Full text data of HNRNPD
HNRNPD
(AUF1, HNRPD)
[Confidence: low (only semi-automatic identification from reviews)]
Heterogeneous nuclear ribonucleoprotein D0; hnRNP D0 (AU-rich element RNA-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heterogeneous nuclear ribonucleoprotein D0; hnRNP D0 (AU-rich element RNA-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q14103
ID HNRPD_HUMAN Reviewed; 355 AA.
AC Q14103; A8K9J2; P07029; Q01858; Q14100; Q14101; Q14102; Q4W5A1;
read moreAC Q9UCE8; Q9UCE9;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 164.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein D0;
DE Short=hnRNP D0;
DE AltName: Full=AU-rich element RNA-binding protein 1;
GN Name=HNRNPD; Synonyms=AUF1, HNRPD;
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 1 AND 3), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 70-355 (ISOFORM 2).
RC TISSUE=Cervix carcinoma;
RX PubMed=7673195; DOI=10.1074/jbc.270.38.22167;
RA Kajita Y., Nakayama J., Aizawa M., Ishikawa F.;
RT "The UUAG-specific RNA binding protein, heterogeneous nuclear
RT ribonucleoprotein D0. Common modular structure and binding properties
RT of the 2xRBD-Gly family.";
RL J. Biol. Chem. 270:22167-22175(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=9615222; DOI=10.1006/geno.1998.5237;
RA Dempsey L.A., Li M.-J., DePace A., Bray-Ward P., Maizels N.;
RT "The human HNRPD locus maps to 4q21 and encodes a highly conserved
RT protein.";
RL Genomics 49:378-384(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-235.
RX PubMed=3754960; DOI=10.1093/nar/14.10.4077;
RA Lahiri D.K., Thomas J.O.;
RT "A cDNA clone of the hnRNP C proteins and its homology with the
RT single-stranded DNA binding protein UP2.";
RL Nucleic Acids Res. 14:4077-4094(1986).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-355 (ISOFORM 3), AND CHARACTERIZATION.
RC TISSUE=Blood;
RX PubMed=10024518; DOI=10.1042/0264-6021:3380417;
RA Tolnay M., Vereshchagina L.A., Tsokos G.C.;
RT "Heterogeneous nuclear ribonucleoprotein D0B is a sequence-specific
RT DNA-binding protein.";
RL Biochem. J. 338:417-425(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-355 (ISOFORM 3).
RX PubMed=1433497;
RA Tay N., Chan S.-H., Ren E.-C.;
RT "Identification and cloning of a novel heterogeneous nuclear
RT ribonucleoprotein C-like protein that functions as a transcriptional
RT activator of the hepatitis B virus enhancer II.";
RL J. Virol. 66:6841-6848(1992).
RN [10]
RP PROTEIN SEQUENCE OF 68-85; 99-110; 112-129; 139-158; 184-218; 224-231
RP AND 261-272, METHYLATION AT LYS-119, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 139-157; 184-203 AND 224-237, AND
RP NUCLEOTIDE-BINDING.
RC TISSUE=Cervix carcinoma;
RX PubMed=8321232;
RA Ishikawa F., Matunis M.J., Dreyfuss G., Cech T.R.;
RT "Nuclear proteins that bind the pre-mRNA 3' splice site sequence
RT r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n.";
RL Mol. Cell. Biol. 13:4301-4310(1993).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 4).
RX PubMed=9521873; DOI=10.1006/geno.1997.5142;
RA Wagner B.J., DeMaria C.T., Sun Y., Wilson G.M., Brewer G.;
RT "Structure and genomic organization of the human AUF1 gene:
RT alternative pre-mRNA splicing generates four protein isoforms.";
RL Genomics 48:195-202(1998).
RN [13]
RP FUNCTION IN TRANSLATIONALLY COUPLED MRNA TURNOVER, AND IDENTIFICATION
RP IN A COMPLEX WITH SYNCRIP; PABPC1; PAIP1 AND CSDE1.
RC TISSUE=Placenta;
RX PubMed=11051545; DOI=10.1016/S0092-8674(00)00102-1;
RA Grosset C., Chen C.-Y.A., Xu N., Sonenberg N., Jacquemin-Sablon H.,
RA Shyu A.-B.;
RT "A mechanism for translationally coupled mRNA turnover: interaction
RT between the poly(A) tail and a c-fos RNA coding determinant via a
RT protein complex.";
RL Cell 103:29-40(2000).
RN [14]
RP INTERACTION WITH IGF2BP2.
RX PubMed=12674497; DOI=10.1515/BC.2003.004;
RA Moraes K.C., Quaresma A.J., Maehnss K., Kobarg J.;
RT "Identification and characterization of proteins that selectively
RT interact with isoforms of the mRNA binding protein AUF1 (hnRNP D).";
RL Biol. Chem. 384:25-37(2003).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-345, 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-190, AND MASS
RP SPECTROMETRY.
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 [17]
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 [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-193, 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-83; SER-190 AND
RP THR-193, 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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [22]
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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-190 AND THR-193,
RP 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 [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165 AND LYS-251, ACETYLATION
RP [LARGE SCALE ANALYSIS] AT LYS-292 (ISOFORM 3), ACETYLATION [LARGE
RP SCALE ANALYSIS] AT LYS-273 (ISOFORM 4), AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71; SER-80; SER-83;
RP SER-190 AND THR-193, 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 [27]
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 [28]
RP INTERACTION WITH GTPBP1.
RX PubMed=21515746; DOI=10.1096/fj.10-178715;
RA Woo K.C., Kim T.D., Lee K.H., Kim D.Y., Kim S., Lee H.R., Kang H.J.,
RA Chung S.J., Senju S., Nishimura Y., Kim K.T.;
RT "Modulation of exosome-mediated mRNA turnover by interaction of GTP-
RT binding protein 1 (GTPBP1) with its target mRNAs.";
RL FASEB J. 25:2757-2769(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80; SER-83 AND SER-190,
RP 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 [30]
RP STRUCTURE BY NMR OF 98-172, AND FUNCTION.
RX PubMed=10080887; DOI=10.1006/jmbi.1999.2616;
RA Nagata T., Kurihara Y., Matsuda G., Saeki J., Kohno T., Yanagida Y.,
RA Ishikawa F., Uesugi S., Katahira M.;
RT "Structure and interactions with RNA of the N-terminal UUAG-specific
RT RNA-binding domain of hnRNP D0.";
RL J. Mol. Biol. 287:221-237(1999).
CC -!- FUNCTION: Binds with high affinity to RNA molecules that contain
CC AU-rich elements (AREs) found within the 3'-UTR of many proto-
CC oncogenes and cytokine mRNAs. Also binds to double- and single-
CC stranded DNA sequences in a specific manner and functions a
CC transcription factor. Each of the RNA-binding domains specifically
CC can bind solely to a single-stranded non-monotonous 5'-UUAG-3'
CC sequence and also weaker to the single-stranded 5'-TTAGGG-3'
CC telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3'
CC repeats more tightly than the telomeric single-stranded DNA 5'-
CC TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation
CC of DNA quadruplex structure which may play a role in telomere
CC elongation. May be involved in translationally coupled mRNA
CC turnover. Implicated with other RNA-binding proteins in the
CC cytoplasmic deadenylation/translational and decay interplay of the
CC FOS mRNA mediated by the major coding-region determinant of
CC instability (mCRD) domain.
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs. Part of a complex associated with
CC the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR and
CC SYNCRIP. Interacts with IGF2BP2. Interacts with GTPBP1.
CC -!- INTERACTION:
CC Q04637:EIF4G1; NbExp=3; IntAct=EBI-432545, EBI-73711;
CC Q9Y6M1:IGF2BP2; NbExp=4; IntAct=EBI-432545, EBI-1024419;
CC Q9UNL4:ING4; NbExp=9; IntAct=EBI-299674, EBI-2866661;
CC Q9BYZ2:LDHAL6B; NbExp=2; IntAct=EBI-299674, EBI-1108377;
CC P11940:PABPC1; NbExp=2; IntAct=EBI-432545, EBI-81531;
CC P31947:SFN; NbExp=7; IntAct=EBI-432545, EBI-476295;
CC O60506:SYNCRIP; NbExp=3; IntAct=EBI-432545, EBI-1024357;
CC P67809:YBX1; NbExp=3; IntAct=EBI-432545, EBI-354065;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs. Component
CC of ribonucleosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=p45, Dx9;
CC IsoId=Q14103-1; Sequence=Displayed;
CC Name=2; Synonyms=p42, Dx4;
CC IsoId=Q14103-2; Sequence=VSP_005834;
CC Name=3; Synonyms=p40, Dx7;
CC IsoId=Q14103-3; Sequence=VSP_005835;
CC Note=Contains a N6-acetyllysine at position 292;
CC Name=4; Synonyms=p37;
CC IsoId=Q14103-4; Sequence=VSP_005834, VSP_005835;
CC Note=Contains a N6-acetyllysine at position 273;
CC -!- PTM: Arg-345 is dimethylated, probably to asymmetric
CC dimethylarginine.
CC -!- PTM: Methylated by PRMT1, in an insulin-dependent manner. The
CC PRMT1-mediated methylation regulates tyrosine phosphorylation (By
CC similarity).
CC -!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35781.1; Type=Frameshift; Positions=45, 59, 355;
CC Sequence=AAA35781.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part;
CC Sequence=CAA27544.1; Type=Miscellaneous discrepancy; Note=Several sequence conflicts;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HNRNPDID40840ch4q21.html";
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DR EMBL; D55671; BAA09522.1; -; mRNA.
DR EMBL; D55672; BAA09523.1; -; mRNA.
DR EMBL; D55673; BAA09524.1; -; mRNA.
DR EMBL; D55674; BAA09525.1; -; mRNA.
DR EMBL; AF026126; AAC23474.1; -; Genomic_DNA.
DR EMBL; AF026126; AAC23475.1; -; Genomic_DNA.
DR EMBL; AF026126; AAC23476.1; -; Genomic_DNA.
DR EMBL; AK292707; BAF85396.1; -; mRNA.
DR EMBL; AC124016; AAY40913.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX05874.1; -; Genomic_DNA.
DR EMBL; BC002401; AAH02401.1; -; mRNA.
DR EMBL; BC023977; AAH23977.1; -; mRNA.
DR EMBL; BC026015; AAH26015.1; -; mRNA.
DR EMBL; X03910; CAA27544.1; ALT_SEQ; mRNA.
DR EMBL; AF039575; AAB96683.1; -; mRNA.
DR EMBL; M94630; AAA35781.1; ALT_SEQ; mRNA.
DR PIR; A24016; A24016.
DR PIR; A44192; A44192.
DR PIR; B48138; B48138.
DR RefSeq; NP_001003810.1; NM_001003810.1.
DR RefSeq; NP_002129.2; NM_002138.3.
DR RefSeq; NP_112737.1; NM_031369.2.
DR RefSeq; NP_112738.1; NM_031370.2.
DR UniGene; Hs.480073; -.
DR PDB; 1HD0; NMR; -; A=98-172.
DR PDB; 1HD1; NMR; -; A=98-172.
DR PDB; 1IQT; NMR; -; A=183-257.
DR PDB; 1WTB; NMR; -; A=181-259.
DR PDB; 1X0F; NMR; -; A=181-259.
DR PDB; 2Z5N; X-ray; 3.20 A; B=332-355.
DR PDBsum; 1HD0; -.
DR PDBsum; 1HD1; -.
DR PDBsum; 1IQT; -.
DR PDBsum; 1WTB; -.
DR PDBsum; 1X0F; -.
DR PDBsum; 2Z5N; -.
DR ProteinModelPortal; Q14103; -.
DR SMR; Q14103; 98-259.
DR IntAct; Q14103; 51.
DR MINT; MINT-5001251; -.
DR PhosphoSite; Q14103; -.
DR DMDM; 13124489; -.
DR SWISS-2DPAGE; Q14103; -.
DR PaxDb; Q14103; -.
DR PRIDE; Q14103; -.
DR DNASU; 3184; -.
DR Ensembl; ENST00000313899; ENSP00000313199; ENSG00000138668.
DR Ensembl; ENST00000352301; ENSP00000305860; ENSG00000138668.
DR Ensembl; ENST00000353341; ENSP00000313327; ENSG00000138668.
DR GeneID; 3184; -.
DR KEGG; hsa:3184; -.
DR UCSC; uc003hmm.1; human.
DR CTD; 3184; -.
DR GeneCards; GC04M083274; -.
DR HGNC; HGNC:5036; HNRNPD.
DR HPA; HPA004911; -.
DR MIM; 601324; gene.
DR neXtProt; NX_Q14103; -.
DR PharmGKB; PA29361; -.
DR eggNOG; COG0724; -.
DR HOVERGEN; HBG002295; -.
DR InParanoid; Q14103; -.
DR KO; K13044; -.
DR OMA; DYNDQSG; -.
DR OrthoDB; EOG715Q6V; -.
DR PhylomeDB; Q14103; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPD; human.
DR EvolutionaryTrace; Q14103; -.
DR GeneWiki; HNRPD; -.
DR GenomeRNAi; 3184; -.
DR NextBio; 12644; -.
DR PMAP-CutDB; Q14103; -.
DR PRO; PR:Q14103; -.
DR ArrayExpress; Q14103; -.
DR Bgee; Q14103; -.
DR Genevestigator; Q14103; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IEA:Ensembl.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012956; CARG-binding_factor_N.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF08143; CBFNT; 1.
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; DNA-binding; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ribonucleoprotein; RNA-binding; Transcription;
KW Transcription regulation.
FT CHAIN 1 355 Heterogeneous nuclear ribonucleoprotein
FT D0.
FT /FTId=PRO_0000081849.
FT DOMAIN 97 179 RRM 1.
FT DOMAIN 182 261 RRM 2.
FT COMPBIAS 11 45 Ala-rich.
FT COMPBIAS 270 347 Gly-rich.
FT COMPBIAS 294 332 Tyr-rich.
FT MOD_RES 71 71 Phosphoserine.
FT MOD_RES 80 80 Phosphoserine.
FT MOD_RES 82 82 Phosphoserine.
FT MOD_RES 83 83 Phosphoserine.
FT MOD_RES 119 119 N6-methyllysine.
FT MOD_RES 165 165 N6-acetyllysine.
FT MOD_RES 190 190 Phosphoserine.
FT MOD_RES 193 193 Phosphothreonine.
FT MOD_RES 251 251 N6-acetyllysine.
FT MOD_RES 345 345 Dimethylated arginine.
FT VAR_SEQ 79 97 Missing (in isoform 2 and isoform 4).
FT /FTId=VSP_005834.
FT VAR_SEQ 285 334 GPSQNWNQGYSNYWNQGYGNYGYNSQGYGGYGGYDYTGYNN
FT YYGYGDYSN -> D (in isoform 3 and isoform
FT 4).
FT /FTId=VSP_005835.
FT CONFLICT 150 150 S -> R (in Ref. 11; AA sequence).
FT CONFLICT 225 225 F -> L (in Ref. 9; AAA35781).
FT STRAND 99 102
FT HELIX 110 118
FT STRAND 123 127
FT TURN 132 135
FT STRAND 139 147
FT HELIX 148 156
FT STRAND 168 170
FT STRAND 184 187
FT HELIX 195 205
FT STRAND 209 211
FT TURN 217 219
FT STRAND 220 222
FT STRAND 226 229
FT STRAND 231 233
FT HELIX 234 240
FT STRAND 244 247
FT STRAND 250 253
FT STRAND 254 256
FT STRAND 349 351
SQ SEQUENCE 355 AA; 38434 MW; D0B6EA177BEF789E CRC64;
MSEEQFGGDG AAAAATAAVG GSAGEQEGAM VAATQGAAAA AGSGAGTGGG TASGGTEGGS
AESEGAKIDA SKNEEDEGHS NSSPRHSEAA TAQREEWKMF IGGLSWDTTK KDLKDYFSKF
GEVVDCTLKL DPITGRSRGF GFVLFKESES VDKVMDQKEH KLNGKVIDPK RAKAMKTKEP
VKKIFVGGLS PDTPEEKIRE YFGGFGEVES IELPMDNKTN KRRGFCFITF KEEEPVKKIM
EKKYHNVGLS KCEIKVAMSK EQYQQQQQWG SRGGFAGRAR GRGGGPSQNW NQGYSNYWNQ
GYGNYGYNSQ GYGGYGGYDY TGYNNYYGYG DYSNQQSGYG KVSRRGGHQN SYKPY
//
ID HNRPD_HUMAN Reviewed; 355 AA.
AC Q14103; A8K9J2; P07029; Q01858; Q14100; Q14101; Q14102; Q4W5A1;
read moreAC Q9UCE8; Q9UCE9;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 164.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein D0;
DE Short=hnRNP D0;
DE AltName: Full=AU-rich element RNA-binding protein 1;
GN Name=HNRNPD; Synonyms=AUF1, HNRPD;
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 1 AND 3), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 70-355 (ISOFORM 2).
RC TISSUE=Cervix carcinoma;
RX PubMed=7673195; DOI=10.1074/jbc.270.38.22167;
RA Kajita Y., Nakayama J., Aizawa M., Ishikawa F.;
RT "The UUAG-specific RNA binding protein, heterogeneous nuclear
RT ribonucleoprotein D0. Common modular structure and binding properties
RT of the 2xRBD-Gly family.";
RL J. Biol. Chem. 270:22167-22175(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=9615222; DOI=10.1006/geno.1998.5237;
RA Dempsey L.A., Li M.-J., DePace A., Bray-Ward P., Maizels N.;
RT "The human HNRPD locus maps to 4q21 and encodes a highly conserved
RT protein.";
RL Genomics 49:378-384(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-235.
RX PubMed=3754960; DOI=10.1093/nar/14.10.4077;
RA Lahiri D.K., Thomas J.O.;
RT "A cDNA clone of the hnRNP C proteins and its homology with the
RT single-stranded DNA binding protein UP2.";
RL Nucleic Acids Res. 14:4077-4094(1986).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-355 (ISOFORM 3), AND CHARACTERIZATION.
RC TISSUE=Blood;
RX PubMed=10024518; DOI=10.1042/0264-6021:3380417;
RA Tolnay M., Vereshchagina L.A., Tsokos G.C.;
RT "Heterogeneous nuclear ribonucleoprotein D0B is a sequence-specific
RT DNA-binding protein.";
RL Biochem. J. 338:417-425(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-355 (ISOFORM 3).
RX PubMed=1433497;
RA Tay N., Chan S.-H., Ren E.-C.;
RT "Identification and cloning of a novel heterogeneous nuclear
RT ribonucleoprotein C-like protein that functions as a transcriptional
RT activator of the hepatitis B virus enhancer II.";
RL J. Virol. 66:6841-6848(1992).
RN [10]
RP PROTEIN SEQUENCE OF 68-85; 99-110; 112-129; 139-158; 184-218; 224-231
RP AND 261-272, METHYLATION AT LYS-119, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 139-157; 184-203 AND 224-237, AND
RP NUCLEOTIDE-BINDING.
RC TISSUE=Cervix carcinoma;
RX PubMed=8321232;
RA Ishikawa F., Matunis M.J., Dreyfuss G., Cech T.R.;
RT "Nuclear proteins that bind the pre-mRNA 3' splice site sequence
RT r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n.";
RL Mol. Cell. Biol. 13:4301-4310(1993).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 4).
RX PubMed=9521873; DOI=10.1006/geno.1997.5142;
RA Wagner B.J., DeMaria C.T., Sun Y., Wilson G.M., Brewer G.;
RT "Structure and genomic organization of the human AUF1 gene:
RT alternative pre-mRNA splicing generates four protein isoforms.";
RL Genomics 48:195-202(1998).
RN [13]
RP FUNCTION IN TRANSLATIONALLY COUPLED MRNA TURNOVER, AND IDENTIFICATION
RP IN A COMPLEX WITH SYNCRIP; PABPC1; PAIP1 AND CSDE1.
RC TISSUE=Placenta;
RX PubMed=11051545; DOI=10.1016/S0092-8674(00)00102-1;
RA Grosset C., Chen C.-Y.A., Xu N., Sonenberg N., Jacquemin-Sablon H.,
RA Shyu A.-B.;
RT "A mechanism for translationally coupled mRNA turnover: interaction
RT between the poly(A) tail and a c-fos RNA coding determinant via a
RT protein complex.";
RL Cell 103:29-40(2000).
RN [14]
RP INTERACTION WITH IGF2BP2.
RX PubMed=12674497; DOI=10.1515/BC.2003.004;
RA Moraes K.C., Quaresma A.J., Maehnss K., Kobarg J.;
RT "Identification and characterization of proteins that selectively
RT interact with isoforms of the mRNA binding protein AUF1 (hnRNP D).";
RL Biol. Chem. 384:25-37(2003).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-345, 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-190, AND MASS
RP SPECTROMETRY.
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 [17]
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 [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-193, 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-83; SER-190 AND
RP THR-193, 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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [22]
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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-190 AND THR-193,
RP 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 [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165 AND LYS-251, ACETYLATION
RP [LARGE SCALE ANALYSIS] AT LYS-292 (ISOFORM 3), ACETYLATION [LARGE
RP SCALE ANALYSIS] AT LYS-273 (ISOFORM 4), AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71; SER-80; SER-83;
RP SER-190 AND THR-193, 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 [27]
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 [28]
RP INTERACTION WITH GTPBP1.
RX PubMed=21515746; DOI=10.1096/fj.10-178715;
RA Woo K.C., Kim T.D., Lee K.H., Kim D.Y., Kim S., Lee H.R., Kang H.J.,
RA Chung S.J., Senju S., Nishimura Y., Kim K.T.;
RT "Modulation of exosome-mediated mRNA turnover by interaction of GTP-
RT binding protein 1 (GTPBP1) with its target mRNAs.";
RL FASEB J. 25:2757-2769(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80; SER-83 AND SER-190,
RP 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 [30]
RP STRUCTURE BY NMR OF 98-172, AND FUNCTION.
RX PubMed=10080887; DOI=10.1006/jmbi.1999.2616;
RA Nagata T., Kurihara Y., Matsuda G., Saeki J., Kohno T., Yanagida Y.,
RA Ishikawa F., Uesugi S., Katahira M.;
RT "Structure and interactions with RNA of the N-terminal UUAG-specific
RT RNA-binding domain of hnRNP D0.";
RL J. Mol. Biol. 287:221-237(1999).
CC -!- FUNCTION: Binds with high affinity to RNA molecules that contain
CC AU-rich elements (AREs) found within the 3'-UTR of many proto-
CC oncogenes and cytokine mRNAs. Also binds to double- and single-
CC stranded DNA sequences in a specific manner and functions a
CC transcription factor. Each of the RNA-binding domains specifically
CC can bind solely to a single-stranded non-monotonous 5'-UUAG-3'
CC sequence and also weaker to the single-stranded 5'-TTAGGG-3'
CC telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3'
CC repeats more tightly than the telomeric single-stranded DNA 5'-
CC TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation
CC of DNA quadruplex structure which may play a role in telomere
CC elongation. May be involved in translationally coupled mRNA
CC turnover. Implicated with other RNA-binding proteins in the
CC cytoplasmic deadenylation/translational and decay interplay of the
CC FOS mRNA mediated by the major coding-region determinant of
CC instability (mCRD) domain.
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs. Part of a complex associated with
CC the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR and
CC SYNCRIP. Interacts with IGF2BP2. Interacts with GTPBP1.
CC -!- INTERACTION:
CC Q04637:EIF4G1; NbExp=3; IntAct=EBI-432545, EBI-73711;
CC Q9Y6M1:IGF2BP2; NbExp=4; IntAct=EBI-432545, EBI-1024419;
CC Q9UNL4:ING4; NbExp=9; IntAct=EBI-299674, EBI-2866661;
CC Q9BYZ2:LDHAL6B; NbExp=2; IntAct=EBI-299674, EBI-1108377;
CC P11940:PABPC1; NbExp=2; IntAct=EBI-432545, EBI-81531;
CC P31947:SFN; NbExp=7; IntAct=EBI-432545, EBI-476295;
CC O60506:SYNCRIP; NbExp=3; IntAct=EBI-432545, EBI-1024357;
CC P67809:YBX1; NbExp=3; IntAct=EBI-432545, EBI-354065;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs. Component
CC of ribonucleosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=p45, Dx9;
CC IsoId=Q14103-1; Sequence=Displayed;
CC Name=2; Synonyms=p42, Dx4;
CC IsoId=Q14103-2; Sequence=VSP_005834;
CC Name=3; Synonyms=p40, Dx7;
CC IsoId=Q14103-3; Sequence=VSP_005835;
CC Note=Contains a N6-acetyllysine at position 292;
CC Name=4; Synonyms=p37;
CC IsoId=Q14103-4; Sequence=VSP_005834, VSP_005835;
CC Note=Contains a N6-acetyllysine at position 273;
CC -!- PTM: Arg-345 is dimethylated, probably to asymmetric
CC dimethylarginine.
CC -!- PTM: Methylated by PRMT1, in an insulin-dependent manner. The
CC PRMT1-mediated methylation regulates tyrosine phosphorylation (By
CC similarity).
CC -!- SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35781.1; Type=Frameshift; Positions=45, 59, 355;
CC Sequence=AAA35781.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part;
CC Sequence=CAA27544.1; Type=Miscellaneous discrepancy; Note=Several sequence conflicts;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HNRNPDID40840ch4q21.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D55671; BAA09522.1; -; mRNA.
DR EMBL; D55672; BAA09523.1; -; mRNA.
DR EMBL; D55673; BAA09524.1; -; mRNA.
DR EMBL; D55674; BAA09525.1; -; mRNA.
DR EMBL; AF026126; AAC23474.1; -; Genomic_DNA.
DR EMBL; AF026126; AAC23475.1; -; Genomic_DNA.
DR EMBL; AF026126; AAC23476.1; -; Genomic_DNA.
DR EMBL; AK292707; BAF85396.1; -; mRNA.
DR EMBL; AC124016; AAY40913.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX05874.1; -; Genomic_DNA.
DR EMBL; BC002401; AAH02401.1; -; mRNA.
DR EMBL; BC023977; AAH23977.1; -; mRNA.
DR EMBL; BC026015; AAH26015.1; -; mRNA.
DR EMBL; X03910; CAA27544.1; ALT_SEQ; mRNA.
DR EMBL; AF039575; AAB96683.1; -; mRNA.
DR EMBL; M94630; AAA35781.1; ALT_SEQ; mRNA.
DR PIR; A24016; A24016.
DR PIR; A44192; A44192.
DR PIR; B48138; B48138.
DR RefSeq; NP_001003810.1; NM_001003810.1.
DR RefSeq; NP_002129.2; NM_002138.3.
DR RefSeq; NP_112737.1; NM_031369.2.
DR RefSeq; NP_112738.1; NM_031370.2.
DR UniGene; Hs.480073; -.
DR PDB; 1HD0; NMR; -; A=98-172.
DR PDB; 1HD1; NMR; -; A=98-172.
DR PDB; 1IQT; NMR; -; A=183-257.
DR PDB; 1WTB; NMR; -; A=181-259.
DR PDB; 1X0F; NMR; -; A=181-259.
DR PDB; 2Z5N; X-ray; 3.20 A; B=332-355.
DR PDBsum; 1HD0; -.
DR PDBsum; 1HD1; -.
DR PDBsum; 1IQT; -.
DR PDBsum; 1WTB; -.
DR PDBsum; 1X0F; -.
DR PDBsum; 2Z5N; -.
DR ProteinModelPortal; Q14103; -.
DR SMR; Q14103; 98-259.
DR IntAct; Q14103; 51.
DR MINT; MINT-5001251; -.
DR PhosphoSite; Q14103; -.
DR DMDM; 13124489; -.
DR SWISS-2DPAGE; Q14103; -.
DR PaxDb; Q14103; -.
DR PRIDE; Q14103; -.
DR DNASU; 3184; -.
DR Ensembl; ENST00000313899; ENSP00000313199; ENSG00000138668.
DR Ensembl; ENST00000352301; ENSP00000305860; ENSG00000138668.
DR Ensembl; ENST00000353341; ENSP00000313327; ENSG00000138668.
DR GeneID; 3184; -.
DR KEGG; hsa:3184; -.
DR UCSC; uc003hmm.1; human.
DR CTD; 3184; -.
DR GeneCards; GC04M083274; -.
DR HGNC; HGNC:5036; HNRNPD.
DR HPA; HPA004911; -.
DR MIM; 601324; gene.
DR neXtProt; NX_Q14103; -.
DR PharmGKB; PA29361; -.
DR eggNOG; COG0724; -.
DR HOVERGEN; HBG002295; -.
DR InParanoid; Q14103; -.
DR KO; K13044; -.
DR OMA; DYNDQSG; -.
DR OrthoDB; EOG715Q6V; -.
DR PhylomeDB; Q14103; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPD; human.
DR EvolutionaryTrace; Q14103; -.
DR GeneWiki; HNRPD; -.
DR GenomeRNAi; 3184; -.
DR NextBio; 12644; -.
DR PMAP-CutDB; Q14103; -.
DR PRO; PR:Q14103; -.
DR ArrayExpress; Q14103; -.
DR Bgee; Q14103; -.
DR Genevestigator; Q14103; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; TAS:Reactome.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IEA:Ensembl.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012956; CARG-binding_factor_N.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF08143; CBFNT; 1.
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; DNA-binding; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ribonucleoprotein; RNA-binding; Transcription;
KW Transcription regulation.
FT CHAIN 1 355 Heterogeneous nuclear ribonucleoprotein
FT D0.
FT /FTId=PRO_0000081849.
FT DOMAIN 97 179 RRM 1.
FT DOMAIN 182 261 RRM 2.
FT COMPBIAS 11 45 Ala-rich.
FT COMPBIAS 270 347 Gly-rich.
FT COMPBIAS 294 332 Tyr-rich.
FT MOD_RES 71 71 Phosphoserine.
FT MOD_RES 80 80 Phosphoserine.
FT MOD_RES 82 82 Phosphoserine.
FT MOD_RES 83 83 Phosphoserine.
FT MOD_RES 119 119 N6-methyllysine.
FT MOD_RES 165 165 N6-acetyllysine.
FT MOD_RES 190 190 Phosphoserine.
FT MOD_RES 193 193 Phosphothreonine.
FT MOD_RES 251 251 N6-acetyllysine.
FT MOD_RES 345 345 Dimethylated arginine.
FT VAR_SEQ 79 97 Missing (in isoform 2 and isoform 4).
FT /FTId=VSP_005834.
FT VAR_SEQ 285 334 GPSQNWNQGYSNYWNQGYGNYGYNSQGYGGYGGYDYTGYNN
FT YYGYGDYSN -> D (in isoform 3 and isoform
FT 4).
FT /FTId=VSP_005835.
FT CONFLICT 150 150 S -> R (in Ref. 11; AA sequence).
FT CONFLICT 225 225 F -> L (in Ref. 9; AAA35781).
FT STRAND 99 102
FT HELIX 110 118
FT STRAND 123 127
FT TURN 132 135
FT STRAND 139 147
FT HELIX 148 156
FT STRAND 168 170
FT STRAND 184 187
FT HELIX 195 205
FT STRAND 209 211
FT TURN 217 219
FT STRAND 220 222
FT STRAND 226 229
FT STRAND 231 233
FT HELIX 234 240
FT STRAND 244 247
FT STRAND 250 253
FT STRAND 254 256
FT STRAND 349 351
SQ SEQUENCE 355 AA; 38434 MW; D0B6EA177BEF789E CRC64;
MSEEQFGGDG AAAAATAAVG GSAGEQEGAM VAATQGAAAA AGSGAGTGGG TASGGTEGGS
AESEGAKIDA SKNEEDEGHS NSSPRHSEAA TAQREEWKMF IGGLSWDTTK KDLKDYFSKF
GEVVDCTLKL DPITGRSRGF GFVLFKESES VDKVMDQKEH KLNGKVIDPK RAKAMKTKEP
VKKIFVGGLS PDTPEEKIRE YFGGFGEVES IELPMDNKTN KRRGFCFITF KEEEPVKKIM
EKKYHNVGLS KCEIKVAMSK EQYQQQQQWG SRGGFAGRAR GRGGGPSQNW NQGYSNYWNQ
GYGNYGYNSQ GYGGYGGYDY TGYNNYYGYG DYSNQQSGYG KVSRRGGHQN SYKPY
//
MIM
601324
*RECORD*
*FIELD* NO
601324
*FIELD* TI
*601324 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN D; HNRNPD
;;HNRPD;;
AU-RICH ELEMENT RNA-BINDING PROTEIN 1, 37-KD; AUF1;;
read moreARE-BINDING PROTEIN AUF1, TYPE A; AUF1A
*FIELD* TX
CLONING
The cytoplasmic instability of certain mRNAs is a critical regulatory
component of gene expression. The mRNAs encoded by many genes important
for controlling cell growth are very unstable, having half-lives on the
order of 15 to 40 minutes. Mutations that stabilize certain mRNAs, such
as FOS (164810) and MYC (190080), can contribute to oncogenic
transformation. One class of cis-acting instability determinants is
composed of AU-rich elements (AREs) found within the 3-prime
untranslated regions of many protooncogenes and cytokine mRNAs
(summarized by Wagner et al., 1996).
Brewer (1991) and Zhang et al. (1993) described the purification and
characterization of AUF1, a potential mediator of ARE-directed mRNA
degradation. AUF1 binds with high affinity to RNA molecules that contain
ARE sequences from MYC, FOS, and GMCSF (138960) mRNAs. By contrast, AUF1
does not bind with high affinity to RNA sequences that lack an ARE. AUF1
is composed of at least 2 immunologically cross-reactive polypeptides
with apparent molecular masses of 37 and 40 kD.
Zhang et al. (1993) used purified AUF1 protein to make polyclonal
anti-AUF1 antibodies. They screened a HeLa cell expression library and
isolated a clone (designated p37AUF1) that bound to AREs when tested.
The 2.5-kb cDNA contains an ORF of 861 bp and produced a 37-kD in vitro
translation product that comigrated with the p37AUF1 polypeptide.
Sequence analysis revealed 2 nonidentical RNA recognition motifs (RRMs),
a glutamine-rich region, and 3 putative phosphorylation sites. Metabolic
labeling experiments showed that the translated protein is
phosphorylated in K562 cells. Biochemical fractionation and
immunofluorescence data suggested to Zhang et al. (1993) that AUF1
protein localizes to both the nucleus and the cytoplasm. Based on its
homology to other RRM-containing proteins in GenBank, Zhang et al.
(1993) speculated that p37AUF1 is part of a family of related proteins
distinct from the hnRNP proteins, which includes the DL4 protein, the
human homolog of lambda C6, and the human hnRNP A/B-like protein (see
600124). Wagner et al. (1996) noted that the RRMs of p37AUF1 are highly
homologous with those of murine AUF1 (98% identity) and those of the
Drosophila melanogaster 'Squid' gene product (43% identity), suggesting
conserved functions. Wagner et al. (1996) cloned cDNAs encoding the AUF1
family of ARE-binding proteins from human and murine cDNA libraries.
Wagner et al. (1998) identified 4 AUF1 isoforms of 37 kD (p37AUF), 40 kD
(p40AUF), 42 kD (p42AUF), and 45 kD (p45AUF), which result from
alternative pre-mRNA splicing. The isoforms differ by the presence or
absence of a 19- and/or a 49-amino acid insert.
GENE FUNCTION
Wagner et al. (1998) showed that the 4 AUF1 isoforms exhibit an
approximately 35-fold range in ARE-binding affinities, with p37AUF
having the highest affinity and p40AUF having the lowest affinity.
Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich
elements in the 3-prime untranslated region. Rapid decay involves
AU-rich binding protein AUF1, which complexes with heat-shock proteins
HSC70 (600816) and HSP70 (see 140550), translation initiation factor
EIF4G (600495), and poly(A)-binding protein (PABP; 604679). AU-rich mRNA
decay is associated with displacement of EIF4G from AUF1, ubiquitination
of AUF1, and degradation of AUF1 by proteasomes. Induction of HSP70 by
heat shock, downregulation of the ubiquitin-proteasome network, or
inactivation of ubiquitinating enzyme E1 (314370), all result in HSP70
sequestration of AUF1 in the perinucleus-nucleus, and all 3 processes
block decay of AU-rich mRNAs and AUF1 protein. These results link the
rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway
(Laroia et al., 1999).
AU-rich elements and protein-coding determinants direct rapid removal of
poly(A) tails as a necessary first step in mRNA decay. Grosset et al.
(2000) determined that 5 proteins form a multiprotein complex associated
with the major protein-coding-region determinant of instability (mCRD)
of the FOS gene: PABP, HNRNPD, PAIP1 (605184), NSAP1, and UNR (191510).
Overexpression of these proteins stabilized mCRD-containing mRNA by
impeding deadenylation.
Shchors et al. (2002) showed that expression of the apparently noncoding
RNA CDIR (613568) in HeLa cells inhibited interferon-gamma
(147570)-induced apoptosis in a dose-dependent manner, and that this
protection was associated with elevated levels of p21 (116899) and BCL2
(151430) transcripts and protein level. CDIR bound a protein complex
that contained all isoforms of AUF1 and HSP27 (HSPB1; 602195). Use of
recombinant proteins revealed that AUF1, but not HSP27, directly bound
CDIR. Transfection of HeLa cells with another AUF1 target, the 3-prime
UTR of MYC (190080), also inhibited interferon-gamma-induced cell
killing, but only in a limited manner. Shchors et al. (2002) concluded
that the antiapoptotic effect of CDIR is due to the sequestration of
AUF1 by CDIR, resulting in elevated levels and activity of p21 and BLC2.
GENE STRUCTURE
Dempsey et al. (1998) found that the HNRPD gene consists of 8 exons and
that use of 2 of these exons is determined by alternative splicing of
the HNRPD mRNA. Wagner et al. (1998) determined that the AUF1 gene
consists of 10 exons.
MAPPING
Using monochromosomal somatic cell hybrids, Wagner et al. (1996)
localized 2 AUF1 loci to chromosomes 4 and X. By fluorescence in situ
hybridization (FISH) analysis using P1 clones as probes, they identified
4q21.1-q21.2 and Xq12 as the locations of the AUF1 genes. The autosomal
gene, AUF1, was alternatively symbolized AUF1A and the X-linked gene,
which maps to Xq12, was provisionally symbolized AUF1B. Two different P1
clones, named G1626 and P0139, were used in the FISH analysis. These
phage P1 clones were obtained from a human genomic library using the
same cDNA probe used in the Southern analysis of the somatic hybrid cell
panels. FISH signals were observed on chromosome 4 only with G1626, and
on the X chromosome only with P0139. By FISH with labeled genomic DNAs
as probes, Dempsey et al. (1998) mapped the HNRPD gene to 4q21. By the
same method, they mapped the mouse Hnrpd gene to the F region of
chromosome 3.
Brewer (1999) stated that AUF1B, also symbolized HNRPDP, is a pseudogene
of HNRPD.
*FIELD* RF
1. Brewer, G.: Personal Communication. Winston-Salem, N.C. 3/4/1999.
2. Brewer, G.: An A+U-rich element RNA-binding factor regulates c-myc
mRNA stability in vitro. Molec. Cell. Biol. 11: 2460-2466, 1991.
3. Dempsey, L. A.; Li, M.; DePace, A.; Bray-Ward, P.; Maizels, N.
: The human HNRPD locus maps to 4q21 and encodes a highly conserved
protein. Genomics 49: 378-384, 1998.
4. Grosset, C.; Chen, C.-Y. A.; Xu, N.; Sonenberg, N.; Jacquemin-Sablon,
H.; Shyu, A.-B.: A mechanism for translationally coupled mRNA turnover:
interaction between the poly(A) tail and a c-fos RNA coding determinant
via a protein complex. Cell 103: 29-40, 2000.
5. Laroia, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.
6. Shchors, K.; Yehiely, F.; Kular, R. K.; Kotlo, K. U.; Brewer, G.;
Deiss, L. P.: Cell death inhibiting RNA (CDIR) derived from a 3-prime-untranslated
region binds AUF1 and heat shock protein 27. J. Biol. Chem. 277:
47061-47072, 2002.
7. Wagner, B. J.; DeMaria, C. T.; Sun, Y.; Wilson, G. M.; Brewer,
G.: Structure and genomic organization of the human AUF1 gene: alternative
pre-mRNA splicing generates four protein isoforms. Genomics 48:
195-202, 1998.
8. Wagner, B. J.; Long, L.; Rao, P. N.; Pettenati, M. J.; Brewer,
G.: Localization and physical mapping of genes encoding the A+U-rich
element RNA-binding protein AUF1 to human chromosomes 4 and X. Genomics 34:
219-222, 1996.
9. Zhang, W.; Wagner, B. J.; Ehrenman, K.; Schaefer, A. W.; DeMaria,
C. T.; Crater, D.; DeHaven, K.; Long, L.; Brewer, G.: Purification,
characterization and cDNA cloning of an AU-rich element RNA-binding
protein, AUF1. Molec. Cell. Biol. 13: 7652-7665, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 9/17/2010
Patricia A. Hartz - updated: 9/10/2004
Carol A. Bocchini - updated: 5/21/2001
Ada Hamosh - updated: 4/16/1999
Carol A. Bocchini - updated: 2/24/1999
Jennifer P. Macke - updated: 8/23/1996
*FIELD* CD
Victor A. McKusick: 6/26/1996
*FIELD* ED
alopez: 03/08/2012
terry: 4/21/2011
alopez: 9/20/2010
terry: 9/17/2010
wwang: 8/27/2008
joanna: 3/23/2005
mgross: 9/10/2004
carol: 5/21/2001
mgross: 3/14/2000
alopez: 4/16/1999
alopez: 3/5/1999
terry: 2/25/1999
carol: 2/24/1999
dkim: 12/16/1998
psherman: 12/1/1998
dkim: 7/30/1998
terry: 6/5/1998
mark: 9/9/1996
mark: 8/23/1996
mark: 7/22/1996
terry: 6/28/1996
mark: 6/27/1996
mark: 6/26/1996
terry: 6/26/1996
mark: 6/26/1996
*RECORD*
*FIELD* NO
601324
*FIELD* TI
*601324 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN D; HNRNPD
;;HNRPD;;
AU-RICH ELEMENT RNA-BINDING PROTEIN 1, 37-KD; AUF1;;
read moreARE-BINDING PROTEIN AUF1, TYPE A; AUF1A
*FIELD* TX
CLONING
The cytoplasmic instability of certain mRNAs is a critical regulatory
component of gene expression. The mRNAs encoded by many genes important
for controlling cell growth are very unstable, having half-lives on the
order of 15 to 40 minutes. Mutations that stabilize certain mRNAs, such
as FOS (164810) and MYC (190080), can contribute to oncogenic
transformation. One class of cis-acting instability determinants is
composed of AU-rich elements (AREs) found within the 3-prime
untranslated regions of many protooncogenes and cytokine mRNAs
(summarized by Wagner et al., 1996).
Brewer (1991) and Zhang et al. (1993) described the purification and
characterization of AUF1, a potential mediator of ARE-directed mRNA
degradation. AUF1 binds with high affinity to RNA molecules that contain
ARE sequences from MYC, FOS, and GMCSF (138960) mRNAs. By contrast, AUF1
does not bind with high affinity to RNA sequences that lack an ARE. AUF1
is composed of at least 2 immunologically cross-reactive polypeptides
with apparent molecular masses of 37 and 40 kD.
Zhang et al. (1993) used purified AUF1 protein to make polyclonal
anti-AUF1 antibodies. They screened a HeLa cell expression library and
isolated a clone (designated p37AUF1) that bound to AREs when tested.
The 2.5-kb cDNA contains an ORF of 861 bp and produced a 37-kD in vitro
translation product that comigrated with the p37AUF1 polypeptide.
Sequence analysis revealed 2 nonidentical RNA recognition motifs (RRMs),
a glutamine-rich region, and 3 putative phosphorylation sites. Metabolic
labeling experiments showed that the translated protein is
phosphorylated in K562 cells. Biochemical fractionation and
immunofluorescence data suggested to Zhang et al. (1993) that AUF1
protein localizes to both the nucleus and the cytoplasm. Based on its
homology to other RRM-containing proteins in GenBank, Zhang et al.
(1993) speculated that p37AUF1 is part of a family of related proteins
distinct from the hnRNP proteins, which includes the DL4 protein, the
human homolog of lambda C6, and the human hnRNP A/B-like protein (see
600124). Wagner et al. (1996) noted that the RRMs of p37AUF1 are highly
homologous with those of murine AUF1 (98% identity) and those of the
Drosophila melanogaster 'Squid' gene product (43% identity), suggesting
conserved functions. Wagner et al. (1996) cloned cDNAs encoding the AUF1
family of ARE-binding proteins from human and murine cDNA libraries.
Wagner et al. (1998) identified 4 AUF1 isoforms of 37 kD (p37AUF), 40 kD
(p40AUF), 42 kD (p42AUF), and 45 kD (p45AUF), which result from
alternative pre-mRNA splicing. The isoforms differ by the presence or
absence of a 19- and/or a 49-amino acid insert.
GENE FUNCTION
Wagner et al. (1998) showed that the 4 AUF1 isoforms exhibit an
approximately 35-fold range in ARE-binding affinities, with p37AUF
having the highest affinity and p40AUF having the lowest affinity.
Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich
elements in the 3-prime untranslated region. Rapid decay involves
AU-rich binding protein AUF1, which complexes with heat-shock proteins
HSC70 (600816) and HSP70 (see 140550), translation initiation factor
EIF4G (600495), and poly(A)-binding protein (PABP; 604679). AU-rich mRNA
decay is associated with displacement of EIF4G from AUF1, ubiquitination
of AUF1, and degradation of AUF1 by proteasomes. Induction of HSP70 by
heat shock, downregulation of the ubiquitin-proteasome network, or
inactivation of ubiquitinating enzyme E1 (314370), all result in HSP70
sequestration of AUF1 in the perinucleus-nucleus, and all 3 processes
block decay of AU-rich mRNAs and AUF1 protein. These results link the
rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway
(Laroia et al., 1999).
AU-rich elements and protein-coding determinants direct rapid removal of
poly(A) tails as a necessary first step in mRNA decay. Grosset et al.
(2000) determined that 5 proteins form a multiprotein complex associated
with the major protein-coding-region determinant of instability (mCRD)
of the FOS gene: PABP, HNRNPD, PAIP1 (605184), NSAP1, and UNR (191510).
Overexpression of these proteins stabilized mCRD-containing mRNA by
impeding deadenylation.
Shchors et al. (2002) showed that expression of the apparently noncoding
RNA CDIR (613568) in HeLa cells inhibited interferon-gamma
(147570)-induced apoptosis in a dose-dependent manner, and that this
protection was associated with elevated levels of p21 (116899) and BCL2
(151430) transcripts and protein level. CDIR bound a protein complex
that contained all isoforms of AUF1 and HSP27 (HSPB1; 602195). Use of
recombinant proteins revealed that AUF1, but not HSP27, directly bound
CDIR. Transfection of HeLa cells with another AUF1 target, the 3-prime
UTR of MYC (190080), also inhibited interferon-gamma-induced cell
killing, but only in a limited manner. Shchors et al. (2002) concluded
that the antiapoptotic effect of CDIR is due to the sequestration of
AUF1 by CDIR, resulting in elevated levels and activity of p21 and BLC2.
GENE STRUCTURE
Dempsey et al. (1998) found that the HNRPD gene consists of 8 exons and
that use of 2 of these exons is determined by alternative splicing of
the HNRPD mRNA. Wagner et al. (1998) determined that the AUF1 gene
consists of 10 exons.
MAPPING
Using monochromosomal somatic cell hybrids, Wagner et al. (1996)
localized 2 AUF1 loci to chromosomes 4 and X. By fluorescence in situ
hybridization (FISH) analysis using P1 clones as probes, they identified
4q21.1-q21.2 and Xq12 as the locations of the AUF1 genes. The autosomal
gene, AUF1, was alternatively symbolized AUF1A and the X-linked gene,
which maps to Xq12, was provisionally symbolized AUF1B. Two different P1
clones, named G1626 and P0139, were used in the FISH analysis. These
phage P1 clones were obtained from a human genomic library using the
same cDNA probe used in the Southern analysis of the somatic hybrid cell
panels. FISH signals were observed on chromosome 4 only with G1626, and
on the X chromosome only with P0139. By FISH with labeled genomic DNAs
as probes, Dempsey et al. (1998) mapped the HNRPD gene to 4q21. By the
same method, they mapped the mouse Hnrpd gene to the F region of
chromosome 3.
Brewer (1999) stated that AUF1B, also symbolized HNRPDP, is a pseudogene
of HNRPD.
*FIELD* RF
1. Brewer, G.: Personal Communication. Winston-Salem, N.C. 3/4/1999.
2. Brewer, G.: An A+U-rich element RNA-binding factor regulates c-myc
mRNA stability in vitro. Molec. Cell. Biol. 11: 2460-2466, 1991.
3. Dempsey, L. A.; Li, M.; DePace, A.; Bray-Ward, P.; Maizels, N.
: The human HNRPD locus maps to 4q21 and encodes a highly conserved
protein. Genomics 49: 378-384, 1998.
4. Grosset, C.; Chen, C.-Y. A.; Xu, N.; Sonenberg, N.; Jacquemin-Sablon,
H.; Shyu, A.-B.: A mechanism for translationally coupled mRNA turnover:
interaction between the poly(A) tail and a c-fos RNA coding determinant
via a protein complex. Cell 103: 29-40, 2000.
5. Laroia, G.; Cuesta, R.; Brewer, G.; Schneider, R. J.: Control
of mRNA decay by heat shock-ubiquitin-proteasome pathway. Science 284:
499-502, 1999.
6. Shchors, K.; Yehiely, F.; Kular, R. K.; Kotlo, K. U.; Brewer, G.;
Deiss, L. P.: Cell death inhibiting RNA (CDIR) derived from a 3-prime-untranslated
region binds AUF1 and heat shock protein 27. J. Biol. Chem. 277:
47061-47072, 2002.
7. Wagner, B. J.; DeMaria, C. T.; Sun, Y.; Wilson, G. M.; Brewer,
G.: Structure and genomic organization of the human AUF1 gene: alternative
pre-mRNA splicing generates four protein isoforms. Genomics 48:
195-202, 1998.
8. Wagner, B. J.; Long, L.; Rao, P. N.; Pettenati, M. J.; Brewer,
G.: Localization and physical mapping of genes encoding the A+U-rich
element RNA-binding protein AUF1 to human chromosomes 4 and X. Genomics 34:
219-222, 1996.
9. Zhang, W.; Wagner, B. J.; Ehrenman, K.; Schaefer, A. W.; DeMaria,
C. T.; Crater, D.; DeHaven, K.; Long, L.; Brewer, G.: Purification,
characterization and cDNA cloning of an AU-rich element RNA-binding
protein, AUF1. Molec. Cell. Biol. 13: 7652-7665, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 9/17/2010
Patricia A. Hartz - updated: 9/10/2004
Carol A. Bocchini - updated: 5/21/2001
Ada Hamosh - updated: 4/16/1999
Carol A. Bocchini - updated: 2/24/1999
Jennifer P. Macke - updated: 8/23/1996
*FIELD* CD
Victor A. McKusick: 6/26/1996
*FIELD* ED
alopez: 03/08/2012
terry: 4/21/2011
alopez: 9/20/2010
terry: 9/17/2010
wwang: 8/27/2008
joanna: 3/23/2005
mgross: 9/10/2004
carol: 5/21/2001
mgross: 3/14/2000
alopez: 4/16/1999
alopez: 3/5/1999
terry: 2/25/1999
carol: 2/24/1999
dkim: 12/16/1998
psherman: 12/1/1998
dkim: 7/30/1998
terry: 6/5/1998
mark: 9/9/1996
mark: 8/23/1996
mark: 7/22/1996
terry: 6/28/1996
mark: 6/27/1996
mark: 6/26/1996
terry: 6/26/1996
mark: 6/26/1996