Affinage

SRSF5

Serine/arginine-rich splicing factor 5 · UniProt Q13243

Length
272 aa
Mass
31.3 kDa
Annotated
2026-04-28
100 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRSF5 (SRp40) is a phosphorylation-regulated SR family splicing factor that controls alternative exon inclusion and skipping across diverse pre-mRNA targets including fibronectin EIIIB, PKCβII, CCAR1, PKM, METTL14, GRβ, and Mcl-1 (PMID:9199345, PMID:11283022, PMID:29942010, PMID:38263157, PMID:33849617). Phosphorylation of its RS domain — by Akt2 at Ser86 downstream of PI3K/insulin signaling or by CLK1 at Ser250 — is required for sequence-specific RNA binding and splicing enhancer activity (PMID:9037021, PMID:15684423, PMID:33849617). SRSF5 protein stability is controlled by a mutually exclusive acetylation–ubiquitylation switch on K125: Tip60-mediated acetylation under glucose-replete conditions stabilizes SRSF5, whereas HDAC1-mediated deacetylation permits Smurf1- or TRIM72-dependent ubiquitylation and proteasomal degradation, coupling cellular metabolic state to splicing output (PMID:29942010, PMID:38263157). SRSF5 levels are further modulated by autoregulation of its own pre-mRNA processing, a circuit that can be overridden by SRSF3 in cancer contexts (PMID:7686911, PMID:29857020).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1993 Medium

    Identifying SRSF5 as a growth-regulated SR protein with autoregulatory mRNA processing established it as a potential alternative splicing regulator whose own expression is feedback-controlled.

    Evidence cDNA cloning and temporal RT-PCR profiling of HRS mRNA isoforms during cell growth response

    PMID:7686911

    Open questions at the time
    • Autoregulation mechanism not biochemically reconstituted
    • No splicing targets identified at this stage
  2. 1997 High

    Demonstrating that RS domain phosphorylation is required for SRSF5 to bind specific RNA sequences and activate splicing enhancers answered how post-translational modification governs substrate selectivity among SR proteins.

    Evidence SELEX selection of high-affinity RNA targets with phosphorylated vs. unphosphorylated SRp40; in vitro splicing reconstitution; SRSF5 uniquely activates its cognate enhancer in S100 complementation

    PMID:9037021

    Open questions at the time
    • Kinase(s) responsible for activating phosphorylation not identified
    • In vivo targets unknown
  3. 1997 High

    Showing that SRSF5 is the specific SR protein required for fibronectin EIIIB exon inclusion via a purine-rich enhancer provided the first physiological splicing target and demonstrated non-redundancy among SR proteins.

    Evidence In vivo minigene splicing assay with RNA binding specificity comparison across multiple SR proteins

    PMID:9199345

    Open questions at the time
    • Structural basis of SRSF5–EIIIB enhancer recognition unknown
    • Physiological consequence of EIIIB inclusion not tested
  4. 2001 High

    Linking insulin/PI3K signaling to SRp40 phosphorylation and PKCβII exon inclusion revealed that SRSF5 acts as a signal-responsive splicing switch coupling extracellular cues to alternative splicing outcomes.

    Evidence PI3K inhibitor (LY294002), antisense oligonucleotides targeting SRp40-binding site, SRp40 overexpression; phosphorylation assay in insulin-stimulated cells

    PMID:11283022

    Open questions at the time
    • Direct kinase phosphorylating SRp40 downstream of PI3K not identified
    • Phosphorylation site not mapped
  5. 2005 High

    Identifying Akt2 as the kinase that directly phosphorylates SRSF5 at Ser86 to promote PKCβII exon inclusion completed the PI3K → Akt2 → SRp40 → splicing signaling axis.

    Evidence In vitro kinase assay, Ser86Ala mutagenesis, Akt2 knockout mouse with defective PKCβII splicing, minigene assay

    PMID:15684423

    Open questions at the time
    • Whether Akt2 phosphorylation affects SRSF5 targets beyond PKCβII is unknown
    • Contribution of other SR protein kinases at the same site not addressed
  6. 2004 Medium

    Mapping SRSF5 binding on HIV-1 RNA near splice acceptor A3 and showing it antagonizes hnRNP A1-mediated silencing expanded SRSF5 function to viral RNA processing and defined the SR/hnRNP competition model at this site.

    Evidence Overexpression in HeLa, in vitro splicing, enzymatic footprinting of HIV-1 RNA, NMR of hnRNP A1 interaction (2006 follow-up)

    PMID:15123677 PMID:16990281

    Open questions at the time
    • Endogenous SRSF5 contribution to HIV-1 splicing not isolated from other SR proteins
    • In vivo viral replication consequence not shown
  7. 2010 Medium

    Showing SRSF5 promotes translation of unspliced HIV-1 gag mRNA through its second RRM and RS domain extended its function beyond splicing to translational regulation of intron-containing RNA.

    Evidence Domain deletion/mutation analysis, Gag protein quantification by Western blot, codon-optimized reporter in HeLa cells

    PMID:20427542

    Open questions at the time
    • Whether SRSF5 promotes translation of endogenous intron-retaining cellular mRNAs is untested
    • Mechanism of translational enhancement (ribosome recruitment vs. RNA export) not distinguished
  8. 2018 High

    Discovering the acetylation–ubiquitylation switch at K125 (Tip60/HDAC1/Smurf1) that couples glucose availability to SRSF5 protein stability and CCAR1 splicing established a metabolic sensing mechanism for splicing factor turnover.

    Evidence In vitro ubiquitylation and acetylation assays, K125R/K125Q mutagenesis, Tip60/HDAC1/Smurf1 perturbation, splicing minigene, xenograft tumor model

    PMID:29942010

    Open questions at the time
    • Whether the K125 switch operates genome-wide on all SRSF5 targets is unknown
    • How glucose signals are transduced to Tip60/HDAC1 is not resolved
  9. 2021 High

    Identifying CLK1 phosphorylation at Ser250 as a second regulatory phosphorylation site controlling METTL14 and Cyclin L2 splicing showed that distinct kinase inputs generate target-specific splicing programs.

    Evidence Phosphorylation mass spectrometry, Ser250 mutagenesis, CLIP-qPCR and RNA pull-down for direct binding, RNA-seq, pancreatic cancer xenograft

    PMID:33849617

    Open questions at the time
    • Relationship between Akt2-Ser86 and CLK1-Ser250 phosphorylation events is unknown
    • Whether CLK1-mediated phosphorylation affects the K125 stability switch is untested
  10. 2024 High

    Identifying TRIM72 as a second E3 ligase for SRSF5 degradation — recruited by lncRNA LINC01852 — and linking SRSF5 loss to a PKM2-to-PKM1 splicing switch demonstrated how non-coding RNA can reprogram cancer cell metabolism via splicing factor turnover.

    Evidence RNA pull-down, RIP, co-IP, ubiquitination assay, siRNA/shRNA knockdown, in vivo colorectal cancer mouse model

    PMID:38263157

    Open questions at the time
    • Whether TRIM72 and Smurf1 act on the same or different lysine residues is not clarified
    • Structural basis of LINC01852-mediated TRIM72 recruitment to SRSF5 is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified model explaining how multiple phosphorylation inputs (Akt2-Ser86, CLK1-Ser250) and stability controls (Tip60/Smurf1/TRIM72 at K125) are integrated to determine target-specific splicing programs in different tissues and metabolic states remains unestablished.
  • No genome-wide map of direct SRSF5-dependent exons under defined signaling conditions
  • Structural basis of SRSF5 RNA target selectivity versus other SR proteins is unresolved
  • Interplay between phosphorylation and acetylation/ubiquitylation switches has not been tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2
Partners
AKT2CLK1CPEB2HDAC1SMURF1SRSF3TIP60TRIM72

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Phosphorylation of the RS domain of SRp40 (SRSF5) is required for sequence-specific RNA binding; unphosphorylated SRp40 fails to select specific RNA sequences, and three copies of the selected high-affinity site (B1) function as a strong splicing enhancer activated specifically by SRp40 but not by ASF/SF2 or SC35. SELEX RNA binding selection, in vitro splicing assay in nuclear extracts and S100 extracts, SR protein-specific complementation Proceedings of the National Academy of Sciences of the United States of America High 9037021
1993 HRS (SRSF5) was identified as a member of the family of regulators of alternative pre-mRNA splicing; different forms of HRS mRNA are temporally regulated during the growth response, suggesting autoregulation of its own pre-mRNA processing. cDNA cloning, sequence analysis, RT-PCR temporal expression profiling The Journal of biological chemistry Medium 7686911
1997 HRS/SRp40 (SRSF5) directly mediates inclusion of the fibronectin EIIIB alternative exon in vivo; this activity depends on a purine-rich splicing enhancer sequence within the EIIIB exon to which HRS specifically binds, and no other SR protein tested could substitute. In vivo splicing minigene assay, RNA binding specificity assay, comparison across SR protein family members Molecular and cellular biology High 9199345
2001 Insulin regulates PKCbetaII exon inclusion via PI 3-kinase-dependent phosphorylation of SRp40 (SRSF5); antisense oligonucleotides targeting a putative SRp40-binding sequence in the betaII-betaI intron blocked both insulin-induced splicing and glucose uptake; overexpression of SRp40 mimicked insulin-induced exon inclusion. Antisense oligonucleotide knockdown, overexpression, PI 3-kinase inhibitor (LY294002), phosphorylation assay The Journal of biological chemistry High 11283022
2005 Akt2 kinase directly phosphorylates SRp40 (SRSF5) on Ser86 in vitro and in vivo; this phosphorylation event promotes PKCbetaII exon inclusion; mutation of Ser86 blocks in vitro phosphorylation and Akt2-deficient mice show defective PKCbetaII splicing. In vitro kinase assay, site-directed mutagenesis (Ser86Ala), Akt2 knockout mouse, quantitative RT-PCR, transfection of splicing minigene The Journal of biological chemistry High 15684423
2010 SRp40 (SRSF5), specifically through its second RNA recognition motif and RS domain, promotes translation of unspliced HIV-1 gRNA (Gag expression) from intron-containing viral RNA; this activity does not correlate with nucleocytoplasmic shuttling capacity and is abolished by codon optimization of the gag-pol region. Overexpression/knockdown in HeLa cells, domain deletion/mutation analysis, Gag protein quantification by Western blot, codon-optimized reporter assay Journal of virology Medium 20427542
2004 SRp40 (SRSF5) strongly activates HIV-1 splice acceptor site A3 both in vivo and in vitro, leading to dramatic accumulation of tat mRNA; its binding site on HIV-1 RNA was delineated by footprinting and shown to overlap with hnRNP A1 sites, indicating SR protein-mediated antagonism of silencer binding. Overexpression in HeLa cells, in vitro splicing, enzymatic footprinting, quantitative RT-PCR The Journal of biological chemistry Medium 15123677
2006 SC35 and SRp40 (SRSF5) bind to overlapping sites on HIV-1 SLS2/SLS3 RNA structures near splice acceptor A3 and counteract hnRNP A1 binding on ESS2 to activate site A3; NMR demonstrates direct interaction of ESS2 with hnRNP A1 RRM domains, and enzymatic/chemical footprints delineate SR protein binding sites. Enzymatic and chemical footprinting, NMR spectroscopy, in vitro splicing, competition binding assays The Journal of biological chemistry Medium 16990281
2012 SRSF5 affects alternative splicing of Mcl-1 pre-mRNA in MCF-7 breast cancer cells, shifting the ratio of Mcl-1(L) to Mcl-1(S) isoforms; siRNA-mediated knockdown of SRSF5 alters this splicing pattern. siRNA knockdown, RT-PCR splicing assay PloS one Medium 23284704
2018 Upon glucose intake, SRSF5 is acetylated on K125 by the acetyltransferase Tip60, which antagonizes Smurf1-mediated ubiquitylation of the same lysine and prevents proteasomal degradation; upon glucose starvation, HDAC1 deacetylates SRSF5, allowing Smurf1 to ubiquitylate K125 and target SRSF5 for proteasomal degradation. Stabilized SRSF5 promotes alternative splicing of CCAR1 to produce the short CCAR1S isoform, enhancing glucose consumption and tumor growth. Co-IP, in vitro ubiquitylation/acetylation assays, mutagenesis (K125R/K125Q), HDAC1/Tip60/Smurf1 knockdown and overexpression, splicing minigene assay, xenograft tumor models Nature communications High 29942010
2018 SRSF5 is upregulated by SRSF3 in oral squamous cell carcinoma; SRSF3 impairs the autoregulation of SRSF5 (a mechanism that normally controls SRSF5 levels) and promotes SRSF5 overexpression, which drives cell proliferation and tumor formation. siRNA knockdown, overexpression, RT-PCR (autoregulation assay), soft-agar transformation assay, xenograft tumor model Biochimica et biophysica acta. Molecular cell research Medium 29857020
2021 CLK1 phosphorylates SRSF5 on Ser250, which inhibits METTL14 exon10 skipping while promoting Cyclin L2 exon6.3 skipping; SRSF5 directly binds METTL14 and Cyclin L2 pre-mRNA (confirmed by RIP, RNA pull-down, and CLIP-qPCR), and these splicing events promote growth and metastasis of pancreatic cancer cells in vitro and in vivo. Phosphorylation mass spectrometry, RNA-seq, RIP assay, RNA pull-down, CLIP-qPCR, site-directed mutagenesis, xenograft mouse model Journal of hematology & oncology High 33849617
2009 SRp40 (SRSF5) induces a GRα-to-GRβ alternative splicing shift of glucocorticoid receptor pre-mRNA in exon 9 in HeLa cells (but not 293T cells), as confirmed by minigene transfection and siRNA knockdown; other SR proteins tested did not produce this shift. Minigene transfection assay, siRNA knockdown, RT-PCR Molecular biology reports Medium 19343537
2014 SRSF5 (SRp40) associates with the lncRNA NEAT1 in 3T3-L1 cells (shown by RNA-IP); depletion of NEAT1 results in failure to phosphorylate SRp40, and siRNA knockdown of SRp40 dysregulates PPARγ2 mRNA levels; overexpression of SRp40 increases PPARγ2 but not PPARγ1, indicating SRp40 selectively promotes PPARγ2 splicing during adipogenesis. RNA immunoprecipitation (RNA-IP), siRNA knockdown, overexpression, RT-PCR Genes Medium 25437750
2022 CPEB2 binds SRSF5 mRNA and increases its stability; in glioblastoma endothelial cells, elevated CPEB2 (through METTL3/IGF2BP3-mediated m6A methylation) stabilizes SRSF5 protein, which promotes ETS1 exon inclusion, leading to upregulation of tight junction proteins ZO-1, occludin, and claudin-5 and reduced blood-tumor barrier permeability. RNA immunoprecipitation, co-immunoprecipitation, shRNA knockdown, splicing minigene assay, in vivo glioblastoma xenograft Communications biology Medium 36064747
2024 LINC01852 promotes TRIM72-mediated ubiquitination and proteasomal degradation of SRSF5, thereby inhibiting SRSF5-mediated alternative splicing of PKM pre-mRNA; loss of SRSF5 shifts PKM splicing from PKM2 to PKM1, inducing a metabolic switch from aerobic glycolysis to oxidative phosphorylation and attenuating chemoresistance in colorectal cancer. RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, ubiquitination assay, chromatin immunoprecipitation, dual-luciferase assay, siRNA/shRNA knockdown, in vivo mouse model Molecular cancer High 38263157

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nature cell biology 587 11988743
2019 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart rhythm 571 31078652
2002 Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell 383 11832215
2002 Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis. Nature cell biology 373 11988742
2001 Hrs recruits clathrin to early endosomes. The EMBO journal 323 11532964
2003 TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation. Proceedings of the National Academy of Sciences of the United States of America 274 12802020
2003 STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes. The Journal of biological chemistry 260 12551915
2001 FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes. Journal of cell science 254 11493665
2003 HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein. The Journal of cell biology 214 12900394
2010 Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochemical and biophysical research communications 210 20673754
2006 Distinct roles for Tsg101 and Hrs in multivesicular body formation and inward vesiculation. Molecular biology of the cell 207 16707569
1999 Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis. Genes & development 207 10364163
2000 A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP. The Journal of biological chemistry 193 10982817
1997 Sequence-specific RNA binding by an SR protein requires RS domain phosphorylation: creation of an SRp40-specific splicing enhancer. Proceedings of the National Academy of Sciences of the United States of America 177 9037021
1980 Expression of leukemogenic recombinant viruses associated with a recessive gene in HRS/J mice. The Journal of experimental medicine 174 7400758
2000 Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor. The Journal of biological chemistry 170 11110793
1997 Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth. The Journal of biological chemistry 169 9407053
2005 Met/Hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Molecular and cellular biology 166 16227611
2001 Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains. The Journal of biological chemistry 161 11390366
1997 Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is localized to the cytoplasmic surface of early endosomes. The Journal of biological chemistry 155 9252367
2003 The UIM domain of Hrs couples receptor sorting to vesicle formation. Journal of cell science 148 12953068
2000 Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA. Molecular and cellular biology 145 11094085
2006 Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting. Nature structural & molecular biology 144 16462748
1995 Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain. Molecular and cellular biology 143 7565774
2019 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary. Heart rhythm 139 31676023
2002 Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs. The Journal of biological chemistry 131 12006563
2006 Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains. Journal of cell science 129 16720641
2014 Long Non-Coding RNA NEAT1 Associates with SRp40 to Temporally Regulate PPARγ2 Splicing during Adipogenesis in 3T3-L1 Cells. Genes 113 25437750
2006 An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Molecular biology of the cell 113 16407403
2005 Essential role of Hrs in a recycling mechanism mediating functional resensitization of cell signaling. The EMBO journal 109 15944737
2007 Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking. Experimental cell research 108 18031739
2005 Molecular and genetic studies imply Akt-mediated signaling promotes protein kinase CbetaII alternative splicing via phosphorylation of serine/arginine-rich splicing factor SRp40. The Journal of biological chemistry 107 15684423
2005 CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling. Molecular biology of the cell 104 15772161
2007 Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes. Blood 98 18070985
1993 Novel delayed-early and highly insulin-induced growth response genes. Identification of HRS, a potential regulator of alternative pre-mRNA splicing. The Journal of biological chemistry 98 7686911
2011 Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway. Virology 97 22138215
2021 CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer. Journal of hematology & oncology 95 33849617
2011 The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS pathogens 91 21304933
2002 Hrs and endocytic sorting of ubiquitinated membrane proteins. Cell structure and function 91 12576633
2009 Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101. Journal of cell science 86 19808888
2008 Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. PLoS biology 84 18767904
2012 Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells. PloS one 78 23284704
2018 Mutually exclusive acetylation and ubiquitylation of the splicing factor SRSF5 control tumor growth. Nature communications 76 29942010
2022 HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8+ T-cell infiltration into tumors. Nature communications 75 35835783
2004 Acquisition of Hrs, an essential component of phagosomal maturation, is impaired by mycobacteria. Molecular and cellular biology 73 15121875
2000 A hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors. Genes to cells : devoted to molecular & cellular mechanisms 71 10651905
1996 Comparison of the rat nucleolar protein nopp140 with its yeast homolog SRP40. Differential phosphorylation in vertebrates and yeast. The Journal of biological chemistry 70 8702624
2001 Insulin regulates alternative splicing of protein kinase C beta II through a phosphatidylinositol 3-kinase-dependent pathway involving the nuclear serine/arginine-rich splicing factor, SRp40, in skeletal muscle cells. The Journal of biological chemistry 68 11283022
2008 An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. The Journal of cell biology 67 18362181
2004 Differential effects of the SR proteins 9G8, SC35, ASF/SF2, and SRp40 on the utilization of the A1 to A5 splicing sites of HIV-1 RNA. The Journal of biological chemistry 66 15123677
2003 Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation. Biochemical and biophysical research communications 66 13679051
2006 Hse1, a component of the yeast Hrs-STAM ubiquitin-sorting complex, associates with ubiquitin peptidases and a ligase to control sorting efficiency into multivesicular bodies. Molecular biology of the cell 65 17079730
2005 The Hrs/STAM complex in the downregulation of receptor tyrosine kinases. Journal of biochemistry 65 15713877
1997 HRS/SRp40-mediated inclusion of the fibronectin EIIIB exon, a possible cause of increased EIIIB expression in proliferating liver. Molecular and cellular biology 64 9199345
2007 STAM and Hrs down-regulate ciliary TRP receptors. Molecular biology of the cell 60 17581863
2007 Role of Hrs in maturation of autophagosomes in mammalian cells. Biochemical and biophysical research communications 60 17624298
2000 Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15. The Journal of biological chemistry 57 10809762
2018 SRSF5 functions as a novel oncogenic splicing factor and is upregulated by oncogene SRSF3 in oral squamous cell carcinoma. Biochimica et biophysica acta. Molecular cell research 56 29857020
2020 Epstein-Barr Virus LMP1 Promotes Syntenin-1- and Hrs-Induced Extracellular Vesicle Formation for Its Own Secretion To Increase Cell Proliferation and Migration. mBio 55 32546618
2010 SRp40 and SRp55 promote the translation of unspliced human immunodeficiency virus type 1 RNA. Journal of virology 55 20427542
2006 Epidermal growth factor receptor fate is controlled by Hrs tyrosine phosphorylation sites that regulate Hrs degradation. Molecular and cellular biology 55 17101784
2002 A ubiquitin-interacting motif from Hrs binds to and occludes the ubiquitin surface necessary for polyubiquitination in monoubiquitinated proteins. Biochemical and biophysical research communications 53 12207904
2018 Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells. Histopathology 46 29380399
2009 Essential role of Hrs in endocytic recycling of full-length TrkB receptor but not its isoform TrkB.T1. The Journal of biological chemistry 46 19351881
2024 LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM. Molecular cancer 45 38263157
2012 An essential role of Hrs/Vps27 in endosomal cholesterol trafficking. Cell reports 45 22832105
2008 Loss of hrs in the central nervous system causes accumulation of ubiquitinated proteins and neurodegeneration. The American journal of pathology 45 19008375
2006 Biochemical and NMR study on the competition between proteins SC35, SRp40, and heterogeneous nuclear ribonucleoprotein A1 at the HIV-1 Tat exon 2 splicing site. The Journal of biological chemistry 45 16990281
2018 HRS-WASH axis governs actin-mediated endosomal recycling and cell invasion. The Journal of cell biology 44 29891722
2016 SRSF5: a novel marker for small-cell lung cancer and pleural metastatic cancer. Lung cancer (Amsterdam, Netherlands) 44 27565915
2006 A novel sorting sequence in the beta2-adrenergic receptor switches recycling from default to the Hrs-dependent mechanism. The Journal of biological chemistry 44 17138565
2005 Growth factors induce differential phosphorylation profiles of the Hrs-STAM complex: a common node in signalling networks with signal-specific properties. The Biochemical journal 44 15828871
2010 The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development. PloS one 42 20422006
2009 Radiation-induced adaptive response is not seen in cell lines showing a bystander effect but is seen in lines showing HRS/IRR response. International journal of radiation biology 42 19205987
2002 Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Human molecular genetics 42 12444102
2000 Early endosomal localization of hrs requires a sequence within the proline- and glutamine-rich region but not the FYVE finger. The Journal of biological chemistry 41 10889197
2007 Increased expression of SRp40 affecting CD44 splicing is associated with the clinical outcome of lymph node metastasis in human breast cancer. Clinica chimica acta; international journal of clinical chemistry 40 17651715
2003 Hrs function: viruses provide the clue. Trends in cell biology 40 14624836
2000 Cultivated H-RS cells are resistant to CD95L-mediated apoptosis despite expression of wild-type CD95. Experimental hematology 40 10658674
2015 Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology 39 26409260
2005 Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) interacts with PELP1 and activates MAPK. The Journal of biological chemistry 39 16352611
2001 Function of Hrs in endocytic trafficking and signalling. Biochemical Society transactions 39 11498011
2004 Association with Hrs is required for the early endosomal localization, stability, and function of STAM. Journal of biochemistry 37 15113837
2002 Phosphorylation of Hrs downstream of the epidermal growth factor receptor. European journal of biochemistry 36 12180964
2004 A role for Hrs in endosomal sorting of ligand-stimulated and unstimulated epidermal growth factor receptor. Experimental cell research 35 15212941
2017 HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection. PLoS pathogens 34 28854257
2001 Hrs and hbp: possible regulators of endocytosis and exocytosis. Biochemical and biophysical research communications 34 11243842
2000 Hrs interacts with SNAP-25 and regulates Ca(2+)-dependent exocytosis. Journal of cell science 34 10825299
2019 Comparison of urine, self-collected vaginal swab, and cervical swab samples for detecting human papillomavirus (HPV) with Roche Cobas HPV, Anyplex II HPV, and RealTime HR-S HPV assay. Journal of virological methods 33 30998958
2006 GRIF1 binds Hrs and is a new regulator of endosomal trafficking. Journal of cell science 33 17062640
2010 Hrs controls sorting of the epithelial Na+ channel between endosomal degradation and recycling pathways. The Journal of biological chemistry 31 20675381
2009 Alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA is regulated by SRp40. Molecular biology reports 31 19343537
1990 Cultured Reed-Sternberg cells HDLM-1 and KM-H2 can be induced to become histiocytelike cells. H-RS cells are not derived from lymphocytes. The American journal of pathology 31 2167011
2003 After Hrs with HIV. The Journal of cell biology 30 12900390
2022 CPEB2 m6A methylation regulates blood-tumor barrier permeability by regulating splicing factor SRSF5 stability. Communications biology 29 36064747
2005 Novel function of POSH, a JNK scaffold, as an E3 ubiquitin ligase for the Hrs stability on early endosomes. Cellular signalling 29 16084064
2016 ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells. Journal of virology 27 26819309
2013 Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: a cell line study in four glioblastoma multiforme (GBM) cell lines. International journal of radiation biology 27 23859266
2006 The endosome-associated protein Hrs is hexameric and controls cargo sorting as a "master molecule". Structure (London, England : 1993) 27 16615908
2006 The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. Journal of virology 27 17182674