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Protein

Heterogeneous nuclear ribonucleoprotein L

Gene

HNRNPL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:22570490, PubMed:24164894, PubMed:25623890, PubMed:26051023). Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts (PubMed:2687284). Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter (PubMed:11809897).5 Publications

Miscellaneous

Excess hnRNP L activates NMD of its own mRNA by promoting the inclusion of a 'poison exon' containing a premature stop codon and leading to nonsense-mediated decay. It also cross-regulates inclusion of an analogous 'poison exon' in the hnRNP L-like pre-mRNA (PubMed:19124611).1 Publication

GO - Molecular functioni

  • mRNA 3'-UTR binding Source: Ensembl
  • mRNA CDS binding Source: Ensembl
  • pre-mRNA intronic binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionRibonucleoprotein, RNA-binding

Enzyme and pathway databases

ReactomeiR-HSA-72163 mRNA Splicing - Major Pathway
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA
SIGNORiP14866

Names & Taxonomyi

Protein namesi
Recommended name:
Heterogeneous nuclear ribonucleoprotein L
Short name:
hnRNP L
Gene namesi
Name:HNRNPL
Synonyms:HNRPL
ORF Names:P/OKcl.14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000104824.16
HGNCiHGNC:5045 HNRNPL
MIMi164021 gene
603083 gene
neXtProtiNX_P14866

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi105H → A: 6-fold decrease in RNA-binding affinity. 1 Publication1
Mutagenesisi132V → A: 4-fold increase in RNA-binding affinity. 1 Publication1
Mutagenesisi141L → A: 15-fold decrease in RNA-binding affinity; when associated with A-174. 1 Publication1
Mutagenesisi172N → A: 1-fold increase in RNA-binding affinity. 1 Publication1
Mutagenesisi174S → A: 15-fold decrease in RNA-binding affinity; when associated with A-174. 1 Publication1
Mutagenesisi504H → A: Significant decrease in RNA-binding affinity. 1 Publication1
Mutagenesisi506F → A: Significant decrease in RNA-binding affinity. 1 Publication1

Organism-specific databases

DisGeNETi3191
OpenTargetsiENSG00000104824
PharmGKBiPA162391389

Polymorphism and mutation databases

BioMutaiHNRNPL
DMDMi215274006

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000818621 – 589Heterogeneous nuclear ribonucleoprotein LAdd BLAST589

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphoserineCombined sources1
Cross-linki59Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki62Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei101PhosphoserineCombined sources1
Cross-linki136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei185PhosphoserineCombined sources1
Modified residuei269N6-acetyllysineCombined sources1
Modified residuei291PhosphoserineCombined sources1
Modified residuei298PhosphoserineCombined sources1
Cross-linki302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei354Asymmetric dimethylarginineBy similarity1
Modified residuei358Asymmetric dimethylarginineBy similarity1
Modified residuei381PhosphoserineBy similarity1
Modified residuei544Phosphoserine; by CaMK41 Publication1
Cross-linki568Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Several isoelectric forms of the L protein are probably the results of post-translational modifications.
Phosphorylation at Ser-544 by CaMK4 enhances interaction with a CaMK4-responsive RNA element (CaRRE1), and prevents inclusion of the stress axis-regulated exon (STREX) of the KCNMA1 potassium channel transcripts upon membrane depolarization.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP14866
MaxQBiP14866
PaxDbiP14866
PeptideAtlasiP14866
PRIDEiP14866
ProteomicsDBi53090

2D gel databases

REPRODUCTION-2DPAGEiIPI00027834
SWISS-2DPAGEiP14866

PTM databases

iPTMnetiP14866
PhosphoSitePlusiP14866
SwissPalmiP14866

Expressioni

Gene expression databases

BgeeiENSG00000104824
CleanExiHS_HNRNPL
ExpressionAtlasiP14866 baseline and differential
GenevisibleiP14866 HS

Organism-specific databases

HPAiCAB016326
HPA051748
HPA052661

Interactioni

Subunit structurei

Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with HNRNPLL (PubMed:18669861). Interacts with APEX1; the interaction is DNA-dependent (PubMed:11809897). Component of a complex with SETD2 (PubMed:19332550). Interacts with ELAVL1 (PubMed:18161049).5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109432, 1668 interactors
CORUMiP14866
DIPiDIP-36355N
IntActiP14866, 60 interactors
MINTiP14866
STRINGi9606.ENSP00000221419

Structurei

Secondary structure

1589
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi102 – 108Combined sources7
Helixi115 – 122Combined sources8
Helixi123 – 125Combined sources3
Beta strandi128 – 134Combined sources7
Turni135 – 138Combined sources4
Beta strandi139 – 146Combined sources8
Helixi147 – 159Combined sources13
Beta strandi162 – 164Combined sources3
Beta strandi167 – 173Combined sources7
Beta strandi382 – 387Combined sources6
Turni391 – 393Combined sources3
Helixi396 – 403Combined sources8
Turni404 – 406Combined sources3
Beta strandi409 – 414Combined sources6
Beta strandi421 – 428Combined sources8
Helixi429 – 439Combined sources11
Beta strandi450 – 453Combined sources4
Beta strandi472 – 476Combined sources5
Helixi488 – 491Combined sources4
Beta strandi501 – 508Combined sources8
Helixi514 – 524Combined sources11
Beta strandi530 – 534Combined sources5
Beta strandi543 – 548Combined sources6
Helixi552 – 562Combined sources11
Beta strandi572 – 574Combined sources3
Beta strandi579 – 582Combined sources4

3D structure databases

ProteinModelPortaliP14866
SMRiP14866
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini102 – 176RRM 1PROSITE-ProRule annotationAdd BLAST75
Domaini193 – 270RRM 2PROSITE-ProRule annotationAdd BLAST78
Domaini382 – 478RRM 3PROSITE-ProRule annotationAdd BLAST97
Domaini495 – 583RRM 4PROSITE-ProRule annotationAdd BLAST89

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi39 – 89Gly-richAdd BLAST51
Compositional biasi335 – 382Pro-richAdd BLAST48

Domaini

RRM domain 2 has moderate RNA-binding affinity. RRM domains 3 and 4 may facilitate RNA looping when binding to two appropriately separated binding sites within the same target pre-mRNA (PubMed:23782695).1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1456 Eukaryota
ENOG410XQHN LUCA
GeneTreeiENSGT00550000074508
HOGENOMiHOG000293298
HOVERGENiHBG105786
InParanoidiP14866
KOiK13159
OMAiRAGAMVK
OrthoDBiEOG091G0PR3
PhylomeDBiP14866
TreeFamiTF354318

Family and domain databases

CDDicd12780 RRM1_hnRNPL, 1 hit
cd12785 RRM2_hnRNPL, 1 hit
cd12699 RRM3_hnRNPL, 1 hit
cd12704 RRM4_hnRNPL, 1 hit
Gene3Di3.30.70.330, 4 hits
InterProiView protein in InterPro
IPR006536 HnRNP-L/PTB
IPR034816 hnRNP-L_RRM3
IPR035005 hnRNPL_RRM1
IPR035008 hnRNPL_RRM2
IPR034817 hnRNPL_RRM4
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PfamiView protein in Pfam
PF00076 RRM_1, 2 hits
SMARTiView protein in SMART
SM00360 RRM, 3 hits
SUPFAMiSSF54928 SSF54928, 3 hits
TIGRFAMsiTIGR01649 hnRNP-L_PTB, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 3 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P14866-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSRRLLPRAE KRRRRLEQRQ QPDEQRRRSG AMVKMAAAGG GGGGGRYYGG
60 70 80 90 100
GSEGGRAPKR LKTDNAGDQH GGGGGGGGGA GAAGGGGGGE NYDDPHKTPA
110 120 130 140 150
SPVVHIRGLI DGVVEADLVE ALQEFGPISY VVVMPKKRQA LVEFEDVLGA
160 170 180 190 200
CNAVNYAADN QIYIAGHPAF VNYSTSQKIS RPGDSDDSRS VNSVLLFTIL
210 220 230 240 250
NPIYSITTDV LYTICNPCGP VQRIVIFRKN GVQAMVEFDS VQSAQRAKAS
260 270 280 290 300
LNGADIYSGC CTLKIEYAKP TRLNVFKNDQ DTWDYTNPNL SGQGDPGSNP
310 320 330 340 350
NKRQRQPPLL GDHPAEYGGP HGGYHSHYHD EGYGPPPPHY EGRRMGPPVG
360 370 380 390 400
GHRRGPSRYG PQYGHPPPPP PPPEYGPHAD SPVLMVYGLD QSKMNCDRVF
410 420 430 440 450
NVFCLYGNVE KVKFMKSKPG AAMVEMADGY AVDRAITHLN NNFMFGQKLN
460 470 480 490 500
VCVSKQPAIM PGQSYGLEDG SCSYKDFSES RNNRFSTPEQ AAKNRIQHPS
510 520 530 540 550
NVLHFFNAPL EVTEENFFEI CDELGVKRPS SVKVFSGKSE RSSSGLLEWE
560 570 580
SKSDALETLG FLNHYQMKNP NGPYPYTLKL CFSTAQHAS
Length:589
Mass (Da):64,133
Last modified:November 25, 2008 - v2
Checksum:i31EEB51AF1C65F83
GO
Isoform 2 (identifier: P14866-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-133: Missing.

Show »
Length:456
Mass (Da):50,561
Checksum:i59DD6B10F1F41E68
GO

Sequence cautioni

The sequence CAA34261 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti396C → G in BAB18649 (PubMed:11280764).Curated1
Sequence conflicti396C → G in CAA34261 (PubMed:2687284).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443011 – 133Missing in isoform 2. 1 PublicationAdd BLAST133

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044547 mRNA Translation: BAB18649.1
AK292115 mRNA Translation: BAF84804.1
AC008982 Genomic DNA No translation available.
CH471126 Genomic DNA Translation: EAW56828.1
X16135 mRNA Translation: CAA34261.1 Different initiation.
CCDSiCCDS33015.1 [P14866-1]
CCDS33016.1 [P14866-2]
PIRiA33616
RefSeqiNP_001005335.1, NM_001005335.1 [P14866-2]
NP_001524.2, NM_001533.2 [P14866-1]
XP_011525191.1, XM_011526889.1 [P14866-2]
UniGeneiHs.644906

Genome annotation databases

EnsembliENST00000221419; ENSP00000221419; ENSG00000104824 [P14866-1]
ENST00000600873; ENSP00000470231; ENSG00000104824 [P14866-2]
ENST00000634237; ENSP00000489244; ENSG00000282947 [P14866-2]
ENST00000634753; ENSP00000489021; ENSG00000282947 [P14866-1]
GeneIDi3191
KEGGihsa:3191
UCSCiuc060yfy.1 human [P14866-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHNRPL_HUMAN
AccessioniPrimary (citable) accession number: P14866
Secondary accession number(s): A6ND69, A6NIT8, Q9H3P3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 25, 2008
Last modified: July 18, 2018
This is version 198 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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