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 27-MAR-2024, entry version 189. 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 OPMD1 ALA-6 INS, AND INVOLVEMENT IN OPMD1. 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 OPMD1 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 1 (OPMD1) [MIM:164300]: An CC autosomal dominant, late-onset, slowly progressive myopathy CC characterized by eyelid ptosis, dysphagia and, sometimes by other CC cranial and limb-muscle involvement. {ECO:0000269|PubMed:12673802}. CC Note=The disease is caused by variants affecting the gene represented CC 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 194. DR ComplexPortal; CPX-2750; Poly(A) tail exosome targeting complex, RBM26 variant. DR ComplexPortal; CPX-2752; Poly(A) tail exosome targeting complex, RBM27 variant. DR DIP; DIP-37968N; -. DR IntAct; Q86U42; 70. DR MINT; Q86U42; -. DR STRING; 9606.ENSP00000216727; -. DR GlyGen; Q86U42; 7 sites, 1 O-linked glycan (7 sites). DR iPTMnet; Q86U42; -. DR PhosphoSitePlus; Q86U42; -. DR SwissPalm; Q86U42; -. DR BioMuta; PABPN1; -. DR DMDM; 46403176; -. DR EPD; Q86U42; -. DR jPOST; Q86U42; -. DR MassIVE; Q86U42; -. DR MaxQB; Q86U42; -. DR PaxDb; 9606-ENSP00000216727; -. DR PeptideAtlas; Q86U42; -. DR ProteomicsDB; 69766; -. [Q86U42-1] DR ProteomicsDB; 69767; -. [Q86U42-2] DR Pumba; Q86U42; -. DR TopDownProteomics; Q86U42-1; -. [Q86U42-1] DR Antibodypedia; 43; 227 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 AGR; HGNC:8565; -. 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; ARFTCHE; -. DR OrthoDB; 155884at2759; -. 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-72187; mRNA 3'-end processing. DR Reactome; R-HSA-72203; Processing of Capped Intron-Containing Pre-mRNA. DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination. DR Reactome; R-HSA-77595; Processing of Intronless Pre-mRNAs. DR Reactome; R-HSA-9820865; Z-decay: degradation of maternal mRNAs by zygotically expressed factors. DR SignaLink; Q86U42; -. DR SIGNOR; Q86U42; -. DR BioGRID-ORCS; 8106; 758 hits in 1106 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 173 other cell types or tissues. DR ExpressionAtlas; Q86U42; baseline and differential. 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:0008143; F:poly(A) binding; IBA:GO_Central. 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 CDD; cd12550; RRM_II_PABPN1; 1. DR Gene3D; 3.30.70.330; -; 1. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR000504; RRM_dom. DR PANTHER; PTHR23236; EUKARYOTIC TRANSLATION INITIATION FACTOR 4B/4H; 1. DR PANTHER; PTHR23236:SF16; POLYADENYLATE-BINDING PROTEIN 2; 1. DR Pfam; PF00076; RRM_1; 1. DR SMART; SM00360; RRM; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS50102; RRM; 1. DR Genevisible; Q86U42; HS. 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 //