Full text data of PABPC1
PABPC1
(PAB1, PABP1, PABPC2)
[Confidence: low (only semi-automatic identification from reviews)]
Polyadenylate-binding protein 1; PABP-1; Poly(A)-binding protein 1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Polyadenylate-binding protein 1; PABP-1; Poly(A)-binding protein 1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P11940
ID PABP1_HUMAN Reviewed; 636 AA.
AC P11940; Q15097; Q93004;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 2.
DT 22-JAN-2014, entry version 178.
DE RecName: Full=Polyadenylate-binding protein 1;
DE Short=PABP-1;
DE Short=Poly(A)-binding protein 1;
GN Name=PABPC1; Synonyms=PAB1, PABP1, PABPC2;
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] (ISOFORM 1).
RX PubMed=2885805; DOI=10.1093/nar/15.12.4771;
RA Grange T., de Sa C.M., Oddos J., Pictet R.;
RT "Human mRNA polyadenylate binding protein: evolutionary conservation
RT of a nucleic acid binding motif.";
RL Nucleic Acids Res. 15:4771-4787(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RA Hornstein E., Abramzon-Talianker A., Wiesel I., Meyuhas O.;
RT "The human poly(A)-binding protein (PABP) gene: structural and
RT functional analysis.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Muscle;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-636 (ISOFORM 2).
RA Murphy E.P., McKenna N.J., Headon D.R.;
RT "Nucleotide sequence of a partial cDNA encoding a novel human
RT polyadenylate-binding protein.";
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 31-41; 51-78; 84-89; 96-104; 158-166; 189-196;
RP 214-221; 232-240; 291-309; 312-324; 357-370; 375-385; 482-506; 566-580
RP AND 605-620, METHYLATION AT ARG-493, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Zebisch A., Lilla S., von Kriegsheim A., Lempens A.,
RA Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 31-41; 51-78; 84-89; 96-104; 114-129; 139-153;
RP 158-166; 187-208; 214-221; 232-240; 291-324; 334-348; 357-370;
RP 375-385; 482-506; 519-559; 566-620 AND 626-636, METHYLATION AT LYS-299
RP AND ARG-493, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [8]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=7908267; DOI=10.1006/excr.1994.1104;
RA Goerlach M., Burd C.G., Dreyfuss G.;
RT "The mRNA poly(A)-binding protein: localization, abundance, and RNA-
RT binding specificity.";
RL Exp. Cell Res. 211:400-407(1994).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=9582337; DOI=10.1074/jbc.273.21.13015;
RA Afonina E., Stauber R., Pavlakis G.N.;
RT "The human poly(A)-binding protein 1 shuttles between the nucleus and
RT the cytoplasm.";
RL J. Biol. Chem. 273:13015-13021(1998).
RN [10]
RP INTERACTION WITH PAIP1.
RX PubMed=9548260; DOI=10.1038/33198;
RA Craig A.W.B., Haghighat A., Yu A.T.K., Sonenberg N.;
RT "Interaction of polyadenylate-binding protein with the eIF4G homologue
RT PAIP enhances translation.";
RL Nature 392:520-523(1998).
RN [11]
RP FUNCTION IN TRANSLATIONALLY COUPLED MRNA TURNOVER, AND IDENTIFICATION
RP IN A COMPLEX WITH HNRPD; SYNCRIP; PAIP1 AND CSDE1.
RX PubMed=11051545; DOI=10.1016/S0092-8674(00)00102-1;
RA Grosset C., Chen C.-Y.A., Xu N., Sonenberg N., Jacquemin-Sablon H.,
RA Shyu A.-B.;
RT "A mechanism for translationally coupled mRNA turnover: interaction
RT between the poly(A) tail and a c-fos RNA coding determinant via a
RT protein complex.";
RL Cell 103:29-40(2000).
RN [12]
RP INTERACTION WITH PAIP2.
RX PubMed=11172725; DOI=10.1016/S1097-2765(01)00168-X;
RA Khaleghpour K., Svitkin Y.V., Craig A.W.B., DeMaria C.T., Deo R.C.,
RA Burley S.K., Sonenberg N.;
RT "Translational repression by a novel partner of human poly(A) binding
RT protein, Paip2.";
RL Mol. Cell 7:205-216(2001).
RN [13]
RP INTERACTION WITH PAIP2.
RX PubMed=11438674; DOI=10.1128/MCB.21.15.5200-5213.2001;
RA Khaleghpour K., Kahvejian A., De Crescenzo G., Roy G., Svitkin Y.V.,
RA Imataka H., O'Connor-McCourt M., Sonenberg N.;
RT "Dual interactions of the translational repressor Paip2 with poly(A)
RT binding protein.";
RL Mol. Cell. Biol. 21:5200-5213(2001).
RN [14]
RP METHYLATION AT ARG-455 AND ARG-460, AND MUTAGENESIS OF ARG-455 AND
RP ARG-460.
RX PubMed=11850402; DOI=10.1093/embo-reports/kvf052;
RA Lee J., Bedford M.T.;
RT "PABP1 identified as an arginine methyltransferase substrate using
RT high-density protein arrays.";
RL EMBO Rep. 3:268-273(2002).
RN [15]
RP INTERACTION WITH PAIP1.
RX PubMed=11997512; DOI=10.1128/MCB.22.11.3769-3782.2002;
RA Roy G., De Crescenzo G., Khaleghpour K., Kahvejian A.,
RA O'Connor-McCourt M., Sonenberg N.;
RT "Paip1 interacts with poly(A) binding protein through two independent
RT binding motifs.";
RL Mol. Cell. Biol. 22:3769-3782(2002).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP SPLICEOSOMAL C COMPLEX.
RX PubMed=11991638; DOI=10.1017/S1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [17]
RP PHOSPHORYLATION BY MAPKAPK2.
RX PubMed=12565831; DOI=10.1016/S0006-291X(03)00015-9;
RA Bollig F., Winzen R., Gaestel M., Kostka S., Resch K., Holtmann H.;
RT "Affinity purification of ARE-binding proteins identifies polyA-
RT binding protein 1 as a potential substrate in MK2-induced mRNA
RT stabilization.";
RL Biochem. Biophys. Res. Commun. 301:665-670(2003).
RN [18]
RP INTERACTION WITH CSDE1.
RX PubMed=15314026; DOI=10.1101/gad.1219104;
RA Chang T.-C., Yamashita A., Chen C.-Y.A., Yamashita Y., Zhu W.,
RA Durdan S., Kahvejian A., Sonenberg N., Shyu A.-B.;
RT "UNR, a new partner of poly(A)-binding protein, plays a key role in
RT translationally coupled mRNA turnover mediated by the c-fos major
RT coding-region determinant.";
RL Genes Dev. 18:2010-2023(2004).
RN [19]
RP IDENTIFICATION IN A MRNP COMPLEX WITH IGF2BP1 AND CSDE1.
RX PubMed=16356927; DOI=10.1093/nar/gki1014;
RA Patel G.P., Ma S., Bag J.;
RT "The autoregulatory translational control element of poly(A)-binding
RT protein mRNA forms a heteromeric ribonucleoprotein complex.";
RL Nucleic Acids Res. 33:7074-7089(2005).
RN [20]
RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH IGF2BP1, AND RNA-BINDING.
RX PubMed=17212783; DOI=10.1111/j.1742-4658.2006.05556.x;
RA Patel G.P., Bag J.;
RT "IMP1 interacts with poly(A)-binding protein (PABP) and the
RT autoregulatory translational control element of PABP-mRNA through the
RT KH III-IV domain.";
RL FEBS J. 273:5678-5690(2006).
RN [21]
RP INTERACTION WITH AGO1 AND AGO2.
RX PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA Urlaub H., Meister G.;
RT "Proteomic and functional analysis of Argonaute-containing mRNA-
RT protein complexes in human cells.";
RL EMBO Rep. 8:1052-1060(2007).
RN [22]
RP INTERACTION WITH NFX1.
RX PubMed=17267499; DOI=10.1128/JVI.02007-06;
RA Katzenellenbogen R.A., Egelkrout E.M., Vliet-Gregg P., Gewin L.C.,
RA Gafken P.R., Galloway D.A.;
RT "NFX1-123 and poly(A) binding proteins synergistically augment
RT activation of telomerase in human papillomavirus type 16 E6-expressing
RT cells.";
RL J. Virol. 81:3786-3796(2007).
RN [23]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, INTERACTION WITH IGF2BP1,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.M600346-MCP200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=18799579; DOI=10.1128/JVI.00872-08;
RA Harb M., Becker M.M., Vitour D., Baron C.H., Vende P., Brown S.C.,
RA Bolte S., Arold S.T., Poncet D.;
RT "Nuclear localization of cytoplasmic poly(A)-binding protein upon
RT rotavirus infection involves the interaction of NSP3 with eIF4G and
RT RoXaN.";
RL J. Virol. 82:11283-11293(2008).
RN [25]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, AND INTERACTION WITH GSPT2.
RX PubMed=18447585; DOI=10.1371/journal.pbio.0060111;
RA Singh G., Rebbapragada I., Lykke-Andersen J.;
RT "A competition between stimulators and antagonists of Upf complex
RT recruitment governs human nonsense-mediated mRNA decay.";
RL PLoS Biol. 6:E111-E111(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, 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 [27]
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 [28]
RP IDENTIFICATION IN A MRNP COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19029303; DOI=10.1261/rna.1175909;
RA Weidensdorfer D., Stoehr N., Baude A., Lederer M., Koehn M.,
RA Schierhorn A., Buchmeier S., Wahle E., Huettelmaiery S.;
RT "Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic
RT RNPs.";
RL RNA 15:104-115(2009).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-512, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [30]
RP REVIEW.
RX PubMed=20102337; DOI=10.1042/BJ20091571;
RA Smith R.W., Gray N.K.;
RT "Poly(A)-binding protein (PABP): a common viral target.";
RL Biochem. J. 426:1-12(2010).
RN [31]
RP INTERACTION WITH HHV-5 PROTEIN UL69.
RX PubMed=20133758; DOI=10.1073/pnas.0914856107;
RA Aoyagi M., Gaspar M., Shenk T.E.;
RT "Human cytomegalovirus UL69 protein facilitates translation by
RT associating with the mRNA cap-binding complex and excluding 4EBP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2640-2645(2010).
RN [32]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PABPC1 AND
RP GNB2L1.
RX PubMed=20573744; DOI=10.1261/rna.2146910;
RA Schaffler K., Schulz K., Hirmer A., Wiesner J., Grimm M., Sickmann A.,
RA Fischer U.;
RT "A stimulatory role for the La-related protein 4B in translation.";
RL RNA 16:1488-1499(2010).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP 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 [34]
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 [35]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-190.
RX PubMed=10499800; DOI=10.1016/S0092-8674(00)81517-2;
RA Deo R.C., Bonanno J.B., Sonenberg N., Burley S.K.;
RT "Recognition of polyadenylate RNA by the poly(A)-binding protein.";
RL Cell 98:835-845(1999).
RN [36]
RP STRUCTURE BY NMR OF 498-636, AND INTERACTION WITH GSPT1; PAIP1 AND
RP PAIP2.
RX PubMed=11287632; DOI=10.1073/pnas.071024998;
RA Kozlov G., Trempe J.F., Khaleghpour K., Kahvejian A., Ekiel I.,
RA Gehring K.;
RT "Structure and function of the C-terminal PABC domain of human
RT poly(A)-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4409-4413(2001).
RN [37]
RP STRUCTURE BY NMR OF 541-623 IN COMPLEX WITH GSPT1.
RA Osawa M., Nakanishi T., Hosoda N., Uchida S., Hoshino T., Katada I.,
RA Shimada I.;
RT "Eukaryotic translation termination factor Gspt/ERF3 recognizes Pabp
RT with chemical exchange using two overlapping motifs.";
RL Submitted (MAY-2009) to the PDB data bank.
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 544-626 IN COMPLEX WITH
RP PAIP2.
RX PubMed=20096703; DOI=10.1016/j.jmb.2010.01.032;
RA Kozlov G., Menade M., Rosenauer A., Nguyen L., Gehring K.;
RT "Molecular determinants of PAM2 recognition by the MLLE domain of
RT poly(A)-binding protein.";
RL J. Mol. Biol. 397:397-407(2010).
CC -!- FUNCTION: Binds the poly(A) tail of mRNA, including that of its
CC own transcript. May be involved in cytoplasmic regulatory
CC processes of mRNA metabolism such as pre-mRNA splicing. Its
CC function in translational initiation regulation can either be
CC enhanced by PAIP1 or repressed by PAIP2. Can probably bind to
CC cytoplasmic RNA sequences other than poly(A) in vivo. Involved in
CC translationally coupled mRNA turnover. Implicated with other RNA-
CC binding proteins in the cytoplasmic deadenylation/translational
CC and decay interplay of the FOS mRNA mediated by the major coding-
CC region determinant of instability (mCRD) domain. Involved in
CC regulation of nonsense-mediated decay (NMD) of mRNAs containing
CC premature stop codons; for the recognition of premature
CC termination codons (PTC) and initiation of NMD a competitive
CC interaction between UPF1 and PABPC1 with the ribosome-bound
CC release factors is proposed.
CC -!- SUBUNIT: May form homodimers. Component of a multisubunit
CC autoregulatory ribonucleoprotein complex (ARC), at least composed
CC of IGF2BP1, PABPC1 and CSDE1. Directly interacts with IGF2BP1.
CC Part of a complex associated with the FOS mCRD domain and
CC consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR. Interacts with
CC the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1 and
CC PAIP2. Interacts with PAIP1 with a 1:1 stoichiometry and with
CC PAIP2 with a 1:2 stoichiometry. The interaction with CSDE1 is
CC direct and RNA-independent. Found in a mRNP complex with YBX2.
CC Interacts with PAPD4/GLD2. Identified in the spliceosome C
CC complex. Identified in a mRNP complex, at least composed of DHX9,
CC DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1,
CC STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP
CC granule complex containing untranslated mRNAs. Interacts with
CC NFX1. Interacts with PIWIL1. Interacts with AGO1, AGO2, GSPT1 and
CC GSPT2. Interacts with human cytomegalovirus/HHV-5 protein UL69.
CC Interacts with LARP4B.
CC -!- INTERACTION:
CC Q99700:ATXN2; NbExp=6; IntAct=EBI-81531, EBI-697691;
CC O00571:DDX3X; NbExp=10; IntAct=EBI-81531, EBI-353779;
CC Q04637:EIF4G1; NbExp=2; IntAct=EBI-81531, EBI-73711;
CC Q8IYD1:GSPT2; NbExp=7; IntAct=EBI-81531, EBI-3869637;
CC Q14103-4:HNRNPD; NbExp=2; IntAct=EBI-81531, EBI-432545;
CC P35568:IRS1; NbExp=2; IntAct=EBI-81531, EBI-517592;
CC Q9H074:PAIP1; NbExp=11; IntAct=EBI-81531, EBI-81519;
CC Q9BPZ3:PAIP2; NbExp=5; IntAct=EBI-81531, EBI-2957445;
CC Q96Q15:SMG1; NbExp=2; IntAct=EBI-81531, EBI-1049832;
CC Q9UPQ9:TNRC6B; NbExp=3; IntAct=EBI-81531, EBI-947158;
CC Q9HCJ0:TNRC6C; NbExp=17; IntAct=EBI-81531, EBI-6507625;
CC Q14106:TOB2; NbExp=4; IntAct=EBI-81531, EBI-2562000;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs. Shuttles
CC between the cytoplasm and the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11940-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11940-2; Sequence=VSP_009846;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The RNA-binding domains RRM1 and RRM2 and the C-terminus
CC (last 138 amino acids) regions interact with the PABPC1-
CC interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively.
CC -!- DOMAIN: The RNA-binding domains RRM2 and RRM3 and the C-terminus
CC (last 138 amino acids) regions interact with the PABPC1-
CC interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively.
CC -!- PTM: Phosphorylated by MAPKAPK2.
CC -!- PTM: Methylated by CARM1. Arg-493 is dimethylated, probably to
CC asymmetric dimethylarginine.
CC -!- MISCELLANEOUS: Many viruses shutoff host mRNA translational
CC machinery by inhibiting cellular PABPC1 activity using different
CC mechanisms. Picornaviruses, caliciviruses or lentiviruses encode
CC proteases that cleave PABPC1 at several defined sites in the
CC proline-rich linker region between RRMs and the C-terminal domain.
CC Rotaviruses, gammherpesviruses and bunyamwera virus relocalize
CC PABPC1 from the cytoplasm to the nucleus thus altering its
CC function. Many of these viruses translate their mRNA in a PABPC1-
CC independent manner and are unaffected by host PABPC1 inhibition.
CC -!- SIMILARITY: Belongs to the polyadenylate-binding protein type-1
CC family.
CC -!- SIMILARITY: Contains 1 PABC domain.
CC -!- SIMILARITY: Contains 4 RRM (RNA recognition motif) domains.
CC -!- CAUTION: Was termed (Ref.5) polyadenylate binding protein II.
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DR EMBL; Y00345; CAA68428.1; -; mRNA.
DR EMBL; U68104; AAD08718.1; -; Genomic_DNA.
DR EMBL; U68093; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68094; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68095; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68097; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68098; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68099; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68100; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68101; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68102; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68103; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; AP001205; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015958; AAH15958.1; -; mRNA.
DR EMBL; BC023520; AAH23520.1; -; mRNA.
DR EMBL; Z48501; CAA88401.1; -; mRNA.
DR PIR; A93668; DNHUPA.
DR PIR; S52491; S52491.
DR RefSeq; NP_002559.2; NM_002568.3.
DR RefSeq; XP_005250918.1; XM_005250861.1.
DR RefSeq; XP_005250919.1; XM_005250862.1.
DR UniGene; Hs.387804; -.
DR PDB; 1CVJ; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-190.
DR PDB; 1G9L; NMR; -; A=498-636.
DR PDB; 1JGN; NMR; -; A=544-636.
DR PDB; 1JH4; NMR; -; A=544-636.
DR PDB; 2K8G; NMR; -; A=90-182.
DR PDB; 2RQG; NMR; -; B=541-623.
DR PDB; 2RQH; NMR; -; B=541-623.
DR PDB; 2X04; X-ray; 1.49 A; A/B=545-619.
DR PDB; 3KTP; X-ray; 1.50 A; A=544-626.
DR PDB; 3KTR; X-ray; 1.70 A; A=544-626.
DR PDB; 3KUI; X-ray; 2.30 A; A=544-626.
DR PDB; 3KUJ; X-ray; 1.40 A; A=544-626.
DR PDB; 3KUR; X-ray; 2.50 A; A/B/C/D/E/F/G/H=544-617.
DR PDB; 3KUS; X-ray; 1.40 A; A/B=544-626.
DR PDB; 3KUT; X-ray; 1.50 A; A/B=544-626.
DR PDB; 3PKN; X-ray; 1.80 A; A=544-626.
DR PDB; 3PTH; X-ray; 1.70 A; A=543-621.
DR PDB; 4F02; X-ray; 2.00 A; A/D=1-190.
DR PDB; 4F25; X-ray; 1.90 A; A=99-199.
DR PDB; 4F26; X-ray; 2.00 A; A=99-199.
DR PDBsum; 1CVJ; -.
DR PDBsum; 1G9L; -.
DR PDBsum; 1JGN; -.
DR PDBsum; 1JH4; -.
DR PDBsum; 2K8G; -.
DR PDBsum; 2RQG; -.
DR PDBsum; 2RQH; -.
DR PDBsum; 2X04; -.
DR PDBsum; 3KTP; -.
DR PDBsum; 3KTR; -.
DR PDBsum; 3KUI; -.
DR PDBsum; 3KUJ; -.
DR PDBsum; 3KUR; -.
DR PDBsum; 3KUS; -.
DR PDBsum; 3KUT; -.
DR PDBsum; 3PKN; -.
DR PDBsum; 3PTH; -.
DR PDBsum; 4F02; -.
DR PDBsum; 4F25; -.
DR PDBsum; 4F26; -.
DR ProteinModelPortal; P11940; -.
DR SMR; P11940; 10-376, 494-636.
DR DIP; DIP-31613N; -.
DR IntAct; P11940; 84.
DR MINT; MINT-96210; -.
DR STRING; 9606.ENSP00000313007; -.
DR BindingDB; P11940; -.
DR ChEMBL; CHEMBL1293286; -.
DR PhosphoSite; P11940; -.
DR DMDM; 3183544; -.
DR PaxDb; P11940; -.
DR PRIDE; P11940; -.
DR DNASU; 26986; -.
DR Ensembl; ENST00000318607; ENSP00000313007; ENSG00000070756.
DR GeneID; 26986; -.
DR KEGG; hsa:26986; -.
DR UCSC; uc003yjs.1; human.
DR CTD; 26986; -.
DR GeneCards; GC08M101715; -.
DR HGNC; HGNC:8554; PABPC1.
DR HPA; CAB011536; -.
DR HPA; HPA045423; -.
DR MIM; 604679; gene.
DR neXtProt; NX_P11940; -.
DR PharmGKB; PA32880; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000217922; -.
DR HOVERGEN; HBG002295; -.
DR InParanoid; P11940; -.
DR KO; K13126; -.
DR OMA; YPTNQLA; -.
DR OrthoDB; EOG7RV9FP; -.
DR PhylomeDB; P11940; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_1762; 3' -UTR-mediated translational regulation.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; PABPC1; human.
DR EvolutionaryTrace; P11940; -.
DR GeneWiki; PABPC1; -.
DR GenomeRNAi; 26986; -.
DR NextBio; 49454; -.
DR PMAP-CutDB; P11940; -.
DR PRO; PR:P11940; -.
DR ArrayExpress; P11940; -.
DR Bgee; P11940; -.
DR CleanEx; HS_PABPC1; -.
DR Genevestigator; P11940; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0008143; F:poly(A) RNA binding; TAS:UniProtKB.
DR GO; GO:0008494; F:translation activator activity; TAS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; TAS:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0048255; P:mRNA stabilization; TAS:UniProtKB.
DR GO; GO:2000623; P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; ISS:UniProtKB.
DR GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR Gene3D; 1.10.1900.10; -; 1.
DR Gene3D; 3.30.70.330; -; 4.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR006515; PABP_1234.
DR InterPro; IPR002004; PABP_HYD.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00658; PABP; 1.
DR Pfam; PF00076; RRM_1; 4.
DR SMART; SM00517; PolyA; 1.
DR SMART; SM00360; RRM; 4.
DR SUPFAM; SSF63570; SSF63570; 1.
DR TIGRFAMs; TIGR01628; PABP-1234; 1.
DR PROSITE; PS51309; PABC; 1.
DR PROSITE; PS50102; RRM; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Methylation; mRNA processing;
KW mRNA splicing; Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Spliceosome.
FT CHAIN 1 636 Polyadenylate-binding protein 1.
FT /FTId=PRO_0000081698.
FT DOMAIN 11 89 RRM 1.
FT DOMAIN 99 175 RRM 2.
FT DOMAIN 191 268 RRM 3.
FT DOMAIN 294 370 RRM 4.
FT DOMAIN 542 619 PABC.
FT REGION 166 289 CSDE1-binding.
FT COMPBIAS 495 501 Poly-Ala.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 299 299 N6-methyllysine.
FT MOD_RES 315 315 Phosphoserine.
FT MOD_RES 455 455 Omega-N-methylated arginine; by CARM1;
FT partial (Probable).
FT MOD_RES 460 460 Omega-N-methylated arginine; by CARM1;
FT partial (Probable).
FT MOD_RES 493 493 Dimethylated arginine; alternate.
FT MOD_RES 493 493 Omega-N-methylarginine; alternate.
FT MOD_RES 512 512 N6-acetyllysine.
FT VAR_SEQ 447 535 Missing (in isoform 2).
FT /FTId=VSP_009846.
FT MUTAGEN 455 455 R->A: Greatly reduces methylation by
FT CARM1 (in vitro); when associated with A-
FT 460.
FT MUTAGEN 460 460 R->A: Greatly reduces methylation by
FT CARM1 (in vitro); when associated with A-
FT 455.
FT CONFLICT 211 213 Missing (in Ref. 1; CAA68428).
FT CONFLICT 410 410 M -> I (in Ref. 5; CAA88401).
FT CONFLICT 428 428 I -> V (in Ref. 1; CAA68428).
FT STRAND 12 17
FT HELIX 24 31
FT HELIX 32 34
FT STRAND 37 44
FT TURN 46 48
FT STRAND 51 61
FT HELIX 62 72
FT STRAND 83 86
FT HELIX 92 96
FT STRAND 100 105
FT HELIX 112 119
FT HELIX 120 122
FT STRAND 125 133
FT STRAND 136 146
FT HELIX 148 158
FT STRAND 161 163
FT STRAND 169 174
FT HELIX 176 183
FT HELIX 547 551
FT HELIX 555 557
FT HELIX 558 573
FT TURN 575 577
FT HELIX 578 585
FT HELIX 590 598
FT HELIX 600 619
FT TURN 623 625
FT STRAND 628 630
SQ SEQUENCE 636 AA; 70671 MW; 2EB1B02A346132EE CRC64;
MNPSAPSYPM ASLYVGDLHP DVTEAMLYEK FSPAGPILSI RVCRDMITRR SLGYAYVNFQ
QPADAERALD TMNFDVIKGK PVRIMWSQRD PSLRKSGVGN IFIKNLDKSI DNKALYDTFS
AFGNILSCKV VCDENGSKGY GFVHFETQEA AERAIEKMNG MLLNDRKVFV GRFKSRKERE
AELGARAKEF TNVYIKNFGE DMDDERLKDL FGKFGPALSV KVMTDESGKS KGFGFVSFER
HEDAQKAVDE MNGKELNGKQ IYVGRAQKKV ERQTELKRKF EQMKQDRITR YQGVNLYVKN
LDDGIDDERL RKEFSPFGTI TSAKVMMEGG RSKGFGFVCF SSPEEATKAV TEMNGRIVAT
KPLYVALAQR KEERQAHLTN QYMQRMASVR AVPNPVINPY QPAPPSGYFM AAIPQTQNRA
AYYPPSQIAQ LRPSPRWTAQ GARPHPFQNM PGAIRPAAPR PPFSTMRPAS SQVPRVMSTQ
RVANTSTQTM GPRPAAAAAA ATPAVRTVPQ YKYAAGVRNP QQHLNAQPQV TMQQPAVHVQ
GQEPLTASML ASAPPQEQKQ MLGERLFPLI QAMHPTLAGK ITGMLLEIDN SELLHMLESP
ESLRSKVDEA VAVLQAHQAK EAAQKAVNSA TGVPTV
//
ID PABP1_HUMAN Reviewed; 636 AA.
AC P11940; Q15097; Q93004;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 2.
DT 22-JAN-2014, entry version 178.
DE RecName: Full=Polyadenylate-binding protein 1;
DE Short=PABP-1;
DE Short=Poly(A)-binding protein 1;
GN Name=PABPC1; Synonyms=PAB1, PABP1, PABPC2;
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] (ISOFORM 1).
RX PubMed=2885805; DOI=10.1093/nar/15.12.4771;
RA Grange T., de Sa C.M., Oddos J., Pictet R.;
RT "Human mRNA polyadenylate binding protein: evolutionary conservation
RT of a nucleic acid binding motif.";
RL Nucleic Acids Res. 15:4771-4787(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RA Hornstein E., Abramzon-Talianker A., Wiesel I., Meyuhas O.;
RT "The human poly(A)-binding protein (PABP) gene: structural and
RT functional analysis.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Muscle;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-636 (ISOFORM 2).
RA Murphy E.P., McKenna N.J., Headon D.R.;
RT "Nucleotide sequence of a partial cDNA encoding a novel human
RT polyadenylate-binding protein.";
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 31-41; 51-78; 84-89; 96-104; 158-166; 189-196;
RP 214-221; 232-240; 291-309; 312-324; 357-370; 375-385; 482-506; 566-580
RP AND 605-620, METHYLATION AT ARG-493, AND MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Zebisch A., Lilla S., von Kriegsheim A., Lempens A.,
RA Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 31-41; 51-78; 84-89; 96-104; 114-129; 139-153;
RP 158-166; 187-208; 214-221; 232-240; 291-324; 334-348; 357-370;
RP 375-385; 482-506; 519-559; 566-620 AND 626-636, METHYLATION AT LYS-299
RP AND ARG-493, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [8]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=7908267; DOI=10.1006/excr.1994.1104;
RA Goerlach M., Burd C.G., Dreyfuss G.;
RT "The mRNA poly(A)-binding protein: localization, abundance, and RNA-
RT binding specificity.";
RL Exp. Cell Res. 211:400-407(1994).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=9582337; DOI=10.1074/jbc.273.21.13015;
RA Afonina E., Stauber R., Pavlakis G.N.;
RT "The human poly(A)-binding protein 1 shuttles between the nucleus and
RT the cytoplasm.";
RL J. Biol. Chem. 273:13015-13021(1998).
RN [10]
RP INTERACTION WITH PAIP1.
RX PubMed=9548260; DOI=10.1038/33198;
RA Craig A.W.B., Haghighat A., Yu A.T.K., Sonenberg N.;
RT "Interaction of polyadenylate-binding protein with the eIF4G homologue
RT PAIP enhances translation.";
RL Nature 392:520-523(1998).
RN [11]
RP FUNCTION IN TRANSLATIONALLY COUPLED MRNA TURNOVER, AND IDENTIFICATION
RP IN A COMPLEX WITH HNRPD; SYNCRIP; PAIP1 AND CSDE1.
RX PubMed=11051545; DOI=10.1016/S0092-8674(00)00102-1;
RA Grosset C., Chen C.-Y.A., Xu N., Sonenberg N., Jacquemin-Sablon H.,
RA Shyu A.-B.;
RT "A mechanism for translationally coupled mRNA turnover: interaction
RT between the poly(A) tail and a c-fos RNA coding determinant via a
RT protein complex.";
RL Cell 103:29-40(2000).
RN [12]
RP INTERACTION WITH PAIP2.
RX PubMed=11172725; DOI=10.1016/S1097-2765(01)00168-X;
RA Khaleghpour K., Svitkin Y.V., Craig A.W.B., DeMaria C.T., Deo R.C.,
RA Burley S.K., Sonenberg N.;
RT "Translational repression by a novel partner of human poly(A) binding
RT protein, Paip2.";
RL Mol. Cell 7:205-216(2001).
RN [13]
RP INTERACTION WITH PAIP2.
RX PubMed=11438674; DOI=10.1128/MCB.21.15.5200-5213.2001;
RA Khaleghpour K., Kahvejian A., De Crescenzo G., Roy G., Svitkin Y.V.,
RA Imataka H., O'Connor-McCourt M., Sonenberg N.;
RT "Dual interactions of the translational repressor Paip2 with poly(A)
RT binding protein.";
RL Mol. Cell. Biol. 21:5200-5213(2001).
RN [14]
RP METHYLATION AT ARG-455 AND ARG-460, AND MUTAGENESIS OF ARG-455 AND
RP ARG-460.
RX PubMed=11850402; DOI=10.1093/embo-reports/kvf052;
RA Lee J., Bedford M.T.;
RT "PABP1 identified as an arginine methyltransferase substrate using
RT high-density protein arrays.";
RL EMBO Rep. 3:268-273(2002).
RN [15]
RP INTERACTION WITH PAIP1.
RX PubMed=11997512; DOI=10.1128/MCB.22.11.3769-3782.2002;
RA Roy G., De Crescenzo G., Khaleghpour K., Kahvejian A.,
RA O'Connor-McCourt M., Sonenberg N.;
RT "Paip1 interacts with poly(A) binding protein through two independent
RT binding motifs.";
RL Mol. Cell. Biol. 22:3769-3782(2002).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP SPLICEOSOMAL C COMPLEX.
RX PubMed=11991638; DOI=10.1017/S1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [17]
RP PHOSPHORYLATION BY MAPKAPK2.
RX PubMed=12565831; DOI=10.1016/S0006-291X(03)00015-9;
RA Bollig F., Winzen R., Gaestel M., Kostka S., Resch K., Holtmann H.;
RT "Affinity purification of ARE-binding proteins identifies polyA-
RT binding protein 1 as a potential substrate in MK2-induced mRNA
RT stabilization.";
RL Biochem. Biophys. Res. Commun. 301:665-670(2003).
RN [18]
RP INTERACTION WITH CSDE1.
RX PubMed=15314026; DOI=10.1101/gad.1219104;
RA Chang T.-C., Yamashita A., Chen C.-Y.A., Yamashita Y., Zhu W.,
RA Durdan S., Kahvejian A., Sonenberg N., Shyu A.-B.;
RT "UNR, a new partner of poly(A)-binding protein, plays a key role in
RT translationally coupled mRNA turnover mediated by the c-fos major
RT coding-region determinant.";
RL Genes Dev. 18:2010-2023(2004).
RN [19]
RP IDENTIFICATION IN A MRNP COMPLEX WITH IGF2BP1 AND CSDE1.
RX PubMed=16356927; DOI=10.1093/nar/gki1014;
RA Patel G.P., Ma S., Bag J.;
RT "The autoregulatory translational control element of poly(A)-binding
RT protein mRNA forms a heteromeric ribonucleoprotein complex.";
RL Nucleic Acids Res. 33:7074-7089(2005).
RN [20]
RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH IGF2BP1, AND RNA-BINDING.
RX PubMed=17212783; DOI=10.1111/j.1742-4658.2006.05556.x;
RA Patel G.P., Bag J.;
RT "IMP1 interacts with poly(A)-binding protein (PABP) and the
RT autoregulatory translational control element of PABP-mRNA through the
RT KH III-IV domain.";
RL FEBS J. 273:5678-5690(2006).
RN [21]
RP INTERACTION WITH AGO1 AND AGO2.
RX PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA Urlaub H., Meister G.;
RT "Proteomic and functional analysis of Argonaute-containing mRNA-
RT protein complexes in human cells.";
RL EMBO Rep. 8:1052-1060(2007).
RN [22]
RP INTERACTION WITH NFX1.
RX PubMed=17267499; DOI=10.1128/JVI.02007-06;
RA Katzenellenbogen R.A., Egelkrout E.M., Vliet-Gregg P., Gewin L.C.,
RA Gafken P.R., Galloway D.A.;
RT "NFX1-123 and poly(A) binding proteins synergistically augment
RT activation of telomerase in human papillomavirus type 16 E6-expressing
RT cells.";
RL J. Virol. 81:3786-3796(2007).
RN [23]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, INTERACTION WITH IGF2BP1,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.M600346-MCP200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=18799579; DOI=10.1128/JVI.00872-08;
RA Harb M., Becker M.M., Vitour D., Baron C.H., Vende P., Brown S.C.,
RA Bolte S., Arold S.T., Poncet D.;
RT "Nuclear localization of cytoplasmic poly(A)-binding protein upon
RT rotavirus infection involves the interaction of NSP3 with eIF4G and
RT RoXaN.";
RL J. Virol. 82:11283-11293(2008).
RN [25]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, AND INTERACTION WITH GSPT2.
RX PubMed=18447585; DOI=10.1371/journal.pbio.0060111;
RA Singh G., Rebbapragada I., Lykke-Andersen J.;
RT "A competition between stimulators and antagonists of Upf complex
RT recruitment governs human nonsense-mediated mRNA decay.";
RL PLoS Biol. 6:E111-E111(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, 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 [27]
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 [28]
RP IDENTIFICATION IN A MRNP COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19029303; DOI=10.1261/rna.1175909;
RA Weidensdorfer D., Stoehr N., Baude A., Lederer M., Koehn M.,
RA Schierhorn A., Buchmeier S., Wahle E., Huettelmaiery S.;
RT "Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic
RT RNPs.";
RL RNA 15:104-115(2009).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-512, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [30]
RP REVIEW.
RX PubMed=20102337; DOI=10.1042/BJ20091571;
RA Smith R.W., Gray N.K.;
RT "Poly(A)-binding protein (PABP): a common viral target.";
RL Biochem. J. 426:1-12(2010).
RN [31]
RP INTERACTION WITH HHV-5 PROTEIN UL69.
RX PubMed=20133758; DOI=10.1073/pnas.0914856107;
RA Aoyagi M., Gaspar M., Shenk T.E.;
RT "Human cytomegalovirus UL69 protein facilitates translation by
RT associating with the mRNA cap-binding complex and excluding 4EBP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2640-2645(2010).
RN [32]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PABPC1 AND
RP GNB2L1.
RX PubMed=20573744; DOI=10.1261/rna.2146910;
RA Schaffler K., Schulz K., Hirmer A., Wiesner J., Grimm M., Sickmann A.,
RA Fischer U.;
RT "A stimulatory role for the La-related protein 4B in translation.";
RL RNA 16:1488-1499(2010).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND MASS
RP 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 [34]
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 [35]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-190.
RX PubMed=10499800; DOI=10.1016/S0092-8674(00)81517-2;
RA Deo R.C., Bonanno J.B., Sonenberg N., Burley S.K.;
RT "Recognition of polyadenylate RNA by the poly(A)-binding protein.";
RL Cell 98:835-845(1999).
RN [36]
RP STRUCTURE BY NMR OF 498-636, AND INTERACTION WITH GSPT1; PAIP1 AND
RP PAIP2.
RX PubMed=11287632; DOI=10.1073/pnas.071024998;
RA Kozlov G., Trempe J.F., Khaleghpour K., Kahvejian A., Ekiel I.,
RA Gehring K.;
RT "Structure and function of the C-terminal PABC domain of human
RT poly(A)-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4409-4413(2001).
RN [37]
RP STRUCTURE BY NMR OF 541-623 IN COMPLEX WITH GSPT1.
RA Osawa M., Nakanishi T., Hosoda N., Uchida S., Hoshino T., Katada I.,
RA Shimada I.;
RT "Eukaryotic translation termination factor Gspt/ERF3 recognizes Pabp
RT with chemical exchange using two overlapping motifs.";
RL Submitted (MAY-2009) to the PDB data bank.
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 544-626 IN COMPLEX WITH
RP PAIP2.
RX PubMed=20096703; DOI=10.1016/j.jmb.2010.01.032;
RA Kozlov G., Menade M., Rosenauer A., Nguyen L., Gehring K.;
RT "Molecular determinants of PAM2 recognition by the MLLE domain of
RT poly(A)-binding protein.";
RL J. Mol. Biol. 397:397-407(2010).
CC -!- FUNCTION: Binds the poly(A) tail of mRNA, including that of its
CC own transcript. May be involved in cytoplasmic regulatory
CC processes of mRNA metabolism such as pre-mRNA splicing. Its
CC function in translational initiation regulation can either be
CC enhanced by PAIP1 or repressed by PAIP2. Can probably bind to
CC cytoplasmic RNA sequences other than poly(A) in vivo. Involved in
CC translationally coupled mRNA turnover. Implicated with other RNA-
CC binding proteins in the cytoplasmic deadenylation/translational
CC and decay interplay of the FOS mRNA mediated by the major coding-
CC region determinant of instability (mCRD) domain. Involved in
CC regulation of nonsense-mediated decay (NMD) of mRNAs containing
CC premature stop codons; for the recognition of premature
CC termination codons (PTC) and initiation of NMD a competitive
CC interaction between UPF1 and PABPC1 with the ribosome-bound
CC release factors is proposed.
CC -!- SUBUNIT: May form homodimers. Component of a multisubunit
CC autoregulatory ribonucleoprotein complex (ARC), at least composed
CC of IGF2BP1, PABPC1 and CSDE1. Directly interacts with IGF2BP1.
CC Part of a complex associated with the FOS mCRD domain and
CC consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR. Interacts with
CC the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1 and
CC PAIP2. Interacts with PAIP1 with a 1:1 stoichiometry and with
CC PAIP2 with a 1:2 stoichiometry. The interaction with CSDE1 is
CC direct and RNA-independent. Found in a mRNP complex with YBX2.
CC Interacts with PAPD4/GLD2. Identified in the spliceosome C
CC complex. Identified in a mRNP complex, at least composed of DHX9,
CC DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1,
CC STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP
CC granule complex containing untranslated mRNAs. Interacts with
CC NFX1. Interacts with PIWIL1. Interacts with AGO1, AGO2, GSPT1 and
CC GSPT2. Interacts with human cytomegalovirus/HHV-5 protein UL69.
CC Interacts with LARP4B.
CC -!- INTERACTION:
CC Q99700:ATXN2; NbExp=6; IntAct=EBI-81531, EBI-697691;
CC O00571:DDX3X; NbExp=10; IntAct=EBI-81531, EBI-353779;
CC Q04637:EIF4G1; NbExp=2; IntAct=EBI-81531, EBI-73711;
CC Q8IYD1:GSPT2; NbExp=7; IntAct=EBI-81531, EBI-3869637;
CC Q14103-4:HNRNPD; NbExp=2; IntAct=EBI-81531, EBI-432545;
CC P35568:IRS1; NbExp=2; IntAct=EBI-81531, EBI-517592;
CC Q9H074:PAIP1; NbExp=11; IntAct=EBI-81531, EBI-81519;
CC Q9BPZ3:PAIP2; NbExp=5; IntAct=EBI-81531, EBI-2957445;
CC Q96Q15:SMG1; NbExp=2; IntAct=EBI-81531, EBI-1049832;
CC Q9UPQ9:TNRC6B; NbExp=3; IntAct=EBI-81531, EBI-947158;
CC Q9HCJ0:TNRC6C; NbExp=17; IntAct=EBI-81531, EBI-6507625;
CC Q14106:TOB2; NbExp=4; IntAct=EBI-81531, EBI-2562000;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs. Shuttles
CC between the cytoplasm and the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11940-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11940-2; Sequence=VSP_009846;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The RNA-binding domains RRM1 and RRM2 and the C-terminus
CC (last 138 amino acids) regions interact with the PABPC1-
CC interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively.
CC -!- DOMAIN: The RNA-binding domains RRM2 and RRM3 and the C-terminus
CC (last 138 amino acids) regions interact with the PABPC1-
CC interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively.
CC -!- PTM: Phosphorylated by MAPKAPK2.
CC -!- PTM: Methylated by CARM1. Arg-493 is dimethylated, probably to
CC asymmetric dimethylarginine.
CC -!- MISCELLANEOUS: Many viruses shutoff host mRNA translational
CC machinery by inhibiting cellular PABPC1 activity using different
CC mechanisms. Picornaviruses, caliciviruses or lentiviruses encode
CC proteases that cleave PABPC1 at several defined sites in the
CC proline-rich linker region between RRMs and the C-terminal domain.
CC Rotaviruses, gammherpesviruses and bunyamwera virus relocalize
CC PABPC1 from the cytoplasm to the nucleus thus altering its
CC function. Many of these viruses translate their mRNA in a PABPC1-
CC independent manner and are unaffected by host PABPC1 inhibition.
CC -!- SIMILARITY: Belongs to the polyadenylate-binding protein type-1
CC family.
CC -!- SIMILARITY: Contains 1 PABC domain.
CC -!- SIMILARITY: Contains 4 RRM (RNA recognition motif) domains.
CC -!- CAUTION: Was termed (Ref.5) polyadenylate binding protein II.
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DR EMBL; Y00345; CAA68428.1; -; mRNA.
DR EMBL; U68104; AAD08718.1; -; Genomic_DNA.
DR EMBL; U68093; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68094; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68095; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68097; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68098; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68099; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68100; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68101; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68102; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; U68103; AAD08718.1; JOINED; Genomic_DNA.
DR EMBL; AP001205; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015958; AAH15958.1; -; mRNA.
DR EMBL; BC023520; AAH23520.1; -; mRNA.
DR EMBL; Z48501; CAA88401.1; -; mRNA.
DR PIR; A93668; DNHUPA.
DR PIR; S52491; S52491.
DR RefSeq; NP_002559.2; NM_002568.3.
DR RefSeq; XP_005250918.1; XM_005250861.1.
DR RefSeq; XP_005250919.1; XM_005250862.1.
DR UniGene; Hs.387804; -.
DR PDB; 1CVJ; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-190.
DR PDB; 1G9L; NMR; -; A=498-636.
DR PDB; 1JGN; NMR; -; A=544-636.
DR PDB; 1JH4; NMR; -; A=544-636.
DR PDB; 2K8G; NMR; -; A=90-182.
DR PDB; 2RQG; NMR; -; B=541-623.
DR PDB; 2RQH; NMR; -; B=541-623.
DR PDB; 2X04; X-ray; 1.49 A; A/B=545-619.
DR PDB; 3KTP; X-ray; 1.50 A; A=544-626.
DR PDB; 3KTR; X-ray; 1.70 A; A=544-626.
DR PDB; 3KUI; X-ray; 2.30 A; A=544-626.
DR PDB; 3KUJ; X-ray; 1.40 A; A=544-626.
DR PDB; 3KUR; X-ray; 2.50 A; A/B/C/D/E/F/G/H=544-617.
DR PDB; 3KUS; X-ray; 1.40 A; A/B=544-626.
DR PDB; 3KUT; X-ray; 1.50 A; A/B=544-626.
DR PDB; 3PKN; X-ray; 1.80 A; A=544-626.
DR PDB; 3PTH; X-ray; 1.70 A; A=543-621.
DR PDB; 4F02; X-ray; 2.00 A; A/D=1-190.
DR PDB; 4F25; X-ray; 1.90 A; A=99-199.
DR PDB; 4F26; X-ray; 2.00 A; A=99-199.
DR PDBsum; 1CVJ; -.
DR PDBsum; 1G9L; -.
DR PDBsum; 1JGN; -.
DR PDBsum; 1JH4; -.
DR PDBsum; 2K8G; -.
DR PDBsum; 2RQG; -.
DR PDBsum; 2RQH; -.
DR PDBsum; 2X04; -.
DR PDBsum; 3KTP; -.
DR PDBsum; 3KTR; -.
DR PDBsum; 3KUI; -.
DR PDBsum; 3KUJ; -.
DR PDBsum; 3KUR; -.
DR PDBsum; 3KUS; -.
DR PDBsum; 3KUT; -.
DR PDBsum; 3PKN; -.
DR PDBsum; 3PTH; -.
DR PDBsum; 4F02; -.
DR PDBsum; 4F25; -.
DR PDBsum; 4F26; -.
DR ProteinModelPortal; P11940; -.
DR SMR; P11940; 10-376, 494-636.
DR DIP; DIP-31613N; -.
DR IntAct; P11940; 84.
DR MINT; MINT-96210; -.
DR STRING; 9606.ENSP00000313007; -.
DR BindingDB; P11940; -.
DR ChEMBL; CHEMBL1293286; -.
DR PhosphoSite; P11940; -.
DR DMDM; 3183544; -.
DR PaxDb; P11940; -.
DR PRIDE; P11940; -.
DR DNASU; 26986; -.
DR Ensembl; ENST00000318607; ENSP00000313007; ENSG00000070756.
DR GeneID; 26986; -.
DR KEGG; hsa:26986; -.
DR UCSC; uc003yjs.1; human.
DR CTD; 26986; -.
DR GeneCards; GC08M101715; -.
DR HGNC; HGNC:8554; PABPC1.
DR HPA; CAB011536; -.
DR HPA; HPA045423; -.
DR MIM; 604679; gene.
DR neXtProt; NX_P11940; -.
DR PharmGKB; PA32880; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000217922; -.
DR HOVERGEN; HBG002295; -.
DR InParanoid; P11940; -.
DR KO; K13126; -.
DR OMA; YPTNQLA; -.
DR OrthoDB; EOG7RV9FP; -.
DR PhylomeDB; P11940; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_1762; 3' -UTR-mediated translational regulation.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; PABPC1; human.
DR EvolutionaryTrace; P11940; -.
DR GeneWiki; PABPC1; -.
DR GenomeRNAi; 26986; -.
DR NextBio; 49454; -.
DR PMAP-CutDB; P11940; -.
DR PRO; PR:P11940; -.
DR ArrayExpress; P11940; -.
DR Bgee; P11940; -.
DR CleanEx; HS_PABPC1; -.
DR Genevestigator; P11940; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0008143; F:poly(A) RNA binding; TAS:UniProtKB.
DR GO; GO:0008494; F:translation activator activity; TAS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; ISS:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; TAS:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0048255; P:mRNA stabilization; TAS:UniProtKB.
DR GO; GO:2000623; P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISS:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; ISS:UniProtKB.
DR GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR Gene3D; 1.10.1900.10; -; 1.
DR Gene3D; 3.30.70.330; -; 4.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR006515; PABP_1234.
DR InterPro; IPR002004; PABP_HYD.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00658; PABP; 1.
DR Pfam; PF00076; RRM_1; 4.
DR SMART; SM00517; PolyA; 1.
DR SMART; SM00360; RRM; 4.
DR SUPFAM; SSF63570; SSF63570; 1.
DR TIGRFAMs; TIGR01628; PABP-1234; 1.
DR PROSITE; PS51309; PABC; 1.
DR PROSITE; PS50102; RRM; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Methylation; mRNA processing;
KW mRNA splicing; Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Spliceosome.
FT CHAIN 1 636 Polyadenylate-binding protein 1.
FT /FTId=PRO_0000081698.
FT DOMAIN 11 89 RRM 1.
FT DOMAIN 99 175 RRM 2.
FT DOMAIN 191 268 RRM 3.
FT DOMAIN 294 370 RRM 4.
FT DOMAIN 542 619 PABC.
FT REGION 166 289 CSDE1-binding.
FT COMPBIAS 495 501 Poly-Ala.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 299 299 N6-methyllysine.
FT MOD_RES 315 315 Phosphoserine.
FT MOD_RES 455 455 Omega-N-methylated arginine; by CARM1;
FT partial (Probable).
FT MOD_RES 460 460 Omega-N-methylated arginine; by CARM1;
FT partial (Probable).
FT MOD_RES 493 493 Dimethylated arginine; alternate.
FT MOD_RES 493 493 Omega-N-methylarginine; alternate.
FT MOD_RES 512 512 N6-acetyllysine.
FT VAR_SEQ 447 535 Missing (in isoform 2).
FT /FTId=VSP_009846.
FT MUTAGEN 455 455 R->A: Greatly reduces methylation by
FT CARM1 (in vitro); when associated with A-
FT 460.
FT MUTAGEN 460 460 R->A: Greatly reduces methylation by
FT CARM1 (in vitro); when associated with A-
FT 455.
FT CONFLICT 211 213 Missing (in Ref. 1; CAA68428).
FT CONFLICT 410 410 M -> I (in Ref. 5; CAA88401).
FT CONFLICT 428 428 I -> V (in Ref. 1; CAA68428).
FT STRAND 12 17
FT HELIX 24 31
FT HELIX 32 34
FT STRAND 37 44
FT TURN 46 48
FT STRAND 51 61
FT HELIX 62 72
FT STRAND 83 86
FT HELIX 92 96
FT STRAND 100 105
FT HELIX 112 119
FT HELIX 120 122
FT STRAND 125 133
FT STRAND 136 146
FT HELIX 148 158
FT STRAND 161 163
FT STRAND 169 174
FT HELIX 176 183
FT HELIX 547 551
FT HELIX 555 557
FT HELIX 558 573
FT TURN 575 577
FT HELIX 578 585
FT HELIX 590 598
FT HELIX 600 619
FT TURN 623 625
FT STRAND 628 630
SQ SEQUENCE 636 AA; 70671 MW; 2EB1B02A346132EE CRC64;
MNPSAPSYPM ASLYVGDLHP DVTEAMLYEK FSPAGPILSI RVCRDMITRR SLGYAYVNFQ
QPADAERALD TMNFDVIKGK PVRIMWSQRD PSLRKSGVGN IFIKNLDKSI DNKALYDTFS
AFGNILSCKV VCDENGSKGY GFVHFETQEA AERAIEKMNG MLLNDRKVFV GRFKSRKERE
AELGARAKEF TNVYIKNFGE DMDDERLKDL FGKFGPALSV KVMTDESGKS KGFGFVSFER
HEDAQKAVDE MNGKELNGKQ IYVGRAQKKV ERQTELKRKF EQMKQDRITR YQGVNLYVKN
LDDGIDDERL RKEFSPFGTI TSAKVMMEGG RSKGFGFVCF SSPEEATKAV TEMNGRIVAT
KPLYVALAQR KEERQAHLTN QYMQRMASVR AVPNPVINPY QPAPPSGYFM AAIPQTQNRA
AYYPPSQIAQ LRPSPRWTAQ GARPHPFQNM PGAIRPAAPR PPFSTMRPAS SQVPRVMSTQ
RVANTSTQTM GPRPAAAAAA ATPAVRTVPQ YKYAAGVRNP QQHLNAQPQV TMQQPAVHVQ
GQEPLTASML ASAPPQEQKQ MLGERLFPLI QAMHPTLAGK ITGMLLEIDN SELLHMLESP
ESLRSKVDEA VAVLQAHQAK EAAQKAVNSA TGVPTV
//
MIM
604679
*RECORD*
*FIELD* NO
604679
*FIELD* TI
*604679 POLYADENYLATE-BINDING PROTEIN, CYTOPLASMIC, 1; PABPC1
;;POLYADENYLATE-BINDING PROTEIN 1; PABP1; PAB1;;
read morePOLY(A)-BINDING PROTEIN 1;;
POLY(A)-BINDING PROTEIN; PABP
*FIELD* TX
DESCRIPTION
The poly(A)-binding protein (PABP), which is found complexed to the
3-prime poly(A) tail of eukaryotic mRNA, is required for poly(A)
shortening and translation initiation. In humans, the PABPs comprise a
small nuclear isoform and a conserved gene family that displays at least
3 functional proteins: PABP1 (PABPC1), inducible PABP (iPABP, or PABPC4;
603407), and PABP3 (PABPC3; 604680). In addition, there are at least 4
pseudogenes, PABPCP1 to PABPCP4.
CLONING
Grange et al. (1987) isolated a melanoma cell cDNA encoding human PABP.
The predicted 633-amino acid protein contains 4 repeats of an
approximately 80-amino acid unit in its N-terminal half. The authors
found that this repeat region is highly conserved between human and
yeast PABP and is sufficient for poly(A) binding. In vitro translation
of the human PABP cDNA yielded a protein with an apparent molecular mass
of 73 kD by SDS-PAGE. Northern blot analysis indicated that PABP is
expressed as a 2.9-kb mRNA in human melanoma cells.
Gorlach et al. (1994) noted that each of the 4 repeats of PABP is a
ribonucleoprotein (RNP) consensus sequence RNA-binding domain. They
determined that PABP has a pI of approximately 10.3 and is a very
abundant, stable protein.
GENE FUNCTION
Immunofluorescence studies of mammalian cells by Gorlach et al. (1994)
indicated that PABP is located exclusively in the cytoplasm. However,
using both indirect immunofluorescence and tagging of PABP1 by fusion to
the green fluorescent protein (GFP), Afonina et al. (1998) demonstrated
that PABP1 shuttles between the nucleus and cytoplasm. PABP1 accumulated
in the nucleus when transcription was inhibited, suggesting that active
transcription is required for nuclear export of PABP1. Deletion
mutagenesis showed that the RNA binding ability of PABP1 is important
for nuclear retention. Afonina et al. (1998) suggested that PABP1 is
involved in nuclear events associated with the formation and transport
of mRNP to the cytoplasm.
Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich
elements in the 3-prime untranslated region. Rapid decay involves
AU-rich binding protein AUF1 (601324), which complexes with heat-shock
proteins HSC70 (600816) and HSP70 (see 140550), translation initiation
factor EIF4G (600495), and PABP. AU-rich mRNA decay is associated with
displacement of EIF4G from AUF1, ubiquitination of AUF1, and degradation
of AUF1 by proteasomes. Induction of HSP70 by heat shock, downregulation
of the ubiquitin-proteasome network, or inactivation of ubiquitinating
enzyme E1 (314370) all result in HSP70 sequestration of AUF1 in the
perinucleus-nucleus, and all 3 processes block decay of AU-rich mRNAs
and AUF1 protein. These results link the rapid degradation of cytokine
mRNAs to the ubiquitin-proteasome pathway (Laroia et al., 1999).
AU-rich elements and protein-coding determinants direct rapid removal of
poly(A) tails as a necessary first step in mRNA decay. Grosset et al.
(2000) determined that 5 proteins form a multiprotein complex associated
with the major protein-coding-region determinant of instability (mCRD)
of the FOS gene (164810): PABP, HNRNPD (AUF1), PAIP1 (605184), NSAP1,
and UNR (191510). Overexpression of these proteins stabilized
mCRD-containing mRNA by impeding deadenylation.
Kahvejian et al. (2005) studied the mechanism by which PABP stimulates
ribosome recruitment and translation by depleting Pabp from
nuclease-treated mouse carcinoma cell-free translation extracts.
Extracts lacking Pabp exhibited reduced rates of translation, reduced
efficiency of 48S and 80S ribosome initiation complex formation, and
impaired interaction of Eif4e (133440) with the mRNA cap structure.
Supplementing Pabp-depleted extracts with wildtype human PABP corrected
the deficiencies, but a PABP mutant with a met161-to-ala substitution
(M161A), which is incapable of interacting with Eif4g, failed to restore
translation. Kahvejian et al. (2005) hypothesized that PABP may increase
translation efficiency via multiple mechanisms. One possibility involves
circularizing mRNA through the simultaneous binding of the poly(A) tail
and EIF4G, thereby stimulating ribosome recycling by bringing the
5-prime and 3-prime ends together. Another possibility is that PABP
increases the binding affinity between EIF4G and EIF4E, leading to
stronger binding between EIF4E and the 5-prime cap.
BIOCHEMICAL FEATURES
Deo et al. (1999) determined the cocrystal structure of human PABP at
2.6-angstrom resolution. PABP recognizes the 3-prime mRNA poly(A) tail
and plays critical roles in eukaryotic translation initiation and mRNA
stabilization/degradation. The minimal PABP used by Deo et al. (1999)
consisted of the N-terminal 2 RRM-type RNA-binding domains connected by
a short linker (collectively referred to as RRM1/2). These 2 RRMs form a
continuous RNA-binding trough lined by an antiparallel beta sheet backed
by 4 alpha helices. The polyadenylate RNA adopts an extended
conformation running the length of the molecular trough. Adenine
recognition is primarily mediated by contacts with conserved residues
found in the RNP motifs of the 2 RRMs. The convex dorsum of RRM1/2
displays a phylogenetically conserved hydrophobic/acidic portion, which
may interact with translation initiation factors and regulatory
proteins.
MAPPING
Morris and Bodger (1993) found evidence from in situ hybridization that
PAB1 represents a multigene family with sites on chromosomes 3 (PABPL1;
173865), 12 (PABPL2; 604681), and 13 (PABPC3). Since only a single
2.9-kb mRNA could be detected in human melanoma cells and a variety of
human leukemia cell lines, it is likely that only 1 of these genes is
functional. In their in situ hybridization studies, the strongest
labeling was found on chromosome 12, and they suggested that this may be
the site of the functional gene.
By amplification of specific DNA fragments from a human-rodent somatic
cell hybrid panel, Feral et al. (1999) mapped PABP1 and PABP3 to 8q22
and 13q11-q12, respectively. They assigned the iPABP gene to chromosome
1; this result, when compared with radiation hybrid database
information, narrowed the assignment to 1p36-p32. The PABP pseudogenes
PABPCP1, PABPCP2, and PABPCP4 were mapped to chromosomes 4, 14, and 15,
respectively. Three loci detected on chromosome spreads were not
associated with any amplified fragment, suggesting that other related
PABP genes remained to be identified.
*FIELD* RF
1. Afonina, E.; Stauber, R.; Pavlakis, G. N.: The human poly(A)-binding
protein 1 shuttles between the nucleus and the cytoplasm. J. Biol.
Chem. 273: 13015-13021, 1998.
2. Deo, R. C.; Bonanno, J. B.; Sonenberg, N.; Burley, S. K.: Recognition
of polyadenylate RNA by the poly(A)-binding protein. Cell 98: 835-845,
1999.
3. Feral, C.; Mattei, M. G.; Pawlak, A.; Guellaen, G.: Chromosomal
localization of three human poly(A)-binding protein genes and four
related pseudogenes. Hum. Genet. 105: 347-353, 1999.
4. Gorlach, M.; Burd, C. G.; Dreyfuss, G.: The mRNA poly(A)-binding
protein: localization, abundance, and RNA-binding specificity. Exp.
Cell Res. 211: 400-407, 1994.
5. Grange, T.; Martins de Sa, C.; Oddos, J.; Pictet, R.: Human mRNA
polyadenylate binding protein: evolutionary conservation of a nucleic
acid binding motif. Nucleic Acids Res. 15: 4771-4787, 1987.
6. Grosset, C.; Chen, C.-Y. A.; Xu, N.; Sonenberg, N.; Jacquemin-Sablon,
H.; Shyu, A.-B.: A mechanism for translationally coupled mRNA turnover:
interaction between the poly(A) tail and a c-fos RNA coding determinant
via a protein complex. Cell 103: 29-40, 2000.
7. Kahvejian, A.; Svitkin, Y. V.; Sukarieh, R.; M'Boutchou, M.-N.;
Sonenberg, N.: Mammalian poly(A)-binding protein is a eukaryotic
translation initiation factor, which acts via multiple mechanisms. Genes
Dev. 19: 104-113, 2005.
8. Laroia, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.
9. Morris, C. M.; Bodger, M. P.: Localization of the human poly(A)-binding
protein gene (PAB1) to chromosomal regions 3q22-q25, 12q13-q14, and
13q12-q13 by in situ hybridization. Genomics 15: 209-211, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 3/14/2005
Patricia A. Hartz - updated: 9/10/2004
*FIELD* CD
Victor A. McKusick: 3/14/2000
*FIELD* ED
mgross: 03/16/2005
terry: 3/14/2005
mgross: 9/10/2004
mgross: 3/15/2000
mgross: 3/14/2000
*RECORD*
*FIELD* NO
604679
*FIELD* TI
*604679 POLYADENYLATE-BINDING PROTEIN, CYTOPLASMIC, 1; PABPC1
;;POLYADENYLATE-BINDING PROTEIN 1; PABP1; PAB1;;
read morePOLY(A)-BINDING PROTEIN 1;;
POLY(A)-BINDING PROTEIN; PABP
*FIELD* TX
DESCRIPTION
The poly(A)-binding protein (PABP), which is found complexed to the
3-prime poly(A) tail of eukaryotic mRNA, is required for poly(A)
shortening and translation initiation. In humans, the PABPs comprise a
small nuclear isoform and a conserved gene family that displays at least
3 functional proteins: PABP1 (PABPC1), inducible PABP (iPABP, or PABPC4;
603407), and PABP3 (PABPC3; 604680). In addition, there are at least 4
pseudogenes, PABPCP1 to PABPCP4.
CLONING
Grange et al. (1987) isolated a melanoma cell cDNA encoding human PABP.
The predicted 633-amino acid protein contains 4 repeats of an
approximately 80-amino acid unit in its N-terminal half. The authors
found that this repeat region is highly conserved between human and
yeast PABP and is sufficient for poly(A) binding. In vitro translation
of the human PABP cDNA yielded a protein with an apparent molecular mass
of 73 kD by SDS-PAGE. Northern blot analysis indicated that PABP is
expressed as a 2.9-kb mRNA in human melanoma cells.
Gorlach et al. (1994) noted that each of the 4 repeats of PABP is a
ribonucleoprotein (RNP) consensus sequence RNA-binding domain. They
determined that PABP has a pI of approximately 10.3 and is a very
abundant, stable protein.
GENE FUNCTION
Immunofluorescence studies of mammalian cells by Gorlach et al. (1994)
indicated that PABP is located exclusively in the cytoplasm. However,
using both indirect immunofluorescence and tagging of PABP1 by fusion to
the green fluorescent protein (GFP), Afonina et al. (1998) demonstrated
that PABP1 shuttles between the nucleus and cytoplasm. PABP1 accumulated
in the nucleus when transcription was inhibited, suggesting that active
transcription is required for nuclear export of PABP1. Deletion
mutagenesis showed that the RNA binding ability of PABP1 is important
for nuclear retention. Afonina et al. (1998) suggested that PABP1 is
involved in nuclear events associated with the formation and transport
of mRNP to the cytoplasm.
Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich
elements in the 3-prime untranslated region. Rapid decay involves
AU-rich binding protein AUF1 (601324), which complexes with heat-shock
proteins HSC70 (600816) and HSP70 (see 140550), translation initiation
factor EIF4G (600495), and PABP. AU-rich mRNA decay is associated with
displacement of EIF4G from AUF1, ubiquitination of AUF1, and degradation
of AUF1 by proteasomes. Induction of HSP70 by heat shock, downregulation
of the ubiquitin-proteasome network, or inactivation of ubiquitinating
enzyme E1 (314370) all result in HSP70 sequestration of AUF1 in the
perinucleus-nucleus, and all 3 processes block decay of AU-rich mRNAs
and AUF1 protein. These results link the rapid degradation of cytokine
mRNAs to the ubiquitin-proteasome pathway (Laroia et al., 1999).
AU-rich elements and protein-coding determinants direct rapid removal of
poly(A) tails as a necessary first step in mRNA decay. Grosset et al.
(2000) determined that 5 proteins form a multiprotein complex associated
with the major protein-coding-region determinant of instability (mCRD)
of the FOS gene (164810): PABP, HNRNPD (AUF1), PAIP1 (605184), NSAP1,
and UNR (191510). Overexpression of these proteins stabilized
mCRD-containing mRNA by impeding deadenylation.
Kahvejian et al. (2005) studied the mechanism by which PABP stimulates
ribosome recruitment and translation by depleting Pabp from
nuclease-treated mouse carcinoma cell-free translation extracts.
Extracts lacking Pabp exhibited reduced rates of translation, reduced
efficiency of 48S and 80S ribosome initiation complex formation, and
impaired interaction of Eif4e (133440) with the mRNA cap structure.
Supplementing Pabp-depleted extracts with wildtype human PABP corrected
the deficiencies, but a PABP mutant with a met161-to-ala substitution
(M161A), which is incapable of interacting with Eif4g, failed to restore
translation. Kahvejian et al. (2005) hypothesized that PABP may increase
translation efficiency via multiple mechanisms. One possibility involves
circularizing mRNA through the simultaneous binding of the poly(A) tail
and EIF4G, thereby stimulating ribosome recycling by bringing the
5-prime and 3-prime ends together. Another possibility is that PABP
increases the binding affinity between EIF4G and EIF4E, leading to
stronger binding between EIF4E and the 5-prime cap.
BIOCHEMICAL FEATURES
Deo et al. (1999) determined the cocrystal structure of human PABP at
2.6-angstrom resolution. PABP recognizes the 3-prime mRNA poly(A) tail
and plays critical roles in eukaryotic translation initiation and mRNA
stabilization/degradation. The minimal PABP used by Deo et al. (1999)
consisted of the N-terminal 2 RRM-type RNA-binding domains connected by
a short linker (collectively referred to as RRM1/2). These 2 RRMs form a
continuous RNA-binding trough lined by an antiparallel beta sheet backed
by 4 alpha helices. The polyadenylate RNA adopts an extended
conformation running the length of the molecular trough. Adenine
recognition is primarily mediated by contacts with conserved residues
found in the RNP motifs of the 2 RRMs. The convex dorsum of RRM1/2
displays a phylogenetically conserved hydrophobic/acidic portion, which
may interact with translation initiation factors and regulatory
proteins.
MAPPING
Morris and Bodger (1993) found evidence from in situ hybridization that
PAB1 represents a multigene family with sites on chromosomes 3 (PABPL1;
173865), 12 (PABPL2; 604681), and 13 (PABPC3). Since only a single
2.9-kb mRNA could be detected in human melanoma cells and a variety of
human leukemia cell lines, it is likely that only 1 of these genes is
functional. In their in situ hybridization studies, the strongest
labeling was found on chromosome 12, and they suggested that this may be
the site of the functional gene.
By amplification of specific DNA fragments from a human-rodent somatic
cell hybrid panel, Feral et al. (1999) mapped PABP1 and PABP3 to 8q22
and 13q11-q12, respectively. They assigned the iPABP gene to chromosome
1; this result, when compared with radiation hybrid database
information, narrowed the assignment to 1p36-p32. The PABP pseudogenes
PABPCP1, PABPCP2, and PABPCP4 were mapped to chromosomes 4, 14, and 15,
respectively. Three loci detected on chromosome spreads were not
associated with any amplified fragment, suggesting that other related
PABP genes remained to be identified.
*FIELD* RF
1. Afonina, E.; Stauber, R.; Pavlakis, G. N.: The human poly(A)-binding
protein 1 shuttles between the nucleus and the cytoplasm. J. Biol.
Chem. 273: 13015-13021, 1998.
2. Deo, R. C.; Bonanno, J. B.; Sonenberg, N.; Burley, S. K.: Recognition
of polyadenylate RNA by the poly(A)-binding protein. Cell 98: 835-845,
1999.
3. Feral, C.; Mattei, M. G.; Pawlak, A.; Guellaen, G.: Chromosomal
localization of three human poly(A)-binding protein genes and four
related pseudogenes. Hum. Genet. 105: 347-353, 1999.
4. Gorlach, M.; Burd, C. G.; Dreyfuss, G.: The mRNA poly(A)-binding
protein: localization, abundance, and RNA-binding specificity. Exp.
Cell Res. 211: 400-407, 1994.
5. Grange, T.; Martins de Sa, C.; Oddos, J.; Pictet, R.: Human mRNA
polyadenylate binding protein: evolutionary conservation of a nucleic
acid binding motif. Nucleic Acids Res. 15: 4771-4787, 1987.
6. Grosset, C.; Chen, C.-Y. A.; Xu, N.; Sonenberg, N.; Jacquemin-Sablon,
H.; Shyu, A.-B.: A mechanism for translationally coupled mRNA turnover:
interaction between the poly(A) tail and a c-fos RNA coding determinant
via a protein complex. Cell 103: 29-40, 2000.
7. Kahvejian, A.; Svitkin, Y. V.; Sukarieh, R.; M'Boutchou, M.-N.;
Sonenberg, N.: Mammalian poly(A)-binding protein is a eukaryotic
translation initiation factor, which acts via multiple mechanisms. Genes
Dev. 19: 104-113, 2005.
8. Laroia, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.
9. Morris, C. M.; Bodger, M. P.: Localization of the human poly(A)-binding
protein gene (PAB1) to chromosomal regions 3q22-q25, 12q13-q14, and
13q12-q13 by in situ hybridization. Genomics 15: 209-211, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 3/14/2005
Patricia A. Hartz - updated: 9/10/2004
*FIELD* CD
Victor A. McKusick: 3/14/2000
*FIELD* ED
mgross: 03/16/2005
terry: 3/14/2005
mgross: 9/10/2004
mgross: 3/15/2000
mgross: 3/14/2000