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Protein

Heterogeneous nuclear ribonucleoprotein U

Gene

Hnrnpu

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA- and RNA-binding protein involved in several cellular processes such as nuclear chromatin organization, telomere-length regulation, transcription, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing and mitotic cell progression (PubMed:20833368, PubMed:21235343, PubMed:22162999, PubMed:26244333). Plays a role in the regulation of interphase large-scale gene-rich chromatin organization through chromatin-associated RNAs (caRNAs) in a transcription-dependent manner, and thereby maintains genomic stability (By similarity). Required for the localization of the long non-coding Xist RNA on the inactive chromosome X (Xi) and the subsequent initiation and maintenance of X-linked transcriptional gene silencing during X-inactivation (PubMed:20833368, PubMed:26244333). Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator (PubMed:21235343, PubMed:22162999). Promotes transcription initiation by direct association with the core-TFIIH basal transcription factor complex for the assembly of a functional pre-initiation complex with Pol II in a actin-dependent manner. Blocks Pol II transcription elongation activity by inhibiting the C-terminal domain (CTD) phosphorylation of Pol II and dissociates from Pol II pre-initiation complex prior to productive transcription elongation. Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus. Negatively regulates glucocorticoid-mediated transcriptional activation (By similarity). Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling (PubMed:21235343). Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression (By similarity). Participates in the circadian regulation of the core clock component ARNTL/BMAL1 transcription (PubMed:18332112). Plays a role in the regulation of telomere length. Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis. Plays a role in mRNA stability. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Enhances the expression of specific genes, such as tumor necrosis factor TNFA, by regulating mRNA stability, possibly through binding to the 3'-untranslated region (UTR). Plays a role in mitotic cell cycle regulation. Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression. Phosphorylation at Ser-58 by PLK1 is required for chromosome alignement and segregation and progression through mitosis. Contributes also to the targeting of AURKA to mitotic spindle MTs. Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides. Binds to chromatin-associated RNAs (caRNAs). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner (By similarity). Binds (via RNA-binding RGG-box region) to the long non-coding Xist RNA; this binding is direct and bridges the Xist RNA and the inactive chromosome X (Xi) (PubMed:20833368, PubMed:26244333). Binds the long non-coding H19 RNA. Binds to SMN1/2 pre-mRNAs at G/U-rich regions. Binds to small nuclear RNAs (snRNAs). Binds to the 3'-UTR of TNFA mRNA (By similarity). Also negatively regulates embryonic stem cell differentiation upon LIF signaling (PubMed:21235343). Required for embryonic development (PubMed:16022389).By similarity6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi480 – 487ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Developmental protein, DNA-binding, Repressor, Ribonucleoprotein, RNA-binding
Biological processBiological rhythms, Cell cycle, Cell division, Differentiation, Mitosis, mRNA processing, mRNA splicing, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-72163. mRNA Splicing - Major Pathway.
R-MMU-72203. Processing of Capped Intron-Containing Pre-mRNA.

Names & Taxonomyi

Protein namesi
Recommended name:
Heterogeneous nuclear ribonucleoprotein UImported
Short name:
hnRNP U1 Publication
Alternative name(s):
Scaffold-attachment factor A1 Publication
Short name:
SAF-A1 Publication
Gene namesi
Name:HnrnpuImported
Synonyms:HnrpuImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1858195. Hnrnpu.

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

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus, Spliceosome

Pathology & Biotechi

Disruption phenotypei

Mice exhibit early embryonic lethality between 9.5 and 11.5 dpc (PubMed:16022389). Mice show retarded development of embryonic ectoderm at 6.5 dpc and growth retardation beginning at 7.5 dpc (PubMed:16022389).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003879472 – 800Heterogeneous nuclear ribonucleoprotein UAdd BLAST799

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei4PhosphoserineBy similarity1
Modified residuei17N6-acetyllysineCombined sources1
Modified residuei21N6-acetyllysineCombined sources1
Modified residuei58PhosphoserineCombined sources1
Modified residuei181N6-acetyllysineCombined sources1
Modified residuei182ADP-ribosylserineBy similarity1
Modified residuei231Citrulline1 Publication1
Modified residuei241N6-acetyllysine; alternateCombined sources1
Cross-linki241Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki241Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei242PhosphotyrosineCombined sources1
Modified residuei243PhosphoserineBy similarity1
Modified residuei247PhosphoserineCombined sources1
Modified residuei262PhosphothreonineBy similarity1
Modified residuei328N6-acetyllysineCombined sources1
Cross-linki471Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei492N6-acetyllysine; alternateBy similarity1
Cross-linki492Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei500N6-acetyllysine; alternateBy similarity1
Cross-linki500Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei508PhosphothreonineBy similarity1
Cross-linki512Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei527N6-acetyllysineBy similarity1
Modified residuei541N6-acetyllysine; alternateBy similarity1
Cross-linki541Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki550Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei558PhosphothreonineBy similarity1
Cross-linki585Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki602Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei611N6-acetyllysine; alternateBy similarity1
Cross-linki611Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki640Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki646Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei678Omega-N-methylarginineBy similarity1
Modified residuei691Asymmetric dimethylarginineCombined sources1
Modified residuei696Asymmetric dimethylarginineCombined sources1
Modified residuei703Asymmetric dimethylarginineCombined sources1
Modified residuei709Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei709Omega-N-methylarginine; alternateCombined sources1
Modified residuei709Omega-N-methylated arginine; alternateBy similarity1
Modified residuei715Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei715Dimethylated arginine; alternateBy similarity1
Modified residuei715Omega-N-methylarginine; alternateCombined sources1
Modified residuei715Omega-N-methylated arginine; alternateBy similarity1
Modified residuei730Asymmetric dimethylarginineBy similarity1
Modified residuei737Asymmetric dimethylarginineCombined sources1
Modified residuei789N6-acetyllysine; alternateBy similarity1
Cross-linki789Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity

Post-translational modificationi

Cleaved at Asp-94 by CASP3 during T-cell apoptosis, resulting in a loss of DNA- and chromatin-binding activities.By similarity
Extensively phosphorylated. Phosphorylated on Ser-58 by PLK1 and dephosphorylated by protein phosphatase 2A (PP2A) in mitosis.By similarity
Arg-709 and Arg-715 are dimethylated, probably to asymmetric dimethylarginine.1 Publication
Citrullinated by PADI4.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei94Cleavage; by CASP3By similarity1

Keywords - PTMi

Acetylation, ADP-ribosylation, Citrullination, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8VEK3.
MaxQBiQ8VEK3.
PaxDbiQ8VEK3.
PeptideAtlasiQ8VEK3.
PRIDEiQ8VEK3.

PTM databases

iPTMnetiQ8VEK3.
PhosphoSitePlusiQ8VEK3.
SwissPalmiQ8VEK3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000100725.
ExpressionAtlasiQ8VEK3. baseline and differential.
GenevisibleiQ8VEK3. MM.

Interactioni

Subunit structurei

Oligomer (via ATPase domain and RNA-binding RGG-box region); oligomerization occurs upon ATP-binding in a chromatin-associated RNAs (caRNAs)- and transcription-dependent manner and is required for chromatin decompaction. ATP hydrolysis is required to cycle from an oligomeric to monomeric state to compact chromatin. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Associates with heterogeneous nuclear ribonucleoprotein (hnRNP) particles (By similarity). Associates (via middle region) with the C-terminal domain (CTD) RNA polymerase II (Pol II) holoenzyme; this association occurs in a RNA-independent manner (PubMed:21235343). Associates (via middle region) with the core-TFIIH basal transcription factor complex; this association inhibits the CTD phosphorylation of RNA polymerase II holoenzyme by downregulating TFIIH kinase activity. Associates with the telomerase holoenzyme complex. Associates with spindle microtubules (MTs) in a TPX2-dependent manner. Interacts (via C-terminus) with actin; this interaction is direct and mediates association with the phosphorylated CTD of RNA polymerase II and is disrupted in presence of the long non-coding H19 RNA. Interacts with AURKA. Interacts (via C-terminus) with CBX5; this interaction is, at least in part, RNA-dependent. Interacts with CR2 (By similarity). Interacts with CRY1 (PubMed:19129230). Interacts (via C-terminus) with EP300; this interaction enhances DNA-binding to nuclear scaffold/matrix attachment region (S/MAR) elements. Interacts with ERBB4. Interacts with GEMIN5. Interacts with IGF2BP1. Interacts with IGF2BP2 and IGF2BP3. Interacts with NCL; this interaction occurs during mitosis. Interacts (via C-terminus) with NR3C1 (via C-terminus). Interacts with PLK1; this interaction induces phosphorylation of HNRNPU at Ser-58 in mitosis. Interacts with POU3F4 (By similarity). Interacts with SMARCA4; this interaction occurs in embryonic stem cells and stimulates global Pol II-mediated transcription (PubMed:22162999). Interacts (via C-terminus) with TOP2A; this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA by TOP2A in a RNA-dependent manner. Interacts with TPX2; this interaction recruits HNRNPU to spindle microtubules (MTs). Interacts with UBQLN2 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Smarca4Q3TKT43EBI-529674,EBI-1210244

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206185. 10 interactors.
DIPiDIP-34257N.
IntActiQ8VEK3. 6 interactors.
STRINGi10090.ENSMUSP00000047571.

Structurei

3D structure databases

ProteinModelPortaliQ8VEK3.
SMRiQ8VEK3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 42SAPPROSITE-ProRule annotation1 PublicationAdd BLAST35
Domaini244 – 440B30.2/SPRYPROSITE-ProRule annotationAdd BLAST197

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni464 – 648ATPase domainBy similarityAdd BLAST185
Regioni587 – 602Actin-bindingBy similarityAdd BLAST16
Regioni690 – 715RNA-binding RGG-box1 PublicationAdd BLAST26

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili626 – 653Sequence analysisAdd BLAST28

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 154Asp/Glu-rich (acidic)Add BLAST153
Compositional biasi679 – 769Gly-richAdd BLAST91

Domaini

The SAP domain is necessary for specific binding to nuclear scaffold/matrix attachment region (S/MAR) elements in DNA. The RNA-binding RGG-box region is necessary for its association with inactive X chromosome (Xi) regions and to chromatin-associated RNAs (caRNAs) (By similarity). Both the DNA-binding domain SAP and the RNA-binding RGG-box region are necessary for the localization of Xist RNA on the Xi (PubMed:20833368). The ATPase and RNA-binding RGG-box regions are necessary for oligomerization (By similarity).By similarity1 Publication

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2242. Eukaryota.
ENOG410Y1WQ. LUCA.
GeneTreeiENSGT00390000020210.
HOGENOMiHOG000253920.
InParanoidiQ8VEK3.
KOiK12888.
OMAiQAFNQSW.
OrthoDBiEOG091G041T.
PhylomeDBiQ8VEK3.
TreeFamiTF317301.

Family and domain databases

CDDicd12884. SPRY_hnRNP. 1 hit.
Gene3Di1.10.720.30. 1 hit.
InterProiView protein in InterPro
IPR001870. B30.2/SPRY.
IPR013320. ConA-like_dom_sf.
IPR026745. hnRNP_U.
IPR027417. P-loop_NTPase.
IPR003034. SAP_dom.
IPR036361. SAP_dom_sf.
IPR003877. SPRY_dom.
IPR035778. SPRY_hnRNP_U.
PANTHERiPTHR12381:SF11. PTHR12381:SF11. 1 hit.
PfamiView protein in Pfam
PF02037. SAP. 1 hit.
PF00622. SPRY. 1 hit.
SMARTiView protein in SMART
SM00513. SAP. 1 hit.
SM00449. SPRY. 1 hit.
SUPFAMiSSF49899. SSF49899. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF68906. SSF68906. 1 hit.
PROSITEiView protein in PROSITE
PS50188. B302_SPRY. 1 hit.
PS50800. SAP. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q8VEK3-1) [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
MSSSPVNVKK LKVSELKEEL KKRRLSDKGL KADLMDRLQA ALDNEAGGRP
60 70 80 90 100
AMEPGNGSLD LGGDAAGRSG AGLEQEAAAG AEDDEEEEGI AALDGDQMEL
110 120 130 140 150
GEENGAAGAA DAGAMEEEEA ASEDENGDDQ GFQEGEDELG DEEEGAGDEN
160 170 180 190 200
GHGEQQSQPP AAAAQQQPSQ QRGAGKEAAG KSSGPTSLFA VTVAPPGARQ
210 220 230 240 250
GQQQAGGDGK TEQKGGDKKR GVKRPREDHG RGYFEYIEEN KYSRAKSPQP
260 270 280 290 300
PVEEEDEHFD DTVVCLDTYN CDLHFKISRD RLSASSLTME SFAFLWAGGR
310 320 330 340 350
ASYGVSKGKV CFEMKVTEKI PVRHLYTKDI DIHEVRIGWS LTTSGMLLGE
360 370 380 390 400
EEFSYGYSLK GIKTCNCETE DYGEKFDEND VITCFANFET DEVELSYAKN
410 420 430 440 450
GQDLGVAFKI SKEVLADRPL FPHVLCHNCA VEFNFGQKEK PYFPIPEDCT
460 470 480 490 500
FIQNVPLEDR VRGPKGPEEK KDCEVVMMIG LPGAGKTTWV TKHAAENPGK
510 520 530 540 550
YNILGTNTIM DKMMVAGFKK QMADTGKLNT LLQRAPQCLG KFIEIAARKK
560 570 580 590 600
RNFILDQTNV SAAAQRRKMC LFAGFQRKAV VVCPKDEDYK QRTQKKAEVE
610 620 630 640 650
GKDLPEHAVL KMKGNFTLPE VAECFDEITY VELQKEEAQK LLEQYKEESK
660 670 680 690 700
KALPPEKKQN TGSKKSNKNK SGKNQFNRGG GHRGRGGFNM RGGNFRGGAP
710 720 730 740 750
GNRGGYNRRG NMPQRGGGGG SGGIGYPYPR GPVFPGRGGY SNRGNYNRGG
760 770 780 790 800
MPNRGNYNQN FRGRGNNRGY KNQSQGYNQW QQGQFWGQKP WSQHYHQGYY
Length:800
Mass (Da):87,918
Last modified:March 1, 2002 - v1
Checksum:i2BA7C73043F847B2
GO
Isoform 2 (identifier: Q8VEK3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     784-800: QFWGQKPWSQHYHQGYY → SVHVNVLCEE

Note: Gene prediction based on EST data.
Show »
Length:793
Mass (Da):86,805
Checksum:i78E12271FF261ABA
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_059004784 – 800QFWGQ…HQGYY → SVHVNVLCEE in isoform 2. Add BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK165844 mRNA. Translation: BAE38409.1.
AC166710 Genomic DNA. No translation available.
CH466555 Genomic DNA. Translation: EDL13176.1.
CH466555 Genomic DNA. Translation: EDL13177.1.
BC018353 mRNA. Translation: AAH18353.1.
AF073991 Genomic DNA. Translation: AAD29847.1.
CCDSiCCDS35804.1. [Q8VEK3-1]
RefSeqiNP_058085.2. NM_016805.2. [Q8VEK3-1]
XP_017177161.1. XM_017321672.1. [Q8VEK3-1]
XP_017177162.1. XM_017321673.1. [Q8VEK3-2]
XP_017177163.1. XM_017321674.1. [Q8VEK3-2]
UniGeneiMm.482674.
Mm.86589.

Genome annotation databases

EnsembliENSMUST00000037748; ENSMUSP00000047571; ENSMUSG00000039630. [Q8VEK3-1]
ENSMUST00000161769; ENSMUSP00000124147; ENSMUSG00000039630. [Q8VEK3-2]
ENSMUST00000213673; ENSMUSP00000148926; ENSMUSG00000111145. [Q8VEK3-2]
ENSMUST00000216820; ENSMUSP00000150782; ENSMUSG00000111145. [Q8VEK3-1]
GeneIDi51810.
KEGGimmu:51810.
UCSCiuc011wxl.1. mouse. [Q8VEK3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHNRPU_MOUSE
AccessioniPrimary (citable) accession number: Q8VEK3
Secondary accession number(s): G3XA10, Q9R205
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 3, 2009
Last sequence update: March 1, 2002
Last modified: November 22, 2017
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot