PABP2_HUMAN
ID PABP2_HUMAN Reviewed; 306 AA.
AC Q86U42; D3DS49; O43484;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Polyadenylate-binding protein 2 {ECO:0000305};
DE Short=PABP-2;
DE Short=Poly(A)-binding protein 2;
DE AltName: Full=Nuclear poly(A)-binding protein 1;
DE AltName: Full=Poly(A)-binding protein II;
DE Short=PABII;
DE AltName: Full=Polyadenylate-binding nuclear protein 1;
GN Name=PABPN1 {ECO:0000312|HGNC:HGNC:8565}; Synonyms=PAB2, PABP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), POLYMORPHISM OF POLY-ALA
RP REGION, AND DISEASE.
RX PubMed=9462747; DOI=10.1038/ng0298-164;
RA Brais B., Bouchard J.-P., Xie Y.-G., Rochefort D.L., Chretien N.,
RA Tome F.M.S., Lafreniere R.G., Rommens J.M., Uyama E., Nohira O., Blumen S.,
RA Korcyn A.D., Heutink P., Mathieu J., Duranceau A., Codere F., Fardeau M.,
RA Rouleau G.A.;
RT "Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular
RT dystrophy.";
RL Nat. Genet. 18:164-167(1998).
RN [2]
RP ERRATUM OF PUBMED:9462747.
RA Brais B., Bouchard J.-P., Xie Y.-G., Rochefort D.L., Chretien N.,
RA Tome F.M.S., Lafreniere R.G., Rommens J.M., Uyama E., Nohira O., Blumen S.,
RA Korcyn A.D., Heutink P., Mathieu J., Duranceau A., Codere F., Fardeau M.,
RA Rouleau G.A.;
RL Nat. Genet. 19:404-404(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA], ASSOCIATION WITH CPSF AND NS/NS1, AND
RP INTERACTION WITH NS/NS1.
RC TISSUE=Cervix carcinoma;
RX PubMed=10205180; DOI=10.1093/emboj/18.8.2273;
RA Chen Z., Li Y., Krug R.M.;
RT "Influenza A virus NS1 protein targets poly(A)-binding protein II of the
RT cellular 3'-end processing machinery.";
RL EMBO J. 18:2273-2283(1999).
RN [7]
RP PROTEIN SEQUENCE OF 2-17 AND 228-238, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (APR-2005) to UniProtKB.
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=11001936; DOI=10.1093/oxfordjournals.hmg.a018924;
RA Calado A., Tome F.M.S., Brais B., Rouleau G.A., Kuehn U., Wahle E.,
RA Carmo-Fonseca M.;
RT "Nuclear inclusions in oculopharyngeal muscular dystrophy consist of
RT poly(A) binding protein 2 aggregates which sequester poly(A) RNA.";
RL Hum. Mol. Genet. 9:2321-2328(2000).
RN [9]
RP SUBCELLULAR LOCATION, AND NUCLEOCYTOPLASMIC SHUTTLING.
RX PubMed=10688363; DOI=10.1017/s1355838200991908;
RA Calado A., Kutay U., Kuehn U., Wahle E., Carmo-Fonseca M.;
RT "Deciphering the cellular pathway for transport of poly(A)-binding protein
RT II.";
RL RNA 6:245-256(2000).
RN [10]
RP FUNCTION IN CELL DEATH, HOMOOLIGOMERIZATION, AND MUTAGENESIS OF
RP 213-LYS--PHE-220 AND 301-SER--TYR-306.
RX PubMed=11689481; DOI=10.1093/hmg/10.21.2341;
RA Fan X., Dion P., Laganiere J., Brais B., Rouleau G.A.;
RT "Oligomerization of polyalanine expanded PABPN1 facilitates nuclear protein
RT aggregation that is associated with cell death.";
RL Hum. Mol. Genet. 10:2341-2351(2001).
RN [11]
RP FUNCTION IN MYOGENIC DIFFERENTIATION, ASSOCIATION WITH SKIP AND MYOD1,
RP INTERACTION WITH SKIP, AND SUBCELLULAR LOCATION.
RX PubMed=11371506; DOI=10.1093/hmg/10.11.1129;
RA Kim Y.-J., Noguchi S., Hayashi Y.K., Tsukahara T., Shimizu T., Arahata K.;
RT "The product of an oculopharyngeal muscular dystrophy gene, poly(A)-binding
RT protein 2, interacts with SKIP and stimulates muscle-specific gene
RT expression.";
RL Hum. Mol. Genet. 10:1129-1139(2001).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=14663186; DOI=10.1097/00001756-200312190-00009;
RA Sugaya K., Matsubara S., Miyamoto K., Kawata A., Hayashi H.;
RT "An aggregate-prone conformational epitope in trinucleotide repeat
RT diseases.";
RL NeuroReport 14:2331-2335(2003).
RN [13]
RP INTERACTION WITH NUDT21/CPSF5.
RX PubMed=15169763; DOI=10.1074/jbc.m403927200;
RA Dettwiler S., Aringhieri C., Cardinale S., Keller W., Barabino S.M.;
RT "Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im
RT mediate RNA binding, protein-protein interactions, and subcellular
RT localization.";
RL J. Biol. Chem. 279:35788-35797(2004).
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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [15]
RP INTERACTION WITH FRG1.
RX PubMed=17103222; DOI=10.1007/s00412-006-0083-3;
RA van Koningsbruggen S., Straasheijm K.R., Sterrenburg E., de Graaf N.,
RA Dauwerse H.G., Frants R.R., van der Maarel S.M.;
RT "FRG1P-mediated aggregation of proteins involved in pre-mRNA processing.";
RL Chromosoma 116:53-64(2007).
RN [16]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; SER-95 AND SER-150, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-19; SER-95 AND SER-150, CLEAVAGE OF INITIATOR METHIONINE
RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
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., Buerckstuemmer T.,
RA 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 [22]
RP INTERACTION WITH SETX.
RX PubMed=21700224; DOI=10.1016/j.molcel.2011.04.026;
RA Skourti-Stathaki K., Proudfoot N.J., Gromak N.;
RT "Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause
RT sites to promote Xrn2-dependent termination.";
RL Mol. Cell 42:794-805(2011).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-19 AND SER-95, CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19 AND SER-150, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-235, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [28]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-259 AND ARG-263, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [29]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH ZFC3H1.
RX PubMed=27871484; DOI=10.1016/j.molcel.2016.09.025;
RA Meola N., Domanski M., Karadoulama E., Chen Y., Gentil C., Pultz D.,
RA Vitting-Seerup K., Lykke-Andersen S., Andersen J.S., Sandelin A.,
RA Jensen T.H.;
RT "Identification of a nuclear exosome decay pathway for processed
RT transcripts.";
RL Mol. Cell 64:520-533(2016).
RN [30]
RP SUBCELLULAR LOCATION.
RX PubMed=27209344; DOI=10.1016/j.nmd.2016.05.001;
RA Matsubara S., Shimizu T., Komori T., Mori-Yoshimura M., Minami N.,
RA Hayashi Y.K.;
RT "Nuclear inclusions mimicking poly(A)-binding protein nuclear 1 inclusions
RT in a case of inclusion body myopathy associated with Paget disease of bone
RT and frontotemporal dementia with a novel mutation in the valosin-containing
RT protein gene.";
RL Neuromuscul. Disord. 26:436-440(2016).
RN [31]
RP VARIANT OPMD ALA-6 INS, AND DISEASE.
RX PubMed=12673802; DOI=10.1002/humu.9138;
RA van der Sluijs B.M., van Engelen B.G.M., Hoefsloot L.H.;
RT "Oculopharyngeal muscular dystrophy (OPMD) due to a small duplication in
RT the PABPN1 gene.";
RL Hum. Mutat. 21:553-553(2003).
CC -!- FUNCTION: Involved in the 3'-end formation of mRNA precursors (pre-
CC mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream
CC cleavage product (By similarity). Stimulates poly(A) polymerase
CC (PAPOLA) conferring processivity on the poly(A) tail elongation
CC reaction and controls also the poly(A) tail length (By similarity).
CC Increases the affinity of poly(A) polymerase for RNA (By similarity).
CC Is also present at various stages of mRNA metabolism including
CC nucleocytoplasmic trafficking and nonsense-mediated decay (NMD) of
CC mRNA. Cooperates with SKIP to synergistically activate E-box-mediated
CC transcription through MYOD1 and may regulate the expression of muscle-
CC specific genes (PubMed:11371506). Binds to poly(A) and to poly(G) with
CC high affinity (By similarity). May protect the poly(A) tail from
CC degradation (By similarity). Subunit of the trimeric poly(A) tail
CC exosome targeting (PAXT) complex, a complex that directs a subset of
CC long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA
CC exosome is fundamental for the degradation of RNA in eukaryotic nuclei.
CC Substrate targeting is facilitated by its cofactor MTREX, which links
CC to RNA-binding protein adapters (PubMed:27871484).
CC {ECO:0000250|UniProtKB:Q28165, ECO:0000269|PubMed:11371506,
CC ECO:0000269|PubMed:27871484}.
CC -!- SUBUNIT: May interact with SETX (PubMed:21700224). Monomer and
CC homooligomer. Binds RNA as a monomer and oligomerizes when bound to
CC poly(A). Interacts with PAPOLA, but only in presence of oligo(A) RNA.
CC Interacts with transportin. Identified in a IGF2BP1-dependent mRNP
CC granule complex containing untranslated mRNAs. Association in a ternary
CC complex with CPSF4 and influenza A virus NS1 blocks pre-mRNAs
CC processing, thereby preventing nuclear export of host cell mRNAs.
CC Associates in a single complex with SKIP and MYOD1 and interacts with
CC SKIP in differentiated myocytes. Interacts with NUDT21/CPSF5. Interacts
CC (via RRM domain and C-terminal arginine-rich region) with ZFP36 (via
CC hypophosphorylated form); this interaction occurs in the nucleus in a
CC RNA-independent manner, decreases in presence of single-stranded
CC poly(A) RNA-oligomer and in a p38-dependent-manner and may down-
CC regulated RNA poly(A) polymerase activity (By similarity). Component of
CC the poly(A) tail exosome targeting (PAXT) complex made of accessory
CC factors, such as PABPN1, ZFC3H1 and MTREX (PubMed:27871484). Interacts
CC with ZFC3H1 in a RNase-insensitive manner (PubMed:27871484). Interacts
CC with FRG1 (PubMed:17103222). {ECO:0000250|UniProtKB:Q8CCS6,
CC ECO:0000269|PubMed:10205180, ECO:0000269|PubMed:11371506,
CC ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:17103222,
CC ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:21700224,
CC ECO:0000269|PubMed:27871484}.
CC -!- INTERACTION:
CC Q86U42; P11940: PABPC1; NbExp=2; IntAct=EBI-1226435, EBI-81531;
CC Q86U42; Q13573: SNW1; NbExp=5; IntAct=EBI-1226435, EBI-632715;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10688363,
CC ECO:0000269|PubMed:11001936, ECO:0000269|PubMed:14663186,
CC ECO:0000269|PubMed:27209344}. Cytoplasm {ECO:0000269|PubMed:10688363,
CC ECO:0000269|PubMed:11001936, ECO:0000269|PubMed:14663186,
CC ECO:0000269|PubMed:17289661}. Nucleus speckle
CC {ECO:0000269|PubMed:10688363, ECO:0000269|PubMed:11371506}.
CC Note=Localized in cytoplasmic mRNP granules containing untranslated
CC mRNAs. Shuttles between the nucleus and the cytoplasm but predominantly
CC found in the nucleus (PubMed:10688363). Its nuclear import may involve
CC the nucleocytoplasmic transport receptor transportin and a RAN-GTP-
CC sensitive import mechanism (By similarity). Is exported to the
CC cytoplasm by a carrier-mediated pathway that is independent of mRNA
CC traffic. Colocalizes with SKIP and poly(A) RNA in nuclear speckles (By
CC similarity). Intranuclear filamentous inclusions or 'aggregates' are
CC detected in the myocytes of patients; these inclusions contain PABPN1,
CC ubiquitin, subunits of the proteasome and poly(A) RNA.
CC {ECO:0000250|UniProtKB:Q28165, ECO:0000269|PubMed:10688363,
CC ECO:0000269|PubMed:11001936, ECO:0000269|PubMed:11371506,
CC ECO:0000269|PubMed:14663186, ECO:0000269|PubMed:17289661,
CC ECO:0000269|PubMed:27209344}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86U42-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86U42-2; Sequence=VSP_009847, VSP_009848;
CC Name=3; Synonyms=BCL2L2-PABPN1;
CC IsoId=Q92843-2; Sequence=External;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The RRM domain is essential for specific adenine bases
CC recognition in the poly(A) tail but not sufficient for poly(A) binding.
CC {ECO:0000250}.
CC -!- PTM: Arginine dimethylation is asymmetric and involves PRMT1 and PRMT3.
CC It does not influence the RNA binding properties (By similarity).
CC {ECO:0000250}.
CC -!- POLYMORPHISM: The poly-Ala region of PABPN1 is polymorphic (6-7
CC repeats) in the population and is expanded to 8-13 repeats in OPMD
CC patients. Compound heterozygotes for (GCG)9 mutation and a (GCG)7
CC allele result in earlier onset and more severe clinical manifestations
CC of the disease.
CC -!- DISEASE: Oculopharyngeal muscular dystrophy (OPMD) [MIM:164300]: A form
CC of late-onset slowly progressive myopathy characterized by eyelid
CC ptosis, dysphagia and, sometimes by other cranial and limb-muscle
CC involvement. {ECO:0000269|PubMed:12673802}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The association of the expanded polyalanine mutations
CC together with the capability to oligomerize may induce intranuclear
CC inclusions and cell death. Expanded polyalanine mutations may either
CC result from unequal crossing over during germ cell homologous
CC recombination or from DNA slippage. The pathogenic mechanisms mediated
CC by polyalanine expansion mutations may be either a general disruption
CC of cellular RNA metabolism due to the trapping by the inclusions of
CC PABPN1, mRNAs and/or nuclear proteins, resulting in the induction of
CC cell death; or may change the normal muscle cell differentiation.
CC {ECO:0000269|PubMed:11689481}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing donor splice
CC site. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD62310.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF026029; AAC39596.1; -; Genomic_DNA.
DR EMBL; BX247976; CAD62310.1; ALT_INIT; mRNA.
DR EMBL; CH471078; EAW66167.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66168.1; -; Genomic_DNA.
DR EMBL; BC010939; AAH10939.1; -; mRNA.
DR CCDS; CCDS86374.1; -. [Q86U42-2]
DR CCDS; CCDS9592.1; -. [Q86U42-1]
DR RefSeq; NP_004634.1; NM_004643.3. [Q86U42-1]
DR PDB; 3B4D; X-ray; 2.00 A; A=167-254.
DR PDB; 3B4M; X-ray; 2.82 A; A/B/C/D=167-254.
DR PDB; 3UCG; X-ray; 1.95 A; A=167-254.
DR PDBsum; 3B4D; -.
DR PDBsum; 3B4M; -.
DR PDBsum; 3UCG; -.
DR AlphaFoldDB; Q86U42; -.
DR SMR; Q86U42; -.
DR BioGRID; 113777; 124.
DR DIP; DIP-37968N; -.
DR IntAct; Q86U42; 62.
DR MINT; Q86U42; -.
DR STRING; 9606.ENSP00000216727; -.
DR GlyGen; Q86U42; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86U42; -.
DR PhosphoSitePlus; Q86U42; -.
DR BioMuta; PABPN1; -.
DR DMDM; 46403176; -.
DR EPD; Q86U42; -.
DR jPOST; Q86U42; -.
DR MassIVE; Q86U42; -.
DR MaxQB; Q86U42; -.
DR PaxDb; Q86U42; -.
DR PeptideAtlas; Q86U42; -.
DR PRIDE; Q86U42; -.
DR ProteomicsDB; 69766; -. [Q86U42-1]
DR ProteomicsDB; 69767; -. [Q86U42-2]
DR TopDownProteomics; Q86U42-1; -. [Q86U42-1]
DR Antibodypedia; 43; 182 antibodies from 30 providers.
DR DNASU; 8106; -.
DR Ensembl; ENST00000216727.9; ENSP00000216727.4; ENSG00000100836.11. [Q86U42-1]
DR Ensembl; ENST00000397276.6; ENSP00000380446.2; ENSG00000100836.11. [Q86U42-2]
DR GeneID; 8106; -.
DR KEGG; hsa:8106; -.
DR MANE-Select; ENST00000216727.9; ENSP00000216727.4; NM_004643.4; NP_004634.1.
DR UCSC; uc001wjj.4; human. [Q86U42-1]
DR CTD; 8106; -.
DR DisGeNET; 8106; -.
DR GeneCards; PABPN1; -.
DR GeneReviews; PABPN1; -.
DR HGNC; HGNC:8565; PABPN1.
DR HPA; ENSG00000100836; Low tissue specificity.
DR MalaCards; PABPN1; -.
DR MIM; 164300; phenotype.
DR MIM; 602279; gene.
DR neXtProt; NX_Q86U42; -.
DR OpenTargets; ENSG00000100836; -.
DR Orphanet; 270; Oculopharyngeal muscular dystrophy.
DR PharmGKB; PA32891; -.
DR VEuPathDB; HostDB:ENSG00000100836; -.
DR eggNOG; KOG4209; Eukaryota.
DR GeneTree; ENSGT00940000154606; -.
DR HOGENOM; CLU_012062_23_1_1; -.
DR InParanoid; Q86U42; -.
DR OMA; ISAEDQF; -.
DR OrthoDB; 1412946at2759; -.
DR PhylomeDB; Q86U42; -.
DR TreeFam; TF105907; -.
DR PathwayCommons; Q86U42; -.
DR Reactome; R-HSA-168315; Inhibition of Host mRNA Processing and RNA Silencing.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72187; mRNA 3'-end processing.
DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-HSA-77595; Processing of Intronless Pre-mRNAs.
DR SignaLink; Q86U42; -.
DR SIGNOR; Q86U42; -.
DR BioGRID-ORCS; 8106; 730 hits in 1038 CRISPR screens.
DR EvolutionaryTrace; Q86U42; -.
DR GeneWiki; PABPN1; -.
DR GenomeRNAi; 8106; -.
DR Pharos; Q86U42; Tbio.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86U42; protein.
DR Bgee; ENSG00000100836; Expressed in right testis and 171 other tissues.
DR ExpressionAtlas; Q86U42; baseline and differential.
DR Genevisible; Q86U42; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042405; C:nuclear inclusion body; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0070063; F:RNA polymerase binding; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0016973; P:poly(A)+ mRNA export from nucleus; IMP:UniProtKB.
DR GO; GO:1904247; P:positive regulation of polynucleotide adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0006396; P:RNA processing; TAS:ProtInc.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR034911; PABP2.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR23236:SF16; PTHR23236:SF16; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coiled coil; Cytoplasm;
KW Direct protein sequencing; Disease variant; Methylation; mRNA processing;
KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding;
KW Triplet repeat expansion.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..306
FT /note="Polyadenylate-binding protein 2"
FT /id="PRO_0000081711"
FT DOMAIN 172..249
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 1..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..145
FT /note="Interaction with SKIP"
FT /evidence="ECO:0000269|PubMed:11371506"
FT REGION 119..147
FT /note="Stimulates PAPOLA"
FT /evidence="ECO:0000250"
FT REGION 155..306
FT /note="Necessary for homooligomerization"
FT REGION 286..306
FT /note="Interaction with PAPOLA"
FT /evidence="ECO:0000250"
FT COILED 115..151
FT /evidence="ECO:0000255"
FT COMPBIAS 51..70
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..115
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 17
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8CCS6"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 238
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 238
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 259
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 259
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 263
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 263
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 265
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 267
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 269
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 277
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 279
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 287
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 289
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 291
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 294
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 296
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT MOD_RES 298
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q28165"
FT VAR_SEQ 295..296
FT /note="GR -> SG (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_009847"
FT VAR_SEQ 297..306
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_009848"
FT VARIANT 6
FT /note="A -> AAAA"
FT /id="VAR_018179"
FT MUTAGEN 213..220
FT /note="Missing: Abolishes self-association, protein
FT aggregation and cell death."
FT /evidence="ECO:0000269|PubMed:11689481"
FT MUTAGEN 301..306
FT /note="Missing: Abolishes self-association, protein
FT aggregation and cell death."
FT /evidence="ECO:0000269|PubMed:11689481"
FT HELIX 167..171
FT /evidence="ECO:0007829|PDB:3UCG"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:3UCG"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:3UCG"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:3UCG"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:3UCG"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:3UCG"
FT STRAND 214..222
FT /evidence="ECO:0007829|PDB:3UCG"
FT HELIX 224..229
FT /evidence="ECO:0007829|PDB:3UCG"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:3UCG"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:3UCG"
FT TURN 247..250
FT /evidence="ECO:0007829|PDB:3UCG"
SQ SEQUENCE 306 AA; 32749 MW; 2E5B0AEFEA5AFBC3 CRC64;
MAAAAAAAAA AGAAGGRGSG PGRRRHLVPG AGGEAGEGAP GGAGDYGNGL ESEELEPEEL
LLEPEPEPEP EEEPPRPRAP PGAPGPGPGS GAPGSQEEEE EPGLVEGDPG DGAIEDPELE
AIKARVREME EEAEKLKELQ NEVEKQMNMS PPPGNAGPVI MSIEEKMEAD ARSIYVGNVD
YGATAEELEA HFHGCGSVNR VTILCDKFSG HPKGFAYIEF SDKESVRTSL ALDESLFRGR
QIKVIPKRTN RPGISTTDRG FPRARYRART TNYNSSRSRF YSGFNSRPRG RVYRGRARAT
SWYSPY
