Full text data of HNRNPK
HNRNPK
(HNRPK)
[Confidence: low (only semi-automatic identification from reviews)]
Heterogeneous nuclear ribonucleoprotein K; hnRNP K (Transformation up-regulated nuclear protein; TUNP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heterogeneous nuclear ribonucleoprotein K; hnRNP K (Transformation up-regulated nuclear protein; TUNP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P61978
ID HNRPK_HUMAN Reviewed; 463 AA.
AC P61978; Q07244; Q15671; Q59F98; Q5T6W4; Q60577; Q922Y7; Q96J62;
read moreDT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein K;
DE Short=hnRNP K;
DE AltName: Full=Transformation up-regulated nuclear protein;
DE Short=TUNP;
GN Name=HNRNPK; Synonyms=HNRPK;
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] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=1729596;
RA Matunis M.J., Michael W.M., Dreyfuss G.;
RT "Characterization and primary structure of the poly(C)-binding
RT heterogeneous nuclear ribonucleoprotein complex K protein.";
RL Mol. Cell. Biol. 12:164-171(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PHOSPHORYLATION.
RX PubMed=8107114; DOI=10.1006/jmbi.1994.1116;
RA Dejgaard K., Leffers H., Rasmussen H.H., Madsen P., Kruse T.A.,
RA Gesser B., Nielsen H., Celis J.E.;
RT "Identification, molecular cloning, expression and chromosome mapping
RT of a family of transformation upregulated hnRNP-K proteins derived by
RT alternative splicing.";
RL J. Mol. Biol. 236:33-48(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
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 2).
RC TISSUE=Muscle;
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 PROTEIN SEQUENCE OF 1-52; 70-103; 149-163; 192-201; 208-219; 317-325;
RP 378-405 AND 423-456, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N.;
RL Submitted (MAR-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 38-46; 149-163; 208-219; 306-316 AND 378-396, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP INTERACTION WITH HCV CORE PROTEIN.
RX PubMed=9651361; DOI=10.1074/jbc.273.28.17651;
RA Hsieh T.-Y., Matsumoto M., Chou H.-C., Schneider R., Hwang S.B.,
RA Lee A.S., Lai M.M.C.;
RT "Hepatitis C virus core protein interacts with heterogeneous nuclear
RT ribonucleoprotein K.";
RL J. Biol. Chem. 273:17651-17659(1998).
RN [10]
RP INTERACTION WITH DDX1.
RX PubMed=12183465; DOI=10.1074/jbc.M206981200;
RA Chen H.C., Lin W.C., Tsay Y.G., Lee S.C., Chang C.J.;
RT "An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous
RT nuclear ribonucleoprotein K.";
RL J. Biol. Chem. 277:40403-40409(2002).
RN [11]
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=11840567;
RX DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H;
RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A.,
RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J.,
RA Zvelebil M.J.;
RT "Cluster analysis of an extensive human breast cancer cell line
RT protein expression map database.";
RL Proteomics 2:212-223(2002).
RN [12]
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 [13]
RP FUNCTION, INTERACTION WITH MDM2 AND TP53, SUBCELLULAR LOCATION,
RP UBIQUITINATION, AND INDUCTION.
RX PubMed=16360036; DOI=10.1016/j.cell.2005.09.032;
RA Moumen A., Masterson P., O'Connor M.J., Jackson S.P.;
RT "hnRNP K: an HDM2 target and transcriptional coactivator of p53 in
RT response to DNA damage.";
RL Cell 123:1065-1078(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, 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 [15]
RP INTERACTION WITH ANKRD28, AND PHOSPHORYLATION AT SER-284.
RX PubMed=16564677; DOI=10.1016/j.cellsig.2006.01.019;
RA Kwiek N.C., Thacker D.F., Datto M.B., Megosh H.B., Haystead T.A.J.;
RT "PITK, a PP1 targeting subunit that modulates the phosphorylation of
RT the transcriptional regulator hnRNP K.";
RL Cell. Signal. 18:1769-1778(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216 AND SER-379, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
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 [18]
RP INTERACTION WITH ASFV PROTEIN P30.
RX PubMed=18775702; DOI=10.1016/j.febslet.2008.08.031;
RA Hernaez B., Escribano J.M., Alonso C.;
RT "African swine fever virus protein p30 interaction with heterogeneous
RT nuclear ribonucleoprotein K (hnRNP-K) during infection.";
RL FEBS Lett. 582:3275-3280(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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-116; SER-216 AND
RP SER-284, 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 ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216 AND TYR-380, AND
RP 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 [23]
RP FUNCTION.
RX PubMed=20673990; DOI=10.1016/j.cell.2010.06.040;
RA Huarte M., Guttman M., Feldser D., Garber M., Koziol M.J.,
RA Kenzelmann-Broz D., Khalil A.M., Zuk O., Amit I., Rabani M.,
RA Attardi L.D., Regev A., Lander E.S., Jacks T., Rinn J.L.;
RT "A large intergenic noncoding RNA induced by p53 mediates global gene
RT repression in the p53 response.";
RL Cell 142:409-419(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-284 AND
RP SER-379, 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 [25]
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214; SER-216; SER-284
RP AND SER-379, 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 [27]
RP GLYCOSYLATION.
RX PubMed=22967762; DOI=10.1016/j.bbagen.2012.08.024;
RA Drougat L., Olivier-Van Stichelen S., Mortuaire M., Foulquier F.,
RA Lacoste A.S., Michalski J.C., Lefebvre T., Vercoutter-Edouart A.S.;
RT "Characterization of O-GlcNAc cycling and proteomic identification of
RT differentially O-GlcNAcylated proteins during G1/S transition.";
RL Biochim. Biophys. Acta 1820:1839-1848(2012).
RN [28]
RP SUBCELLULAR LOCATION.
RX PubMed=22721921; DOI=10.1016/j.ejcb.2012.05.005;
RA Cervero P., Himmel M., Kruger M., Linder S.;
RT "Proteomic analysis of podosome fractions from macrophages reveals
RT similarities to spreading initiation centres.";
RL Eur. J. Cell Biol. 91:908-922(2012).
RN [29]
RP FUNCTION, SUMOYLATION AT LYS-422, UBIQUITINATION, AND MUTAGENESIS OF
RP LYS-422 AND ASP-424.
RX PubMed=22825850; DOI=10.1074/jbc.M112.390120;
RA Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.;
RT "DNA damage-induced heterogeneous nuclear ribonucleoprotein K
RT SUMOylation regulates p53 transcriptional activation.";
RL J. Biol. Chem. 287:30789-30799(2012).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP STRUCTURE BY NMR OF 375-463.
RX PubMed=10369774; DOI=10.1006/jmbi.1999.2818;
RA Baber J.L., Libutti D., Levens D., Tjandra N.;
RT "High precision solution structure of the C-terminal KH domain of
RT heterogeneous nuclear ribonucleoprotein K, a c-myc transcription
RT factor.";
RL J. Mol. Biol. 289:949-962(1999).
RN [32]
RP STRUCTURE BY NMR OF 379-463 IN COMPLEX WITH SINGLE-STRANDED DNA.
RX PubMed=12093748; DOI=10.1093/emboj/cdf352;
RA Braddock D.T., Baber J.L., Levens D., Clore G.M.;
RT "Molecular basis of sequence-specific single-stranded DNA recognition
RT by KH domains: solution structure of a complex between hnRNP K KH3 and
RT single-stranded DNA.";
RL EMBO J. 21:3476-3485(2002).
CC -!- FUNCTION: One of the major pre-mRNA-binding proteins. Binds
CC tenaciously to poly(C) sequences. Likely to play a role in the
CC nuclear metabolism of hnRNAs, particularly for pre-mRNAs that
CC contain cytidine-rich sequences. Can also bind poly(C) single-
CC stranded DNA. Plays an important role in p53/TP53 response to DNA
CC damage, acting at the level of both transcription activation and
CC repression. When sumoylated, acts as a transcriptional coactivator
CC of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN
CC induction (By similarity). As far as transcription repression is
CC concerned, acts by interacting with long intergenic RNA p21
CC (lincRNA-p21), a non-coding RNA induced by p53/TP53. This
CC interaction is necessary for the induction of apoptosis, but not
CC cell cycle arrest.
CC -!- SUBUNIT: Interacts with RBM42 and ZIK1. Interacts with BRDT (By
CC similarity). Identified in the spliceosome C complex. Interacts
CC with ANKRD28. Interacts with HCV core protein. Interacts with ASFV
CC p30 protein. Interacts with DDX1. Interacts with MDM2; this
CC interaction leads to ubiquitination and proteasomal degradation.
CC Interacts with p53/TP53.
CC -!- INTERACTION:
CC O14965:AURKA; NbExp=2; IntAct=EBI-304185, EBI-448680;
CC Q8V1E7:C'204L (xeno); NbExp=5; IntAct=EBI-304185, EBI-8068745;
CC Q00987:MDM2; NbExp=2; IntAct=EBI-304185, EBI-389668;
CC Q99873:PRMT1; NbExp=3; IntAct=EBI-304185, EBI-78738;
CC Q96PU8:QKI; NbExp=3; IntAct=EBI-304185, EBI-945792;
CC P38159:RBMX; NbExp=3; IntAct=EBI-304185, EBI-743526;
CC P12931:SRC; NbExp=6; IntAct=EBI-304185, EBI-621482;
CC P04637:TP53; NbExp=2; IntAct=EBI-304185, EBI-366083;
CC Q9H3D4:TP63; NbExp=2; IntAct=EBI-304185, EBI-2337775;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm. Cell
CC projection, podosome. Note=Recruited to p53/TP53-responsive
CC promoters, in the presence of functional p53/TP53. In case of ASFV
CC infection, there is a shift in the localization which becomes
CC predominantly nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P61978-1, Q07244-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P61978-2, Q07244-2;
CC Sequence=VSP_002822;
CC Name=3;
CC IsoId=P61978-3; Sequence=VSP_021669, VSP_002822;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: By DNA damage, including ionizing radiations and
CC phleomycin treatment or UV irradiation. This induction requires
CC ATM kinase activity (ionizing radiations and phleomycin) or ATR
CC activity (UV irradiation). Up-regulation is due to protein
CC stabilization. Constitutive protein levels are controlled by MDM2-
CC mediated ubiquitination and degradation via the proteasome
CC pathway.
CC -!- PTM: Arg-296 and Arg-299 are dimethylated, probably to asymmetric
CC dimethylarginine.
CC -!- PTM: Sumoylated by CBX4. Sumoylation is increased upon DNA damage,
CC such as that produced by doxorubicin, etoposide, UV light and
CC camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under
CC these conditions.
CC -!- PTM: Ubiquitinated by MDM2. Doxorubicin treatment does not affect
CC monoubiquitination, but slightly decreases HNRNPK poly-
CC ubiquitination.
CC -!- PTM: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent
CC manner.
CC -!- MASS SPECTROMETRY: Mass=50976.25; Method=MALDI; Range=1-463
CC (P61978-1); Source=PubMed:11840567;
CC -!- SIMILARITY: Contains 3 KH domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92799.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HNRNPKID44314ch9q21.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; S74678; AAB20770.1; -; mRNA.
DR EMBL; X72727; CAA51267.1; -; mRNA.
DR EMBL; AB209562; BAD92799.1; ALT_INIT; mRNA.
DR EMBL; AL354733; CAI16020.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62675.1; -; Genomic_DNA.
DR EMBL; BC000355; AAH00355.1; -; mRNA.
DR EMBL; BC014980; AAH14980.1; -; mRNA.
DR PIR; S43363; S43363.
DR RefSeq; NP_002131.2; NM_002140.3.
DR RefSeq; NP_112552.1; NM_031262.2.
DR RefSeq; NP_112553.1; NM_031263.2.
DR RefSeq; XP_005252017.1; XM_005251960.1.
DR RefSeq; XP_005252018.1; XM_005251961.1.
DR RefSeq; XP_005252020.1; XM_005251963.1.
DR RefSeq; XP_005252021.1; XM_005251964.1.
DR RefSeq; XP_005252022.1; XM_005251965.1.
DR UniGene; Hs.522257; -.
DR PDB; 1J5K; NMR; -; A=379-463.
DR PDB; 1KHM; NMR; -; A=379-463.
DR PDB; 1ZZI; X-ray; 1.80 A; A/B=385-463.
DR PDB; 1ZZJ; X-ray; 2.30 A; A/B/C=385-463.
DR PDB; 1ZZK; X-ray; 0.95 A; A=385-463.
DR PDBsum; 1J5K; -.
DR PDBsum; 1KHM; -.
DR PDBsum; 1ZZI; -.
DR PDBsum; 1ZZJ; -.
DR PDBsum; 1ZZK; -.
DR ProteinModelPortal; P61978; -.
DR SMR; P61978; 45-216, 385-463.
DR DIP; DIP-31805N; -.
DR IntAct; P61978; 95.
DR MINT; MINT-225422; -.
DR STRING; 9606.ENSP00000365439; -.
DR PhosphoSite; P61978; -.
DR DMDM; 48429103; -.
DR SWISS-2DPAGE; P61978; -.
DR PaxDb; P61978; -.
DR PRIDE; P61978; -.
DR DNASU; 3190; -.
DR Ensembl; ENST00000351839; ENSP00000317788; ENSG00000165119.
DR Ensembl; ENST00000360384; ENSP00000353552; ENSG00000165119.
DR Ensembl; ENST00000376263; ENSP00000365439; ENSG00000165119.
DR Ensembl; ENST00000376264; ENSP00000365440; ENSG00000165119.
DR Ensembl; ENST00000376281; ENSP00000365458; ENSG00000165119.
DR GeneID; 3190; -.
DR KEGG; hsa:3190; -.
DR UCSC; uc004ang.4; human.
DR CTD; 3190; -.
DR GeneCards; GC09M086582; -.
DR HGNC; HGNC:5044; HNRNPK.
DR HPA; CAB004435; -.
DR HPA; CAB016225; -.
DR HPA; HPA007644; -.
DR MIM; 600712; gene.
DR neXtProt; NX_P61978; -.
DR PharmGKB; PA162391350; -.
DR eggNOG; NOG285495; -.
DR HOVERGEN; HBG051916; -.
DR KO; K12886; -.
DR OMA; KALRTDX; -.
DR OrthoDB; EOG7CZK81; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPK; human.
DR EvolutionaryTrace; P61978; -.
DR GeneWiki; HNRPK; -.
DR GenomeRNAi; 3190; -.
DR NextBio; 12686; -.
DR PMAP-CutDB; P61978; -.
DR PRO; PR:P61978; -.
DR ArrayExpress; P61978; -.
DR Bgee; P61978; -.
DR CleanEx; HS_HNRNPK; -.
DR Genevestigator; P61978; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; TAS:ProtInc.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IMP:BHF-UCL.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IMP:BHF-UCL.
DR GO; GO:0003697; F:single-stranded DNA binding; TAS:BHF-UCL.
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:0045716; P:positive regulation of low-density lipoprotein particle receptor biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0072369; P:regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0010988; P:regulation of low-density lipoprotein particle clearance; IMP:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR012987; ROK_N.
DR Pfam; PF00013; KH_1; 3.
DR Pfam; PF08067; ROKNT; 1.
DR SMART; SM00322; KH; 3.
DR PROSITE; PS50084; KH_TYPE_1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Cell junction; Cell projection; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Glycoprotein;
KW Host-virus interaction; Isopeptide bond; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Ribonucleoprotein; RNA-binding; Spliceosome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 463 Heterogeneous nuclear ribonucleoprotein
FT K.
FT /FTId=PRO_0000050096.
FT DOMAIN 42 104 KH 1.
FT REPEAT 54 76 1-1.
FT REPEAT 59 62 3-1.
FT DOMAIN 144 209 KH 2.
FT REPEAT 245 250 2-1.
FT REPEAT 257 260 3-2.
FT REPEAT 267 270 3-3.
FT REPEAT 295 298 3-4.
FT REPEAT 324 329 2-2.
FT DOMAIN 387 451 KH 3.
FT REPEAT 399 421 1-2.
FT REPEAT 404 407 3-5.
FT REGION 1 276 Necessary for interaction with DDX1.
FT REGION 35 197 Interaction with ASFV p30.
FT REGION 54 421 2 X 22 AA approximate repeats.
FT REGION 59 407 5 X 4 AA repeats of G-X-G-G.
FT REGION 209 337 Interaction with ZIK1 (By similarity).
FT REGION 236 273 RNA-binding RGG-box.
FT REGION 245 329 2 X 6 AA approximate repeats.
FT COMPBIAS 289 294 Poly-Pro.
FT COMPBIAS 310 315 Poly-Pro.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 116 116 Phosphoserine.
FT MOD_RES 214 214 Phosphoserine.
FT MOD_RES 216 216 Phosphoserine.
FT MOD_RES 284 284 Phosphoserine.
FT MOD_RES 379 379 Phosphoserine.
FT MOD_RES 380 380 Phosphotyrosine.
FT CROSSLNK 422 422 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 111 134 Missing (in isoform 3).
FT /FTId=VSP_021669.
FT VAR_SEQ 459 463 SGKFF -> ADVEGF (in isoform 2 and isoform
FT 3).
FT /FTId=VSP_002822.
FT MUTAGEN 422 422 K->R: Loss of sumoylation. Loss of TP53
FT transcriptional stimulation.
FT MUTAGEN 424 424 D->A: Loss of sumoylation.
FT CONFLICT 32 32 A -> D (in Ref. 2; CAA51267).
FT HELIX 381 384
FT STRAND 388 395
FT TURN 396 398
FT HELIX 399 402
FT HELIX 405 407
FT HELIX 408 417
FT STRAND 420 423
FT STRAND 430 439
FT HELIX 441 459
SQ SEQUENCE 463 AA; 50976 MW; 0F70EE169B2A064A CRC64;
METEQPEETF PNTETNGEFG KRPAEDMEEE QAFKRSRNTD EMVELRILLQ SKNAGAVIGK
GGKNIKALRT DYNASVSVPD SSGPERILSI SADIETIGEI LKKIIPTLEE GLQLPSPTAT
SQLPLESDAV ECLNYQHYKG SDFDCELRLL IHQSLAGGII GVKGAKIKEL RENTQTTIKL
FQECCPHSTD RVVLIGGKPD RVVECIKIIL DLISESPIKG RAQPYDPNFY DETYDYGGFT
MMFDDRRGRP VGFPMRGRGG FDRMPPGRGG RPMPPSRRDY DDMSPRRGPP PPPPGRGGRG
GSRARNLPLP PPPPPRGGDL MAYDRRGRPG DRYDGMVGFS ADETWDSAID TWSPSEWQMA
YEPQGGSGYD YSYAGGRGSY GDLGGPIITT QVTIPKDLAG SIIGKGGQRI KQIRHESGAS
IKIDEPLEGS EDRIITITGT QDQIQNAQYL LQNSVKQYSG KFF
//
ID HNRPK_HUMAN Reviewed; 463 AA.
AC P61978; Q07244; Q15671; Q59F98; Q5T6W4; Q60577; Q922Y7; Q96J62;
read moreDT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein K;
DE Short=hnRNP K;
DE AltName: Full=Transformation up-regulated nuclear protein;
DE Short=TUNP;
GN Name=HNRNPK; Synonyms=HNRPK;
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] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=1729596;
RA Matunis M.J., Michael W.M., Dreyfuss G.;
RT "Characterization and primary structure of the poly(C)-binding
RT heterogeneous nuclear ribonucleoprotein complex K protein.";
RL Mol. Cell. Biol. 12:164-171(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PHOSPHORYLATION.
RX PubMed=8107114; DOI=10.1006/jmbi.1994.1116;
RA Dejgaard K., Leffers H., Rasmussen H.H., Madsen P., Kruse T.A.,
RA Gesser B., Nielsen H., Celis J.E.;
RT "Identification, molecular cloning, expression and chromosome mapping
RT of a family of transformation upregulated hnRNP-K proteins derived by
RT alternative splicing.";
RL J. Mol. Biol. 236:33-48(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
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 2).
RC TISSUE=Muscle;
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 PROTEIN SEQUENCE OF 1-52; 70-103; 149-163; 192-201; 208-219; 317-325;
RP 378-405 AND 423-456, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N.;
RL Submitted (MAR-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 38-46; 149-163; 208-219; 306-316 AND 378-396, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP INTERACTION WITH HCV CORE PROTEIN.
RX PubMed=9651361; DOI=10.1074/jbc.273.28.17651;
RA Hsieh T.-Y., Matsumoto M., Chou H.-C., Schneider R., Hwang S.B.,
RA Lee A.S., Lai M.M.C.;
RT "Hepatitis C virus core protein interacts with heterogeneous nuclear
RT ribonucleoprotein K.";
RL J. Biol. Chem. 273:17651-17659(1998).
RN [10]
RP INTERACTION WITH DDX1.
RX PubMed=12183465; DOI=10.1074/jbc.M206981200;
RA Chen H.C., Lin W.C., Tsay Y.G., Lee S.C., Chang C.J.;
RT "An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous
RT nuclear ribonucleoprotein K.";
RL J. Biol. Chem. 277:40403-40409(2002).
RN [11]
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=11840567;
RX DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H;
RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A.,
RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J.,
RA Zvelebil M.J.;
RT "Cluster analysis of an extensive human breast cancer cell line
RT protein expression map database.";
RL Proteomics 2:212-223(2002).
RN [12]
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 [13]
RP FUNCTION, INTERACTION WITH MDM2 AND TP53, SUBCELLULAR LOCATION,
RP UBIQUITINATION, AND INDUCTION.
RX PubMed=16360036; DOI=10.1016/j.cell.2005.09.032;
RA Moumen A., Masterson P., O'Connor M.J., Jackson S.P.;
RT "hnRNP K: an HDM2 target and transcriptional coactivator of p53 in
RT response to DNA damage.";
RL Cell 123:1065-1078(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, 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 [15]
RP INTERACTION WITH ANKRD28, AND PHOSPHORYLATION AT SER-284.
RX PubMed=16564677; DOI=10.1016/j.cellsig.2006.01.019;
RA Kwiek N.C., Thacker D.F., Datto M.B., Megosh H.B., Haystead T.A.J.;
RT "PITK, a PP1 targeting subunit that modulates the phosphorylation of
RT the transcriptional regulator hnRNP K.";
RL Cell. Signal. 18:1769-1778(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216 AND SER-379, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
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 [18]
RP INTERACTION WITH ASFV PROTEIN P30.
RX PubMed=18775702; DOI=10.1016/j.febslet.2008.08.031;
RA Hernaez B., Escribano J.M., Alonso C.;
RT "African swine fever virus protein p30 interaction with heterogeneous
RT nuclear ribonucleoprotein K (hnRNP-K) during infection.";
RL FEBS Lett. 582:3275-3280(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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-116; SER-216 AND
RP SER-284, 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 ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216 AND TYR-380, AND
RP 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 [23]
RP FUNCTION.
RX PubMed=20673990; DOI=10.1016/j.cell.2010.06.040;
RA Huarte M., Guttman M., Feldser D., Garber M., Koziol M.J.,
RA Kenzelmann-Broz D., Khalil A.M., Zuk O., Amit I., Rabani M.,
RA Attardi L.D., Regev A., Lander E.S., Jacks T., Rinn J.L.;
RT "A large intergenic noncoding RNA induced by p53 mediates global gene
RT repression in the p53 response.";
RL Cell 142:409-419(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-284 AND
RP SER-379, 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 [25]
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214; SER-216; SER-284
RP AND SER-379, 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 [27]
RP GLYCOSYLATION.
RX PubMed=22967762; DOI=10.1016/j.bbagen.2012.08.024;
RA Drougat L., Olivier-Van Stichelen S., Mortuaire M., Foulquier F.,
RA Lacoste A.S., Michalski J.C., Lefebvre T., Vercoutter-Edouart A.S.;
RT "Characterization of O-GlcNAc cycling and proteomic identification of
RT differentially O-GlcNAcylated proteins during G1/S transition.";
RL Biochim. Biophys. Acta 1820:1839-1848(2012).
RN [28]
RP SUBCELLULAR LOCATION.
RX PubMed=22721921; DOI=10.1016/j.ejcb.2012.05.005;
RA Cervero P., Himmel M., Kruger M., Linder S.;
RT "Proteomic analysis of podosome fractions from macrophages reveals
RT similarities to spreading initiation centres.";
RL Eur. J. Cell Biol. 91:908-922(2012).
RN [29]
RP FUNCTION, SUMOYLATION AT LYS-422, UBIQUITINATION, AND MUTAGENESIS OF
RP LYS-422 AND ASP-424.
RX PubMed=22825850; DOI=10.1074/jbc.M112.390120;
RA Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.;
RT "DNA damage-induced heterogeneous nuclear ribonucleoprotein K
RT SUMOylation regulates p53 transcriptional activation.";
RL J. Biol. Chem. 287:30789-30799(2012).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP STRUCTURE BY NMR OF 375-463.
RX PubMed=10369774; DOI=10.1006/jmbi.1999.2818;
RA Baber J.L., Libutti D., Levens D., Tjandra N.;
RT "High precision solution structure of the C-terminal KH domain of
RT heterogeneous nuclear ribonucleoprotein K, a c-myc transcription
RT factor.";
RL J. Mol. Biol. 289:949-962(1999).
RN [32]
RP STRUCTURE BY NMR OF 379-463 IN COMPLEX WITH SINGLE-STRANDED DNA.
RX PubMed=12093748; DOI=10.1093/emboj/cdf352;
RA Braddock D.T., Baber J.L., Levens D., Clore G.M.;
RT "Molecular basis of sequence-specific single-stranded DNA recognition
RT by KH domains: solution structure of a complex between hnRNP K KH3 and
RT single-stranded DNA.";
RL EMBO J. 21:3476-3485(2002).
CC -!- FUNCTION: One of the major pre-mRNA-binding proteins. Binds
CC tenaciously to poly(C) sequences. Likely to play a role in the
CC nuclear metabolism of hnRNAs, particularly for pre-mRNAs that
CC contain cytidine-rich sequences. Can also bind poly(C) single-
CC stranded DNA. Plays an important role in p53/TP53 response to DNA
CC damage, acting at the level of both transcription activation and
CC repression. When sumoylated, acts as a transcriptional coactivator
CC of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN
CC induction (By similarity). As far as transcription repression is
CC concerned, acts by interacting with long intergenic RNA p21
CC (lincRNA-p21), a non-coding RNA induced by p53/TP53. This
CC interaction is necessary for the induction of apoptosis, but not
CC cell cycle arrest.
CC -!- SUBUNIT: Interacts with RBM42 and ZIK1. Interacts with BRDT (By
CC similarity). Identified in the spliceosome C complex. Interacts
CC with ANKRD28. Interacts with HCV core protein. Interacts with ASFV
CC p30 protein. Interacts with DDX1. Interacts with MDM2; this
CC interaction leads to ubiquitination and proteasomal degradation.
CC Interacts with p53/TP53.
CC -!- INTERACTION:
CC O14965:AURKA; NbExp=2; IntAct=EBI-304185, EBI-448680;
CC Q8V1E7:C'204L (xeno); NbExp=5; IntAct=EBI-304185, EBI-8068745;
CC Q00987:MDM2; NbExp=2; IntAct=EBI-304185, EBI-389668;
CC Q99873:PRMT1; NbExp=3; IntAct=EBI-304185, EBI-78738;
CC Q96PU8:QKI; NbExp=3; IntAct=EBI-304185, EBI-945792;
CC P38159:RBMX; NbExp=3; IntAct=EBI-304185, EBI-743526;
CC P12931:SRC; NbExp=6; IntAct=EBI-304185, EBI-621482;
CC P04637:TP53; NbExp=2; IntAct=EBI-304185, EBI-366083;
CC Q9H3D4:TP63; NbExp=2; IntAct=EBI-304185, EBI-2337775;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm. Cell
CC projection, podosome. Note=Recruited to p53/TP53-responsive
CC promoters, in the presence of functional p53/TP53. In case of ASFV
CC infection, there is a shift in the localization which becomes
CC predominantly nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P61978-1, Q07244-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P61978-2, Q07244-2;
CC Sequence=VSP_002822;
CC Name=3;
CC IsoId=P61978-3; Sequence=VSP_021669, VSP_002822;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: By DNA damage, including ionizing radiations and
CC phleomycin treatment or UV irradiation. This induction requires
CC ATM kinase activity (ionizing radiations and phleomycin) or ATR
CC activity (UV irradiation). Up-regulation is due to protein
CC stabilization. Constitutive protein levels are controlled by MDM2-
CC mediated ubiquitination and degradation via the proteasome
CC pathway.
CC -!- PTM: Arg-296 and Arg-299 are dimethylated, probably to asymmetric
CC dimethylarginine.
CC -!- PTM: Sumoylated by CBX4. Sumoylation is increased upon DNA damage,
CC such as that produced by doxorubicin, etoposide, UV light and
CC camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under
CC these conditions.
CC -!- PTM: Ubiquitinated by MDM2. Doxorubicin treatment does not affect
CC monoubiquitination, but slightly decreases HNRNPK poly-
CC ubiquitination.
CC -!- PTM: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent
CC manner.
CC -!- MASS SPECTROMETRY: Mass=50976.25; Method=MALDI; Range=1-463
CC (P61978-1); Source=PubMed:11840567;
CC -!- SIMILARITY: Contains 3 KH domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92799.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HNRNPKID44314ch9q21.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; S74678; AAB20770.1; -; mRNA.
DR EMBL; X72727; CAA51267.1; -; mRNA.
DR EMBL; AB209562; BAD92799.1; ALT_INIT; mRNA.
DR EMBL; AL354733; CAI16020.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62675.1; -; Genomic_DNA.
DR EMBL; BC000355; AAH00355.1; -; mRNA.
DR EMBL; BC014980; AAH14980.1; -; mRNA.
DR PIR; S43363; S43363.
DR RefSeq; NP_002131.2; NM_002140.3.
DR RefSeq; NP_112552.1; NM_031262.2.
DR RefSeq; NP_112553.1; NM_031263.2.
DR RefSeq; XP_005252017.1; XM_005251960.1.
DR RefSeq; XP_005252018.1; XM_005251961.1.
DR RefSeq; XP_005252020.1; XM_005251963.1.
DR RefSeq; XP_005252021.1; XM_005251964.1.
DR RefSeq; XP_005252022.1; XM_005251965.1.
DR UniGene; Hs.522257; -.
DR PDB; 1J5K; NMR; -; A=379-463.
DR PDB; 1KHM; NMR; -; A=379-463.
DR PDB; 1ZZI; X-ray; 1.80 A; A/B=385-463.
DR PDB; 1ZZJ; X-ray; 2.30 A; A/B/C=385-463.
DR PDB; 1ZZK; X-ray; 0.95 A; A=385-463.
DR PDBsum; 1J5K; -.
DR PDBsum; 1KHM; -.
DR PDBsum; 1ZZI; -.
DR PDBsum; 1ZZJ; -.
DR PDBsum; 1ZZK; -.
DR ProteinModelPortal; P61978; -.
DR SMR; P61978; 45-216, 385-463.
DR DIP; DIP-31805N; -.
DR IntAct; P61978; 95.
DR MINT; MINT-225422; -.
DR STRING; 9606.ENSP00000365439; -.
DR PhosphoSite; P61978; -.
DR DMDM; 48429103; -.
DR SWISS-2DPAGE; P61978; -.
DR PaxDb; P61978; -.
DR PRIDE; P61978; -.
DR DNASU; 3190; -.
DR Ensembl; ENST00000351839; ENSP00000317788; ENSG00000165119.
DR Ensembl; ENST00000360384; ENSP00000353552; ENSG00000165119.
DR Ensembl; ENST00000376263; ENSP00000365439; ENSG00000165119.
DR Ensembl; ENST00000376264; ENSP00000365440; ENSG00000165119.
DR Ensembl; ENST00000376281; ENSP00000365458; ENSG00000165119.
DR GeneID; 3190; -.
DR KEGG; hsa:3190; -.
DR UCSC; uc004ang.4; human.
DR CTD; 3190; -.
DR GeneCards; GC09M086582; -.
DR HGNC; HGNC:5044; HNRNPK.
DR HPA; CAB004435; -.
DR HPA; CAB016225; -.
DR HPA; HPA007644; -.
DR MIM; 600712; gene.
DR neXtProt; NX_P61978; -.
DR PharmGKB; PA162391350; -.
DR eggNOG; NOG285495; -.
DR HOVERGEN; HBG051916; -.
DR KO; K12886; -.
DR OMA; KALRTDX; -.
DR OrthoDB; EOG7CZK81; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; HNRNPK; human.
DR EvolutionaryTrace; P61978; -.
DR GeneWiki; HNRPK; -.
DR GenomeRNAi; 3190; -.
DR NextBio; 12686; -.
DR PMAP-CutDB; P61978; -.
DR PRO; PR:P61978; -.
DR ArrayExpress; P61978; -.
DR Bgee; P61978; -.
DR CleanEx; HS_HNRNPK; -.
DR Genevestigator; P61978; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; TAS:ProtInc.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IMP:BHF-UCL.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IMP:BHF-UCL.
DR GO; GO:0003697; F:single-stranded DNA binding; TAS:BHF-UCL.
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:0045716; P:positive regulation of low-density lipoprotein particle receptor biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0072369; P:regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0010988; P:regulation of low-density lipoprotein particle clearance; IMP:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR012987; ROK_N.
DR Pfam; PF00013; KH_1; 3.
DR Pfam; PF08067; ROKNT; 1.
DR SMART; SM00322; KH; 3.
DR PROSITE; PS50084; KH_TYPE_1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Cell junction; Cell projection; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Glycoprotein;
KW Host-virus interaction; Isopeptide bond; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Ribonucleoprotein; RNA-binding; Spliceosome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 463 Heterogeneous nuclear ribonucleoprotein
FT K.
FT /FTId=PRO_0000050096.
FT DOMAIN 42 104 KH 1.
FT REPEAT 54 76 1-1.
FT REPEAT 59 62 3-1.
FT DOMAIN 144 209 KH 2.
FT REPEAT 245 250 2-1.
FT REPEAT 257 260 3-2.
FT REPEAT 267 270 3-3.
FT REPEAT 295 298 3-4.
FT REPEAT 324 329 2-2.
FT DOMAIN 387 451 KH 3.
FT REPEAT 399 421 1-2.
FT REPEAT 404 407 3-5.
FT REGION 1 276 Necessary for interaction with DDX1.
FT REGION 35 197 Interaction with ASFV p30.
FT REGION 54 421 2 X 22 AA approximate repeats.
FT REGION 59 407 5 X 4 AA repeats of G-X-G-G.
FT REGION 209 337 Interaction with ZIK1 (By similarity).
FT REGION 236 273 RNA-binding RGG-box.
FT REGION 245 329 2 X 6 AA approximate repeats.
FT COMPBIAS 289 294 Poly-Pro.
FT COMPBIAS 310 315 Poly-Pro.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 116 116 Phosphoserine.
FT MOD_RES 214 214 Phosphoserine.
FT MOD_RES 216 216 Phosphoserine.
FT MOD_RES 284 284 Phosphoserine.
FT MOD_RES 379 379 Phosphoserine.
FT MOD_RES 380 380 Phosphotyrosine.
FT CROSSLNK 422 422 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 111 134 Missing (in isoform 3).
FT /FTId=VSP_021669.
FT VAR_SEQ 459 463 SGKFF -> ADVEGF (in isoform 2 and isoform
FT 3).
FT /FTId=VSP_002822.
FT MUTAGEN 422 422 K->R: Loss of sumoylation. Loss of TP53
FT transcriptional stimulation.
FT MUTAGEN 424 424 D->A: Loss of sumoylation.
FT CONFLICT 32 32 A -> D (in Ref. 2; CAA51267).
FT HELIX 381 384
FT STRAND 388 395
FT TURN 396 398
FT HELIX 399 402
FT HELIX 405 407
FT HELIX 408 417
FT STRAND 420 423
FT STRAND 430 439
FT HELIX 441 459
SQ SEQUENCE 463 AA; 50976 MW; 0F70EE169B2A064A CRC64;
METEQPEETF PNTETNGEFG KRPAEDMEEE QAFKRSRNTD EMVELRILLQ SKNAGAVIGK
GGKNIKALRT DYNASVSVPD SSGPERILSI SADIETIGEI LKKIIPTLEE GLQLPSPTAT
SQLPLESDAV ECLNYQHYKG SDFDCELRLL IHQSLAGGII GVKGAKIKEL RENTQTTIKL
FQECCPHSTD RVVLIGGKPD RVVECIKIIL DLISESPIKG RAQPYDPNFY DETYDYGGFT
MMFDDRRGRP VGFPMRGRGG FDRMPPGRGG RPMPPSRRDY DDMSPRRGPP PPPPGRGGRG
GSRARNLPLP PPPPPRGGDL MAYDRRGRPG DRYDGMVGFS ADETWDSAID TWSPSEWQMA
YEPQGGSGYD YSYAGGRGSY GDLGGPIITT QVTIPKDLAG SIIGKGGQRI KQIRHESGAS
IKIDEPLEGS EDRIITITGT QDQIQNAQYL LQNSVKQYSG KFF
//
MIM
600712
*RECORD*
*FIELD* NO
600712
*FIELD* TI
*600712 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K; HNRNPK
;;HNRPK
*FIELD* TX
DESCRIPTION
read more
HNRNPK is a conserved RNA-binding protein that is involved in multiple
processes of gene expression, including chromatin remodeling,
transcription, and mRNA splicing, translation, and stability. These
multiple functions of HNRNPK reflect its ability to associate with a
diverse group of molecular partners (summary by Fukuda et al., 2009).
CLONING
Dejgaard et al. (1994) identified HNRNPK acidic nuclear proteins using a
monoclonal antibody that distinguished between quiescent and
proliferating human keratinocytes. At least 4 major HNRNPK proteins
(HNRNPK-A, -B, -C, and -D) and their modified forms were present in
similar overall levels in quiescent and proliferating normal
keratinocytes, although clear differences were observed in levels of
some of the individual isoforms. Using a monoclonal antibody as a probe,
Dejgaard et al. (1994) cloned a cDNA coding for HNRNPK-B, and this was
used to screen for additional clones. Sequencing of positive clones
revealed 4 HNRNPK splice variants encoding HNRNPK-A, -B, -C, and -D. The
HNRNPK isoforms contain 458 to 464 amino acids and have calculated
molecular masses of 50 to 51 kD. The 458-amino acid isoform A contains
an N-terminal acidic domain, followed by 2 repeats of about 70 amino
acids each, an RGG box, a proline-rich segment, and a third repeat at
the C terminus. The 4 proteins resolved in a 2-dimensional gel with
apparent molecular masses of 64 to 66 kD and pI from 4.9 to 5.5.
By Northern blot analysis, Fukuda et al. (2009) detected variable Hnrnpk
expression in all mouse tissues examined except skeletal muscle.
Expression was also detected in 2 mouse and 2 human cell lines.
GENE FUNCTION
Dejgaard et al. (1994) noted that HNRNPK has been implicated in pre-mRNA
metabolism of transcripts containing cytidine-rich sequences. The
results of Dejgaard et al. (1994) pointed toward a role in cell cycle
progression.
Inoue et al. (2007) found that intracellular anti-HNRNPK compromised
cell migration of human fibrosarcoma cells. They found that cytoplasmic
accumulation of HNRNPK was crucial for cell migration and metastasis.
Using yeast 2-hybrid assays, Fukuda et al. (2009) found that rat Rbm42
(613232) interacted with human HNRNPK, and mutation analyses revealed
that the C-terminal RRM of Rbm42 interacted with the C-terminal KH
domain of HNRNPK. Epitope-tagged and endogenous human RBM42 isoforms and
HNRNPK coimmunoprecipitat ed in reciprocal reactions using HEK293 and
HeLa cell lysates, and both RBM42 and HNRNPK also independently bound
RNA. The isolated C-terminal domains of human RBM42 and HNRNPK
interacted in vitro. In vivo, however, RNA appeared to mediate the
association of the full-length proteins, since RNase treatment disrupted
their interaction. Immunofluorescence microscopy revealed that both
proteins predominantly localized in the nucleus of MTD-1A mouse mammary
tumor cells. Following cell stress, they independently localized in
cytoplasmic stress granules, transient foci that sequester mRNAs of
housekeeping genes during cell stress. Depletion of Hnrnpk, but not
Rbm42, in MTD-1A cells interfered with the recovery of ATP production
following release from cell stress. However, simultaneous Hnrnpk and
Rbm42 depletion further reduced cellular ATP levels following release
from cell stress. Fukuda et al. (2009) concluded that HNRNPK and RBM42
are involved in the maintenance of cellular ATP levels during stress,
possibly by protecting critical mRNAs.
GENE STRUCTURE
Sweetser et al. (2005) determined that the HNRNPK gene contains 15
exons.
By genomic sequence analysis, Reddy et al. (2008) found that the first
intron of HNRNPK contains the gene for microRNA-7-1 (MIR7-1; 615239).
MAPPING
Dejgaard et al. (1994) mapped the HNRNPK gene to chromosome 9 by
Southern blot analysis of human/rodent somatic cell hybrids. Tommerup
and Leffers (1996) mapped the HNRNPK gene to chromosome 9q21.32-q21.33
by fluorescence in situ hybridization.
*FIELD* RF
1. Dejgaard, K.; Leffers, H.; Rasmussen, H. H.; Madsen, P.; Kruse,
T. A.; Gesser, B.; Nielsen, H.; Celis, J. E.: Identification, molecular
cloning, expression and chromosome mapping of a family of transformation
upregulated hnRNP-K proteins derived by alternative splicing. J.
Molec. Biol. 236: 33-48, 1994.
2. Fukuda, T.; Naiki, T.; Saito, M.; Irie, K.: hnRNP K interacts
with RNA binding motif protein 42 and functions in the maintenance
of cellular ATP level during stress conditions. Genes Cells 14:
113-128, 2009.
3. Inoue, A.; Sawata, S. Y.; Taira, K.; Wadhwa, R.: Loss-of-function
screening by randomized intracellular antibodies: identification of
hnRNP-K as a potential target for metastasis. Proc. Nat. Acad. Sci. 104:
8983-8988, 2007.
4. Reddy, S. D. N.; Ohshiro, K.; Rayala, S. K.; Kumar, R.: MicroRNA-7,
a homeobox D10 target, inhibits p21-activated kinase 1 and regulates
its function. Cancer Res. 68: 8195-8200, 2008.
5. Sweetser, D. A.; Peniket, A. J.; Haaland, C.; Blomberg, A. A.;
Zhang, Y.; Zaidi, S. T.; Dayyani, F.; Zhao, Z.; Heerema, N. A.; Boultwood,
J.; Dewald, G. W.; Paietta, E.; Slovak, M. L.; Willman, C. L.; Wainscoat,
J. S.; Bernstein, I. D.; Daly, S. B.: Delineation of the minimal
commonly deleted segment and identification of candidate tumor-suppressor
genes in del(9q) acute myeloid leukemia. Genes Chromosomes Cancer 44:
279-291, 2005.
6. Tommerup, N.; Leffers, H.: Assignment of human KH-box-containing
genes by in situ hybridization: HNRNPK maps to 9q21.32-q21.33, PCBP1
to 2p12-p13, and PCBP2 to 12q13.12-q13.13, distal to FRA12A. Genomics 32:
297-298, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 05/20/2013
Patricia A. Hartz - updated: 1/26/2010
Patricia A. Hartz - updated: 1/16/2008
Patricia A. Hartz - updated: 8/9/2007
Alan F. Scott - updated: 4/4/1996
*FIELD* CD
Victor A. McKusick: 8/3/1995
*FIELD* ED
mgross: 05/20/2013
mgross: 11/18/2011
terry: 11/11/2011
mgross: 1/26/2010
terry: 1/26/2010
mgross: 1/25/2008
terry: 1/16/2008
mgross: 8/17/2007
terry: 8/9/2007
jamie: 5/29/1997
mark: 4/17/1996
mark: 4/4/1996
terry: 4/4/1996
mark: 4/4/1996
mark: 8/3/1995
*RECORD*
*FIELD* NO
600712
*FIELD* TI
*600712 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K; HNRNPK
;;HNRPK
*FIELD* TX
DESCRIPTION
read more
HNRNPK is a conserved RNA-binding protein that is involved in multiple
processes of gene expression, including chromatin remodeling,
transcription, and mRNA splicing, translation, and stability. These
multiple functions of HNRNPK reflect its ability to associate with a
diverse group of molecular partners (summary by Fukuda et al., 2009).
CLONING
Dejgaard et al. (1994) identified HNRNPK acidic nuclear proteins using a
monoclonal antibody that distinguished between quiescent and
proliferating human keratinocytes. At least 4 major HNRNPK proteins
(HNRNPK-A, -B, -C, and -D) and their modified forms were present in
similar overall levels in quiescent and proliferating normal
keratinocytes, although clear differences were observed in levels of
some of the individual isoforms. Using a monoclonal antibody as a probe,
Dejgaard et al. (1994) cloned a cDNA coding for HNRNPK-B, and this was
used to screen for additional clones. Sequencing of positive clones
revealed 4 HNRNPK splice variants encoding HNRNPK-A, -B, -C, and -D. The
HNRNPK isoforms contain 458 to 464 amino acids and have calculated
molecular masses of 50 to 51 kD. The 458-amino acid isoform A contains
an N-terminal acidic domain, followed by 2 repeats of about 70 amino
acids each, an RGG box, a proline-rich segment, and a third repeat at
the C terminus. The 4 proteins resolved in a 2-dimensional gel with
apparent molecular masses of 64 to 66 kD and pI from 4.9 to 5.5.
By Northern blot analysis, Fukuda et al. (2009) detected variable Hnrnpk
expression in all mouse tissues examined except skeletal muscle.
Expression was also detected in 2 mouse and 2 human cell lines.
GENE FUNCTION
Dejgaard et al. (1994) noted that HNRNPK has been implicated in pre-mRNA
metabolism of transcripts containing cytidine-rich sequences. The
results of Dejgaard et al. (1994) pointed toward a role in cell cycle
progression.
Inoue et al. (2007) found that intracellular anti-HNRNPK compromised
cell migration of human fibrosarcoma cells. They found that cytoplasmic
accumulation of HNRNPK was crucial for cell migration and metastasis.
Using yeast 2-hybrid assays, Fukuda et al. (2009) found that rat Rbm42
(613232) interacted with human HNRNPK, and mutation analyses revealed
that the C-terminal RRM of Rbm42 interacted with the C-terminal KH
domain of HNRNPK. Epitope-tagged and endogenous human RBM42 isoforms and
HNRNPK coimmunoprecipitat ed in reciprocal reactions using HEK293 and
HeLa cell lysates, and both RBM42 and HNRNPK also independently bound
RNA. The isolated C-terminal domains of human RBM42 and HNRNPK
interacted in vitro. In vivo, however, RNA appeared to mediate the
association of the full-length proteins, since RNase treatment disrupted
their interaction. Immunofluorescence microscopy revealed that both
proteins predominantly localized in the nucleus of MTD-1A mouse mammary
tumor cells. Following cell stress, they independently localized in
cytoplasmic stress granules, transient foci that sequester mRNAs of
housekeeping genes during cell stress. Depletion of Hnrnpk, but not
Rbm42, in MTD-1A cells interfered with the recovery of ATP production
following release from cell stress. However, simultaneous Hnrnpk and
Rbm42 depletion further reduced cellular ATP levels following release
from cell stress. Fukuda et al. (2009) concluded that HNRNPK and RBM42
are involved in the maintenance of cellular ATP levels during stress,
possibly by protecting critical mRNAs.
GENE STRUCTURE
Sweetser et al. (2005) determined that the HNRNPK gene contains 15
exons.
By genomic sequence analysis, Reddy et al. (2008) found that the first
intron of HNRNPK contains the gene for microRNA-7-1 (MIR7-1; 615239).
MAPPING
Dejgaard et al. (1994) mapped the HNRNPK gene to chromosome 9 by
Southern blot analysis of human/rodent somatic cell hybrids. Tommerup
and Leffers (1996) mapped the HNRNPK gene to chromosome 9q21.32-q21.33
by fluorescence in situ hybridization.
*FIELD* RF
1. Dejgaard, K.; Leffers, H.; Rasmussen, H. H.; Madsen, P.; Kruse,
T. A.; Gesser, B.; Nielsen, H.; Celis, J. E.: Identification, molecular
cloning, expression and chromosome mapping of a family of transformation
upregulated hnRNP-K proteins derived by alternative splicing. J.
Molec. Biol. 236: 33-48, 1994.
2. Fukuda, T.; Naiki, T.; Saito, M.; Irie, K.: hnRNP K interacts
with RNA binding motif protein 42 and functions in the maintenance
of cellular ATP level during stress conditions. Genes Cells 14:
113-128, 2009.
3. Inoue, A.; Sawata, S. Y.; Taira, K.; Wadhwa, R.: Loss-of-function
screening by randomized intracellular antibodies: identification of
hnRNP-K as a potential target for metastasis. Proc. Nat. Acad. Sci. 104:
8983-8988, 2007.
4. Reddy, S. D. N.; Ohshiro, K.; Rayala, S. K.; Kumar, R.: MicroRNA-7,
a homeobox D10 target, inhibits p21-activated kinase 1 and regulates
its function. Cancer Res. 68: 8195-8200, 2008.
5. Sweetser, D. A.; Peniket, A. J.; Haaland, C.; Blomberg, A. A.;
Zhang, Y.; Zaidi, S. T.; Dayyani, F.; Zhao, Z.; Heerema, N. A.; Boultwood,
J.; Dewald, G. W.; Paietta, E.; Slovak, M. L.; Willman, C. L.; Wainscoat,
J. S.; Bernstein, I. D.; Daly, S. B.: Delineation of the minimal
commonly deleted segment and identification of candidate tumor-suppressor
genes in del(9q) acute myeloid leukemia. Genes Chromosomes Cancer 44:
279-291, 2005.
6. Tommerup, N.; Leffers, H.: Assignment of human KH-box-containing
genes by in situ hybridization: HNRNPK maps to 9q21.32-q21.33, PCBP1
to 2p12-p13, and PCBP2 to 12q13.12-q13.13, distal to FRA12A. Genomics 32:
297-298, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 05/20/2013
Patricia A. Hartz - updated: 1/26/2010
Patricia A. Hartz - updated: 1/16/2008
Patricia A. Hartz - updated: 8/9/2007
Alan F. Scott - updated: 4/4/1996
*FIELD* CD
Victor A. McKusick: 8/3/1995
*FIELD* ED
mgross: 05/20/2013
mgross: 11/18/2011
terry: 11/11/2011
mgross: 1/26/2010
terry: 1/26/2010
mgross: 1/25/2008
terry: 1/16/2008
mgross: 8/17/2007
terry: 8/9/2007
jamie: 5/29/1997
mark: 4/17/1996
mark: 4/4/1996
terry: 4/4/1996
mark: 4/4/1996
mark: 8/3/1995