HNRPL_HUMAN
ID HNRPL_HUMAN Reviewed; 589 AA.
AC P14866; A6ND69; A6NIT8; Q9H3P3;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Heterogeneous nuclear ribonucleoprotein L;
DE Short=hnRNP L;
GN Name=HNRNPL; Synonyms=HNRPL; ORFNames=P/OKcl.14;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pancreatic cancer;
RX PubMed=11280764;
RA Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.;
RT "Molecular basis of T cell-mediated recognition of pancreatic cancer
RT cells.";
RL Cancer Res. 61:2038-2046(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Synovium;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-589 (ISOFORM 1), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=2687284; DOI=10.1083/jcb.109.6.2575;
RA Pinol-Roma S., Swanson M.S., Gall J.G., Dreyfuss G.;
RT "A novel heterogeneous nuclear RNP protein with a unique distribution on
RT nascent transcripts.";
RL J. Cell Biol. 109:2575-2587(1989).
RN [6]
RP PROTEIN SEQUENCE OF 67-76; 199-215; 218-233; 386-403; 425-448 AND 549-558,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [8]
RP FUNCTION, AND INTERACTION WITH APEX1.
RX PubMed=11809897; DOI=10.1093/nar/30.3.823;
RA Kuninger D.T., Izumi T., Papaconstantinou J., Mitra S.;
RT "Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor
RT element in the AP-endonuclease 1 promoter.";
RL Nucleic Acids Res. 30:823-829(2002).
RN [9]
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 [10]
RP INTERACTION WITH ELAVL1.
RX PubMed=18161049; DOI=10.1002/hep.22036;
RA Matsui K., Nishizawa M., Ozaki T., Kimura T., Hashimoto I., Yamada M.,
RA Kaibori M., Kamiyama Y., Ito S., Okumura T.;
RT "Natural antisense transcript stabilizes inducible nitric oxide synthase
RT messenger RNA in rat hepatocytes.";
RL Hepatology 47:686-697(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-298, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP INTERACTION WITH HNRNPLL.
RX PubMed=18669861; DOI=10.1126/science.1157610;
RA Oberdoerffer S., Moita L.F., Neems D., Freitas R.P., Hacohen N., Rao A.;
RT "Regulation of CD45 alternative splicing by heterogeneous
RT ribonucleoprotein, hnRNPLL.";
RL Science 321:686-691(2008).
RN [13]
RP INTERACTION WITH SETD2.
RX PubMed=19332550; DOI=10.1074/jbc.m808431200;
RA Yuan W., Xie J., Long C., Erdjument-Bromage H., Ding X., Zheng Y.,
RA Tempst P., Chen S., Zhu B., Reinberg D.;
RT "Heterogeneous nuclear ribonucleoprotein L is a subunit of human KMT3a/Set2
RT complex required for H3 Lys-36 trimethylation activity in vivo.";
RL J. Biol. Chem. 284:15701-15707(2009).
RN [14]
RP ALTERNATIVE SPLICING, AND MISCELLANEOUS.
RX PubMed=19124611; DOI=10.1128/mcb.01689-08;
RA Rossbach O., Hung L.H., Schreiner S., Grishina I., Heiner M., Hui J.,
RA Bindereif A.;
RT "Auto- and cross-regulation of the hnRNP L proteins by alternative
RT splicing.";
RL Mol. Cell. Biol. 29:1442-1451(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-269, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; SER-185 AND SER-298, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; SER-101; SER-185; SER-291
RP AND SER-298, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP PHOSPHORYLATION AT SER-544, AND FUNCTION.
RX PubMed=22570490; DOI=10.1074/jbc.m112.357343;
RA Liu G., Razanau A., Hai Y., Yu J., Sohail M., Lobo V.G., Chu J., Kung S.K.,
RA Xie J.;
RT "A conserved serine of heterogeneous nuclear ribonucleoprotein L (hnRNP L)
RT mediates depolarization-regulated alternative splicing of potassium
RT channels.";
RL J. Biol. Chem. 287:22709-22716(2012).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; SER-101; SER-185 AND
RP SER-298, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP FUNCTION.
RX PubMed=24164894; DOI=10.1128/mcb.00740-13;
RA Shankarling G., Cole B.S., Mallory M.J., Lynch K.W.;
RT "Transcriptome-wide RNA interaction profiling reveals physical and
RT functional targets of hnRNP L in human T cells.";
RL Mol. Cell. Biol. 34:71-83(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-62, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [25]
RP FUNCTION.
RX PubMed=25623890; DOI=10.1016/j.bbagrm.2015.01.004;
RA Loh T.J., Cho S., Moon H., Jang H.N., Williams D.R., Jung D.W., Kim I.C.,
RA Ghigna C., Biamonti G., Zheng X., Shen H.;
RT "hnRNP L inhibits CD44 V10 exon splicing through interacting with its
RT upstream intron.";
RL Biochim. Biophys. Acta 1849:743-750(2015).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-136, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [27]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26051023; DOI=10.1016/j.jmb.2015.05.020;
RA Blatter M., Dunin-Horkawicz S., Grishina I., Maris C., Thore S., Maier T.,
RA Bindereif A., Bujnicki J.M., Allain F.H.;
RT "The signature of the five-stranded vRRM fold defined by functional,
RT structural and computational analysis of the hnRNP L protein.";
RL J. Mol. Biol. 427:3001-3022(2015).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-62, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-59; LYS-62; LYS-136; LYS-302 AND
RP LYS-568, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [31]
RP FUNCTION, AND SUBUNIT.
RX PubMed=33174841; DOI=10.7554/elife.58478;
RA Hollensen A.K., Thomsen H.S., Lloret-Llinares M., Kamstrup A.B.,
RA Jensen J.M., Luckmann M., Birkmose N., Palmfeldt J., Jensen T.H.,
RA Hansen T.B., Damgaard C.K.;
RT "circZNF827 nucleates a transcription inhibitory complex to balance
RT neuronal differentiation.";
RL Elife 9:0-0(2020).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 90-180, X-RAY CRYSTALLOGRAPHY
RP (1.82 ANGSTROMS) OF 380-589, RNA-BINDING, RRM DOMAINS, AND MUTAGENESIS OF
RP HIS-105; VAL-132; LEU-141; ASN-172; SER-174; HIS-504 AND PHE-506.
RX PubMed=23782695; DOI=10.1074/jbc.m113.463901;
RA Zhang W., Zeng F., Liu Y., Zhao Y., Lv H., Niu L., Teng M., Li X.;
RT "Crystal structures and RNA-binding properties of the RNA recognition
RT motifs of heterogeneous nuclear ribonucleoprotein L: insights into its
RT roles in alternative splicing regulation.";
RL J. Biol. Chem. 288:22636-22649(2013).
CC -!- FUNCTION: Splicing factor binding to exonic or intronic sites and
CC acting as either an activator or repressor of exon inclusion. Exhibits
CC a binding preference for CA-rich elements (PubMed:11809897,
CC PubMed:22570490, PubMed:24164894, PubMed:25623890, PubMed:26051023).
CC Component of the heterogeneous nuclear ribonucleoprotein (hnRNP)
CC complexes and associated with most nascent transcripts
CC (PubMed:2687284). Associates, together with APEX1, to the negative
CC calcium responsive element (nCaRE) B2 of the APEX2 promoter
CC (PubMed:11809897). As part of a ribonucleoprotein complex composed at
CC least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates
CC the complex on chromatin, may negatively regulate the transcription of
CC genes involved in neuronal differentiation (PubMed:33174841).
CC {ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:22570490,
CC ECO:0000269|PubMed:25623890, ECO:0000269|PubMed:26051023,
CC ECO:0000269|PubMed:2687284, ECO:0000269|PubMed:33174841}.
CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex
CC containing untranslated mRNAs (PubMed:17289661). Interacts with HNRNPLL
CC (PubMed:18669861). Interacts with APEX1; the interaction is DNA-
CC dependent (PubMed:11809897). Component of a complex with SETD2
CC (PubMed:19332550). Interacts with ELAVL1 (PubMed:18161049). Part of a
CC transcription inhibitory ribonucleoprotein complex composed at least of
CC the circular RNA circZNF827, ZNF827 and HNRNPK (PubMed:33174841).
CC {ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:17289661,
CC ECO:0000269|PubMed:18161049, ECO:0000269|PubMed:18669861,
CC ECO:0000269|PubMed:19332550, ECO:0000269|PubMed:33174841}.
CC -!- INTERACTION:
CC P14866; P22626: HNRNPA2B1; NbExp=2; IntAct=EBI-719024, EBI-299649;
CC P14866; P61978: HNRNPK; NbExp=4; IntAct=EBI-719024, EBI-304185;
CC P14866; P40337: VHL; NbExp=2; IntAct=EBI-719024, EBI-301246;
CC P14866-1; P22626: HNRNPA2B1; NbExp=4; IntAct=EBI-16071645, EBI-299649;
CC P14866-1; Q12906: ILF3; NbExp=2; IntAct=EBI-16071645, EBI-78756;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:2687284,
CC ECO:0000305|PubMed:26051023}. Cytoplasm {ECO:0000269|PubMed:17289661}.
CC Note=Localized in cytoplasmic mRNP granules containing untranslated
CC mRNAs. These granules are not identical with P bodies or stress
CC granules. {ECO:0000269|PubMed:17289661}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P14866-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P14866-2; Sequence=VSP_044301;
CC -!- DOMAIN: RRM domain 2 has moderate RNA-binding affinity. RRM domains 3
CC and 4 may facilitate RNA looping when binding to two appropriately
CC separated binding sites within the same target pre-mRNA
CC (PubMed:23782695). {ECO:0000269|PubMed:23782695}.
CC -!- PTM: Several isoelectric forms of the L protein are probably the
CC results of post-translational modifications.
CC -!- PTM: Phosphorylation at Ser-544 by CaMK4 enhances interaction with a
CC CaMK4-responsive RNA element (CaRRE1), and prevents inclusion of the
CC stress axis-regulated exon (STREX) of the KCNMA1 potassium channel
CC transcripts upon membrane depolarization.
CC {ECO:0000269|PubMed:22570490}.
CC -!- MISCELLANEOUS: Excess hnRNP L activates NMD of its own mRNA by
CC promoting the inclusion of a 'poison exon' containing a premature stop
CC codon and leading to nonsense-mediated decay. It also cross-regulates
CC inclusion of an analogous 'poison exon' in the hnRNP L-like pre-mRNA
CC (PubMed:19124611). {ECO:0000305|PubMed:19124611}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA34261.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB044547; BAB18649.1; -; mRNA.
DR EMBL; AK292115; BAF84804.1; -; mRNA.
DR EMBL; AC008982; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW56828.1; -; Genomic_DNA.
DR EMBL; X16135; CAA34261.1; ALT_INIT; mRNA.
DR CCDS; CCDS33015.1; -. [P14866-1]
DR CCDS; CCDS33016.1; -. [P14866-2]
DR PIR; A33616; A33616.
DR RefSeq; NP_001005335.1; NM_001005335.1. [P14866-2]
DR RefSeq; NP_001524.2; NM_001533.2. [P14866-1]
DR RefSeq; XP_011525191.1; XM_011526889.1.
DR PDB; 3R27; X-ray; 2.04 A; A/B=90-180.
DR PDB; 3TO8; X-ray; 1.82 A; A=380-589.
DR PDB; 7EVR; X-ray; 1.80 A; A/C=186-289.
DR PDBsum; 3R27; -.
DR PDBsum; 3TO8; -.
DR PDBsum; 7EVR; -.
DR AlphaFoldDB; P14866; -.
DR BMRB; P14866; -.
DR SMR; P14866; -.
DR BioGRID; 109432; 1819.
DR CORUM; P14866; -.
DR DIP; DIP-36355N; -.
DR IntAct; P14866; 73.
DR MINT; P14866; -.
DR STRING; 9606.ENSP00000221419; -.
DR DrugBank; DB09130; Copper.
DR GlyGen; P14866; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P14866; -.
DR MetOSite; P14866; -.
DR PhosphoSitePlus; P14866; -.
DR SwissPalm; P14866; -.
DR BioMuta; HNRNPL; -.
DR DMDM; 215274006; -.
DR REPRODUCTION-2DPAGE; IPI00027834; -.
DR SWISS-2DPAGE; P14866; -.
DR EPD; P14866; -.
DR jPOST; P14866; -.
DR MassIVE; P14866; -.
DR MaxQB; P14866; -.
DR PaxDb; P14866; -.
DR PeptideAtlas; P14866; -.
DR PRIDE; P14866; -.
DR ProteomicsDB; 1284; -.
DR ProteomicsDB; 53090; -. [P14866-1]
DR Antibodypedia; 4276; 465 antibodies from 37 providers.
DR DNASU; 3191; -.
DR Ensembl; ENST00000221419.10; ENSP00000221419.4; ENSG00000104824.18. [P14866-1]
DR Ensembl; ENST00000600873.5; ENSP00000470231.1; ENSG00000104824.18. [P14866-2]
DR Ensembl; ENST00000634237.1; ENSP00000489244.1; ENSG00000282947.2. [P14866-2]
DR Ensembl; ENST00000634753.1; ENSP00000489021.1; ENSG00000282947.2. [P14866-1]
DR GeneID; 3191; -.
DR KEGG; hsa:3191; -.
DR MANE-Select; ENST00000221419.10; ENSP00000221419.4; NM_001533.3; NP_001524.2.
DR UCSC; uc060yfy.1; human. [P14866-1]
DR CTD; 3191; -.
DR DisGeNET; 3191; -.
DR GeneCards; HNRNPL; -.
DR HGNC; HGNC:5045; HNRNPL.
DR HPA; ENSG00000104824; Low tissue specificity.
DR MIM; 603083; gene.
DR neXtProt; NX_P14866; -.
DR OpenTargets; ENSG00000104824; -.
DR PharmGKB; PA162391389; -.
DR VEuPathDB; HostDB:ENSG00000104824; -.
DR eggNOG; KOG1456; Eukaryota.
DR GeneTree; ENSGT01030000234642; -.
DR HOGENOM; CLU_015171_0_0_1; -.
DR InParanoid; P14866; -.
DR OMA; VYNAQYP; -.
DR OrthoDB; 1545178at2759; -.
DR PhylomeDB; P14866; -.
DR TreeFam; TF354318; -.
DR PathwayCommons; P14866; -.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR Reactome; R-HSA-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR SignaLink; P14866; -.
DR SIGNOR; P14866; -.
DR BioGRID-ORCS; 3191; 736 hits in 1079 CRISPR screens.
DR ChiTaRS; HNRNPL; human.
DR GeneWiki; HNRNPL; -.
DR GenomeRNAi; 3191; -.
DR Pharos; P14866; Tbio.
DR PRO; PR:P14866; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P14866; protein.
DR Bgee; ENSG00000104824; Expressed in ventricular zone and 193 other tissues.
DR ExpressionAtlas; P14866; baseline and differential.
DR Genevisible; P14866; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0035770; C:ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IEA:Ensembl.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1990715; F:mRNA CDS binding; IEA:Ensembl.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IEA:InterPro.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:1902416; P:positive regulation of mRNA binding; IEA:Ensembl.
DR GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; IBA:GO_Central.
DR GO; GO:1901652; P:response to peptide; IEA:Ensembl.
DR GO; GO:0006396; P:RNA processing; TAS:ProtInc.
DR CDD; cd12780; RRM1_hnRNPL; 1.
DR CDD; cd12785; RRM2_hnRNPL; 1.
DR CDD; cd12699; RRM3_hnRNPL; 1.
DR CDD; cd12704; RRM4_hnRNPL; 1.
DR Gene3D; 3.30.70.330; -; 4.
DR InterPro; IPR006536; HnRNP-L/PTB.
DR InterPro; IPR034816; hnRNP-L_RRM3.
DR InterPro; IPR035005; hnRNPL_RRM1.
DR InterPro; IPR035008; hnRNPL_RRM2.
DR InterPro; IPR034817; hnRNPL_RRM4.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR021790; PTBP1-like_RRM2.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR Pfam; PF11835; RRM_8; 1.
DR SMART; SM00360; RRM; 3.
DR SUPFAM; SSF54928; SSF54928; 3.
DR TIGRFAMs; TIGR01649; hnRNP-L_PTB; 1.
DR PROSITE; PS50102; RRM; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Isopeptide bond; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ribonucleoprotein; RNA-binding;
KW Ubl conjugation.
FT CHAIN 1..589
FT /note="Heterogeneous nuclear ribonucleoprotein L"
FT /id="PRO_0000081862"
FT DOMAIN 102..176
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 193..270
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 382..478
FT /note="RRM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 495..583
FT /note="RRM 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 1..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 284..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 11..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..305
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 323..337
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..378
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 269
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 354
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8R081"
FT MOD_RES 358
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8R081"
FT MOD_RES 381
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R081"
FT MOD_RES 544
FT /note="Phosphoserine; by CaMK4"
FT /evidence="ECO:0000269|PubMed:22570490"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 62
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 568
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044301"
FT MUTAGEN 105
FT /note="H->A: 6-fold decrease in RNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:23782695"
FT MUTAGEN 132
FT /note="V->A: 4-fold increase in RNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:23782695"
FT MUTAGEN 141
FT /note="L->A: 15-fold decrease in RNA-binding affinity; when
FT associated with A-174."
FT /evidence="ECO:0000269|PubMed:23782695"
FT MUTAGEN 172
FT /note="N->A: 1-fold increase in RNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:23782695"
FT MUTAGEN 174
FT /note="S->A: 15-fold decrease in RNA-binding affinity; when
FT associated with A-174."
FT /evidence="ECO:0000269|PubMed:23782695"
FT MUTAGEN 504
FT /note="H->A: Significant decrease in RNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:23782695"
FT MUTAGEN 506
FT /note="F->A: Significant decrease in RNA-binding affinity."
FT /evidence="ECO:0000269|PubMed:23782695"
FT CONFLICT 396
FT /note="C -> G (in Ref. 1; BAB18649 and 5; CAA34261)"
FT /evidence="ECO:0000305"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:3R27"
FT HELIX 115..122
FT /evidence="ECO:0007829|PDB:3R27"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:3R27"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:3R27"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:3R27"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:3R27"
FT HELIX 147..159
FT /evidence="ECO:0007829|PDB:3R27"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:3R27"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:3R27"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:7EVR"
FT HELIX 208..215
FT /evidence="ECO:0007829|PDB:7EVR"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:7EVR"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:7EVR"
FT STRAND 229..240
FT /evidence="ECO:0007829|PDB:7EVR"
FT HELIX 241..251
FT /evidence="ECO:0007829|PDB:7EVR"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:7EVR"
FT STRAND 260..267
FT /evidence="ECO:0007829|PDB:7EVR"
FT STRAND 279..284
FT /evidence="ECO:0007829|PDB:7EVR"
FT STRAND 382..387
FT /evidence="ECO:0007829|PDB:3TO8"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:3TO8"
FT HELIX 396..403
FT /evidence="ECO:0007829|PDB:3TO8"
FT TURN 404..406
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 409..414
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 421..428
FT /evidence="ECO:0007829|PDB:3TO8"
FT HELIX 429..439
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 450..453
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 472..476
FT /evidence="ECO:0007829|PDB:3TO8"
FT HELIX 488..491
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 501..508
FT /evidence="ECO:0007829|PDB:3TO8"
FT HELIX 514..524
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 530..534
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 543..548
FT /evidence="ECO:0007829|PDB:3TO8"
FT HELIX 552..562
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 572..574
FT /evidence="ECO:0007829|PDB:3TO8"
FT STRAND 579..582
FT /evidence="ECO:0007829|PDB:3TO8"
SQ SEQUENCE 589 AA; 64133 MW; 31EEB51AF1C65F83 CRC64;
MSRRLLPRAE KRRRRLEQRQ QPDEQRRRSG AMVKMAAAGG GGGGGRYYGG GSEGGRAPKR
LKTDNAGDQH GGGGGGGGGA GAAGGGGGGE NYDDPHKTPA SPVVHIRGLI DGVVEADLVE
ALQEFGPISY VVVMPKKRQA LVEFEDVLGA CNAVNYAADN QIYIAGHPAF VNYSTSQKIS
RPGDSDDSRS VNSVLLFTIL NPIYSITTDV LYTICNPCGP VQRIVIFRKN GVQAMVEFDS
VQSAQRAKAS LNGADIYSGC CTLKIEYAKP TRLNVFKNDQ DTWDYTNPNL SGQGDPGSNP
NKRQRQPPLL GDHPAEYGGP HGGYHSHYHD EGYGPPPPHY EGRRMGPPVG GHRRGPSRYG
PQYGHPPPPP PPPEYGPHAD SPVLMVYGLD QSKMNCDRVF NVFCLYGNVE KVKFMKSKPG
AAMVEMADGY AVDRAITHLN NNFMFGQKLN VCVSKQPAIM PGQSYGLEDG SCSYKDFSES
RNNRFSTPEQ AAKNRIQHPS NVLHFFNAPL EVTEENFFEI CDELGVKRPS SVKVFSGKSE
RSSSGLLEWE SKSDALETLG FLNHYQMKNP NGPYPYTLKL CFSTAQHAS
