black D.L.,
RA Allain F.H.;
RT "Structure of PTB bound to RNA: specific binding and implications for
RT splicing regulation.";
RL Science 309:2054-2057(2005).
RN [26]
RP STRUCTURE BY NMR OF 324-531.
RX PubMed=16362043; DOI=10.1038/sj.emboj.7600911;
RA Vitali F., Henning A., Oberstrass F.C., Hargous Y., Auweter S.D.,
RA Erat M., Allain F.H.;
RT "Structure of the two most C-terminal RNA recognition motifs of PTB
RT using segmental isotope labeling.";
RL EMBO J. 25:150-162(2006).
CC -!- FUNCTION: Plays a role in pre-mRNA splicing and in the regulation
CC of alternative splicing events. Activates exon skipping of its own
CC pre-mRNA during muscle cell differentiation. Binds to the
CC polypyrimidine tract of introns. May promote RNA looping when
CC bound to two separate polypyrimidine tracts in the same pre-mRNA.
CC May promote the binding of U2 snRNP to pre-mRNA. Cooperates with
CC RAVER1 to modulate switching between mutually exclusive exons
CC during maturation of the TPM1 pre-mRNA. Represses the splicing of
CC MAPT/Tau exon 10.
CC -!- SUBUNIT: Monomer. Part of a ternary complex containing KHSRP,
CC PTBP1, PTBP2 and HNRPH1. Interacts with RAVER1 and SFPQ.
CC -!- INTERACTION:
CC P29991:- (xeno); NbExp=5; IntAct=EBI-350540, EBI-8826689;
CC Q7ZYE9:hnrnpab (xeno); NbExp=4; IntAct=EBI-350540, EBI-1086317;
CC Q15365:PCBP1; NbExp=2; IntAct=EBI-350540, EBI-946095;
CC Q96PU8:QKI; NbExp=3; IntAct=EBI-350540, EBI-945792;
CC P23246:SFPQ; NbExp=2; IntAct=EBI-350540, EBI-355453;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=1;
CC IsoId=P26599-1; Sequence=Displayed;
CC Name=2; Synonyms=PTB2;
CC IsoId=P26599-2; Sequence=VSP_005802;
CC Name=3;
CC IsoId=P26599-3; Sequence=VSP_043649;
CC -!- SIMILARITY: Contains 4 RRM (RNA recognition motif) domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PTBP1ID46504ch19p13.html";
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DR EMBL; X62006; CAA43973.1; -; mRNA.
DR EMBL; X65371; CAA46443.1; -; mRNA.
DR EMBL; X65372; CAA46444.1; -; mRNA.
DR EMBL; X60648; CAA43056.1; -; mRNA.
DR EMBL; X66975; CAA47386.1; -; mRNA.
DR EMBL; BT006819; AAP35465.1; -; mRNA.
DR EMBL; AC006273; AAC99798.1; -; Genomic_DNA.
DR EMBL; CH471242; EAW61154.1; -; Genomic_DNA.
DR EMBL; BC002397; AAH02397.1; -; mRNA.
DR EMBL; BC004383; AAH04383.1; -; mRNA.
DR EMBL; BC013694; AAH13694.1; -; mRNA.
DR PIR; S23016; S23016.
DR RefSeq; NP_002810.1; NM_002819.4.
DR RefSeq; NP_114367.1; NM_031990.3.
DR RefSeq; NP_114368.1; NM_031991.3.
DR UniGene; Hs.172550; -.
DR PDB; 1QM9; NMR; -; A=335-531.
DR PDB; 1SJQ; NMR; -; A=55-147.
DR PDB; 1SJR; NMR; -; A=147-301.
DR PDB; 2AD9; NMR; -; A=49-146.
DR PDB; 2ADB; NMR; -; A=172-298.
DR PDB; 2ADC; NMR; -; A=324-531.
DR PDB; 2EVZ; NMR; -; A=324-531.
DR PDB; 3ZZY; X-ray; 1.40 A; A/B=156-285.
DR PDB; 3ZZZ; X-ray; 1.55 A; A/B=156-285.
DR PDBsum; 1QM9; -.
DR PDBsum; 1SJQ; -.
DR PDBsum; 1SJR; -.
DR PDBsum; 2AD9; -.
DR PDBsum; 2ADB; -.
DR PDBsum; 2ADC; -.
DR PDBsum; 2EVZ; -.
DR PDBsum; 3ZZY; -.
DR PDBsum; 3ZZZ; -.
DR ProteinModelPortal; P26599; -.
DR SMR; P26599; 49-146, 172-298, 324-531.
DR IntAct; P26599; 41.
DR MINT; MINT-1348690; -.
DR STRING; 9606.ENSP00000349428; -.
DR ChEMBL; CHEMBL1293230; -.
DR PhosphoSite; P26599; -.
DR DMDM; 131528; -.
DR SWISS-2DPAGE; P26599; -.
DR PaxDb; P26599; -.
DR PRIDE; P26599; -.
DR DNASU; 5725; -.
DR Ensembl; ENST00000349038; ENSP00000014112; ENSG00000011304.
DR Ensembl; ENST00000356948; ENSP00000349428; ENSG00000011304.
DR Ensembl; ENST00000394601; ENSP00000408096; ENSG00000011304.
DR GeneID; 5725; -.
DR KEGG; hsa:5725; -.
DR UCSC; uc002lpr.2; human.
DR CTD; 5725; -.
DR GeneCards; GC19P000797; -.
DR H-InvDB; HIX0137476; -.
DR HGNC; HGNC:9583; PTBP1.
DR HPA; CAB013507; -.
DR MIM; 600693; gene.
DR neXtProt; NX_P26599; -.
DR PharmGKB; PA33934; -.
DR eggNOG; NOG263741; -.
DR HOGENOM; HOG000231699; -.
DR HOVERGEN; HBG069548; -.
DR KO; K13218; -.
DR OMA; SEECAQT; -.
DR OrthoDB; EOG7V7691; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR EvolutionaryTrace; P26599; -.
DR GeneWiki; PTBP1; -.
DR GenomeRNAi; 5725; -.
DR NextBio; 22252; -.
DR PMAP-CutDB; P26599; -.
DR PRO; PR:P26599; -.
DR ArrayExpress; P26599; -.
DR Bgee; P26599; -.
DR CleanEx; HS_PTBP1; -.
DR Genevestigator; P26599; -.
DR GO; GO:0005730; C:nucleolus; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0008187; F:poly-pyrimidine tract binding; TAS:ProtInc.
DR GO; GO:0036002; F:pre-mRNA binding; IDA:UniProtKB.
DR GO; GO:0000380; P:alternative mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IDA:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR Gene3D; 3.30.70.330; -; 4.
DR InterPro; IPR006536; HnRNP-L_PTB.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 4.
DR TIGRFAMs; TIGR01649; hnRNP-L_PTB; 1.
DR PROSITE; PS50102; RRM; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Complete proteome; Direct protein sequencing; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; RNA-binding.
FT CHAIN 1 531 Polypyrimidine tract-binding protein 1.
FT /FTId=PRO_0000081737.
FT DOMAIN 59 143 RRM 1.
FT DOMAIN 184 260 RRM 2.
FT DOMAIN 337 411 RRM 3.
FT DOMAIN 454 529 RRM 4.
FT COMPBIAS 316 323 Poly-Ala.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 16 16 Phosphoserine.
FT MOD_RES 138 138 Phosphothreonine.
FT MOD_RES 141 141 Phosphoserine.
FT MOD_RES 433 433 Phosphoserine.
FT VAR_SEQ 297 297 F -> FASPYAGAGFPPTFAIPQAA (in isoform 2).
FT /FTId=VSP_005802.
FT VAR_SEQ 297 297 F -> FGAPGIISASPYAGAGFPPTFAIPQAA (in
FT isoform 3).
FT /FTId=VSP_043649.
FT STRAND 60 63
FT HELIX 72 82
FT STRAND 85 91
FT TURN 92 95
FT STRAND 96 103
FT HELIX 104 114
FT STRAND 127 130
FT STRAND 132 135
FT TURN 142 145
FT STRAND 182 190
FT HELIX 197 204
FT HELIX 205 207
FT STRAND 210 218
FT STRAND 221 229
FT HELIX 231 241
FT STRAND 245 247
FT STRAND 250 257
FT STRAND 259 262
FT STRAND 269 274
FT TURN 289 291
FT TURN 294 296
FT HELIX 329 332
FT STRAND 339 342
FT STRAND 346 348
FT HELIX 351 359
FT STRAND 365 368
FT TURN 371 373
FT STRAND 378 380
FT TURN 382 384
FT HELIX 385 394
FT STRAND 400 403
FT STRAND 405 408
FT STRAND 417 425
FT STRAND 427 431
FT STRAND 437 440
FT HELIX 444 446
FT STRAND 455 458
FT HELIX 467 476
FT STRAND 483 488
FT STRAND 494 497
FT HELIX 501 511
FT STRAND 515 519
FT STRAND 524 527
SQ SEQUENCE 531 AA; 57221 MW; BE12D5EA21537BED CRC64;
MDGIVPDIAV GTKRGSDELF STCVTNGPFI MSSNSASAAN GNDSKKFKGD SRSAGVPSRV
IHIRKLPIDV TEGEVISLGL PFGKVTNLLM LKGKNQAFIE MNTEEAANTM VNYYTSVTPV
LRGQPIYIQF SNHKELKTDS SPNQARAQAA LQAVNSVQSG NLALAASAAA VDAGMAMAGQ
SPVLRIIVEN LFYPVTLDVL HQIFSKFGTV LKIITFTKNN QFQALLQYAD PVSAQHAKLS
LDGQNIYNAC CTLRIDFSKL TSLNVKYNND KSRDYTRPDL PSGDSQPSLD QTMAAAFGLS
VPNVHGALAP LAIPSAAAAA AAAGRIAIPG LAGAGNSVLL VSNLNPERVT PQSLFILFGV
YGDVQRVKIL FNKKENALVQ MADGNQAQLA MSHLNGHKLH GKPIRITLSK HQNVQLPREG
QEDQGLTKDY GNSPLHRFKK PGSKNFQNIF PPSATLHLSN IPPSVSEEDL KVLFSSNGGV
VKGFKFFQKD RKMALIQMGS VEEAVQALID LHNHDLGENH HLRVSFSKST I
//
MIM
600693
*RECORD*
*FIELD* NO
600693
*FIELD* TI
*600693 POLYPYRIMIDINE TRACT-BINDING PROTEIN 1; PTBP1
;;PTB;;
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE I;;
read moreHNRNPI
*FIELD* TX
DESCRIPTION
Polypyrimidine tract-binding protein (PTB), also known as heterogeneous
nuclear ribonucleoprotein type I (hnRNP I), is a 59.6-kD nuclear protein
that binds pre-mRNAs in specific regions of the hnRNA-protein complexes
sensitive to micrococcal nuclease. The hnRNP I protein shows an unusual
pattern of nuclear localization (Ghetti et al., 1992). It has been
implicated in pre-mRNA splicing.
GENE FUNCTION
Inclusion of cardiac troponin T (TNNT2; 191045) exon 5 in embryonic
muscle requires conserved flanking intronic elements (MSEs). Charlet-B.
et al. (2002) found that ETR3 (CUGBP2; 602538), a member of the CELF
family, binds U/G motifs in 2 MSEs and directly activates exon inclusion
in vitro. They showed that binding and activation by ETR3 are directly
antagonized by PTB. The use of dominant-negative mutants demonstrated
that endogenous CELF and PTB activities are required for MSE-dependent
activation and repression in muscle and nonmuscle cells, respectively.
Combined use of CELF and PTB dominant-negative mutants provided an in
vivo demonstration that antagonistic splicing activities exist within
the same cells.
Makeyev et al. (2007) showed that the expression of miR124 (see 609327)
in mouse neuronal cells induced a switch from general to neuron-specific
alternative splicing by directly targeting the mRNA of Ptbp1. They
showed that miR124 increased the abundance of neuron-specific Ptbp2
(608449) and Gabbr1 (603540) mRNAs by preventing Ptbp1-dependent exon
skipping that leads to nonsense-mediated decay of these mRNAs. Makeyev
et al. (2007) further showed that retinoic acid-induced neuronal
differentiation in a mouse embryonal carcinoma cell line resulted in the
accumulation of miR124, which correlated with decreased Ptbp1 protein
levels, increased Ptbp2 levels, and a switch to neuron-specific
alternative splicing.
David et al. (2010) showed that 3 heterogeneous nuclear
ribonucleoprotein (hnRNP) proteins, PTB, hnRNPA1 (164017), and hnRNPA2
(600124), bind repressively to sequences flanking exon 9 of the PKM2
gene (179050), resulting in exon 10 inclusion and the expression of the
PKM2 (embryonic) isoform. David et al. (2010) also demonstrated that the
oncogenic transcription factor c-MYC (190080) upregulates transcription
of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1 ratio.
Establishing a relevance to cancer, David et al. (2010) showed that
human gliomas (137800) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2 in a
manner that correlates with PKM2 expression. David et al. (2010)
concluded that their results defined a pathway that regulates an
alternative splicing event required for tumor cell proliferation.
Luco et al. (2010) demonstrated a direct role for histone modifications,
specifically, trimethylation of H3 at lys36 (H3-K36me3; see 602810), in
alternative splicing. The authors found that MRG15 (607303) distribution
along the PTB-dependent alternatively spliced genes FGFR2 (176943), TPM2
(190990), TPM1 (191010), and PKM2, but not along the control gene CD44
(107269), mimicked H3-K36me3 distribution. Overexpression of MRG15 was
sufficient to force exclusion of the PTB-dependent exons but did not
significantly alter the inclusion levels of CD44 exon v6. Additional
experiments led Luco et al. (2010) to conclude that the
chromatin-binding protein MRG15 is a modulator of PTB-dependent
alternative splice site selection. The results of Luco et al. (2010) led
them to propose the existence of an adaptor system for the reading of
histone marks by the pre-mRNA splicing machinery. The adaptor system
consists of histone modifications, a chromatin-binding protein that
reads the histone marks, and an interacting splicing regulator. Luco et
al. (2010) concluded that for a subset of PTB-dependent genes, the
adaptor system consists of H3-K36me3, its binding protein MRG15, and the
splicing regulator PTBP1.
GENE STRUCTURE
Using RT-PCR and genomic sequence analysis, Romanelli et al. (2000)
showed that the PTB gene contains 15 exons and spans 13.5 kb.
MAPPING
By fluorescence in situ hybridization, Raimondi et al. (1995) assigned
the PTB gene to 14q23-q24.1. Other hnRNP protein genes that had been
mapped include A1 (164017) to 12q13.1, A2 (600124) to 7p15, and K
(600712) to chromosome 9. Southern blot analysis of human DNA
demonstrated that the PTB gene is present in single copy.
Using RT-PCR and genomic sequence analysis, Romanelli et al. (2000)
showed that the PTB gene is actually localized on chromosome 19,
probably at 19p13.3. A highly homologous processed pseudogene maps to
chromosome 14.
BIOCHEMICAL FEATURES
Oberstrass et al. (2005) determined the solution structures of the 4
RNA-binding domains (RBDs) of PTB, each bound to a CUCUCU
oligonucleotide. Each RNA-binding domain binds RNA with a different
binding specificity. RBD3 and RBD4 interact, resulting in an
antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA
looping when bound to 2 separated pyrimidine tracts within the same RNA.
Oberstrass et al. (2005) concluded that their data leads to structural
models for how PTB functions as an alternative splicing repressor.
*FIELD* RF
1. Charlet-B., N.; Logan, P.; Singh, G.; Cooper, T. A.: Dynamic antagonism
between ETR-3 and PTB regulates cell type-specific alternative splicing. Molec.
Cell 9: 649-658, 2002.
2. David, C. J.; Chen, M.; Assanah, M.; Canoll, P.; Manley, J. L.
: HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA
spicing in cancer. Nature 463: 364-368, 2010.
3. Ghetti, A.; Pinol-Roma, S.; Michael, W. M.; Morandi, C.; Dreyfuss,
G.: HNRNP I, the polypyrimidine tract-binding protein: distinct nuclear
localization and association with hnRNAs. Nucleic Acids Res. 20:
3671-3678, 1992.
4. Luco, R. F.; Pan, Q.; Tominaga, K.; Blencowe, B. J.; Pereira-Smith,
O. M.; Misteli, T.: Regulation of alternative splicing by histone
modifications. Science 327: 996-1000, 2010.
5. Makeyev, E. V.; Zhang, J.; Carrasco, M. A.; Maniatis, T.: The
microRNA miR-124 promotes neuronal differentiation by triggering brain-specific
alternative pre-mRNA splicing. Molec. Cell 27: 435-448, 2007.
6. Oberstrass, F. C.; Auweter, S. D.; Erat, M.; Hargous, Y.; Henning,
A.; Wenter, P.; Reymond, L.; Amir-Ahmady, B.; Pitsch, S.; Black, D.
L.; Allain, F. H.-T.: Structure of PTB bound to RNA: specific binding
and implications for splicing regulation. Science 309: 2054-2057,
2005.
7. Raimondi, E.; Romanelli, M. G.; Moralli, D.; Gamberi, C.; Russo,
M. P.; Morandi, C.: Assignment of the human gene encoding heterogeneous
nuclear RNA ribonucleoprotein I (PTB) to chromosome 14q23-q24.1. Genomics 27:
553-555, 1995.
8. Romanelli, M. G.; Lorenzi, P.; Morandi, C.: Organization of the
human gene encoding heterogeneous nuclear ribonucleoprotein type I
(hnRNP I) and characterization of hnRNP I related pseudogene. Gene 255:
267-272, 2000.
*FIELD* CN
Ada Hamosh - updated: 3/9/2010
Ada Hamosh - updated: 2/18/2010
Patricia A. Hartz - updated: 9/14/2007
Ada Hamosh - updated: 11/2/2005
Stylianos E. Antonarakis - updated: 9/23/2002
Paul J. Converse - updated: 12/10/2001
*FIELD* CD
Victor A. McKusick: 7/27/1995
*FIELD* ED
mgross: 02/05/2013
alopez: 3/11/2010
terry: 3/9/2010
alopez: 2/24/2010
terry: 2/18/2010
alopez: 9/17/2007
terry: 9/14/2007
alopez: 11/4/2005
terry: 11/2/2005
mgross: 9/23/2002
mgross: 1/28/2002
mgross: 12/10/2001
psherman: 6/30/1999
alopez: 6/29/1999
terry: 9/11/1995
mark: 7/27/1995
*RECORD*
*FIELD* NO
600693
*FIELD* TI
*600693 POLYPYRIMIDINE TRACT-BINDING PROTEIN 1; PTBP1
;;PTB;;
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE I;;
read moreHNRNPI
*FIELD* TX
DESCRIPTION
Polypyrimidine tract-binding protein (PTB), also known as heterogeneous
nuclear ribonucleoprotein type I (hnRNP I), is a 59.6-kD nuclear protein
that binds pre-mRNAs in specific regions of the hnRNA-protein complexes
sensitive to micrococcal nuclease. The hnRNP I protein shows an unusual
pattern of nuclear localization (Ghetti et al., 1992). It has been
implicated in pre-mRNA splicing.
GENE FUNCTION
Inclusion of cardiac troponin T (TNNT2; 191045) exon 5 in embryonic
muscle requires conserved flanking intronic elements (MSEs). Charlet-B.
et al. (2002) found that ETR3 (CUGBP2; 602538), a member of the CELF
family, binds U/G motifs in 2 MSEs and directly activates exon inclusion
in vitro. They showed that binding and activation by ETR3 are directly
antagonized by PTB. The use of dominant-negative mutants demonstrated
that endogenous CELF and PTB activities are required for MSE-dependent
activation and repression in muscle and nonmuscle cells, respectively.
Combined use of CELF and PTB dominant-negative mutants provided an in
vivo demonstration that antagonistic splicing activities exist within
the same cells.
Makeyev et al. (2007) showed that the expression of miR124 (see 609327)
in mouse neuronal cells induced a switch from general to neuron-specific
alternative splicing by directly targeting the mRNA of Ptbp1. They
showed that miR124 increased the abundance of neuron-specific Ptbp2
(608449) and Gabbr1 (603540) mRNAs by preventing Ptbp1-dependent exon
skipping that leads to nonsense-mediated decay of these mRNAs. Makeyev
et al. (2007) further showed that retinoic acid-induced neuronal
differentiation in a mouse embryonal carcinoma cell line resulted in the
accumulation of miR124, which correlated with decreased Ptbp1 protein
levels, increased Ptbp2 levels, and a switch to neuron-specific
alternative splicing.
David et al. (2010) showed that 3 heterogeneous nuclear
ribonucleoprotein (hnRNP) proteins, PTB, hnRNPA1 (164017), and hnRNPA2
(600124), bind repressively to sequences flanking exon 9 of the PKM2
gene (179050), resulting in exon 10 inclusion and the expression of the
PKM2 (embryonic) isoform. David et al. (2010) also demonstrated that the
oncogenic transcription factor c-MYC (190080) upregulates transcription
of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1 ratio.
Establishing a relevance to cancer, David et al. (2010) showed that
human gliomas (137800) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2 in a
manner that correlates with PKM2 expression. David et al. (2010)
concluded that their results defined a pathway that regulates an
alternative splicing event required for tumor cell proliferation.
Luco et al. (2010) demonstrated a direct role for histone modifications,
specifically, trimethylation of H3 at lys36 (H3-K36me3; see 602810), in
alternative splicing. The authors found that MRG15 (607303) distribution
along the PTB-dependent alternatively spliced genes FGFR2 (176943), TPM2
(190990), TPM1 (191010), and PKM2, but not along the control gene CD44
(107269), mimicked H3-K36me3 distribution. Overexpression of MRG15 was
sufficient to force exclusion of the PTB-dependent exons but did not
significantly alter the inclusion levels of CD44 exon v6. Additional
experiments led Luco et al. (2010) to conclude that the
chromatin-binding protein MRG15 is a modulator of PTB-dependent
alternative splice site selection. The results of Luco et al. (2010) led
them to propose the existence of an adaptor system for the reading of
histone marks by the pre-mRNA splicing machinery. The adaptor system
consists of histone modifications, a chromatin-binding protein that
reads the histone marks, and an interacting splicing regulator. Luco et
al. (2010) concluded that for a subset of PTB-dependent genes, the
adaptor system consists of H3-K36me3, its binding protein MRG15, and the
splicing regulator PTBP1.
GENE STRUCTURE
Using RT-PCR and genomic sequence analysis, Romanelli et al. (2000)
showed that the PTB gene contains 15 exons and spans 13.5 kb.
MAPPING
By fluorescence in situ hybridization, Raimondi et al. (1995) assigned
the PTB gene to 14q23-q24.1. Other hnRNP protein genes that had been
mapped include A1 (164017) to 12q13.1, A2 (600124) to 7p15, and K
(600712) to chromosome 9. Southern blot analysis of human DNA
demonstrated that the PTB gene is present in single copy.
Using RT-PCR and genomic sequence analysis, Romanelli et al. (2000)
showed that the PTB gene is actually localized on chromosome 19,
probably at 19p13.3. A highly homologous processed pseudogene maps to
chromosome 14.
BIOCHEMICAL FEATURES
Oberstrass et al. (2005) determined the solution structures of the 4
RNA-binding domains (RBDs) of PTB, each bound to a CUCUCU
oligonucleotide. Each RNA-binding domain binds RNA with a different
binding specificity. RBD3 and RBD4 interact, resulting in an
antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA
looping when bound to 2 separated pyrimidine tracts within the same RNA.
Oberstrass et al. (2005) concluded that their data leads to structural
models for how PTB functions as an alternative splicing repressor.
*FIELD* RF
1. Charlet-B., N.; Logan, P.; Singh, G.; Cooper, T. A.: Dynamic antagonism
between ETR-3 and PTB regulates cell type-specific alternative splicing. Molec.
Cell 9: 649-658, 2002.
2. David, C. J.; Chen, M.; Assanah, M.; Canoll, P.; Manley, J. L.
: HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA
spicing in cancer. Nature 463: 364-368, 2010.
3. Ghetti, A.; Pinol-Roma, S.; Michael, W. M.; Morandi, C.; Dreyfuss,
G.: HNRNP I, the polypyrimidine tract-binding protein: distinct nuclear
localization and association with hnRNAs. Nucleic Acids Res. 20:
3671-3678, 1992.
4. Luco, R. F.; Pan, Q.; Tominaga, K.; Blencowe, B. J.; Pereira-Smith,
O. M.; Misteli, T.: Regulation of alternative splicing by histone
modifications. Science 327: 996-1000, 2010.
5. Makeyev, E. V.; Zhang, J.; Carrasco, M. A.; Maniatis, T.: The
microRNA miR-124 promotes neuronal differentiation by triggering brain-specific
alternative pre-mRNA splicing. Molec. Cell 27: 435-448, 2007.
6. Oberstrass, F. C.; Auweter, S. D.; Erat, M.; Hargous, Y.; Henning,
A.; Wenter, P.; Reymond, L.; Amir-Ahmady, B.; Pitsch, S.; Black, D.
L.; Allain, F. H.-T.: Structure of PTB bound to RNA: specific binding
and implications for splicing regulation. Science 309: 2054-2057,
2005.
7. Raimondi, E.; Romanelli, M. G.; Moralli, D.; Gamberi, C.; Russo,
M. P.; Morandi, C.: Assignment of the human gene encoding heterogeneous
nuclear RNA ribonucleoprotein I (PTB) to chromosome 14q23-q24.1. Genomics 27:
553-555, 1995.
8. Romanelli, M. G.; Lorenzi, P.; Morandi, C.: Organization of the
human gene encoding heterogeneous nuclear ribonucleoprotein type I
(hnRNP I) and characterization of hnRNP I related pseudogene. Gene 255:
267-272, 2000.
*FIELD* CN
Ada Hamosh - updated: 3/9/2010
Ada Hamosh - updated: 2/18/2010
Patricia A. Hartz - updated: 9/14/2007
Ada Hamosh - updated: 11/2/2005
Stylianos E. Antonarakis - updated: 9/23/2002
Paul J. Converse - updated: 12/10/2001
*FIELD* CD
Victor A. McKusick: 7/27/1995
*FIELD* ED
mgross: 02/05/2013
alopez: 3/11/2010
terry: 3/9/2010
alopez: 2/24/2010
terry: 2/18/2010
alopez: 9/17/2007
terry: 9/14/2007
alopez: 11/4/2005
terry: 11/2/2005
mgross: 9/23/2002
mgross: 1/28/2002
mgross: 12/10/2001
psherman: 6/30/1999
alopez: 6/29/1999
terry: 9/11/1995
mark: 7/27/1995