Full text data of HNRNPA2B1
HNRNPA2B1
(HNRPA2B1)
[Confidence: low (only semi-automatic identification from reviews)]
Heterogeneous nuclear ribonucleoproteins A2/B1; hnRNP A2/B1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heterogeneous nuclear ribonucleoproteins A2/B1; hnRNP A2/B1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P22626
ID ROA2_HUMAN Reviewed; 353 AA.
AC P22626; A8K064; P22627; Q9UC98; Q9UDJ2;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1991, sequence version 2.
DT 22-JAN-2014, entry version 157.
DE RecName: Full=Heterogeneous nuclear ribonucleoproteins A2/B1;
DE Short=hnRNP A2/B1;
GN Name=HNRNPA2B1; Synonyms=HNRPA2B1;
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] (ISOFORMS B1 AND A2).
RX PubMed=2557628; DOI=10.1073/pnas.86.24.9788;
RA Burd C.G., Swanson M.S., Goerlach M., Dreyfuss G.;
RT "Primary structures of the heterogeneous nuclear ribonucleoprotein A2,
RT B1, and C2 proteins: a diversity of RNA binding proteins is generated
RT by small peptide inserts.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9788-9792(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8029005; DOI=10.1093/nar/22.11.1996;
RA Biamonti G., Ruggiu M., Saccone S., Della Valle G., Riva S.;
RT "Two homologous genes, originated by duplication, encode the human
RT hnRNP proteins A2 and A1.";
RL Nucleic Acids Res. 22:1996-2002(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7789969; DOI=10.1016/0888-7543(95)80035-K;
RA Kozu T., Henrich B., Schaefer K.P.;
RT "Structure and expression of the gene (HNRPA2B1) encoding the human
RT hnRNP protein A2/B1.";
RL Genomics 25:365-371(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B1).
RC TISSUE=Glial tumor;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP PROTEIN SEQUENCE OF 1-12; 22-59; 63-89; 100-147; 153-185; 201-266 AND
RP 326-350, ACETYLATION AT MET-1, METHYLATION AT LYS-104; ARG-203 AND
RP ARG-213, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Dozynkiewicz M., Norman J.C.;
RL Submitted (JUN-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 22-38; 154-168; 174-185; 214-228 AND 326-350, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 39-46; 154-168; 204-228 AND 267-286.
RC TISSUE=Cervix carcinoma;
RX PubMed=1522214; DOI=10.1172/JCI115921;
RA Steiner G., Hartmuth K., Skriner K., Maurer-Fogy I., Sinski A.,
RA Thalmann E., Hassfeld W., Barta A., Smolen J.S.;
RT "Purification and partial sequencing of the nuclear autoantigen RA33
RT shows that it is indistinguishable from the A2 protein of the
RT heterogeneous nuclear ribonucleoprotein complex.";
RL J. Clin. Invest. 90:1061-1066(1992).
RN [8]
RP PROTEIN SEQUENCE OF 80-100.
RC TISSUE=Cervix carcinoma;
RX PubMed=7980541; DOI=10.1006/bbrc.1994.2526;
RA Prasad S., Walent J., Dritschilo A.;
RT "ADP-ribosylation of heterogeneous ribonucleoproteins in HeLa cells.";
RL Biochem. Biophys. Res. Commun. 204:772-779(1994).
RN [9]
RP PROTEIN SEQUENCE OF 100-107; 121-128 AND 174-180.
RX PubMed=3733753;
RA Kumar A., Willams K.R., Szer W.;
RT "Purification and domain structure of core hnRNP proteins A1 and A2
RT and their relationship to single-stranded DNA-binding proteins.";
RL J. Biol. Chem. 261:11266-11273(1986).
RN [10]
RP PROTEIN SEQUENCE OF 154-160; 204-212 AND 214-228.
RX PubMed=1699755; DOI=10.1002/elps.1150110703;
RA Bauw G., Rasmussen H.H., van den Bulcke M., van Damme J., Puype M.,
RA Gesser B., Celis J.E., Vandekerckhove J.;
RT "Two-dimensional gel electrophoresis, protein electroblotting and
RT microsequencing: a direct link between proteins and genes.";
RL Electrophoresis 11:528-536(1990).
RN [11]
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 [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-203, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=15782174; DOI=10.1038/nmeth715;
RA Ong S.E., Mittler G., Mann M.;
RT "Identifying and quantifying in vivo methylation sites by heavy methyl
RT SILAC.";
RL Nat. Methods 1:119-126(2004).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [14]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, INTERACTION WITH IGF2BP1,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; SER-341 AND
RP SER-344, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-212; SER-259 AND
RP SER-344, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-168 AND LYS-173, AND MASS
RP 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-149; SER-212;
RP SER-225; SER-231; SER-259; SER-341 AND SER-344, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212; SER-225; SER-231;
RP SER-236; SER-259; SER-324; TYR-331 AND SER-344, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP STRUCTURE BY NMR OF 1-103.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RRM domain in heterogeneous nuclear
RT ribonucleoproteins A2/B1.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Involved with pre-mRNA processing. Forms complexes
CC (ribonucleosomes) with at least 20 other different hnRNP and
CC heterogeneous nuclear RNA in the nucleus.
CC -!- SUBUNIT: Identified in the spliceosome C complex. Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated
CC mRNAs. Interacts with IGF2BP1.
CC -!- INTERACTION:
CC Q9HA38:ZMAT3; NbExp=3; IntAct=EBI-299649, EBI-2548480;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm.
CC Note=Localized in cytoplasmic mRNP granules containing
CC untranslated mRNAs. Component of ribonucleosomes. Predominantly
CC nucleoplasmic, however isoform A2 is also found in the cytoplasm
CC of cells in some tissues. Not found in the nucleolus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B1;
CC IsoId=P22626-1; Sequence=Displayed;
CC Name=A2;
CC IsoId=P22626-2; Sequence=VSP_005830;
CC -!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
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DR EMBL; M29064; AAA60271.1; -; mRNA.
DR EMBL; M29065; AAA36574.1; -; mRNA.
DR EMBL; U09123; AAB60650.1; -; Genomic_DNA.
DR EMBL; U09120; AAB60650.1; JOINED; Genomic_DNA.
DR EMBL; U09121; AAB60650.1; JOINED; Genomic_DNA.
DR EMBL; U09122; AAB60650.1; JOINED; Genomic_DNA.
DR EMBL; D28877; BAA06031.1; -; Genomic_DNA.
DR EMBL; D28877; BAA06032.1; -; Genomic_DNA.
DR EMBL; AK289429; BAF82118.1; -; mRNA.
DR PIR; A56845; B34504.
DR RefSeq; NP_002128.1; NM_002137.3.
DR RefSeq; NP_112533.1; NM_031243.2.
DR RefSeq; XP_005249786.1; XM_005249729.1.
DR UniGene; Hs.487774; -.
DR PDB; 1X4B; NMR; -; A=1-103.
DR PDBsum; 1X4B; -.
DR ProteinModelPortal; P22626; -.
DR SMR; P22626; 1-193.
DR DIP; DIP-32877N; -.
DR IntAct; P22626; 70.
DR MINT; MINT-4998934; -.
DR STRING; 9606.ENSP00000346694; -.
DR PhosphoSite; P22626; -.
DR DMDM; 133257; -.
DR REPRODUCTION-2DPAGE; IPI00396378; -.
DR REPRODUCTION-2DPAGE; IPI00414696; -.
DR REPRODUCTION-2DPAGE; P22626; -.
DR SWISS-2DPAGE; P22626; -.
DR UCD-2DPAGE; P22626; -.
DR PaxDb; P22626; -.
DR PRIDE; P22626; -.
DR Ensembl; ENST00000354667; ENSP00000346694; ENSG00000122566.
DR Ensembl; ENST00000356674; ENSP00000349101; ENSG00000122566.
DR Ensembl; ENST00000360787; ENSP00000354021; ENSG00000122566.
DR GeneID; 3181; -.
DR KEGG; hsa:3181; -.
DR UCSC; uc003sxr.4; human.
DR CTD; 3181; -.
DR GeneCards; GC07M026229; -.
DR HGNC; HGNC:5033; HNRNPA2B1.
DR HPA; CAB012403; -.
DR HPA; HPA001666; -.
DR MIM; 600124; gene.
DR neXtProt; NX_P22626; -.
DR Orphanet; 52430; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia.
DR PharmGKB; PA162391140; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000234442; -.
DR HOVERGEN; HBG002295; -.
DR KO; K13158; -.
DR OMA; YSARTSP; -.
DR OrthoDB; EOG715Q6V; -.
DR PhylomeDB; P22626; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPA2B1; human.
DR EvolutionaryTrace; P22626; -.
DR GeneWiki; HNRPA2B1; -.
DR GenomeRNAi; 3181; -.
DR NextBio; 12622; -.
DR PMAP-CutDB; P22626; -.
DR PRO; PR:P22626; -.
DR Bgee; P22626; -.
DR CleanEx; HS_HNRNPA2B1; -.
DR Genevestigator; P22626; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IDA:HGNC.
DR GO; GO:0043047; F:single-stranded telomeric DNA binding; IDA:HGNC.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0050658; P:RNA transport; IDA:HGNC.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 2.
DR PROSITE; PS50102; RRM; 2.
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; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ribonucleoprotein; RNA-binding; Spliceosome.
FT CHAIN 1 353 Heterogeneous nuclear ribonucleoproteins
FT A2/B1.
FT /FTId=PRO_0000081836.
FT DOMAIN 21 104 RRM 1.
FT DOMAIN 112 191 RRM 2.
FT REGION 308 347 Nuclear targeting sequence (By
FT similarity).
FT MOTIF 9 15 Nuclear localization signal (Potential).
FT COMPBIAS 202 353 Gly-rich.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 85 85 Phosphoserine.
FT MOD_RES 104 104 N6,N6-dimethyllysine.
FT MOD_RES 149 149 Phosphoserine.
FT MOD_RES 168 168 N6-acetyllysine.
FT MOD_RES 173 173 N6-acetyllysine.
FT MOD_RES 203 203 Dimethylated arginine; alternate.
FT MOD_RES 203 203 Omega-N-methylarginine; alternate.
FT MOD_RES 212 212 Phosphoserine.
FT MOD_RES 213 213 Dimethylated arginine; alternate.
FT MOD_RES 213 213 Omega-N-methylarginine; alternate.
FT MOD_RES 225 225 Phosphoserine.
FT MOD_RES 231 231 Phosphoserine.
FT MOD_RES 236 236 Phosphoserine.
FT MOD_RES 259 259 Phosphoserine.
FT MOD_RES 324 324 Phosphoserine.
FT MOD_RES 331 331 Phosphotyrosine.
FT MOD_RES 341 341 Phosphoserine.
FT MOD_RES 344 344 Phosphoserine.
FT VAR_SEQ 3 14 Missing (in isoform A2).
FT /FTId=VSP_005830.
FT CONFLICT 205 205 G -> S (in Ref. 4; BAF82118).
FT HELIX 16 20
FT STRAND 22 26
FT HELIX 34 41
FT STRAND 48 52
FT TURN 56 58
FT STRAND 63 68
FT HELIX 72 79
FT STRAND 83 86
FT STRAND 89 94
SQ SEQUENCE 353 AA; 37430 MW; 4C2560A3D8E99D62 CRC64;
MEKTLETVPL ERKKREKEQF RKLFIGGLSF ETTEESLRNY YEQWGKLTDC VVMRDPASKR
SRGFGFVTFS SMAEVDAAMA ARPHSIDGRV VEPKRAVARE ESGKPGAHVT VKKLFVGGIK
EDTEEHHLRD YFEEYGKIDT IEIITDRQSG KKRGFGFVTF DDHDPVDKIV LQKYHTINGH
NAEVRKALSR QEMQEVQSSR SGRGGNFGFG DSRGGGGNFG PGPGSNFRGG SDGYGSGRGF
GDGYNGYGGG PGGGNFGGSP GYGGGRGGYG GGGPGYGNQG GGYGGGYDNY GGGNYGSGNY
NDFGNYNQQP SNYGPMKSGN FGGSRNMGGP YGGGNYGPGG SGGSGGYGGR SRY
//
ID ROA2_HUMAN Reviewed; 353 AA.
AC P22626; A8K064; P22627; Q9UC98; Q9UDJ2;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1991, sequence version 2.
DT 22-JAN-2014, entry version 157.
DE RecName: Full=Heterogeneous nuclear ribonucleoproteins A2/B1;
DE Short=hnRNP A2/B1;
GN Name=HNRNPA2B1; Synonyms=HNRPA2B1;
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] (ISOFORMS B1 AND A2).
RX PubMed=2557628; DOI=10.1073/pnas.86.24.9788;
RA Burd C.G., Swanson M.S., Goerlach M., Dreyfuss G.;
RT "Primary structures of the heterogeneous nuclear ribonucleoprotein A2,
RT B1, and C2 proteins: a diversity of RNA binding proteins is generated
RT by small peptide inserts.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9788-9792(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8029005; DOI=10.1093/nar/22.11.1996;
RA Biamonti G., Ruggiu M., Saccone S., Della Valle G., Riva S.;
RT "Two homologous genes, originated by duplication, encode the human
RT hnRNP proteins A2 and A1.";
RL Nucleic Acids Res. 22:1996-2002(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7789969; DOI=10.1016/0888-7543(95)80035-K;
RA Kozu T., Henrich B., Schaefer K.P.;
RT "Structure and expression of the gene (HNRPA2B1) encoding the human
RT hnRNP protein A2/B1.";
RL Genomics 25:365-371(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B1).
RC TISSUE=Glial tumor;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP PROTEIN SEQUENCE OF 1-12; 22-59; 63-89; 100-147; 153-185; 201-266 AND
RP 326-350, ACETYLATION AT MET-1, METHYLATION AT LYS-104; ARG-203 AND
RP ARG-213, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Dozynkiewicz M., Norman J.C.;
RL Submitted (JUN-2009) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 22-38; 154-168; 174-185; 214-228 AND 326-350, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 39-46; 154-168; 204-228 AND 267-286.
RC TISSUE=Cervix carcinoma;
RX PubMed=1522214; DOI=10.1172/JCI115921;
RA Steiner G., Hartmuth K., Skriner K., Maurer-Fogy I., Sinski A.,
RA Thalmann E., Hassfeld W., Barta A., Smolen J.S.;
RT "Purification and partial sequencing of the nuclear autoantigen RA33
RT shows that it is indistinguishable from the A2 protein of the
RT heterogeneous nuclear ribonucleoprotein complex.";
RL J. Clin. Invest. 90:1061-1066(1992).
RN [8]
RP PROTEIN SEQUENCE OF 80-100.
RC TISSUE=Cervix carcinoma;
RX PubMed=7980541; DOI=10.1006/bbrc.1994.2526;
RA Prasad S., Walent J., Dritschilo A.;
RT "ADP-ribosylation of heterogeneous ribonucleoproteins in HeLa cells.";
RL Biochem. Biophys. Res. Commun. 204:772-779(1994).
RN [9]
RP PROTEIN SEQUENCE OF 100-107; 121-128 AND 174-180.
RX PubMed=3733753;
RA Kumar A., Willams K.R., Szer W.;
RT "Purification and domain structure of core hnRNP proteins A1 and A2
RT and their relationship to single-stranded DNA-binding proteins.";
RL J. Biol. Chem. 261:11266-11273(1986).
RN [10]
RP PROTEIN SEQUENCE OF 154-160; 204-212 AND 214-228.
RX PubMed=1699755; DOI=10.1002/elps.1150110703;
RA Bauw G., Rasmussen H.H., van den Bulcke M., van Damme J., Puype M.,
RA Gesser B., Celis J.E., Vandekerckhove J.;
RT "Two-dimensional gel electrophoresis, protein electroblotting and
RT microsequencing: a direct link between proteins and genes.";
RL Electrophoresis 11:528-536(1990).
RN [11]
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 [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-203, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=15782174; DOI=10.1038/nmeth715;
RA Ong S.E., Mittler G., Mann M.;
RT "Identifying and quantifying in vivo methylation sites by heavy methyl
RT SILAC.";
RL Nat. Methods 1:119-126(2004).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [14]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, INTERACTION WITH IGF2BP1,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; SER-341 AND
RP SER-344, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-212; SER-259 AND
RP SER-344, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-168 AND LYS-173, AND MASS
RP 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-149; SER-212;
RP SER-225; SER-231; SER-259; SER-341 AND SER-344, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212; SER-225; SER-231;
RP SER-236; SER-259; SER-324; TYR-331 AND SER-344, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP STRUCTURE BY NMR OF 1-103.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RRM domain in heterogeneous nuclear
RT ribonucleoproteins A2/B1.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Involved with pre-mRNA processing. Forms complexes
CC (ribonucleosomes) with at least 20 other different hnRNP and
CC heterogeneous nuclear RNA in the nucleus.
CC -!- SUBUNIT: Identified in the spliceosome C complex. Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated
CC mRNAs. Interacts with IGF2BP1.
CC -!- INTERACTION:
CC Q9HA38:ZMAT3; NbExp=3; IntAct=EBI-299649, EBI-2548480;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm.
CC Note=Localized in cytoplasmic mRNP granules containing
CC untranslated mRNAs. Component of ribonucleosomes. Predominantly
CC nucleoplasmic, however isoform A2 is also found in the cytoplasm
CC of cells in some tissues. Not found in the nucleolus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B1;
CC IsoId=P22626-1; Sequence=Displayed;
CC Name=A2;
CC IsoId=P22626-2; Sequence=VSP_005830;
CC -!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
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DR EMBL; M29064; AAA60271.1; -; mRNA.
DR EMBL; M29065; AAA36574.1; -; mRNA.
DR EMBL; U09123; AAB60650.1; -; Genomic_DNA.
DR EMBL; U09120; AAB60650.1; JOINED; Genomic_DNA.
DR EMBL; U09121; AAB60650.1; JOINED; Genomic_DNA.
DR EMBL; U09122; AAB60650.1; JOINED; Genomic_DNA.
DR EMBL; D28877; BAA06031.1; -; Genomic_DNA.
DR EMBL; D28877; BAA06032.1; -; Genomic_DNA.
DR EMBL; AK289429; BAF82118.1; -; mRNA.
DR PIR; A56845; B34504.
DR RefSeq; NP_002128.1; NM_002137.3.
DR RefSeq; NP_112533.1; NM_031243.2.
DR RefSeq; XP_005249786.1; XM_005249729.1.
DR UniGene; Hs.487774; -.
DR PDB; 1X4B; NMR; -; A=1-103.
DR PDBsum; 1X4B; -.
DR ProteinModelPortal; P22626; -.
DR SMR; P22626; 1-193.
DR DIP; DIP-32877N; -.
DR IntAct; P22626; 70.
DR MINT; MINT-4998934; -.
DR STRING; 9606.ENSP00000346694; -.
DR PhosphoSite; P22626; -.
DR DMDM; 133257; -.
DR REPRODUCTION-2DPAGE; IPI00396378; -.
DR REPRODUCTION-2DPAGE; IPI00414696; -.
DR REPRODUCTION-2DPAGE; P22626; -.
DR SWISS-2DPAGE; P22626; -.
DR UCD-2DPAGE; P22626; -.
DR PaxDb; P22626; -.
DR PRIDE; P22626; -.
DR Ensembl; ENST00000354667; ENSP00000346694; ENSG00000122566.
DR Ensembl; ENST00000356674; ENSP00000349101; ENSG00000122566.
DR Ensembl; ENST00000360787; ENSP00000354021; ENSG00000122566.
DR GeneID; 3181; -.
DR KEGG; hsa:3181; -.
DR UCSC; uc003sxr.4; human.
DR CTD; 3181; -.
DR GeneCards; GC07M026229; -.
DR HGNC; HGNC:5033; HNRNPA2B1.
DR HPA; CAB012403; -.
DR HPA; HPA001666; -.
DR MIM; 600124; gene.
DR neXtProt; NX_P22626; -.
DR Orphanet; 52430; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia.
DR PharmGKB; PA162391140; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000234442; -.
DR HOVERGEN; HBG002295; -.
DR KO; K13158; -.
DR OMA; YSARTSP; -.
DR OrthoDB; EOG715Q6V; -.
DR PhylomeDB; P22626; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPA2B1; human.
DR EvolutionaryTrace; P22626; -.
DR GeneWiki; HNRPA2B1; -.
DR GenomeRNAi; 3181; -.
DR NextBio; 12622; -.
DR PMAP-CutDB; P22626; -.
DR PRO; PR:P22626; -.
DR Bgee; P22626; -.
DR CleanEx; HS_HNRNPA2B1; -.
DR Genevestigator; P22626; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IDA:HGNC.
DR GO; GO:0043047; F:single-stranded telomeric DNA binding; IDA:HGNC.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0050658; P:RNA transport; IDA:HGNC.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 2.
DR PROSITE; PS50102; RRM; 2.
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; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ribonucleoprotein; RNA-binding; Spliceosome.
FT CHAIN 1 353 Heterogeneous nuclear ribonucleoproteins
FT A2/B1.
FT /FTId=PRO_0000081836.
FT DOMAIN 21 104 RRM 1.
FT DOMAIN 112 191 RRM 2.
FT REGION 308 347 Nuclear targeting sequence (By
FT similarity).
FT MOTIF 9 15 Nuclear localization signal (Potential).
FT COMPBIAS 202 353 Gly-rich.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 85 85 Phosphoserine.
FT MOD_RES 104 104 N6,N6-dimethyllysine.
FT MOD_RES 149 149 Phosphoserine.
FT MOD_RES 168 168 N6-acetyllysine.
FT MOD_RES 173 173 N6-acetyllysine.
FT MOD_RES 203 203 Dimethylated arginine; alternate.
FT MOD_RES 203 203 Omega-N-methylarginine; alternate.
FT MOD_RES 212 212 Phosphoserine.
FT MOD_RES 213 213 Dimethylated arginine; alternate.
FT MOD_RES 213 213 Omega-N-methylarginine; alternate.
FT MOD_RES 225 225 Phosphoserine.
FT MOD_RES 231 231 Phosphoserine.
FT MOD_RES 236 236 Phosphoserine.
FT MOD_RES 259 259 Phosphoserine.
FT MOD_RES 324 324 Phosphoserine.
FT MOD_RES 331 331 Phosphotyrosine.
FT MOD_RES 341 341 Phosphoserine.
FT MOD_RES 344 344 Phosphoserine.
FT VAR_SEQ 3 14 Missing (in isoform A2).
FT /FTId=VSP_005830.
FT CONFLICT 205 205 G -> S (in Ref. 4; BAF82118).
FT HELIX 16 20
FT STRAND 22 26
FT HELIX 34 41
FT STRAND 48 52
FT TURN 56 58
FT STRAND 63 68
FT HELIX 72 79
FT STRAND 83 86
FT STRAND 89 94
SQ SEQUENCE 353 AA; 37430 MW; 4C2560A3D8E99D62 CRC64;
MEKTLETVPL ERKKREKEQF RKLFIGGLSF ETTEESLRNY YEQWGKLTDC VVMRDPASKR
SRGFGFVTFS SMAEVDAAMA ARPHSIDGRV VEPKRAVARE ESGKPGAHVT VKKLFVGGIK
EDTEEHHLRD YFEEYGKIDT IEIITDRQSG KKRGFGFVTF DDHDPVDKIV LQKYHTINGH
NAEVRKALSR QEMQEVQSSR SGRGGNFGFG DSRGGGGNFG PGPGSNFRGG SDGYGSGRGF
GDGYNGYGGG PGGGNFGGSP GYGGGRGGYG GGGPGYGNQG GGYGGGYDNY GGGNYGSGNY
NDFGNYNQQP SNYGPMKSGN FGGSRNMGGP YGGGNYGPGG SGGSGGYGGR SRY
//
MIM
600124
*RECORD*
*FIELD* NO
600124
*FIELD* TI
*600124 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2/B1; HNRNPA2B1
;;HNRPA2B1
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2, INCLUDED; HNRPA2, INCLUDED;;
read moreHETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1, INCLUDED; HNRPB1, INCLUDED
*FIELD* TX
DESCRIPTION
The HNRNPA2B1 gene encodes 2 major proteins, HNRNPA2 and HNRNPB1,
through alternative splicing. HNRNPA/B proteins, such as HNRNPA2 and
HNRNPB1, are involved in packaging nascent mRNA, in alternative
splicing, and in cytoplasmic RNA trafficking, translation, and
stabilization. HNRNPA2 and HNRNPB1 also appear to function in telomere
maintenance, cell proliferation and differentiation, and glucose
transport (Moran-Jones et al., 2005; Iwanaga et al., 2005).
CLONING
By immunoscreening a HeLa cell cDNA expression library using mouse
anti-A2 and anti-B1 antibodies, followed by screening a human
osteosarcoma cDNA library, Burd et al. (1989) obtained full-length A2
and B1 clones. The B1 cDNA has a 36-nucleotide insertion near its
5-prime end relative to A2, but they are otherwise identical. The
deduced A2 protein contains 341 amino acids, and the deduced B1 protein
contains an in-frame 12-amino acid insert after glu2 compared with A2.
Both proteins contain 2 consensus-type RNA-binding domains, followed by
an extended C-terminal glycine-rich region. The insert in B1 introduces
a putative nuclear localization signal. In vitro translation produced A2
and B1 proteins that comigrated with purified endogenous HeLa cell A2
and B1 at apparent molecular masses of 36 and 38 kD, respectively.
Biamonti et al. (1994) and Kozu et al. (1995) independently cloned
HNRNPA2B1. Biamonti et al. (1994) determined that the 36-nucleotide
insertion in the B1 transcript arises from inclusion of exon 2. Using
Northern blot and RT-PCR analyses, Kozu et al. (1995) detected a 1.8-kb
transcript representing total A2/B1 mRNA in all 3 human cell lines
examined. The levels of B1 expression were about 2 to 5% of total A2/B1
levels in these cell lines. RT-PCR of mouse tissues suggested ubiquitous
expression of both A2 and B1 transcripts.
GENE FUNCTION
Translational repression of glucose transporter-1 (GLUT1, or SLC2A1;
138140) in glioblastoma multiforme (GBM; 137800) is mediated by a
specific RNA-binding protein that interacts with an AU-rich response
element in the 3-prime UTR of the GLUT1 transcript. Hamilton et al.
(1999) showed that HNRNPA2 and HNRNPL (603083) bound the 3-prime UTR of
GLUT1 mRNA. Induction of brain ischemia in rats or hypoglycemic stress
in 293 cells increased GLUT1 expression via mRNA stability. Polysomes
isolated from ischemic rat brains or hypoglycemic 293 cells showed loss
of HNRNPA2 and HNRNPL, suggesting that reduced levels of these
RNA-binding proteins results in GLUT1 mRNA stability.
Immunoprecipitation of polysomes from activated human T lymphocytes
suggested that HNRNPA2 and HNRNPL form a complex in vivo.
Using pull-down assays and EMSA, Moran-Jones et al. (2005) identified
Hnrnpa2 and Hnrnpa3 (605372) as the predominant single-stranded telomere
repeat-binding proteins in rat brain. Using rat and human constructs,
they identified 2 oligonucleotide-binding sites in HNRNPA2. One site
bound single-stranded DNA (ssDNA) with little or no nucleotide sequence
preference, whereas the second site bound specific RNA and DNA
sequences. The latter site bound single-stranded TTAGGG telomere repeats
and a cytoplasmic RNA-trafficking element (A2RE11). Mutation analysis
indicated that the tandem RRM domains also bound the telomerase RNA
(TERC; 602322), but the individual RRM domains did not. Full-length
HNRNPA2, but not HNRNPA2 truncation mutants, protected telomeric DNA
from DNase, suggesting that the glycine-rich domain as well as the RRM
domains are required for telomere protection. Moran-Jones et al. (2005)
proposed that HNRNPA2 can potentially bind telomeric DNA repeats and the
RNA component of telomerase simultaneously, or that it may bind ssDNA in
both sites and act as an intramolecular or intermolecular crosslink.
DNA-dependent protein kinase (DNAPK; see 600899) is a multisubunit
kinase involved in the repair of DNA double-strand breaks through
nonhomologous end-joining. Iwanaga et al. (2005) found that HNRNPB1
interacted directly with the DNAPK subunit Ku70 (XRCC6; 152690) and
inhibited DNAPK activity in a dose-dependent manner in vitro. Knockdown
of HNRNPA2B1 in irradiated normal human bronchial epithelial cells
reduced HNRNPB1 levels and enhanced recovery of DNA strand breaks
compared with controls.
By yeast 2-hybrid analysis of a human brain cDNA library, Kosturko et
al. (2006) found that mouse Hnrnpa2 interacted with human HNRNPE1
(PCBP1; 601209). They confirmed the interaction with in vivo and in
vitro protein interaction assays. Hnrnpe1 colocalized with Hnrnpa2 and
A2RE mRNA in granules in dendrites of rat oligodendrocytes.
Overexpression of HNRNPE1 or microinjection of exogenous HNRNPE1 in rat
neural cells inhibited translation of A2RE mRNA, but not translation of
mutated A2RE mRNA. Excess HNRNPE1 added to an in vitro translation
system reduced translation efficiency of A2RE mRNA in an
Hnrnpa2-dependent manner. Kosturko et al. (2006) hypothesized that
binding of HNRNPE1 to HNRNPA2 inhibits A2RE mRNA translation during
granule transport.
A transgenic fly model of fragile X-associated tremor/ataxia syndrome
(FXTAS; 300623) in which the 5-prime UTR of human FMR1 (309550)
containing 90 CGG repeats is expressed specifically in the eye results
in disorganized ommatidia, depigmentation, and progressive loss of
photoreceptor neurons. Sofola et al. (2007) found that overexpression of
human CUGBP1 (601074) suppressed the neurodegenerative eye phenotype in
transgenic flies. CUGBP1 did not interact directly with the CGG repeats,
but did so via HNRNPA2B1. Expression of the A2 isoform of human
HNRNPA2B1, or the Drosophila orthologs, also suppressed the eye
phenotype of FXTAS flies. Mouse Hnrnpa2b1 interacted directly with CGG
repeat RNA (rCGG) in mouse cerebellar lysates, and increased repeat
length increased the binding affinity. The interaction was most evident
in cytoplasmic cerebellar lysates. Nuclear Hnrnpa2b1 showed little or no
interaction with rCGG repeats, suggesting that protein modification, in
either the nuclear or cytoplasmic compartment, affects the interaction.
David et al. (2010) showed that 3 hnRNP proteins, polypyrimidine
tract-binding protein (PTB, also known as hnRNPI; 600693), hnRNPA1
(164017), and hnRNPA2, bind repressively to sequences flanking exon 9 of
the PKM2 gene (179050), resulting in exon 10 inclusion and expression of
the PKM2 (embryonic) isoform. David et al. (2010) also demonstrated that
the oncogenic transcription factor c-MYC (190080) upregulates
transcription of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1
ratio. Establishing a relevance to cancer, David et al. (2010) showed
that human gliomas (137800) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2
in a manner that correlates with PKM2 expression. David et al. (2010)
concluded that their results defined a pathway that regulates an
alternative splicing event required for tumor cell proliferation.
Kim et al. (2013) reported that HNRNPA2B1 has a C-terminal glycine-rich
domain that is essential for activity and mediates interaction with
TDP43 (605078). This low-complexity domain is predicted to be
intrinsically unfolded and has an amino acid composition similar to that
of yeast prion domains. Approximately 250 human proteins, including
several RNA-binding proteins associated with neurodegenerative disease,
harbor a similar distinctive prion-like domain (PrLD) enriched in
uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins
are essential for the assembly of ribonucleoprotein granules. Kim et al.
(2013) showed that HNRNPA2, the most abundant form of HNRNPA2B1, has an
intrinsic tendency to assemble into self-seeding fibrils.
GENE STRUCTURE
Biamonti et al. (1994) determined that the HNRNPA2B1 gene contains 12
exons, including an alternatively spliced 36-nucleotide mini-exon
specific for the B1 protein. The intron/exon organization of HNRNPA2B1
is identical to that of the HNRNPA1 gene over its entire length,
indicating a common origin by gene duplication.
Kozu et al. (1995) determined that the HNRNPA2B1 gene spans over 9 kb.
The 5-prime region is GC rich and contains several binding sites for
ubiquitous transcription factors, including 7 H4TF1 elements and 2 CCAAT
boxes, but no TATA sequence. The 3-prime region contains a
pyrimidine-rich RNA degradation motif prior to the polyadenylation
signal. Intron 8 contains an Alu repeat that is not found in the HNRNPA1
gene.
MAPPING
Biamonti et al. (1994) mapped the HNRNPA2B1 gene to chromosome 7p15 by
fluorescence in situ hybridization.
MOLECULAR GENETICS
In a family (family 1, previously described by Waggoner et al. (2002))
with dominantly inherited degeneration of muscle, bone, brain, and motor
neurons (IBMPFD2; 615422), Kim et al. (2013) identified a missense
mutation in the HNRNPA2B1 gene that altered a conserved aspartic acid at
position 290 of the short (A2) isoform and 302 of the long (B1) isoform
(600124.0001). Kim et al. (2013) showed that the intrinsic tendency of
HNRNPA2, the most abundant form of HNRNPA2B1, and HNRNPA1 (164017) to
assemble into self-seeding fibrils is exacerbated by disease mutations.
The pathogenic mutations strengthen a 'steric zipper' motif in the
prion-like domain (PrLD) that accelerates the formation of self-seeding
fibrils that cross-seed polymerization of wildtype HNRNP. Notably,
disease mutations promoted excess incorporation of HNRNPA2 and HNRNPA1
into stress granules and drove the formation of cytoplasmic inclusions
in animal models that recapitulated the human pathology. Kim et al.
(2013) concluded that dysregulated polymerization caused by a potent
mutant steric zipper motif in a PrLD can initiate degenerative disease.
*FIELD* AV
.0001
INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE AND FRONTOTEMPORAL
DEMENTIA 2 (1 family)
HNRNPA2B1, ASP290VAL
In affected members of a family (family 1) segregating autosomal
dominant inclusion body myopathy with Paget disease of the bone and
frontotemporal dementia (IBMPFD2; 615422), Kim et al. (2013) identified
an 869A-T transversion in the A2 isoform of the HNRNPA2B1 gene (905A-T
in the B1 isoform) resulting in an aspartic acid-to-valine substitution
at codon 290 (D290V; ASP302VAL, D302V in the B1 isoform). This was the
family originally reported by Waggoner et al. (2002). The aspartic acid
at this position is evolutionarily conserved to Drosophila, and is
centered in a motif, the prion-like domain (PrLD), that is conserved in
multiple human paralogs of the HNRNP A/B family. The mutation segregated
with the disease in the family and was not identified in the NHLBI Exome
Sequencing Project. In another family with a similar phenotype, Kim et
al. (2013) detected an aspartic acid-to-valine substitution at the
analogous residue of HNRNPA1 (164017.0001).
*FIELD* RF
1. Biamonti, G.; Ruggiu, M.; Saccone, S.; Della Valle, G.; Riva, S.
: Two homologous genes, originated by duplication, encode the human
hnRNP proteins A2 and A1. Nucleic Acids Res. 22: 1996-2002, 1994.
2. Burd, C. G.; Swanson, M. S.; Gorlach, M.; Dreyfuss, G.: Primary
structures of the heterogeneous nuclear ribonucleoprotein A2, B1,
and C2 proteins: a diversity of RNA binding proteins is generated
by small peptide inserts. Proc. Nat. Acad. Sci. 86: 9788-9792, 1989.
3. David, C. J.; Chen, M.; Assanah, M.; Canoll, P.; Manley, J. L.
: HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA
spicing in cancer. Nature 463: 364-368, 2010.
4. Hamilton, B. J.; Nichols, R. C.; Tsukamoto, H.; Boado, R. J.; Pardridge,
W. M.; Rigby, W. F. C.: hnRNP A2 and hnRNP L bind the 3-prime UTR
of glucose transporter 1 mRNA and exist as a complex in vivo. Biochem.
Biophys. Res. Commun. 261: 646-651, 1999.
5. Iwanaga, K.; Sueoka, N.; Sato, A.; Hayashi, S.; Sueoka, E.: Heterogeneous
nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through
the inhibition of DNA-dependent protein kinase activity. Biochem.
Biophys. Res. Commun. 333: 888-895, 2005.
6. Kim, H. J.; Kim, N. C.; Wang, Y.-D.; Scarborough, E. A.; Moore,
J.; Diaz, Z.; MacLea, K. S.; Freibaum, B.; Li, S.; Molliex, A.; and
25 others: Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1
cause multisystem proteinopathy and ALS. Nature 495: 467-473, 2013.
7. Kosturko, L. D.; Maggipinto, M. J.; Korza, G.; Lee, J. W.; Carson,
J. H.; Barbarese, E.: Heterogeneous nuclear ribonucleoprotein (hnRNP)
E1 binds to hnRNP A2 and inhibits translation of A2 response element
mRNAs. Molec. Biol. Cell 17: 3521-3533, 2006.
8. Kozu, T.; Henrich, B.; Schafer, K. P.: Structure and expression
of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1. Genomics 25:
365-371, 1995.
9. Moran-Jones, K.; Wayman, L.; Kennedy, D. D.; Reddel, R. R.; Sara,
S.; Snee, M. J.; Smith, R.: hnRNP A2, a potential ssDNA/RNA molecular
adapter at the telomere. Nucleic Acids Res. 33: 486-496, 2005.
10. Sofola, O. A.; Jin, P.; Qin, Y.; Duan, R.; Liu, H.; de Haro, M.;
Nelson, D. L.; Botas, J.: RNA-binding proteins hnRNP A2/B1 and CUGBP1
suppress fragile X CGG premutation repeat-induced neurodegeneration
in a Drosophila model of FXTAS. Neuron 55: 565-571, 2007.
11. Waggoner, B.; Kovach, M. J.; Winkelman, M.; Cai, D.; Khardori,
R.; Gelber, D.; Kimonis, V. E.: Heterogeneity in familial dominant
Paget disease of bone and muscular dystrophy. Am. J. Med. Genet. 108:
187-191, 2002.
*FIELD* CN
Ada Hamosh - updated: 9/24/2013
Ada Hamosh - updated: 2/18/2010
Patricia A. Hartz - updated: 9/10/2009
Alan F. Scott - edited: 12/9/1996
*FIELD* CD
Victor A. McKusick: 9/22/1994
*FIELD* ED
alopez: 01/15/2014
alopez: 10/18/2013
alopez: 9/24/2013
alopez: 2/24/2010
terry: 2/18/2010
mgross: 9/17/2009
terry: 9/10/2009
wwang: 8/27/2008
alopez: 6/10/2005
alopez: 6/13/1997
mark: 12/9/1996
mark: 2/2/1996
mark: 5/19/1995
carol: 10/13/1994
carol: 9/22/1994
*RECORD*
*FIELD* NO
600124
*FIELD* TI
*600124 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2/B1; HNRNPA2B1
;;HNRPA2B1
HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A2, INCLUDED; HNRPA2, INCLUDED;;
read moreHETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1, INCLUDED; HNRPB1, INCLUDED
*FIELD* TX
DESCRIPTION
The HNRNPA2B1 gene encodes 2 major proteins, HNRNPA2 and HNRNPB1,
through alternative splicing. HNRNPA/B proteins, such as HNRNPA2 and
HNRNPB1, are involved in packaging nascent mRNA, in alternative
splicing, and in cytoplasmic RNA trafficking, translation, and
stabilization. HNRNPA2 and HNRNPB1 also appear to function in telomere
maintenance, cell proliferation and differentiation, and glucose
transport (Moran-Jones et al., 2005; Iwanaga et al., 2005).
CLONING
By immunoscreening a HeLa cell cDNA expression library using mouse
anti-A2 and anti-B1 antibodies, followed by screening a human
osteosarcoma cDNA library, Burd et al. (1989) obtained full-length A2
and B1 clones. The B1 cDNA has a 36-nucleotide insertion near its
5-prime end relative to A2, but they are otherwise identical. The
deduced A2 protein contains 341 amino acids, and the deduced B1 protein
contains an in-frame 12-amino acid insert after glu2 compared with A2.
Both proteins contain 2 consensus-type RNA-binding domains, followed by
an extended C-terminal glycine-rich region. The insert in B1 introduces
a putative nuclear localization signal. In vitro translation produced A2
and B1 proteins that comigrated with purified endogenous HeLa cell A2
and B1 at apparent molecular masses of 36 and 38 kD, respectively.
Biamonti et al. (1994) and Kozu et al. (1995) independently cloned
HNRNPA2B1. Biamonti et al. (1994) determined that the 36-nucleotide
insertion in the B1 transcript arises from inclusion of exon 2. Using
Northern blot and RT-PCR analyses, Kozu et al. (1995) detected a 1.8-kb
transcript representing total A2/B1 mRNA in all 3 human cell lines
examined. The levels of B1 expression were about 2 to 5% of total A2/B1
levels in these cell lines. RT-PCR of mouse tissues suggested ubiquitous
expression of both A2 and B1 transcripts.
GENE FUNCTION
Translational repression of glucose transporter-1 (GLUT1, or SLC2A1;
138140) in glioblastoma multiforme (GBM; 137800) is mediated by a
specific RNA-binding protein that interacts with an AU-rich response
element in the 3-prime UTR of the GLUT1 transcript. Hamilton et al.
(1999) showed that HNRNPA2 and HNRNPL (603083) bound the 3-prime UTR of
GLUT1 mRNA. Induction of brain ischemia in rats or hypoglycemic stress
in 293 cells increased GLUT1 expression via mRNA stability. Polysomes
isolated from ischemic rat brains or hypoglycemic 293 cells showed loss
of HNRNPA2 and HNRNPL, suggesting that reduced levels of these
RNA-binding proteins results in GLUT1 mRNA stability.
Immunoprecipitation of polysomes from activated human T lymphocytes
suggested that HNRNPA2 and HNRNPL form a complex in vivo.
Using pull-down assays and EMSA, Moran-Jones et al. (2005) identified
Hnrnpa2 and Hnrnpa3 (605372) as the predominant single-stranded telomere
repeat-binding proteins in rat brain. Using rat and human constructs,
they identified 2 oligonucleotide-binding sites in HNRNPA2. One site
bound single-stranded DNA (ssDNA) with little or no nucleotide sequence
preference, whereas the second site bound specific RNA and DNA
sequences. The latter site bound single-stranded TTAGGG telomere repeats
and a cytoplasmic RNA-trafficking element (A2RE11). Mutation analysis
indicated that the tandem RRM domains also bound the telomerase RNA
(TERC; 602322), but the individual RRM domains did not. Full-length
HNRNPA2, but not HNRNPA2 truncation mutants, protected telomeric DNA
from DNase, suggesting that the glycine-rich domain as well as the RRM
domains are required for telomere protection. Moran-Jones et al. (2005)
proposed that HNRNPA2 can potentially bind telomeric DNA repeats and the
RNA component of telomerase simultaneously, or that it may bind ssDNA in
both sites and act as an intramolecular or intermolecular crosslink.
DNA-dependent protein kinase (DNAPK; see 600899) is a multisubunit
kinase involved in the repair of DNA double-strand breaks through
nonhomologous end-joining. Iwanaga et al. (2005) found that HNRNPB1
interacted directly with the DNAPK subunit Ku70 (XRCC6; 152690) and
inhibited DNAPK activity in a dose-dependent manner in vitro. Knockdown
of HNRNPA2B1 in irradiated normal human bronchial epithelial cells
reduced HNRNPB1 levels and enhanced recovery of DNA strand breaks
compared with controls.
By yeast 2-hybrid analysis of a human brain cDNA library, Kosturko et
al. (2006) found that mouse Hnrnpa2 interacted with human HNRNPE1
(PCBP1; 601209). They confirmed the interaction with in vivo and in
vitro protein interaction assays. Hnrnpe1 colocalized with Hnrnpa2 and
A2RE mRNA in granules in dendrites of rat oligodendrocytes.
Overexpression of HNRNPE1 or microinjection of exogenous HNRNPE1 in rat
neural cells inhibited translation of A2RE mRNA, but not translation of
mutated A2RE mRNA. Excess HNRNPE1 added to an in vitro translation
system reduced translation efficiency of A2RE mRNA in an
Hnrnpa2-dependent manner. Kosturko et al. (2006) hypothesized that
binding of HNRNPE1 to HNRNPA2 inhibits A2RE mRNA translation during
granule transport.
A transgenic fly model of fragile X-associated tremor/ataxia syndrome
(FXTAS; 300623) in which the 5-prime UTR of human FMR1 (309550)
containing 90 CGG repeats is expressed specifically in the eye results
in disorganized ommatidia, depigmentation, and progressive loss of
photoreceptor neurons. Sofola et al. (2007) found that overexpression of
human CUGBP1 (601074) suppressed the neurodegenerative eye phenotype in
transgenic flies. CUGBP1 did not interact directly with the CGG repeats,
but did so via HNRNPA2B1. Expression of the A2 isoform of human
HNRNPA2B1, or the Drosophila orthologs, also suppressed the eye
phenotype of FXTAS flies. Mouse Hnrnpa2b1 interacted directly with CGG
repeat RNA (rCGG) in mouse cerebellar lysates, and increased repeat
length increased the binding affinity. The interaction was most evident
in cytoplasmic cerebellar lysates. Nuclear Hnrnpa2b1 showed little or no
interaction with rCGG repeats, suggesting that protein modification, in
either the nuclear or cytoplasmic compartment, affects the interaction.
David et al. (2010) showed that 3 hnRNP proteins, polypyrimidine
tract-binding protein (PTB, also known as hnRNPI; 600693), hnRNPA1
(164017), and hnRNPA2, bind repressively to sequences flanking exon 9 of
the PKM2 gene (179050), resulting in exon 10 inclusion and expression of
the PKM2 (embryonic) isoform. David et al. (2010) also demonstrated that
the oncogenic transcription factor c-MYC (190080) upregulates
transcription of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1
ratio. Establishing a relevance to cancer, David et al. (2010) showed
that human gliomas (137800) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2
in a manner that correlates with PKM2 expression. David et al. (2010)
concluded that their results defined a pathway that regulates an
alternative splicing event required for tumor cell proliferation.
Kim et al. (2013) reported that HNRNPA2B1 has a C-terminal glycine-rich
domain that is essential for activity and mediates interaction with
TDP43 (605078). This low-complexity domain is predicted to be
intrinsically unfolded and has an amino acid composition similar to that
of yeast prion domains. Approximately 250 human proteins, including
several RNA-binding proteins associated with neurodegenerative disease,
harbor a similar distinctive prion-like domain (PrLD) enriched in
uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins
are essential for the assembly of ribonucleoprotein granules. Kim et al.
(2013) showed that HNRNPA2, the most abundant form of HNRNPA2B1, has an
intrinsic tendency to assemble into self-seeding fibrils.
GENE STRUCTURE
Biamonti et al. (1994) determined that the HNRNPA2B1 gene contains 12
exons, including an alternatively spliced 36-nucleotide mini-exon
specific for the B1 protein. The intron/exon organization of HNRNPA2B1
is identical to that of the HNRNPA1 gene over its entire length,
indicating a common origin by gene duplication.
Kozu et al. (1995) determined that the HNRNPA2B1 gene spans over 9 kb.
The 5-prime region is GC rich and contains several binding sites for
ubiquitous transcription factors, including 7 H4TF1 elements and 2 CCAAT
boxes, but no TATA sequence. The 3-prime region contains a
pyrimidine-rich RNA degradation motif prior to the polyadenylation
signal. Intron 8 contains an Alu repeat that is not found in the HNRNPA1
gene.
MAPPING
Biamonti et al. (1994) mapped the HNRNPA2B1 gene to chromosome 7p15 by
fluorescence in situ hybridization.
MOLECULAR GENETICS
In a family (family 1, previously described by Waggoner et al. (2002))
with dominantly inherited degeneration of muscle, bone, brain, and motor
neurons (IBMPFD2; 615422), Kim et al. (2013) identified a missense
mutation in the HNRNPA2B1 gene that altered a conserved aspartic acid at
position 290 of the short (A2) isoform and 302 of the long (B1) isoform
(600124.0001). Kim et al. (2013) showed that the intrinsic tendency of
HNRNPA2, the most abundant form of HNRNPA2B1, and HNRNPA1 (164017) to
assemble into self-seeding fibrils is exacerbated by disease mutations.
The pathogenic mutations strengthen a 'steric zipper' motif in the
prion-like domain (PrLD) that accelerates the formation of self-seeding
fibrils that cross-seed polymerization of wildtype HNRNP. Notably,
disease mutations promoted excess incorporation of HNRNPA2 and HNRNPA1
into stress granules and drove the formation of cytoplasmic inclusions
in animal models that recapitulated the human pathology. Kim et al.
(2013) concluded that dysregulated polymerization caused by a potent
mutant steric zipper motif in a PrLD can initiate degenerative disease.
*FIELD* AV
.0001
INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE AND FRONTOTEMPORAL
DEMENTIA 2 (1 family)
HNRNPA2B1, ASP290VAL
In affected members of a family (family 1) segregating autosomal
dominant inclusion body myopathy with Paget disease of the bone and
frontotemporal dementia (IBMPFD2; 615422), Kim et al. (2013) identified
an 869A-T transversion in the A2 isoform of the HNRNPA2B1 gene (905A-T
in the B1 isoform) resulting in an aspartic acid-to-valine substitution
at codon 290 (D290V; ASP302VAL, D302V in the B1 isoform). This was the
family originally reported by Waggoner et al. (2002). The aspartic acid
at this position is evolutionarily conserved to Drosophila, and is
centered in a motif, the prion-like domain (PrLD), that is conserved in
multiple human paralogs of the HNRNP A/B family. The mutation segregated
with the disease in the family and was not identified in the NHLBI Exome
Sequencing Project. In another family with a similar phenotype, Kim et
al. (2013) detected an aspartic acid-to-valine substitution at the
analogous residue of HNRNPA1 (164017.0001).
*FIELD* RF
1. Biamonti, G.; Ruggiu, M.; Saccone, S.; Della Valle, G.; Riva, S.
: Two homologous genes, originated by duplication, encode the human
hnRNP proteins A2 and A1. Nucleic Acids Res. 22: 1996-2002, 1994.
2. Burd, C. G.; Swanson, M. S.; Gorlach, M.; Dreyfuss, G.: Primary
structures of the heterogeneous nuclear ribonucleoprotein A2, B1,
and C2 proteins: a diversity of RNA binding proteins is generated
by small peptide inserts. Proc. Nat. Acad. Sci. 86: 9788-9792, 1989.
3. David, C. J.; Chen, M.; Assanah, M.; Canoll, P.; Manley, J. L.
: HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA
spicing in cancer. Nature 463: 364-368, 2010.
4. Hamilton, B. J.; Nichols, R. C.; Tsukamoto, H.; Boado, R. J.; Pardridge,
W. M.; Rigby, W. F. C.: hnRNP A2 and hnRNP L bind the 3-prime UTR
of glucose transporter 1 mRNA and exist as a complex in vivo. Biochem.
Biophys. Res. Commun. 261: 646-651, 1999.
5. Iwanaga, K.; Sueoka, N.; Sato, A.; Hayashi, S.; Sueoka, E.: Heterogeneous
nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through
the inhibition of DNA-dependent protein kinase activity. Biochem.
Biophys. Res. Commun. 333: 888-895, 2005.
6. Kim, H. J.; Kim, N. C.; Wang, Y.-D.; Scarborough, E. A.; Moore,
J.; Diaz, Z.; MacLea, K. S.; Freibaum, B.; Li, S.; Molliex, A.; and
25 others: Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1
cause multisystem proteinopathy and ALS. Nature 495: 467-473, 2013.
7. Kosturko, L. D.; Maggipinto, M. J.; Korza, G.; Lee, J. W.; Carson,
J. H.; Barbarese, E.: Heterogeneous nuclear ribonucleoprotein (hnRNP)
E1 binds to hnRNP A2 and inhibits translation of A2 response element
mRNAs. Molec. Biol. Cell 17: 3521-3533, 2006.
8. Kozu, T.; Henrich, B.; Schafer, K. P.: Structure and expression
of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1. Genomics 25:
365-371, 1995.
9. Moran-Jones, K.; Wayman, L.; Kennedy, D. D.; Reddel, R. R.; Sara,
S.; Snee, M. J.; Smith, R.: hnRNP A2, a potential ssDNA/RNA molecular
adapter at the telomere. Nucleic Acids Res. 33: 486-496, 2005.
10. Sofola, O. A.; Jin, P.; Qin, Y.; Duan, R.; Liu, H.; de Haro, M.;
Nelson, D. L.; Botas, J.: RNA-binding proteins hnRNP A2/B1 and CUGBP1
suppress fragile X CGG premutation repeat-induced neurodegeneration
in a Drosophila model of FXTAS. Neuron 55: 565-571, 2007.
11. Waggoner, B.; Kovach, M. J.; Winkelman, M.; Cai, D.; Khardori,
R.; Gelber, D.; Kimonis, V. E.: Heterogeneity in familial dominant
Paget disease of bone and muscular dystrophy. Am. J. Med. Genet. 108:
187-191, 2002.
*FIELD* CN
Ada Hamosh - updated: 9/24/2013
Ada Hamosh - updated: 2/18/2010
Patricia A. Hartz - updated: 9/10/2009
Alan F. Scott - edited: 12/9/1996
*FIELD* CD
Victor A. McKusick: 9/22/1994
*FIELD* ED
alopez: 01/15/2014
alopez: 10/18/2013
alopez: 9/24/2013
alopez: 2/24/2010
terry: 2/18/2010
mgross: 9/17/2009
terry: 9/10/2009
wwang: 8/27/2008
alopez: 6/10/2005
alopez: 6/13/1997
mark: 12/9/1996
mark: 2/2/1996
mark: 5/19/1995
carol: 10/13/1994
carol: 9/22/1994