Full text data of HNRNPA1
HNRNPA1
(HNRPA1)
[Confidence: low (only semi-automatic identification from reviews)]
Heterogeneous nuclear ribonucleoprotein A1; hnRNP A1 (Helix-destabilizing protein; Single-strand RNA-binding protein; hnRNP core protein A1; Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heterogeneous nuclear ribonucleoprotein A1; hnRNP A1 (Helix-destabilizing protein; Single-strand RNA-binding protein; hnRNP core protein A1; Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P09651
ID ROA1_HUMAN Reviewed; 372 AA.
AC P09651; A8K4Z8; Q3MIB7; Q6PJZ7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 09-FEB-2010, sequence version 5.
DT 22-JAN-2014, entry version 188.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein A1;
DE Short=hnRNP A1;
DE AltName: Full=Helix-destabilizing protein;
DE AltName: Full=Single-strand RNA-binding protein;
DE AltName: Full=hnRNP core protein A1;
DE Contains:
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed;
GN Name=HNRNPA1; Synonyms=HNRPA1;
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 [GENOMIC DNA] (ISOFORM A1-A).
RC TISSUE=Liver;
RX PubMed=2760922; DOI=10.1016/0022-2836(89)90459-2;
RA Biamonti G., Buvoli M., Bassi M.T., Morandi C., Cobianchi F., Riva S.;
RT "Isolation of an active gene encoding human hnRNP protein A1. Evidence
RT for alternative splicing.";
RL J. Mol. Biol. 207:491-503(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A1-A).
RC TISSUE=Fibroblast;
RX PubMed=2836799; DOI=10.1093/nar/16.9.3751;
RA Buvoli M., Biamonti G., Ghetti A., Riva S., Bassi M.T., Horandi C.;
RT "cDNA cloning of human hnRNP protein A1 reveals the existence of
RT multiple mRNA isoforms.";
RL Nucleic Acids Res. 16:3751-3770(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A1-A).
RC TISSUE=Lung;
RA Knudsen S.M., Leffers H.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A1-A).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A1-A AND 2).
RC TISSUE=Bone marrow, Cervix, Eye, Kidney, Liver, Lung, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3023065;
RA Riva S., Morandi C., Tsoulfas P., Pandolfo M., Biamonti G.,
RA Merrill B., Williams K.R., Multhaup G., Beyreuther K., Werr H.,
RA Heinrich B., Schaefer K.P.;
RT "Mammalian single-stranded DNA binding protein UP I is derived from
RT the hnRNP core protein A1.";
RL EMBO J. 5:2267-2273(1986).
RN [9]
RP PROTEIN SEQUENCE OF 2-47; 56-78; 93-140; 146-178; 197-232 AND 337-370,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, METHYLATION AT
RP ARG-206 AND ARG-225, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Calvo F., Lilla S., von Kriegsheim A., Lempens A.,
RA Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 15-47; 147-161 AND 353-370, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE OF 252-303 (ISOFORM A1-B).
RX PubMed=1691095;
RA Buvoli M., Cobianchi F., Bestagno M.G., Mangiarotti A., Bassi M.T.,
RA Biamonti G., Riva S.;
RT "Alternative splicing in the human gene for the core protein A1
RT generates another hnRNP protein.";
RL EMBO J. 9:1229-1235(1990).
RN [12]
RP NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF GLY-326; PRO-327 AND
RP 334-GLY-GLY-335.
RX PubMed=7730395; DOI=10.1083/jcb.129.3.551;
RA Siomi H., Dreyfuss G.;
RT "A nuclear localization domain in the hnRNP A1 protein.";
RL J. Cell Biol. 129:551-560(1995).
RN [13]
RP NUCLEAR LOCALIZATION SIGNAL, AND NUCLEAR EXPORT.
RX PubMed=8521471; DOI=10.1016/0092-8674(95)90119-1;
RA Michael W.M., Choi M., Dreyfuss G.;
RT "A nuclear export signal in hnRNP A1: a signal-mediated, temperature-
RT dependent nuclear protein export pathway.";
RL Cell 83:415-422(1995).
RN [14]
RP NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=7769000;
RA Weighardt F., Biamonti G., Riva S.;
RT "Nucleo-cytoplasmic distribution of human hnRNP proteins: a search for
RT the targeting domains in hnRNP A1.";
RL J. Cell Sci. 108:545-555(1995).
RN [15]
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 [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-194; ARG-206 AND ARG-225,
RP 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 [17]
RP SUMOYLATION AT LYS-113.
RX PubMed=15161980; DOI=10.1073/pnas.0402889101;
RA Li T., Evdokimov E., Shen R.F., Chao C.C., Tekle E., Wang T.,
RA Stadtman E.R., Yang D.C., Chock P.B.;
RT "Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger
RT proteins, and nuclear pore complex proteins: a proteomic analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8551-8556(2004).
RN [18]
RP PHOSPHORYLATION AT SER-192; SER-362; SER-363 AND SER-364 BY MKNK2.
RX PubMed=16111636; DOI=10.1016/j.immuni.2005.06.009;
RA Buxade M., Parra J.L., Rousseau S., Shpiro N., Marquez R., Morrice N.,
RA Bain J., Espel E., Proud C.G.;
RT "The Mnks are novel components in the control of TNF alpha
RT biosynthesis and phosphorylate and regulate hnRNP A1.";
RL Immunity 23:177-189(2005).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [21]
RP INTERACTION WITH SEPT6 AND HCV NS5B, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17229681; DOI=10.1128/JVI.01311-06;
RA Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.;
RT "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6,
RT facilitate hepatitis C virus replication.";
RL J. Virol. 81:3852-3865(2007).
RN [22]
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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-368, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
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 [26]
RP IDENTIFICATION BY 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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-3 AND LYS-350, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-4 AND SER-6, 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 [29]
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-6; SER-199;
RP SER-365 AND SER-368, 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 [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND SER-2, AND MASS
RP 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 [32]
RP 3D-STRUCTURE MODELING OF 107-190.
RX PubMed=2176620; DOI=10.1016/0014-5793(90)80863-E;
RA Ghetti A., Bolognesi M., Cobianchi F., Morandi C.;
RT "Modeling by homology of RNA binding domain in A1 hnRNP protein.";
RL FEBS Lett. 277:272-276(1990).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 9-181.
RX PubMed=9164463; DOI=10.1038/nsb0397-215;
RA Shamoo Y., Krueger U., Rice L.M., Williams K.R., Steitz T.A.;
RT "Crystal structure of the two RNA binding domains of human hnRNP A1 at
RT 1.75-A resolution.";
RL Nat. Struct. Biol. 4:215-222(1997).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 7-182.
RX PubMed=9115444; DOI=10.1016/S0969-2126(97)00211-6;
RA Xu R.M., Jokhan L., Cheng X., Mayeda A., Krainer A.R.;
RT "Crystal structure of human UP1, the domain of hnRNP A1 that contains
RT two RNA-recognition motifs.";
RL Structure 5:559-570(1997).
CC -!- FUNCTION: Involved in the packaging of pre-mRNA into hnRNP
CC particles, transport of poly(A) mRNA from the nucleus to the
CC cytoplasm and may modulate splice site selection. May play a role
CC in HCV RNA replication.
CC -!- SUBUNIT: Identified in the spliceosome C complex. Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated
CC mRNAs. Interacts with SEPT6. Interacts with HCV NS5B and with the
CC 5'-UTR and 3'-UTR of HCV RNA.
CC -!- INTERACTION:
CC Q07666:KHDRBS1; NbExp=2; IntAct=EBI-352662, EBI-1364;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs. Shuttles
CC continuously between the nucleus and the cytoplasm along with
CC mRNA. Component of ribonucleosomes. In the course of viral
CC infection, colocalizes with HCV NS5B at speckles in the cytoplasm
CC in a HCV-replication dependent manner.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A1-B;
CC IsoId=P09651-1; Sequence=Displayed;
CC Name=A1-A;
CC IsoId=P09651-2; Sequence=VSP_005824;
CC Note=Is twenty times more abundant than isoform A1-B;
CC Name=2;
CC IsoId=P09651-3; Sequence=VSP_034076;
CC Note=No experimental confirmation available;
CC -!- PTM: Arg-194, Arg-206 and Arg-225 are dimethylated, probably to
CC asymmetric dimethylarginine.
CC -!- PTM: Sumoylated.
CC -!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
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DR EMBL; X12671; CAA31191.1; -; Genomic_DNA.
DR EMBL; X06747; CAA29922.1; -; mRNA.
DR EMBL; X79536; CAA56072.1; -; mRNA.
DR EMBL; AK291113; BAF83802.1; -; mRNA.
DR EMBL; AC078778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96761.1; -; Genomic_DNA.
DR EMBL; BC002355; AAH02355.1; -; mRNA.
DR EMBL; BC009600; AAH09600.1; -; mRNA.
DR EMBL; BC012158; AAH12158.1; -; mRNA.
DR EMBL; BC033714; AAH33714.1; -; mRNA.
DR EMBL; BC052296; AAH52296.1; -; mRNA.
DR EMBL; BC070315; AAH70315.1; -; mRNA.
DR EMBL; BC074502; AAH74502.1; -; mRNA.
DR EMBL; BC103707; AAI03708.1; -; mRNA.
DR EMBL; X04347; CAA27874.1; -; mRNA.
DR PIR; S02061; S02061.
DR PIR; S12520; S12520.
DR RefSeq; NP_002127.1; NM_002136.2.
DR RefSeq; NP_112420.1; NM_031157.2.
DR RefSeq; XP_005268883.1; XM_005268826.1.
DR UniGene; Hs.546261; -.
DR UniGene; Hs.655424; -.
DR PDB; 1HA1; X-ray; 1.75 A; A=1-184.
DR PDB; 1L3K; X-ray; 1.10 A; A=1-196.
DR PDB; 1PGZ; X-ray; 2.60 A; A=2-195.
DR PDB; 1PO6; X-ray; 2.10 A; A=8-189.
DR PDB; 1U1K; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1L; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1M; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1N; X-ray; 2.10 A; A=1-196.
DR PDB; 1U1O; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1P; X-ray; 1.90 A; A=1-196.
DR PDB; 1U1Q; X-ray; 1.80 A; A=1-196.
DR PDB; 1U1R; X-ray; 1.80 A; A=1-196.
DR PDB; 1UP1; X-ray; 1.90 A; A=3-184.
DR PDB; 2H4M; X-ray; 3.05 A; C/D=309-357.
DR PDB; 2LYV; NMR; -; A=2-196.
DR PDB; 2UP1; X-ray; 2.10 A; A=8-190.
DR PDBsum; 1HA1; -.
DR PDBsum; 1L3K; -.
DR PDBsum; 1PGZ; -.
DR PDBsum; 1PO6; -.
DR PDBsum; 1U1K; -.
DR PDBsum; 1U1L; -.
DR PDBsum; 1U1M; -.
DR PDBsum; 1U1N; -.
DR PDBsum; 1U1O; -.
DR PDBsum; 1U1P; -.
DR PDBsum; 1U1Q; -.
DR PDBsum; 1U1R; -.
DR PDBsum; 1UP1; -.
DR PDBsum; 2H4M; -.
DR PDBsum; 2LYV; -.
DR PDBsum; 2UP1; -.
DR DisProt; DP00324; -.
DR ProteinModelPortal; P09651; -.
DR SMR; P09651; 8-190.
DR DIP; DIP-29338N; -.
DR IntAct; P09651; 102.
DR MINT; MINT-1035550; -.
DR STRING; 9606.ENSP00000341826; -.
DR BindingDB; P09651; -.
DR ChEMBL; CHEMBL1955709; -.
DR PhosphoSite; P09651; -.
DR DMDM; 288558857; -.
DR SWISS-2DPAGE; P09651; -.
DR PaxDb; P09651; -.
DR PRIDE; P09651; -.
DR Ensembl; ENST00000340913; ENSP00000341826; ENSG00000135486.
DR Ensembl; ENST00000546500; ENSP00000448617; ENSG00000135486.
DR Ensembl; ENST00000547276; ENSP00000447260; ENSG00000135486.
DR Ensembl; ENST00000547566; ENSP00000449913; ENSG00000135486.
DR GeneID; 3178; -.
DR KEGG; hsa:3178; -.
DR UCSC; uc001sfl.3; human.
DR CTD; 3178; -.
DR GeneCards; GC12P054674; -.
DR H-InvDB; HIX0032087; -.
DR H-InvDB; HIX0040127; -.
DR H-InvDB; HIX0202582; -.
DR HGNC; HGNC:5031; HNRNPA1.
DR HPA; CAB010894; -.
DR HPA; HPA001609; -.
DR HPA; HPA001666; -.
DR MIM; 164017; gene.
DR neXtProt; NX_P09651; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR PharmGKB; PA162391113; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000234442; -.
DR HOVERGEN; HBG002295; -.
DR InParanoid; P09651; -.
DR KO; K12741; -.
DR OMA; KIVNIVQ; -.
DR OrthoDB; EOG715Q6V; -.
DR PhylomeDB; P09651; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPA1; human.
DR EvolutionaryTrace; P09651; -.
DR GeneWiki; Heterogeneous_nuclear_ribonucleoprotein_A1; -.
DR GenomeRNAi; 3178; -.
DR NextBio; 12614; -.
DR PRO; PR:P09651; -.
DR ArrayExpress; P09651; -.
DR Bgee; P09651; -.
DR CleanEx; HS_HNRNPA1; -.
DR Genevestigator; P09651; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HGNC.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:HGNC.
DR GO; GO:0003727; F:single-stranded RNA binding; IC:HGNC.
DR GO; GO:0000380; P:alternative mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0051170; P:nuclear import; IDA:HGNC.
DR GO; GO:0006405; P:RNA export from nucleus; IC: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; 2.
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; Host-virus interaction;
KW Isopeptide bond; Methylation; mRNA processing; mRNA splicing;
KW mRNA transport; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Ribonucleoprotein; RNA-binding;
KW Spliceosome; Transport; Ubl conjugation.
FT CHAIN 1 372 Heterogeneous nuclear ribonucleoprotein
FT A1.
FT /FTId=PRO_0000424509.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 372 Heterogeneous nuclear ribonucleoprotein
FT A1, N-terminally processed.
FT /FTId=PRO_0000081828.
FT DOMAIN 14 97 RRM 1.
FT DOMAIN 105 184 RRM 2.
FT REGION 4 94 Globular A domain.
FT REGION 95 185 Globular B domain.
FT REGION 218 240 RNA-binding RGG-box.
FT REGION 320 357 Nuclear targeting sequence (M9).
FT COMPBIAS 195 372 Gly-rich.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylserine; in Heterogeneous nuclear
FT ribonucleoprotein A1, N-terminally
FT processed.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 3 3 N6-acetyllysine.
FT MOD_RES 4 4 Phosphoserine.
FT MOD_RES 6 6 Phosphoserine.
FT MOD_RES 192 192 Phosphoserine; by MKNK2.
FT MOD_RES 194 194 Asymmetric dimethylarginine; alternate
FT (By similarity).
FT MOD_RES 194 194 Dimethylated arginine; alternate.
FT MOD_RES 199 199 Phosphoserine.
FT MOD_RES 206 206 Dimethylated arginine; alternate.
FT MOD_RES 206 206 Omega-N-methylarginine; alternate.
FT MOD_RES 225 225 Dimethylated arginine; alternate.
FT MOD_RES 225 225 Omega-N-methylarginine; alternate.
FT MOD_RES 350 350 N6-acetyllysine.
FT MOD_RES 362 362 Phosphoserine; by MKNK2.
FT MOD_RES 363 363 Phosphoserine; by MKNK2.
FT MOD_RES 364 364 Phosphoserine; by MKNK2.
FT MOD_RES 365 365 Phosphoserine.
FT MOD_RES 368 368 Phosphoserine.
FT CROSSLNK 113 113 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 203 307 Missing (in isoform 2).
FT /FTId=VSP_034076.
FT VAR_SEQ 252 303 Missing (in isoform A1-A).
FT /FTId=VSP_005824.
FT VARIANT 73 73 N -> S (in dbSNP:rs6533).
FT /FTId=VAR_014711.
FT MUTAGEN 326 326 G->A: No nuclear import nor export.
FT MUTAGEN 327 327 P->A: No nuclear import nor export.
FT MUTAGEN 334 335 GG->LL: Normal nuclear import and export.
FT CONFLICT 128 128 Y -> F (in Ref. 2; CAA29922).
FT CONFLICT 140 140 R -> P (in Ref. 8; CAA27874).
FT CONFLICT 146 146 R -> K (in Ref. 2; CAA29922).
FT HELIX 11 14
FT STRAND 15 20
FT HELIX 27 34
FT HELIX 35 37
FT STRAND 40 47
FT TURN 49 51
FT STRAND 54 64
FT HELIX 65 73
FT STRAND 76 79
FT STRAND 85 88
FT HELIX 94 96
FT TURN 98 101
FT STRAND 105 110
FT TURN 113 115
FT HELIX 118 125
FT TURN 126 128
FT STRAND 131 138
FT TURN 140 142
FT STRAND 145 155
FT HELIX 156 164
FT STRAND 168 170
FT STRAND 176 179
FT HELIX 183 188
SQ SEQUENCE 372 AA; 38747 MW; A06683571C6C109F CRC64;
MSKSESPKEP EQLRKLFIGG LSFETTDESL RSHFEQWGTL TDCVVMRDPN TKRSRGFGFV
TYATVEEVDA AMNARPHKVD GRVVEPKRAV SREDSQRPGA HLTVKKIFVG GIKEDTEEHH
LRDYFEQYGK IEVIEIMTDR GSGKKRGFAF VTFDDHDSVD KIVIQKYHTV NGHNCEVRKA
LSKQEMASAS SSQRGRSGSG NFGGGRGGGF GGNDNFGRGG NFSGRGGFGG SRGGGGYGGS
GDGYNGFGND GGYGGGGPGY SGGSRGYGSG GQGYGNQGSG YGGSGSYDSY NNGGGGGFGG
GSGSNFGGGG SYNDFGNYNN QSSNFGPMKG GNFGGRSSGP YGGGGQYFAK PRNQGGYGGS
SSSSSYGSGR RF
//
ID ROA1_HUMAN Reviewed; 372 AA.
AC P09651; A8K4Z8; Q3MIB7; Q6PJZ7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 09-FEB-2010, sequence version 5.
DT 22-JAN-2014, entry version 188.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein A1;
DE Short=hnRNP A1;
DE AltName: Full=Helix-destabilizing protein;
DE AltName: Full=Single-strand RNA-binding protein;
DE AltName: Full=hnRNP core protein A1;
DE Contains:
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed;
GN Name=HNRNPA1; Synonyms=HNRPA1;
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 [GENOMIC DNA] (ISOFORM A1-A).
RC TISSUE=Liver;
RX PubMed=2760922; DOI=10.1016/0022-2836(89)90459-2;
RA Biamonti G., Buvoli M., Bassi M.T., Morandi C., Cobianchi F., Riva S.;
RT "Isolation of an active gene encoding human hnRNP protein A1. Evidence
RT for alternative splicing.";
RL J. Mol. Biol. 207:491-503(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A1-A).
RC TISSUE=Fibroblast;
RX PubMed=2836799; DOI=10.1093/nar/16.9.3751;
RA Buvoli M., Biamonti G., Ghetti A., Riva S., Bassi M.T., Horandi C.;
RT "cDNA cloning of human hnRNP protein A1 reveals the existence of
RT multiple mRNA isoforms.";
RL Nucleic Acids Res. 16:3751-3770(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A1-A).
RC TISSUE=Lung;
RA Knudsen S.M., Leffers H.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A1-A).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A1-A AND 2).
RC TISSUE=Bone marrow, Cervix, Eye, Kidney, Liver, Lung, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3023065;
RA Riva S., Morandi C., Tsoulfas P., Pandolfo M., Biamonti G.,
RA Merrill B., Williams K.R., Multhaup G., Beyreuther K., Werr H.,
RA Heinrich B., Schaefer K.P.;
RT "Mammalian single-stranded DNA binding protein UP I is derived from
RT the hnRNP core protein A1.";
RL EMBO J. 5:2267-2273(1986).
RN [9]
RP PROTEIN SEQUENCE OF 2-47; 56-78; 93-140; 146-178; 197-232 AND 337-370,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, METHYLATION AT
RP ARG-206 AND ARG-225, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Calvo F., Lilla S., von Kriegsheim A., Lempens A.,
RA Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 15-47; 147-161 AND 353-370, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE OF 252-303 (ISOFORM A1-B).
RX PubMed=1691095;
RA Buvoli M., Cobianchi F., Bestagno M.G., Mangiarotti A., Bassi M.T.,
RA Biamonti G., Riva S.;
RT "Alternative splicing in the human gene for the core protein A1
RT generates another hnRNP protein.";
RL EMBO J. 9:1229-1235(1990).
RN [12]
RP NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF GLY-326; PRO-327 AND
RP 334-GLY-GLY-335.
RX PubMed=7730395; DOI=10.1083/jcb.129.3.551;
RA Siomi H., Dreyfuss G.;
RT "A nuclear localization domain in the hnRNP A1 protein.";
RL J. Cell Biol. 129:551-560(1995).
RN [13]
RP NUCLEAR LOCALIZATION SIGNAL, AND NUCLEAR EXPORT.
RX PubMed=8521471; DOI=10.1016/0092-8674(95)90119-1;
RA Michael W.M., Choi M., Dreyfuss G.;
RT "A nuclear export signal in hnRNP A1: a signal-mediated, temperature-
RT dependent nuclear protein export pathway.";
RL Cell 83:415-422(1995).
RN [14]
RP NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=7769000;
RA Weighardt F., Biamonti G., Riva S.;
RT "Nucleo-cytoplasmic distribution of human hnRNP proteins: a search for
RT the targeting domains in hnRNP A1.";
RL J. Cell Sci. 108:545-555(1995).
RN [15]
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 [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-194; ARG-206 AND ARG-225,
RP 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 [17]
RP SUMOYLATION AT LYS-113.
RX PubMed=15161980; DOI=10.1073/pnas.0402889101;
RA Li T., Evdokimov E., Shen R.F., Chao C.C., Tekle E., Wang T.,
RA Stadtman E.R., Yang D.C., Chock P.B.;
RT "Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger
RT proteins, and nuclear pore complex proteins: a proteomic analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8551-8556(2004).
RN [18]
RP PHOSPHORYLATION AT SER-192; SER-362; SER-363 AND SER-364 BY MKNK2.
RX PubMed=16111636; DOI=10.1016/j.immuni.2005.06.009;
RA Buxade M., Parra J.L., Rousseau S., Shpiro N., Marquez R., Morrice N.,
RA Bain J., Espel E., Proud C.G.;
RT "The Mnks are novel components in the control of TNF alpha
RT biosynthesis and phosphorylate and regulate hnRNP A1.";
RL Immunity 23:177-189(2005).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [21]
RP INTERACTION WITH SEPT6 AND HCV NS5B, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17229681; DOI=10.1128/JVI.01311-06;
RA Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.;
RT "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6,
RT facilitate hepatitis C virus replication.";
RL J. Virol. 81:3852-3865(2007).
RN [22]
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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-368, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
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 [26]
RP IDENTIFICATION BY 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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-3 AND LYS-350, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-4 AND SER-6, 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 [29]
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-6; SER-199;
RP SER-365 AND SER-368, 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 [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND SER-2, AND MASS
RP 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 [32]
RP 3D-STRUCTURE MODELING OF 107-190.
RX PubMed=2176620; DOI=10.1016/0014-5793(90)80863-E;
RA Ghetti A., Bolognesi M., Cobianchi F., Morandi C.;
RT "Modeling by homology of RNA binding domain in A1 hnRNP protein.";
RL FEBS Lett. 277:272-276(1990).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 9-181.
RX PubMed=9164463; DOI=10.1038/nsb0397-215;
RA Shamoo Y., Krueger U., Rice L.M., Williams K.R., Steitz T.A.;
RT "Crystal structure of the two RNA binding domains of human hnRNP A1 at
RT 1.75-A resolution.";
RL Nat. Struct. Biol. 4:215-222(1997).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 7-182.
RX PubMed=9115444; DOI=10.1016/S0969-2126(97)00211-6;
RA Xu R.M., Jokhan L., Cheng X., Mayeda A., Krainer A.R.;
RT "Crystal structure of human UP1, the domain of hnRNP A1 that contains
RT two RNA-recognition motifs.";
RL Structure 5:559-570(1997).
CC -!- FUNCTION: Involved in the packaging of pre-mRNA into hnRNP
CC particles, transport of poly(A) mRNA from the nucleus to the
CC cytoplasm and may modulate splice site selection. May play a role
CC in HCV RNA replication.
CC -!- SUBUNIT: Identified in the spliceosome C complex. Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated
CC mRNAs. Interacts with SEPT6. Interacts with HCV NS5B and with the
CC 5'-UTR and 3'-UTR of HCV RNA.
CC -!- INTERACTION:
CC Q07666:KHDRBS1; NbExp=2; IntAct=EBI-352662, EBI-1364;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs. Shuttles
CC continuously between the nucleus and the cytoplasm along with
CC mRNA. Component of ribonucleosomes. In the course of viral
CC infection, colocalizes with HCV NS5B at speckles in the cytoplasm
CC in a HCV-replication dependent manner.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A1-B;
CC IsoId=P09651-1; Sequence=Displayed;
CC Name=A1-A;
CC IsoId=P09651-2; Sequence=VSP_005824;
CC Note=Is twenty times more abundant than isoform A1-B;
CC Name=2;
CC IsoId=P09651-3; Sequence=VSP_034076;
CC Note=No experimental confirmation available;
CC -!- PTM: Arg-194, Arg-206 and Arg-225 are dimethylated, probably to
CC asymmetric dimethylarginine.
CC -!- PTM: Sumoylated.
CC -!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
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DR EMBL; X12671; CAA31191.1; -; Genomic_DNA.
DR EMBL; X06747; CAA29922.1; -; mRNA.
DR EMBL; X79536; CAA56072.1; -; mRNA.
DR EMBL; AK291113; BAF83802.1; -; mRNA.
DR EMBL; AC078778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96761.1; -; Genomic_DNA.
DR EMBL; BC002355; AAH02355.1; -; mRNA.
DR EMBL; BC009600; AAH09600.1; -; mRNA.
DR EMBL; BC012158; AAH12158.1; -; mRNA.
DR EMBL; BC033714; AAH33714.1; -; mRNA.
DR EMBL; BC052296; AAH52296.1; -; mRNA.
DR EMBL; BC070315; AAH70315.1; -; mRNA.
DR EMBL; BC074502; AAH74502.1; -; mRNA.
DR EMBL; BC103707; AAI03708.1; -; mRNA.
DR EMBL; X04347; CAA27874.1; -; mRNA.
DR PIR; S02061; S02061.
DR PIR; S12520; S12520.
DR RefSeq; NP_002127.1; NM_002136.2.
DR RefSeq; NP_112420.1; NM_031157.2.
DR RefSeq; XP_005268883.1; XM_005268826.1.
DR UniGene; Hs.546261; -.
DR UniGene; Hs.655424; -.
DR PDB; 1HA1; X-ray; 1.75 A; A=1-184.
DR PDB; 1L3K; X-ray; 1.10 A; A=1-196.
DR PDB; 1PGZ; X-ray; 2.60 A; A=2-195.
DR PDB; 1PO6; X-ray; 2.10 A; A=8-189.
DR PDB; 1U1K; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1L; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1M; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1N; X-ray; 2.10 A; A=1-196.
DR PDB; 1U1O; X-ray; 2.00 A; A=1-196.
DR PDB; 1U1P; X-ray; 1.90 A; A=1-196.
DR PDB; 1U1Q; X-ray; 1.80 A; A=1-196.
DR PDB; 1U1R; X-ray; 1.80 A; A=1-196.
DR PDB; 1UP1; X-ray; 1.90 A; A=3-184.
DR PDB; 2H4M; X-ray; 3.05 A; C/D=309-357.
DR PDB; 2LYV; NMR; -; A=2-196.
DR PDB; 2UP1; X-ray; 2.10 A; A=8-190.
DR PDBsum; 1HA1; -.
DR PDBsum; 1L3K; -.
DR PDBsum; 1PGZ; -.
DR PDBsum; 1PO6; -.
DR PDBsum; 1U1K; -.
DR PDBsum; 1U1L; -.
DR PDBsum; 1U1M; -.
DR PDBsum; 1U1N; -.
DR PDBsum; 1U1O; -.
DR PDBsum; 1U1P; -.
DR PDBsum; 1U1Q; -.
DR PDBsum; 1U1R; -.
DR PDBsum; 1UP1; -.
DR PDBsum; 2H4M; -.
DR PDBsum; 2LYV; -.
DR PDBsum; 2UP1; -.
DR DisProt; DP00324; -.
DR ProteinModelPortal; P09651; -.
DR SMR; P09651; 8-190.
DR DIP; DIP-29338N; -.
DR IntAct; P09651; 102.
DR MINT; MINT-1035550; -.
DR STRING; 9606.ENSP00000341826; -.
DR BindingDB; P09651; -.
DR ChEMBL; CHEMBL1955709; -.
DR PhosphoSite; P09651; -.
DR DMDM; 288558857; -.
DR SWISS-2DPAGE; P09651; -.
DR PaxDb; P09651; -.
DR PRIDE; P09651; -.
DR Ensembl; ENST00000340913; ENSP00000341826; ENSG00000135486.
DR Ensembl; ENST00000546500; ENSP00000448617; ENSG00000135486.
DR Ensembl; ENST00000547276; ENSP00000447260; ENSG00000135486.
DR Ensembl; ENST00000547566; ENSP00000449913; ENSG00000135486.
DR GeneID; 3178; -.
DR KEGG; hsa:3178; -.
DR UCSC; uc001sfl.3; human.
DR CTD; 3178; -.
DR GeneCards; GC12P054674; -.
DR H-InvDB; HIX0032087; -.
DR H-InvDB; HIX0040127; -.
DR H-InvDB; HIX0202582; -.
DR HGNC; HGNC:5031; HNRNPA1.
DR HPA; CAB010894; -.
DR HPA; HPA001609; -.
DR HPA; HPA001666; -.
DR MIM; 164017; gene.
DR neXtProt; NX_P09651; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR PharmGKB; PA162391113; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000234442; -.
DR HOVERGEN; HBG002295; -.
DR InParanoid; P09651; -.
DR KO; K12741; -.
DR OMA; KIVNIVQ; -.
DR OrthoDB; EOG715Q6V; -.
DR PhylomeDB; P09651; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPA1; human.
DR EvolutionaryTrace; P09651; -.
DR GeneWiki; Heterogeneous_nuclear_ribonucleoprotein_A1; -.
DR GenomeRNAi; 3178; -.
DR NextBio; 12614; -.
DR PRO; PR:P09651; -.
DR ArrayExpress; P09651; -.
DR Bgee; P09651; -.
DR CleanEx; HS_HNRNPA1; -.
DR Genevestigator; P09651; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HGNC.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:HGNC.
DR GO; GO:0003727; F:single-stranded RNA binding; IC:HGNC.
DR GO; GO:0000380; P:alternative mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0051170; P:nuclear import; IDA:HGNC.
DR GO; GO:0006405; P:RNA export from nucleus; IC: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; 2.
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; Host-virus interaction;
KW Isopeptide bond; Methylation; mRNA processing; mRNA splicing;
KW mRNA transport; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Ribonucleoprotein; RNA-binding;
KW Spliceosome; Transport; Ubl conjugation.
FT CHAIN 1 372 Heterogeneous nuclear ribonucleoprotein
FT A1.
FT /FTId=PRO_0000424509.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 372 Heterogeneous nuclear ribonucleoprotein
FT A1, N-terminally processed.
FT /FTId=PRO_0000081828.
FT DOMAIN 14 97 RRM 1.
FT DOMAIN 105 184 RRM 2.
FT REGION 4 94 Globular A domain.
FT REGION 95 185 Globular B domain.
FT REGION 218 240 RNA-binding RGG-box.
FT REGION 320 357 Nuclear targeting sequence (M9).
FT COMPBIAS 195 372 Gly-rich.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylserine; in Heterogeneous nuclear
FT ribonucleoprotein A1, N-terminally
FT processed.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 3 3 N6-acetyllysine.
FT MOD_RES 4 4 Phosphoserine.
FT MOD_RES 6 6 Phosphoserine.
FT MOD_RES 192 192 Phosphoserine; by MKNK2.
FT MOD_RES 194 194 Asymmetric dimethylarginine; alternate
FT (By similarity).
FT MOD_RES 194 194 Dimethylated arginine; alternate.
FT MOD_RES 199 199 Phosphoserine.
FT MOD_RES 206 206 Dimethylated arginine; alternate.
FT MOD_RES 206 206 Omega-N-methylarginine; alternate.
FT MOD_RES 225 225 Dimethylated arginine; alternate.
FT MOD_RES 225 225 Omega-N-methylarginine; alternate.
FT MOD_RES 350 350 N6-acetyllysine.
FT MOD_RES 362 362 Phosphoserine; by MKNK2.
FT MOD_RES 363 363 Phosphoserine; by MKNK2.
FT MOD_RES 364 364 Phosphoserine; by MKNK2.
FT MOD_RES 365 365 Phosphoserine.
FT MOD_RES 368 368 Phosphoserine.
FT CROSSLNK 113 113 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 203 307 Missing (in isoform 2).
FT /FTId=VSP_034076.
FT VAR_SEQ 252 303 Missing (in isoform A1-A).
FT /FTId=VSP_005824.
FT VARIANT 73 73 N -> S (in dbSNP:rs6533).
FT /FTId=VAR_014711.
FT MUTAGEN 326 326 G->A: No nuclear import nor export.
FT MUTAGEN 327 327 P->A: No nuclear import nor export.
FT MUTAGEN 334 335 GG->LL: Normal nuclear import and export.
FT CONFLICT 128 128 Y -> F (in Ref. 2; CAA29922).
FT CONFLICT 140 140 R -> P (in Ref. 8; CAA27874).
FT CONFLICT 146 146 R -> K (in Ref. 2; CAA29922).
FT HELIX 11 14
FT STRAND 15 20
FT HELIX 27 34
FT HELIX 35 37
FT STRAND 40 47
FT TURN 49 51
FT STRAND 54 64
FT HELIX 65 73
FT STRAND 76 79
FT STRAND 85 88
FT HELIX 94 96
FT TURN 98 101
FT STRAND 105 110
FT TURN 113 115
FT HELIX 118 125
FT TURN 126 128
FT STRAND 131 138
FT TURN 140 142
FT STRAND 145 155
FT HELIX 156 164
FT STRAND 168 170
FT STRAND 176 179
FT HELIX 183 188
SQ SEQUENCE 372 AA; 38747 MW; A06683571C6C109F CRC64;
MSKSESPKEP EQLRKLFIGG LSFETTDESL RSHFEQWGTL TDCVVMRDPN TKRSRGFGFV
TYATVEEVDA AMNARPHKVD GRVVEPKRAV SREDSQRPGA HLTVKKIFVG GIKEDTEEHH
LRDYFEQYGK IEVIEIMTDR GSGKKRGFAF VTFDDHDSVD KIVIQKYHTV NGHNCEVRKA
LSKQEMASAS SSQRGRSGSG NFGGGRGGGF GGNDNFGRGG NFSGRGGFGG SRGGGGYGGS
GDGYNGFGND GGYGGGGPGY SGGSRGYGSG GQGYGNQGSG YGGSGSYDSY NNGGGGGFGG
GSGSNFGGGG SYNDFGNYNN QSSNFGPMKG GNFGGRSSGP YGGGGQYFAK PRNQGGYGGS
SSSSSYGSGR RF
//
MIM
164017
*RECORD*
*FIELD* NO
164017
*FIELD* TI
*164017 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A1; HNRNPA1
;;HNRPA1;;
NUCLEAR RIBONUCLEOPROTEIN PARTICLE A1 PROTEIN
read more*FIELD* TX
CLONING
In eukaryotic cells, nascent RNA polymerase II transcripts are
associated in the nucleus with specific proteins to form
ribonucleoprotein complexes called HNRP or 40S. Protein moiety of the
40S particle has 6 major components called core proteins, A1/A2, B1/B2,
and C1/C2, plus a number of other proteins. Buvoli et al. (1988)
isolated and sequenced the cDNA for human HNRPA1.
GENE STRUCTURE
Biamonti et al. (1989) isolated an active HNRNPA1 gene. The gene
contains 10 exons and spans 4.6 kb.
MAPPING
By nonisotopic in situ hybridization using a phage genomic clone that
contained the active HNRNPA1 gene as well as 13.5-kb flanking sequences,
Saccone et al. (1992) mapped the gene to chromosome 12q13.1. To suppress
hybridization to pseudogene sequences, unlabeled HNRNPA1 cDNA was added
in excess over the probe to the hybridization mixture.
GENE FUNCTION
Michael et al. (1995) reported that HNRPA1 shuttles continuously between
the nucleus and cytoplasm and contains a 38-amino acid domain, termed
M9, that acts as both a nuclear localization and nuclear export signal.
They suggested that HNRPA1 and other shuttling hnRNPs function as
carriers for RNA during export to the cytoplasm.
Pollard et al. (2000) sought to determine if the nuclear concentrations
of the trans-acting splicing regulators SF2/ASF (600812) and HNRNPA1 and
its splice variant, HNRNPA1B, are fundamental in regulating the
expression of specific protein isoforms derived from alternative
splicing of single pre-mRNA transcripts. SF2/ASF and HNRNPA1/A1B
expression was determined in paired upper (corpus) and lower segment
myometrial samples taken from individual women at term or during
spontaneous labor and compared with nonpregnant control samples using
specific monoclonal antibodies. SF2/ASF levels were substantially
increased in the lower uterine region, and this was associated with a
parallel decrease in levels of HNRNPA1/A1B during gestation. Conversely,
the opposite pattern was observed within the upper uterine region during
pregnancy, where HNRNPA1/A1B was significantly upregulated and SF2/ASF
levels were much lower than those found in the lower uterine segment.
The authors concluded that differential expression of HNRNPA1/A1B and
SF2/ASF in the upper and lower uterine segments may have a primary role
in defining the formation of specific myometrial protein species
associated with the known contractile and relaxatory properties of these
regions before and during parturition.
Kashima et al. (2007) identified a high-affinity HNRNPA1-binding site
near exon 7 of the SMN2 gene (601627) and showed that HNRNPA1 promoted
skipping of this exon. Depletion of HNRNPA1 and HNRNPA2 (600124) in HeLa
cells restored exon 7 inclusion. Kashima et al. (2007) showed that
disease-related exon-skipping mutations in BRCA1 (113705) and FBN1
(134797) introduced identical high-affinity HNRNPA1-binding sites.
HNRNPA1 and HNRNPA2 depletion had no effect on splicing of mutant BRCA1,
but it partially rescued splicing in FBN1. Kashima et al. (2007)
concluded that HNRNPA1 functions as a splice site repressor.
Using coimmunoprecipitation analysis, Kim et al. (2007) found that the
hepatitis C virus (HCV; see 609532) NS5b RNA polymerase interacted with
HNRPA1. HNRPA1 also interacted with another NS5b-binding protein, SEPT6
(300683), suggesting the existence of a trimolecular complex. Knockdown
of either HNRPA1 or SEPT6 inhibited HCV replication.
David et al. (2010) showed that 3 heterogeneous nuclear
ribonucleoprotein (hnRNP) proteins, polypyrimidine tract-binding protein
(PTB, also known as hnRNPI; 600693), hnRNPA1, and hnRNPA2 (600124), bind
repressively to sequences flanking exon 9 of the PKM2 gene (179050),
resulting in exon 10 inclusion and the expression of the PKM2
(embryonic) isoform of muscle pyruvate kinase. 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.
Maintenance of telomeres requires both DNA replication and telomere
capping by shelterin. These 2 processes use 2 single-stranded DNA
(ssDNA)-binding proteins, replication protein A (RPA; see 179835) and
protection of telomeres-1 (POT1; 606478). POT1 ablation leads to
activation of the ataxia-telangiectasia and Rad3-related checkpoint
kinase (ATR; 601215) at telomeres, suggesting that POT1 antagonizes RPA
binding to telomeric ssDNA. Unexpectedly, Flynn et al. (2011) found that
purified POT1 and its functional partner TPP1 (609377) are unable to
prevent RPA binding to telomeric ssDNA efficiently. In cell extracts,
they identified a novel activity that specifically displaces RPA, but
not POT1, from telomeric ssDNA. Using purified protein, Flynn et al.
(2011) showed that hnRNPA1 recapitulates the RPA displacing activity.
The RPA displacing activity is inhibited by the telomeric
repeat-containing RNA (TERRA) in early S phase, but is then unleashed in
late S phase when TERRA levels decline at telomeres. Interestingly,
TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1,
suggesting that the reaccumulation of TERRA after S phase helps to
complete the RPA-to-POT1 switch on telomeric ssDNA. Flynn et al. (2011)
concluded that hnRNPA1, TERRA, and POT1 act in concert to displace RPA
from telomeric ssDNA after DNA replication, and promote telomere capping
to preserve genomic integrity.
Kim et al. (2013) reported that HNRNPA1 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 HNRNPA1 has an intrinsic tendency to assemble into
self-seeding fibrils.
GENE FAMILY
Buvoli et al. (1988) demonstrated by Southern analysis that
HNRPA1-specific sequences are present in the human genome as a multigene
family of about 30 members, most of them corresponding to pseudogenes of
the processed type.
New World primates show relative target organ resistance to adrenal,
gonadal, and vitamin D sterol/steroid hormones. This occurs in the
absence of abnormal expression of cognate nuclear receptors. Rather,
these animals have elevated levels of heterogeneous nuclear
ribonucleoproteins (hnRNPs) that act as hormone response element-binding
proteins and attenuate target gene transactivation. Chen et al. (2003)
presented evidence for a similar mechanism in humans through study of a
patient with resistance to the active form of vitamin D who presented
with normal vitamin D receptor (VDR; 601769) expression. The patient
presented with skeletal abnormalities and biochemical features
classically associated with vitamin D-resistant rickets (277440). These
included hypocalcemia, raised serum alkaline phosphatase, and raised
circulating levels of 1,25-dihydroxyvitamin D3. Initial cotransfection
studies showed that the cells of the patient suppressed basal and
hormone-induced transactivation by wildtype VDR. Electrophoretic
mobility-shift assays and Western/Southwestern blot analyses indicated
that this suppressive effect was due to overexpression of a nuclear
protein that specifically interacted with a DNA response element known
to bind retinoid X receptor (see 180247)-VDR heterodimers. Antibody
blocking in electrophoretic mobility-shift assays indicated that this
dominant-negative-acting protein was in the hnRNPA family of nucleic
acid-binding proteins. Further studies showed that several members of
this family, most notably HNRNPA1, were able to suppress basal and
1,25-dihydroxyvitamin D3-induced luciferase activity. Therefore, Chen et
al. (2003) proposed that vitamin D resistance in the patient was similar
to that described in New World primates, in which abnormal expression of
a hormone response element-binding protein can cause target cell
resistance to vitamin D. That this protein is a member of the hnRNP
family capable of interacting with double-stranded DNA highlights a
potentially important new component of the complex machinery required
for steroid hormone signal transduction.
MOLECULAR GENETICS
Kim et al. (2013) identified missense mutations in the HNRNPA1 gene in a
family (family 2, originally described by Kottlors et al. (2010)) with
an autosomal dominant multisystem proteinopathy (IBMPFD3; 615424).
Different changes in the same domain resulted in autosomal dominant
familial amyotrophic lateral sclerosis (ALS20; 615426).
*FIELD* AV
.0001
INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE WITHOUT FRONTOTEMPORAL
DEMENTIA 3 (1 family)
HNRNPA1, ASP314VAL
In a family (family 2) with autosomal dominant inclusion body myopathy
and Paget disease of the bone (IBMPFD3; 615424) originally described by
Kottlors et al. (2010), Kim et al. (2013) identified an A-to-T
transversion at nucleotide 941 in the long isoform of HNRNPA1 (785 in
the short isoform) resulting in an aspartic acid-to-valine substitution
at codon 314 (D314V; ASP262V, D262V of the short isoform). This mutation
was not identified in the NHLBI Exome Sequencing Project and changed an
aspartic acid conserved through Drosophila that is centered in a motif,
the prion-like domain (PrLD), that is conserved in multiple human
paralogs of the human HNRNPA/B family. The mutation was predicted to
enhance prion-like behavior.
.0002
AMYOTROPHIC LATERAL SCLEROSIS 20
HNRNPA1, ASP314ASN
In a family segregating autosomal dominant ALS (ALS20; 615426), Kim et
al. (2013) identified a heterozygous G-to-A transition at nucleotide 940
of the long isoform of HNRNPA1 (784 of the short isoform) that resulted
in an aspartic acid-to-asparagine substitution at codon 314 (D314N;
ASP262ASN, D262N in the short isoform). This mutation replaced the same
highly conserved aspartic acid that was substituted in patients with
IBMPFD3 (see 164017.0001). This mutation was not identified in the NHLBI
Exome Sequencing Project.
.0003
AMYOTROPHIC LATERAL SCLEROSIS 20
HNRNPA1, ASN319SER
In an individual with sporadic classic late-onset amyotrophic lateral
sclerosis (ALS20; 615426), Kim et al. (2013) detected heterozygosity for
an A-to-G transition at nucleotide 956 of the long isoform of HNRNPA1
(800 of the short isoform) that resulted in an asparagine-to-serine
substitution at codon 319 (N319S; ASN267SER, N267S in the short
isoform). This variant is centered in the core PrLD of HNRNPA1 and
introduces a potent steric zipper that accelerates the formation of
pathogenic fibrillization.
*FIELD* RF
1. Biamonti, G.; Buvoli, M.; Bassi, M. T.; Morandi, C.; Cobianchi,
F.; Riva, S.: Isolation of an active gene encoding human hnRNP protein
A1: evidence for alternative splicing. J. Molec. Biol. 207: 491-503,
1989.
2. Buvoli, M.; Biamonti, G.; Tsoulfas, P.; Bassi, M. T.; Ghetti, A.;
Riva, S.; Morandi, C.: cDNA cloning of human hnRNP protein A1 reveals
the existence of multiple mRNA isoforms. Nucleic Acids Res. 16:
3751-3770, 1988.
3. Chen, H.; Hewison, M.; Hu, B.; Adams, J. S.: Heterogeneous nuclear
ribonucleoprotein (hnRNP) binding to hormone response elements: a
cause of vitamin D resistance. Proc. Nat. Acad. Sci. 100: 6109-6114,
2003.
4. 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.
5. Flynn, R. L.; Centore, R. C.; O'Sullivan, R. J.; Rai, R.; Tse,
A.; Songyang, Z.; Chang, S.; Karlseder, J.; Zou, L.: TERRA and hnRNPA1
orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471:
532-536, 2011.
6. Kashima, T.; Rao, N.; David, C. J.; Manley, J. L.: hnRNP A1 functions
with specificity in repression of SMN2 exon 7 splicing. Hum. Molec.
Genet. 16: 3149-3159, 2007.
7. Kim, C. S.; Seol, S. K.; Song, O.-K.; Park, J. H.; Jang, S. K.
: An RNA-binding protein, hnRNP A1, and a scaffold protein, septin
6, facilitate hepatitis C virus replication. J. Virol. 81: 3852-3865,
2007.
8. 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.
9. Kottlors, M.; Moske-Eick, O.; Huebner, A.; Krause, S.; Mueller,
K.; Kress, W.; Schwarzwald, R.; Bornemann, A.; Haug, V.; Heitzer,
M.; Kirschner, J.: Late-onset autosomal dominant limb girdle muscular
dystrophy and Paget's disease of bone unlinked to the VCP gene locus. J.
Neurol. Sci. 291: 79-85, 2010.
10. Michael, W. M.; Choi, M.; Dreyfuss, G.: A nuclear export signal
in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein
export pathway. Cell 83: 415-422, 1995.
11. Pollard, A. J.; Sparey, C.; Robson, S. C.; Krainer, A. R.; Europe-Finner,
G. N.: Spatio-temporal expression of the trans-acting splicing factors
SF2/ASF and heterogeneous ribonuclear proteins A1/A1B in the myometrium
of the pregnant human uterus: a molecular mechanism for regulating
regional protein isoform expression in vivo. J. Clin. Endocr. Metab. 85:
1928-1936, 2000.
12. Saccone, S.; Biamonti, G.; Maugeri, S.; Bassi, M. T.; Bunone,
G.; Riva, S.; Della Valle, G.: Assignment of the human heterogeneous
nuclear ribonucleoprotein A1 gene (HNRPA1) to chromosome 12q13.1 by
cDNA competitive in situ hybridization. Genomics 12: 171-174, 1992.
*FIELD* CN
Ada Hamosh - updated: 9/24/2013
Ada Hamosh - updated: 5/9/2011
Ada Hamosh - updated: 2/18/2010
Patricia A. Hartz - updated: 10/14/2009
Paul J. Converse - updated: 10/25/2007
Victor A. McKusick - updated: 6/19/2003
John A. Phillips, III - updated: 2/13/2001
Rebekah S. Rasooly - updated: 7/29/1998
*FIELD* CD
Victor A. McKusick: 1/12/1990
*FIELD* ED
alopez: 01/15/2014
carol: 11/5/2013
alopez: 9/24/2013
alopez: 5/12/2011
terry: 5/9/2011
alopez: 2/24/2010
terry: 2/18/2010
mgross: 10/26/2009
terry: 10/14/2009
wwang: 8/27/2008
mgross: 10/30/2007
terry: 10/25/2007
alopez: 6/27/2003
terry: 6/19/2003
mgross: 3/5/2001
terry: 2/13/2001
alopez: 6/25/1999
alopez: 7/29/1998
mark: 2/2/1996
supermim: 3/16/1992
carol: 1/6/1992
supermim: 3/20/1990
supermim: 1/12/1990
*RECORD*
*FIELD* NO
164017
*FIELD* TI
*164017 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A1; HNRNPA1
;;HNRPA1;;
NUCLEAR RIBONUCLEOPROTEIN PARTICLE A1 PROTEIN
read more*FIELD* TX
CLONING
In eukaryotic cells, nascent RNA polymerase II transcripts are
associated in the nucleus with specific proteins to form
ribonucleoprotein complexes called HNRP or 40S. Protein moiety of the
40S particle has 6 major components called core proteins, A1/A2, B1/B2,
and C1/C2, plus a number of other proteins. Buvoli et al. (1988)
isolated and sequenced the cDNA for human HNRPA1.
GENE STRUCTURE
Biamonti et al. (1989) isolated an active HNRNPA1 gene. The gene
contains 10 exons and spans 4.6 kb.
MAPPING
By nonisotopic in situ hybridization using a phage genomic clone that
contained the active HNRNPA1 gene as well as 13.5-kb flanking sequences,
Saccone et al. (1992) mapped the gene to chromosome 12q13.1. To suppress
hybridization to pseudogene sequences, unlabeled HNRNPA1 cDNA was added
in excess over the probe to the hybridization mixture.
GENE FUNCTION
Michael et al. (1995) reported that HNRPA1 shuttles continuously between
the nucleus and cytoplasm and contains a 38-amino acid domain, termed
M9, that acts as both a nuclear localization and nuclear export signal.
They suggested that HNRPA1 and other shuttling hnRNPs function as
carriers for RNA during export to the cytoplasm.
Pollard et al. (2000) sought to determine if the nuclear concentrations
of the trans-acting splicing regulators SF2/ASF (600812) and HNRNPA1 and
its splice variant, HNRNPA1B, are fundamental in regulating the
expression of specific protein isoforms derived from alternative
splicing of single pre-mRNA transcripts. SF2/ASF and HNRNPA1/A1B
expression was determined in paired upper (corpus) and lower segment
myometrial samples taken from individual women at term or during
spontaneous labor and compared with nonpregnant control samples using
specific monoclonal antibodies. SF2/ASF levels were substantially
increased in the lower uterine region, and this was associated with a
parallel decrease in levels of HNRNPA1/A1B during gestation. Conversely,
the opposite pattern was observed within the upper uterine region during
pregnancy, where HNRNPA1/A1B was significantly upregulated and SF2/ASF
levels were much lower than those found in the lower uterine segment.
The authors concluded that differential expression of HNRNPA1/A1B and
SF2/ASF in the upper and lower uterine segments may have a primary role
in defining the formation of specific myometrial protein species
associated with the known contractile and relaxatory properties of these
regions before and during parturition.
Kashima et al. (2007) identified a high-affinity HNRNPA1-binding site
near exon 7 of the SMN2 gene (601627) and showed that HNRNPA1 promoted
skipping of this exon. Depletion of HNRNPA1 and HNRNPA2 (600124) in HeLa
cells restored exon 7 inclusion. Kashima et al. (2007) showed that
disease-related exon-skipping mutations in BRCA1 (113705) and FBN1
(134797) introduced identical high-affinity HNRNPA1-binding sites.
HNRNPA1 and HNRNPA2 depletion had no effect on splicing of mutant BRCA1,
but it partially rescued splicing in FBN1. Kashima et al. (2007)
concluded that HNRNPA1 functions as a splice site repressor.
Using coimmunoprecipitation analysis, Kim et al. (2007) found that the
hepatitis C virus (HCV; see 609532) NS5b RNA polymerase interacted with
HNRPA1. HNRPA1 also interacted with another NS5b-binding protein, SEPT6
(300683), suggesting the existence of a trimolecular complex. Knockdown
of either HNRPA1 or SEPT6 inhibited HCV replication.
David et al. (2010) showed that 3 heterogeneous nuclear
ribonucleoprotein (hnRNP) proteins, polypyrimidine tract-binding protein
(PTB, also known as hnRNPI; 600693), hnRNPA1, and hnRNPA2 (600124), bind
repressively to sequences flanking exon 9 of the PKM2 gene (179050),
resulting in exon 10 inclusion and the expression of the PKM2
(embryonic) isoform of muscle pyruvate kinase. 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.
Maintenance of telomeres requires both DNA replication and telomere
capping by shelterin. These 2 processes use 2 single-stranded DNA
(ssDNA)-binding proteins, replication protein A (RPA; see 179835) and
protection of telomeres-1 (POT1; 606478). POT1 ablation leads to
activation of the ataxia-telangiectasia and Rad3-related checkpoint
kinase (ATR; 601215) at telomeres, suggesting that POT1 antagonizes RPA
binding to telomeric ssDNA. Unexpectedly, Flynn et al. (2011) found that
purified POT1 and its functional partner TPP1 (609377) are unable to
prevent RPA binding to telomeric ssDNA efficiently. In cell extracts,
they identified a novel activity that specifically displaces RPA, but
not POT1, from telomeric ssDNA. Using purified protein, Flynn et al.
(2011) showed that hnRNPA1 recapitulates the RPA displacing activity.
The RPA displacing activity is inhibited by the telomeric
repeat-containing RNA (TERRA) in early S phase, but is then unleashed in
late S phase when TERRA levels decline at telomeres. Interestingly,
TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1,
suggesting that the reaccumulation of TERRA after S phase helps to
complete the RPA-to-POT1 switch on telomeric ssDNA. Flynn et al. (2011)
concluded that hnRNPA1, TERRA, and POT1 act in concert to displace RPA
from telomeric ssDNA after DNA replication, and promote telomere capping
to preserve genomic integrity.
Kim et al. (2013) reported that HNRNPA1 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 HNRNPA1 has an intrinsic tendency to assemble into
self-seeding fibrils.
GENE FAMILY
Buvoli et al. (1988) demonstrated by Southern analysis that
HNRPA1-specific sequences are present in the human genome as a multigene
family of about 30 members, most of them corresponding to pseudogenes of
the processed type.
New World primates show relative target organ resistance to adrenal,
gonadal, and vitamin D sterol/steroid hormones. This occurs in the
absence of abnormal expression of cognate nuclear receptors. Rather,
these animals have elevated levels of heterogeneous nuclear
ribonucleoproteins (hnRNPs) that act as hormone response element-binding
proteins and attenuate target gene transactivation. Chen et al. (2003)
presented evidence for a similar mechanism in humans through study of a
patient with resistance to the active form of vitamin D who presented
with normal vitamin D receptor (VDR; 601769) expression. The patient
presented with skeletal abnormalities and biochemical features
classically associated with vitamin D-resistant rickets (277440). These
included hypocalcemia, raised serum alkaline phosphatase, and raised
circulating levels of 1,25-dihydroxyvitamin D3. Initial cotransfection
studies showed that the cells of the patient suppressed basal and
hormone-induced transactivation by wildtype VDR. Electrophoretic
mobility-shift assays and Western/Southwestern blot analyses indicated
that this suppressive effect was due to overexpression of a nuclear
protein that specifically interacted with a DNA response element known
to bind retinoid X receptor (see 180247)-VDR heterodimers. Antibody
blocking in electrophoretic mobility-shift assays indicated that this
dominant-negative-acting protein was in the hnRNPA family of nucleic
acid-binding proteins. Further studies showed that several members of
this family, most notably HNRNPA1, were able to suppress basal and
1,25-dihydroxyvitamin D3-induced luciferase activity. Therefore, Chen et
al. (2003) proposed that vitamin D resistance in the patient was similar
to that described in New World primates, in which abnormal expression of
a hormone response element-binding protein can cause target cell
resistance to vitamin D. That this protein is a member of the hnRNP
family capable of interacting with double-stranded DNA highlights a
potentially important new component of the complex machinery required
for steroid hormone signal transduction.
MOLECULAR GENETICS
Kim et al. (2013) identified missense mutations in the HNRNPA1 gene in a
family (family 2, originally described by Kottlors et al. (2010)) with
an autosomal dominant multisystem proteinopathy (IBMPFD3; 615424).
Different changes in the same domain resulted in autosomal dominant
familial amyotrophic lateral sclerosis (ALS20; 615426).
*FIELD* AV
.0001
INCLUSION BODY MYOPATHY WITH EARLY-ONSET PAGET DISEASE WITHOUT FRONTOTEMPORAL
DEMENTIA 3 (1 family)
HNRNPA1, ASP314VAL
In a family (family 2) with autosomal dominant inclusion body myopathy
and Paget disease of the bone (IBMPFD3; 615424) originally described by
Kottlors et al. (2010), Kim et al. (2013) identified an A-to-T
transversion at nucleotide 941 in the long isoform of HNRNPA1 (785 in
the short isoform) resulting in an aspartic acid-to-valine substitution
at codon 314 (D314V; ASP262V, D262V of the short isoform). This mutation
was not identified in the NHLBI Exome Sequencing Project and changed an
aspartic acid conserved through Drosophila that is centered in a motif,
the prion-like domain (PrLD), that is conserved in multiple human
paralogs of the human HNRNPA/B family. The mutation was predicted to
enhance prion-like behavior.
.0002
AMYOTROPHIC LATERAL SCLEROSIS 20
HNRNPA1, ASP314ASN
In a family segregating autosomal dominant ALS (ALS20; 615426), Kim et
al. (2013) identified a heterozygous G-to-A transition at nucleotide 940
of the long isoform of HNRNPA1 (784 of the short isoform) that resulted
in an aspartic acid-to-asparagine substitution at codon 314 (D314N;
ASP262ASN, D262N in the short isoform). This mutation replaced the same
highly conserved aspartic acid that was substituted in patients with
IBMPFD3 (see 164017.0001). This mutation was not identified in the NHLBI
Exome Sequencing Project.
.0003
AMYOTROPHIC LATERAL SCLEROSIS 20
HNRNPA1, ASN319SER
In an individual with sporadic classic late-onset amyotrophic lateral
sclerosis (ALS20; 615426), Kim et al. (2013) detected heterozygosity for
an A-to-G transition at nucleotide 956 of the long isoform of HNRNPA1
(800 of the short isoform) that resulted in an asparagine-to-serine
substitution at codon 319 (N319S; ASN267SER, N267S in the short
isoform). This variant is centered in the core PrLD of HNRNPA1 and
introduces a potent steric zipper that accelerates the formation of
pathogenic fibrillization.
*FIELD* RF
1. Biamonti, G.; Buvoli, M.; Bassi, M. T.; Morandi, C.; Cobianchi,
F.; Riva, S.: Isolation of an active gene encoding human hnRNP protein
A1: evidence for alternative splicing. J. Molec. Biol. 207: 491-503,
1989.
2. Buvoli, M.; Biamonti, G.; Tsoulfas, P.; Bassi, M. T.; Ghetti, A.;
Riva, S.; Morandi, C.: cDNA cloning of human hnRNP protein A1 reveals
the existence of multiple mRNA isoforms. Nucleic Acids Res. 16:
3751-3770, 1988.
3. Chen, H.; Hewison, M.; Hu, B.; Adams, J. S.: Heterogeneous nuclear
ribonucleoprotein (hnRNP) binding to hormone response elements: a
cause of vitamin D resistance. Proc. Nat. Acad. Sci. 100: 6109-6114,
2003.
4. 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.
5. Flynn, R. L.; Centore, R. C.; O'Sullivan, R. J.; Rai, R.; Tse,
A.; Songyang, Z.; Chang, S.; Karlseder, J.; Zou, L.: TERRA and hnRNPA1
orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471:
532-536, 2011.
6. Kashima, T.; Rao, N.; David, C. J.; Manley, J. L.: hnRNP A1 functions
with specificity in repression of SMN2 exon 7 splicing. Hum. Molec.
Genet. 16: 3149-3159, 2007.
7. Kim, C. S.; Seol, S. K.; Song, O.-K.; Park, J. H.; Jang, S. K.
: An RNA-binding protein, hnRNP A1, and a scaffold protein, septin
6, facilitate hepatitis C virus replication. J. Virol. 81: 3852-3865,
2007.
8. 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.
9. Kottlors, M.; Moske-Eick, O.; Huebner, A.; Krause, S.; Mueller,
K.; Kress, W.; Schwarzwald, R.; Bornemann, A.; Haug, V.; Heitzer,
M.; Kirschner, J.: Late-onset autosomal dominant limb girdle muscular
dystrophy and Paget's disease of bone unlinked to the VCP gene locus. J.
Neurol. Sci. 291: 79-85, 2010.
10. Michael, W. M.; Choi, M.; Dreyfuss, G.: A nuclear export signal
in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein
export pathway. Cell 83: 415-422, 1995.
11. Pollard, A. J.; Sparey, C.; Robson, S. C.; Krainer, A. R.; Europe-Finner,
G. N.: Spatio-temporal expression of the trans-acting splicing factors
SF2/ASF and heterogeneous ribonuclear proteins A1/A1B in the myometrium
of the pregnant human uterus: a molecular mechanism for regulating
regional protein isoform expression in vivo. J. Clin. Endocr. Metab. 85:
1928-1936, 2000.
12. Saccone, S.; Biamonti, G.; Maugeri, S.; Bassi, M. T.; Bunone,
G.; Riva, S.; Della Valle, G.: Assignment of the human heterogeneous
nuclear ribonucleoprotein A1 gene (HNRPA1) to chromosome 12q13.1 by
cDNA competitive in situ hybridization. Genomics 12: 171-174, 1992.
*FIELD* CN
Ada Hamosh - updated: 9/24/2013
Ada Hamosh - updated: 5/9/2011
Ada Hamosh - updated: 2/18/2010
Patricia A. Hartz - updated: 10/14/2009
Paul J. Converse - updated: 10/25/2007
Victor A. McKusick - updated: 6/19/2003
John A. Phillips, III - updated: 2/13/2001
Rebekah S. Rasooly - updated: 7/29/1998
*FIELD* CD
Victor A. McKusick: 1/12/1990
*FIELD* ED
alopez: 01/15/2014
carol: 11/5/2013
alopez: 9/24/2013
alopez: 5/12/2011
terry: 5/9/2011
alopez: 2/24/2010
terry: 2/18/2010
mgross: 10/26/2009
terry: 10/14/2009
wwang: 8/27/2008
mgross: 10/30/2007
terry: 10/25/2007
alopez: 6/27/2003
terry: 6/19/2003
mgross: 3/5/2001
terry: 2/13/2001
alopez: 6/25/1999
alopez: 7/29/1998
mark: 2/2/1996
supermim: 3/16/1992
carol: 1/6/1992
supermim: 3/20/1990
supermim: 1/12/1990