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 27-MAR-2024, entry version 235. 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 FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHD8 AND SETD2. RX PubMed=36537238; DOI=10.1093/nar/gkac1134; RA Kerschbamer E., Arnoldi M., Tripathi T., Pellegrini M., Maturi S., RA Erdin S., Salviato E., Di Leva F., Sebestyen E., Dassi E., Zarantonello G., RA Benelli M., Campos E., Basson M.A., Gusella J.F., Gustincich S., Piazza S., RA Demichelis F., Talkowski M.E., Ferrari F., Biagioli M.; RT "CHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters RT RNA alternative splicing."; RL Nucleic Acids Res. 50:12809-12828(2022). RN [33] 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). Regulates CC alternative splicing of a core group of genes involved in neuronal CC differentiation, likely by mediating H3K36me3-coupled transcription CC elongation and co-transcriptional RNA processing via interaction with CC CHD8. {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 ECO:0000269|PubMed:36537238}. 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, PubMed:36537238). Interacts with ELAVL1 CC (PubMed:18161049). Part of a transcription inhibitory ribonucleoprotein CC complex composed at least of the circular RNA circZNF827, ZNF827 and CC HNRNPK (PubMed:33174841). Interacts with CHD8 in an RNA-dependent CC manner. {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 ECO:0000269|PubMed:36537238}. 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; Q8IUH3: RBM45; NbExp=5; IntAct=EBI-719024, EBI-2512147; 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, ECO:0000305|PubMed:36537238}. Cytoplasm CC {ECO:0000269|PubMed:17289661}. Note=Localized in cytoplasmic mRNP CC granules containing untranslated mRNAs. These granules are not CC identical with P bodies or stress granules. CC {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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 1967. DR CORUM; P14866; -. DR DIP; DIP-36355N; -. DR IntAct; P14866; 77. 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 EPD; P14866; -. DR jPOST; P14866; -. DR MassIVE; P14866; -. DR MaxQB; P14866; -. DR PaxDb; 9606-ENSP00000221419; -. DR PeptideAtlas; P14866; -. DR ProteomicsDB; 1284; -. DR ProteomicsDB; 53090; -. [P14866-1] DR Pumba; P14866; -. DR Antibodypedia; 4276; 513 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 AGR; HGNC:5045; -. 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; 4825346at2759; -. 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; 763 hits in 1158 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 195 other cell types or tissues. DR ExpressionAtlas; P14866; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0035770; C:ribonucleoprotein granule; IDA:UniProtKB. DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central. 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:0006397; P:mRNA processing; IEA:InterPro. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB. 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: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 NCBIfam; TIGR01649; hnRNP-L_PTB; 1. DR PANTHER; PTHR15592:SF20; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN L; 1. DR PANTHER; PTHR15592; MATRIN 3/NUCLEAR PROTEIN 220-RELATED; 1. DR Pfam; PF00076; RRM_1; 1. DR Pfam; PF13893; RRM_5; 1. DR Pfam; PF11835; RRM_8; 1. DR SMART; SM00360; RRM; 3. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 3. DR PROSITE; PS50102; RRM; 3. DR SWISS-2DPAGE; P14866; -. DR Genevisible; P14866; HS. 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 //