BioPAX pathway converted from "Formation of the Spliceosomal B Complex" in the Reactome database. Formation of the Spliceosomal B Complex Formation of the Spliceosomal B Complex The formation of the B complex is ATP-dependent, and both the 5' and 3' splice sites are essential for B complex assembly. The U4 and U6 snRNPS are extensively base-paired, and this U4:U6 complex associates with the U5 snRNP to form a tri-snRNP particle. This tri-snRNP particle then binds to the spliceosomal A complex, to form the spliceosomal B complex. Authored: Krainer, AR, 2003-06-05 08:30:23 Edited: Joshi-Tope, G, 0000-00-00 00:00:00 Reactome DB_ID: 8867896 1 nucleoplasm GO 0005654 UniProt:Q92733 PRCC PRCC PRCC TPRC FUNCTION May regulate cell cycle progression through interaction with MAD2L2.SUBUNIT Interacts with MAD2L2; the interaction is direct.TISSUE SPECIFICITY Ubiquitous in fetal and adult tissues.DISEASE A chromosomal aberration involving PRCC is found in patients with papillary renal cell carcinoma. Translocation t(X;1)(p11.2;q21.2) with TFE3. Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 UniProt Q92733 Chain Coordinates 1 EQUAL 491 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 8952109 1 PPIL [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PPIL1 [nucleoplasm] UniProt Q9Y3C6 Reactome DB_ID: 351663 1 UniProt:Q13573 SNW1 SNW1 SNW1 SKIP SKIIP FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346). Is required in the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. Is proposed to recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD.FUNCTION (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter.FUNCTION (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs). Interacts with SKI, SMAD2,SMAD3, RBPJ, RB1, PABPN1, MAGEA1, SIRT1, FOXN3, U2AF2, DAXX and ATP1B4. Interacts with PPIL1 (PubMed:16595688, PubMed:20007319, PubMed:20368803, PubMed:33220177). Interacts with VDR and RXRA; preferentially associates with VDR:RXRA heterodimers (PubMed:9632709, PubMed:12529369). Interacts with NCOR2 (PubMed:10644367). Interacts with MAML1 (PubMed:21245387). Interacts with NOTCH1 NICD; the interaction involves multimerized NOTCH1 NICD (PubMed:21245387). Forms a complex with NOTCH1 NICD and MAML1; the association is dissociated by RBPJ (PubMed:21245387). Associates with positive transcription elongation factor b (P-TEFb) (PubMed:15905409). Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN (PubMed:18794151).SUBUNIT (Microbial infection) Interacts with human papillomavirus type-16 (HPV16) E7 protein.SUBUNIT (Microbial infection) Interacts with EBV EBNA2; EBNA2 competes with NCOR2 for interaction with SNW1.SIMILARITY Belongs to the SNW family. UniProt Q13573 2 EQUAL 536 EQUAL Reactome DB_ID: 6781960 1 UniProt:O60306 AQR AQR AQR KIAA0560 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:25599396, PubMed:28502770, PubMed:28076346). Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis (PubMed:16949364). Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly (PubMed:16949364). May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing (PubMed:16949364). Has ATP-dependent RNA helicase activity and can unwind double-stranded RNA molecules with a 3' overhang (in vitro) (PubMed:25599396).SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:16949364, PubMed:25599396, PubMed:28502770, PubMed:28076346). Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE (PubMed:17981804). Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex (PubMed:25599396). The IB complex does not contain PRPF19 (PubMed:25599396). Within the spliceosome, interacts with SNRPA1, SF3B1, SF3B3, SF3A1 and SF3A2 (PubMed:25599396).DOMAIN Contains an N-terminal domain with structural similarity to ARM repeat regions; this domain functions as scaffold for protein-protein interactions, but is not required for RNA binding or for ATP-dependent RNA helicase activity.SIMILARITY Belongs to the CWF11 family. UniProt O60306 1 EQUAL 1485 EQUAL Reactome DB_ID: 8867891 1 UniProt:P41223 BUD31 BUD31 BUD31 EDG2 FUNCTION Involved in the pre-mRNA splicing process (PubMed:28502770, PubMed:28076346). May play a role as regulator of AR transcriptional activity; may increase AR transcriptional activity (PubMed:25091737).SUBUNIT Identified in the spliceosome C complex (PubMed:28502770, PubMed:28076346). May interact with AR (PubMed:25091737).TISSUE SPECIFICITY Detected in epithelial and stromal cells in benign prostate hyperplasia tissue (at protein level).DOMAIN Contains a short sequence motif (Phe-Xaa-Xaa-Phe-Tyr) that can bind to AR and may modulate AR activity.SIMILARITY Belongs to the BUD31 (G10) family. UniProt P41223 1 EQUAL 144 EQUAL Reactome DB_ID: 8867899 1 UniProt:Q9BZJ0 CRNKL1 CRNKL1 CGI-201 MSTP021 CRNKL1 CRN FUNCTION Involved in pre-mRNA splicing process.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Present in a spliceosome complex assembled in vitro containing CRNKL1, HPRP8BP and SNRPB2 (PubMed:12084575). Isoform 2 seems to be predominant in the spliceosome complex (PubMed:12084575). Interacts with PPIL2 (via the PPIase cyclophilin-type domain); they may form a trimeric complex with HSP90 (PubMed:15189447).TISSUE SPECIFICITY Widely expressed (PubMed:11342225). Highly expressed in testis (PubMed:12084575). Not detected in brain and lung (PubMed:12084575).SIMILARITY Belongs to the crooked-neck family. UniProt Q9BZJ0 1 EQUAL 848 EQUAL Reactome DB_ID: 6781963 1 UniProt:Q9ULR0 ISY1 ISY1 ISY1 KIAA1160 FUNCTION Component of the spliceosome C complex required for the selective processing of microRNAs during embryonic stem cell differentiation (By similarity). Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (By similarity). Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (By similarity). Required during the transition of embryonic stem cells (ESCs) from the naive to primed state (By similarity). By enhancing miRNA biogenesis, promotes exit of ESCs from the naive state to an intermediate state of poised pluripotency, which precedes transition to the primed state (By similarity). Involved in pre-mRNA splicing as component of the spliceosome.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:29301961). Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE (PubMed:17981804). Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex (PubMed:25599396). The IB complex does not contain PRPF19 (PubMed:25599396). Interacts with CPSF3; this interaction is in an RNA independent manner (By similarity). Interacts with the microprocessor complex subunits DGCR8 and DROSHA; this interaction is in an RNA dependent manner (By similarity).SIMILARITY Belongs to the ISY1 family. UniProt Q9ULR0 1 EQUAL 285 EQUAL Reactome DB_ID: 8867897 1 UniProt:Q8NAV1 PRPF38A PRPF38A PRPF38A FUNCTION Involved in pre-mRNA splicing as a component of the spliceosome.SUBUNIT Component of the spliceosome B complex (Probable) (PubMed:28781166). Interacts (via N-terminal interaction domain) with ZMAT2 AND MFAP1 (Probable) (PubMed:27773687).SIMILARITY Belongs to the PRP38 family. UniProt Q8NAV1 1 EQUAL 312 EQUAL Reactome DB_ID: 5215975 1 UniProt:Q9NW64 RBM22 RBM22 199G4 RBM22 ZC3H16 FUNCTION Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30705154). Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.SUBUNIT Component of the pre-catalytic and catalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961). Component of the postcatalytic spliceosome P complex (PubMed:30705154). Interacts with PDCD6; the interaction induces translocation of PDCD6 in the cytoplasm. Interacts with PPIL1 (PubMed:33220177).DOMAIN The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding.SIMILARITY Belongs to the SLT11 family. UniProt Q9NW64 2 EQUAL 420 EQUAL Reactome DB_ID: 72068 1 Spliceosomal A Complex [nucleoplasm] Spliceosomal A Complex Reactome DB_ID: 156649 1 UniProt:Q86V81 ALYREF ALYREF BEF ALYREF THOC4 ALY FUNCTION Export adapter involved in nuclear export of spliced and unspliced mRNA. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway) (PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:11707413, PubMed:11675789, PubMed:11979277, PubMed:18364396, PubMed:22144908, PubMed:22893130, PubMed:23222130, PubMed:25662211). Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1 (PubMed:15833825, PubMed:15998806, PubMed:17190602). The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production; ALYREF/THOC4 mediates the recruitment of the TREX complex to the intronless viral mRNA (PubMed:18974867). Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC) (PubMed:15998806, PubMed:17984224). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim (PubMed:19165146). Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Involved in transcription elongation and genome stability (PubMed:12438613, PubMed:17984224). Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling (PubMed:28418038).FUNCTION Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.SUBUNIT Homomultimer. Is part of several complexes involved in mRNA processing and export. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have a dynamic structure involving ATP-dependent remodeling; in the complex interacts (via C-terminus) directly with DDX39B and interacts directly with THOC1 and THOC2. Found in mRNA splicing-dependent exon junction complexes (EJC). Identified in the spliceosome C complex. Found in a mRNP complex with UPF3A and UPF3B. Interacts with RBM8A, NCBP1, THOC5, LEF1, RUNX1, EIF4A3, RNPS1, SRRM1, IWS1 and EXOSC1. Interacts with RBM15B (PubMed:19586903). Interacts with NXF1; the interaction is direct.SUBUNIT (Microbial infection) Interacts with human Kaposi's sarcoma-associated herpesvirus (HHV-8) ORF57 protein; this interaction allows efficient export of HHV-8 early and late intronless transcripts.SUBUNIT (Microbial infection) Interacts with HHV-1 ICP27 protein; this interaction recruits ALYREF to viral replication compartments and probably directs viral mRNA to the TAP/NFX1 pathway.TISSUE SPECIFICITY Expressed in a wide variety of cancer types.PTM Arg-204 is dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding.PTM Citrullinated by PADI4.MISCELLANEOUS Antibodies against ALYREF/THOC4 are found in sera of patients with systemic lupus erythematosus (SLE).SIMILARITY Belongs to the ALYREF family. UniProt Q86V81 2 EQUAL 257 EQUAL Reactome DB_ID: 72028 1 UniProt:Q13243 SRSF5 SRSF5 SFRS5 SRP40 HRS SRSF5 FUNCTION Plays a role in constitutive splicing and can modulate the selection of alternative splice sites.SUBUNIT Interacts (via RS domain) with PHF5A (via N-terminus) (By similarity). Found in a pre-mRNA splicing complex with SRSF4/SFRS4, SRSF5/SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2.PTM Extensively phosphorylated on serine residues in the RS domain.SIMILARITY Belongs to the splicing factor SR family. UniProt Q13243 1 EQUAL 272 EQUAL Reactome DB_ID: 71929 1 UniProt:P22626 HNRNPA2B1 HNRNPA2B1 HNRNPA2B1 HNRPA2B1 FUNCTION Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs (PubMed:19099192). Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm (PubMed:10567417). Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts (PubMed:26321680). Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs (PubMed:24356509). Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs (PubMed:26321680). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). Also plays a role in the activation of the innate immune response (PubMed:31320558). Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6 (PubMed:31320558). In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production (PubMed:31320558).FUNCTION (Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport.SUBUNIT Homodimer; dimerization is required for nucleocytoplasmic translocation (PubMed:31320558). Identified in the spliceosome C complex (PubMed:11991638). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with IGF2BP1 (PubMed:17289661). Interacts with C9orf72 (PubMed:24549040). Interacts with DGCR8 (PubMed:26321680). Interacts with TARDBP (PubMed:19429692). Interacts with CKAP5 (PubMed:15703215). Interacts with TBK1 (PubMed:31320558). Interacts with STING1 (PubMed:31320558). Interacts with SRC (PubMed:31320558). Interacts with PPIA/CYPA (PubMed:25678563).DOMAIN The disordered region, when incubated at high concentration, is able to polymerize into labile, amyloid-like fibers and form cross-beta polymerization structures, probably driving the formation of hydrogels. In contrast to irreversible, pathogenic amyloids, the fibers polymerized from LC regions disassemble upon dilution. A number of evidence suggests that formation of cross-beta structures by LC regions mediate the formation of RNA granules, liquid-like droplets, and hydrogels.PTM Sumoylated in exosomes, promoting miRNAs-binding.PTM Asymmetric dimethylation at Arg-266 constitutes the major methylation site (By similarity). According to a report, methylation affects subcellular location and promotes nuclear localization (PubMed:10772824). According to another report, methylation at Arg-266 does not influence nucleocytoplasmic shuttling (By similarity). UniProt P22626 1 EQUAL 353 EQUAL Reactome DB_ID: 8867895 1 UniProt:O75554 WBP4 WBP4 WBP4 FNBP21 FBP21 FUNCTION Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:9724750, PubMed:19592703, PubMed:28781166). May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex (PubMed:9724750).SUBUNIT Component of the spliceosome B complex (PubMed:9724750, PubMed:28781166). Associated with U2 snRNPs (PubMed:9724750, PubMed:28781166). Binds splicing factors SNRPB, SNRPC and SF1 (PubMed:9724750). Interacts via the WW domains with the Pro-rich domains of KHDRBS1/SAM68 (By similarity). Interacts via the WW domains with the Pro-rich domains of WBP11 (PubMed:19592703).DOMAIN The WW domain recognizes the proline, glycine and methionine-rich (PGM) motif present in the splicing factors, as well as the Arg/Gly-rich-flanked Pro-rich domains found in several WW domain-binding proteins. UniProt O75554 1 EQUAL 376 EQUAL Reactome DB_ID: 71987 1 UniProt:P26368 U2AF2 U2AF2 U2AF2 U2AF65 FUNCTION Plays a role in pre-mRNA splicing and 3'-end processing (PubMed:17024186). By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing (PubMed:21536736). Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186).SUBUNIT Interacts with U2AF1L4 (By similarity). Heterodimer with U2AF1 (PubMed:11551507). Binds unphosphorylated SF1 (PubMed:10449420, PubMed:12718882). Interacts with SCAF11 and SNW1 (PubMed:9447963, PubMed:21460037). Interacts with ZRSR2/U2AF1-RS2. Interacts with RBM17 (PubMed:17589525). Interacts with PRPF19; the interaction is direct. Interacts with POLR2A (via the C-terminal domain); recruits PRPF19 and the Prp19 complex to the pre-mRNA (PubMed:21536736). Interacts with KHDC4 (Isoform 2) (PubMed:19641227). Interacts with ZRSR2 (PubMed:9237760). Interacts with the SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A (PubMed:27720643). Interacts (via N-terminus) with CPSF7 (via C-terminus); this interaction stimulates pre-mRNA 3'-end processing by promoting the recruitment of the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186).PTM Lysyl-hydroxylation at Lys-15 and Lys-276 affects the mRNA splicing activity of the protein, leading to regulate some, but not all, alternative splicing events.SIMILARITY Belongs to the splicing factor SR family. UniProt P26368 2 EQUAL 475 EQUAL Reactome DB_ID: 53703 1 UniProt:O75937 DNAJC8 DNAJC8 SPF31 HSPC315 HSPC331 DNAJC8 FUNCTION Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells (PubMed:27133716).SUBUNIT Interacts with SRPK1 (PubMed:19240134). Interacts with HSP70 (HSPA1A or HSPA1B) (PubMed:27133716).TISSUE SPECIFICITY Ubiquitous. UniProt O75937 2 EQUAL 253 EQUAL Reactome DB_ID: 72040 1 UniProt:P35637 FUS FUS FUS TLS FUNCTION DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Binds also its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity).SUBUNIT Self-oligomerizes (via N-terminal region) (PubMed:25453086). Oligomerization is essential for chromatin binding (PubMed:25453086). Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1 (PubMed:9660765). Interacts through its C-terminus with SFRS13A (PubMed:9774382). Interacts with OTUB1 and SARNP. Interacts with LRSAM1 (PubMed:27615052). Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin (PubMed:27731383). Interacts with MATR3 (PubMed:27731383). Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing (PubMed:26124092). Interacts (through its RNA-binding domain) with RALY (through its RNA-binding domain); both are components of the same RNPs (PubMed:30354839).TISSUE SPECIFICITY Ubiquitous.PTM Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine.PTM Phosphorylated in its N-terminal serine residues upon induced DNA damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region.DISEASE A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3.DISEASE A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG.SIMILARITY Belongs to the RRM TET family. UniProt P35637 1 EQUAL 526 EQUAL Reactome DB_ID: 72106 1 UniProt:Q9BUJ2 HNRNPUL1 HNRNPUL1 HNRNPUL1 HNRPUL1 E1BAP5 FUNCTION Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Also plays a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro.SUBUNIT Interacts with the adenovirus type 5 (Ad5) E1B-55 kDa, BRD7, PRMT2, TP53 and NXF1. Associates with histones and BRD7.DOMAIN The RGG-box domain is methylated.PTM Methylated.MISCELLANEOUS Its methylation is enhanced in the late phase of adenoviral infection. UniProt Q9BUJ2 1 EQUAL 856 EQUAL Reactome DB_ID: 71919 1 UniProt:Q15365 PCBP1 PCBP1 PCBP1 FUNCTION Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943).TISSUE SPECIFICITY Abundantly expressed in skeletal muscle, thymus and peripheral blood leukocytes while a lower expression is observed in prostate, spleen, testis, ovary, small intestine, heart, liver, adrenal and thyroid glands.PTM Phosphorylated; lowers poly(rC)-binding activity. UniProt Q15365 1 EQUAL 356 EQUAL Reactome DB_ID: 71937 1 UniProt:P52597 HNRNPF HNRNPF HNRNPF HNRPF FUNCTION Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state.SUBUNIT Identified in the spliceosome C complex. Interacts with AGO1, AGO2, TBP and TXNL4/DIM1.TISSUE SPECIFICITY Expressed ubiquitously.DOMAIN The N-terminal RRM domains are responsible for recognizing the G-tract of BCL-X RNA.PTM Sumoylated. UniProt P52597 1 EQUAL 415 EQUAL Reactome DB_ID: 71923 1 UniProt:P26599 PTBP1 PTBP1 PTBP1 PTB FUNCTION Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10 (PubMed:15009664). Binds to polypyrimidine-rich controlling element (PCE) of CFTR and promotes exon skipping of CFTR exon 9, thereby antagonizing TIA1 and its role in exon inclusion of CFTR exon 9 (PubMed:14966131). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to a polypyrimidine tract flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). In case of infection by picornaviruses, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:21518806).SUBUNIT Monomer. Part of a ternary complex containing KHSRP, PTBP1, PTBP2 and HNRPH1. Interacts with RAVER1 and SFPQ. UniProt P26599 1 EQUAL 531 EQUAL Reactome DB_ID: 71921 1 UniProt:Q15366 PCBP2 PCBP2 PCBP2 FUNCTION Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Major cellular poly(rC)-binding protein. Binds also poly(rU). Negatively regulates cellular antiviral responses mediated by MAVS signaling (PubMed:19881509). It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation (PubMed:19881509).FUNCTION (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12414943, PubMed:24371074). Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943).SUBUNIT Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with IFIH1 and RNF135. Interacts with MAVS (via C-terminus) and ITCH (via WW domains).TISSUE SPECIFICITY Detected in all tissues examined.DOMAIN The KH domains mediates poly(C) binding.PTM Phosphorylated. The non-phosphorylated form(s) exhibited the strongest poly(rC)-binding activity.PTM (Microbial infection) Proteolyticaly cleaved by picornavirus proteinase 3CD. UniProt Q15366 1 EQUAL 365 EQUAL Reactome DB_ID: 8865911 1 SRRM1:SRRM2 [nucleoplasm] SRRM1:SRRM2 SRm160:SRm300 Reactome DB_ID: 156781 1 UniProt:Q8IYB3 SRRM1 SRRM1 SRM160 SRRM1 FUNCTION Part of pre- and post-splicing multiprotein mRNP complexes. Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.SUBUNIT Identified in the spliceosome C complex. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRP70, SNRPA1, SRRM1 and SRRM2. Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRP70, SNRPA1, SRRM1 and TRA2B/SFRS10. Found in a mRNA splicing-dependent exon junction complex (EJC) with DEK, PRPF8, NCBP1, RBM8A, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with DDX39B, CPSF1, RBM8A, RNPS1, and ALYREF/THOC4. Seems to be a compound of RNA export complexes that are released from speckles in a ATP-dependent manner.PTM Phosphorylated on multiple serine and threonine residues by DYRK3 during the G2-to-M transition, after the nuclear-envelope breakdown (PubMed:29973724). Phosphorylation by DYRK3 promotes disassembly of nuclear speckles (PubMed:29973724).PTM Citrullinated by PADI4.SIMILARITY Belongs to the splicing factor SR family. UniProt Q8IYB3 1 EQUAL 904 EQUAL Reactome DB_ID: 8865888 1 UniProt:Q9UQ35 SRRM2 SRRM2 SRRM2 KIAA0324 HSPC075 SRM300 SRL300 FUNCTION Required for pre-mRNA splicing as component of the spliceosome.SUBUNIT Component of pre-catalytic, catalytic and post-catalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30705154). Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRP70, SNRPA1, SRRM1 and SRRM2 (PubMed:9531537).TISSUE SPECIFICITY Expressed in liver, placenta, and white blood cells.MISCELLANEOUS Can functionally substitute for CWC12 in yeast.SIMILARITY Belongs to the CWC21 family. UniProt Q9UQ35 1 EQUAL 2752 EQUAL Reactome Database ID Release 82 8865911 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8865911 Reactome R-HSA-8865911 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8865911.2 Reactome DB_ID: 71945 1 UniProt:P61978 HNRNPK HNRNPK HNRNPK HNRPK FUNCTION One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841).SUBUNIT Interacts with RBM42 and ZIK1 (By similarity). Interacts with BRDT (By similarity). Identified in the spliceosome C complex (PubMed:11991638). Interacts with ANKRD28 (PubMed:16564677). Interacts with ASFV p30 protein (PubMed:18775702). Interacts with DDX1 (PubMed:12183465). Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation (PubMed:16360036). Interacts with p53/TP53 (PubMed:16360036). Interacts with IVNS1ABP (PubMed:23825951). Interacts with PPIA/CYPA (PubMed:25678563). Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, ZNF827 and HNRNPL (PubMed:33174841).SUBUNIT (Microbial infection) Interacts with HCV core protein (PubMed:9651361).INDUCTION By DNA damage, including ionizing radiations and phleomycin treatment or UV irradiation. This induction requires ATM kinase activity (ionizing radiations and phleomycin) or ATR activity (UV irradiation). Up-regulation is due to protein stabilization. Constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway.PTM Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine.PTM Sumoylated by CBX4. Sumoylation is increased upon DNA damage, such as that produced by doxorubicin, etoposide, UV light and camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under these conditions.PTM Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination.PTM O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. UniProt P61978 1 EQUAL 463 EQUAL Reactome DB_ID: 72029 1 UniProt:Q16629 SRSF7 SRSF7 SFRS7 SRSF7 FUNCTION Required for pre-mRNA splicing. Can also modulate alternative splicing in vitro. Represses the splicing of MAPT/Tau exon 10. May function as export adapter involved in mRNA nuclear export such as of histone H2A. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. RNA-binding is semi-sequence specific.SUBUNIT Found in large molecular weight complexes containing CCNL1 and the p110 isoforms of either CDC2L1 or CDC2L2 (PubMed:12501247, PubMed:14684736). Interacts with CCNL2 and CPSF6 (PubMed:15169763, PubMed:12501247). Interacts with NXF1 (PubMed:12667464, PubMed:17036044). Interacts with YTHDC1 (By similarity).TISSUE SPECIFICITY Brain, liver, kidney and lung.PTM Extensively phosphorylated on serine residues in the RS domain.SIMILARITY Belongs to the splicing factor SR family. UniProt Q16629 1 EQUAL 238 EQUAL Reactome DB_ID: 72031 1 UniProt:Q07955 SRSF1 SRSF1 ASF SF2P33 OK/SW-cl.3 SRSF1 SF2 SFRS1 FUNCTION Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway.SUBUNIT Consists of two polypeptides of p32 and p33. Identified in the spliceosome C complex (PubMed:11991638). Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF (PubMed:24644279). In vitro, self-associates and binds SRSF2, SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with SAFB/SAFB1. Interacts with PSIP1/LEDGF. Interacts with RSRC1 (via Arg/Ser-rich domain). Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus). Interacts with SRPK1 and a sliding docking interaction is essential for its sequential and processive phosphorylation by SRPK1. Interacts with NXF1. Interacts with CCNL1, CCNL2 and CDK11B (PubMed:18216018). Interacts with RRP1B (PubMed:23604122). Interacts (when phosphorylated in its RS domain) with TNPO3; promoting nuclear import (PubMed:24449914). Interacts with ILDR1 (via C-terminus) and ILDR2 (By similarity).DOMAIN The RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling.PTM Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Phosphorylated by SRPK1 at multiple serines in its RS domain via a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds to a docking groove in the large lobe of the kinase domain of SRPK1 and this induces certain structural changes in SRPK1 and/or RRM 2 domain of SRSF1, allowing RRM 2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM 2, which then docks at the docking groove of SRPK1. This also signals RRM 2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed.PTM Asymmetrically dimethylated at arginines, probably by PRMT1, methylation promotes localization to nuclear speckles.SIMILARITY Belongs to the splicing factor SR family. UniProt Q07955 2 EQUAL 248 EQUAL Reactome DB_ID: 450601 1 UniProt:Q15717 ELAVL1 ELAVL1 HUR ELAVL1 FUNCTION RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability (PubMed:14517288, PubMed:18285462, PubMed:31358969). Involved in embryonic stem cell (ESC) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESC differentiation (By similarity). Has also been shown to be capable of binding to m6A-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:8626503, PubMed:17632515, PubMed:18285462, PubMed:23519412, PubMed:14731398). Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro (PubMed:8626503). With ZNF385A, binds the 3'-UTR of p53/TP53 mRNA to control their nuclear export induced by CDKN2A. Hence, may regulate p53/TP53 expression and mediate in part the CDKN2A anti-proliferative activity. May also bind with ZNF385A the CCNB1 mRNA (By similarity). Increases the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR (PubMed:29180010).SUBUNIT Monomer and homodimer (in vitro) (PubMed:17632515, PubMed:20219472). Interacts with ANP32A (PubMed:11729309). Interacts with ZNF385A; the interaction is indirect and mRNA-dependent and may regulate p53/TP53 expression (By similarity). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 (PubMed:19029303). Interacts with AGO1 and AGO2 (PubMed:17932509). Interacts with IGF2BP1; the interaction is enhanced by SEPIN14P20 peptide RBPR (PubMed:32245947, PubMed:29476152). Interacts with IGF2BP2 and IGF2BP3 (PubMed:23640942, PubMed:29476152). Interacts with HNRNPL (PubMed:18161049). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:14731398). Interacts with ILF3; this interaction occurs in a RNA-dependent manner (PubMed:14731398). Interacts with PLEKHN1 (PubMed:18191643, PubMed:27616329). Interacts with SHFL; the interaction increases in presence of RNA (PubMed:27974568). Interacts with YBX1; interaction recruits ELAVL1 on C5-methylcytosine (m5C)-containing mRNAs, thereby promoting mRNA stability (PubMed:31358969).TISSUE SPECIFICITY Ubiquitous. Detected in brain, liver, thymus and muscle.DOMAIN The first RRM (RNA recognition motif) domain is essential for binding to AU-rich elements.PTM Phosphorylated by MAPKAPK2 (PubMed:14517288). Phosphorylated by PRKCD (PubMed:18285462).PTM Methylated at Arg-217 by CARM1 in macrophages in response to LPS challenge.SIMILARITY Belongs to the RRM elav family. UniProt Q15717 2 EQUAL 326 EQUAL Reactome DB_ID: 71947 1 UniProt:P14866 HNRNPL HNRNPL HNRNPL HNRPL P/OKcl.14 FUNCTION 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). As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841).SUBUNIT 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). Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, ZNF827 and HNRNPK (PubMed:33174841).DOMAIN 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).PTM Several isoelectric forms of the L protein are probably the results of post-translational modifications.PTM 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.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). UniProt P14866 1 EQUAL 589 EQUAL Reactome DB_ID: 72041 1 UniProt:P67809 YBX1 YBX1 NSEP1 YB1 YBX1 FUNCTION DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:8188694, PubMed:10817758, PubMed:11698476, PubMed:14718551, PubMed:18809583, PubMed:31358969). Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (PubMed:19561594, PubMed:31358969). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (PubMed:10817758, PubMed:11698476, PubMed:31358969). Component of the CRD-mediated complex that promotes MYC mRNA stability (PubMed:19029303). Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs (PubMed:27559612, PubMed:29073095). Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (PubMed:28341602, PubMed:29073095). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (PubMed:29712925). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (PubMed:12604611). Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7' (PubMed:18809583). Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (PubMed:8188694, PubMed:18809583). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (PubMed:14718551). Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (PubMed:14718551). The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (PubMed:19483673).SUBUNIT Homodimer in the presence of ATP (PubMed:10817758, PubMed:11851341). Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (PubMed:19029303). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (By similarity). Interacts with IGF2BP1 and RBBP6 (PubMed:17289661, PubMed:18851979). Component of cytoplasmic messenger ribonucleoprotein particles (mRNPs) (PubMed:19029303). Interacts with AKT1, MBNL1, SFRS9, SFRS12, ALYREF/THOC4, MSH2, XRCC5, WRN and NCL (PubMed:12604611, PubMed:14559993, PubMed:14718551, PubMed:15806160, PubMed:18335541). Interacts (via C-terminus) with APEX1 (via N-terminus); the interaction is increased with APEX1 acetylated at 'Lys-6' and 'Lys-7' (PubMed:18809583). Interacts with AGO1 and AGO2 (PubMed:17932509). Interacts with ANKRD2 (PubMed:15136035). Interacts with DERA (PubMed:25229427). Interacts with FMR1; this interaction occurs in association with polyribosome (By similarity). Interacts with ZBTB7B (By similarity). Interacts with HDGF (isoform 1) (PubMed:26845719). Interacts with ELAVL1; leading to ELAVL1 recruitment on C5-methylcytosine (m5C)-containing mRNAs and subsequent mRNA stability (PubMed:31358969).DOMAIN In the CSD domain, Trp-65 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring.PTM Ubiquitinated by RBBP6; leading to a decrease of YBX1 transcactivational ability.PTM In the absence of phosphorylation the protein is retained in the cytoplasm.PTM Cleaved by a 20S proteasomal protease in response to agents that damage DNA. Cleavage takes place in the absence of ubiquitination and ATP. The resulting N-terminal fragment accumulates in the nucleus (By similarity).SIMILARITY Belongs to the YBX1 family. UniProt P67809 2 EQUAL 324 EQUAL Reactome DB_ID: 72026 1 UniProt:Q13247 SRSF6 SRSF6 SFRS6 SRP55 SRSF6 FUNCTION Plays a role in constitutive splicing and modulates the selection of alternative splice sites. Plays a role in the alternative splicing of MAPT/Tau exon 10. Binds to alternative exons of TNC pre-mRNA and promotes the expression of alternatively spliced TNC. Plays a role in wound healing and in the regulation of keratinocyte differentiation and proliferation via its role in alternative splicing.SUBUNIT Binds SREK1/SFRS12. Interacts with DYRK1A.PTM Extensively phosphorylated on serine residues in the RS domain. Phosphorylated by DYRK1A, probably in the RS domain. Phosphorylation by DYRK1A modulates alternative splice site selection and inhibits the expression of MAPT/Tau exon 10.SIMILARITY Belongs to the splicing factor SR family. UniProt Q13247 1 EQUAL 344 EQUAL Reactome DB_ID: 71917 1 U1 snRNP [nucleoplasm] U1 snRNP Reactome DB_ID: 71911 1 EMBL:V00590 U1A snRNA U1A snRNA EMBL V00590 Reactome DB_ID: 71915 1 UniProt:P09012 SNRPA SNRPA SNRPA FUNCTION Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. U1 snRNP is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. SNRPA binds stem loop II of U1 snRNA. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. May bind preferentially to the 5'-UGCAC-3' motif on RNAs.SUBUNIT U1 snRNP is composed of the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Interacts with SFPQ; component of a snRNP-free complex with SFPQ.SIMILARITY Belongs to the RRM U1 A/B'' family. UniProt P09012 2 EQUAL 282 EQUAL Reactome DB_ID: 71910 1 snRNP Sm core complex [nucleoplasm] snRNP Sm core complex Reactome DB_ID: 71909 1 UniProt:P62308 SNRPG SNRPG PBSCG SNRPG FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077). As part of the U7 snRNP it is involved in histone 3'-end processing (PubMed:12975319).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:11574479, PubMed:12975319). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:18984161, PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP (PubMed:18984161, PubMed:23333303). Interacts with GEMIN2 (via N-terminus); the interaction is direct (PubMed:21816274). Interacts with SNRPE; the interaction is direct (PubMed:21816274, PubMed:31799625).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt P62308 1 EQUAL 76 EQUAL Reactome DB_ID: 192215 1 UniProt:P62314 SNRPD1 SNRPD1 SNRPD1 FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077). May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through non-specific electrostatic contacts with RNA (Probable).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:19325628, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:10025403, PubMed:19325628, PubMed:21113136, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:21113136, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:21113136, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts (via C-terminus) with SMN1 (via Tudor domain); the interaction is direct (PubMed:10500148, PubMed:11135666). Interacts with GEMIN2; the interaction is direct (PubMed:21816274). Interacts with SNRPD2; the interaction is direct (PubMed:21816274, PubMed:31799625).PTM Methylated on arginine residues by PRMT5 and PRMT7; probable asymmetric dimethylation which is required for assembly and biogenesis of snRNPs.MISCELLANEOUS In the autoimmune disease systemic lupus erythematosus, antinuclear antibodies are developed with Sm specificity.SIMILARITY Belongs to the snRNP core protein family. UniProt P62314 monomethylated residue at unknown position monomethylated residue [MOD:00599] monomethylated residue at unknown position 1 EQUAL 119 EQUAL Reactome DB_ID: 192219 1 UniProt:P62318 SNRPD3 SNRPD3 SNRPD3 FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (By similarity).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:11574479). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts (via C-terminus) with SMN1 (via Tudor domain); the interaction is direct (PubMed:12628254, PubMed:10500148, PubMed:11135666).PTM Methylated on arginine residues by PRMT5 and PRMT7; probable asymmetric dimethylation which is required for assembly and biogenesis of snRNPs.MISCELLANEOUS In the autoimmune disease systemic lupus erythematosus, antinuclear antibodies are developed with Sm specificity.SIMILARITY Belongs to the snRNP core protein family. UniProt P62318 monomethylated residue at unknown position monomethylated residue at unknown position 1 EQUAL 126 EQUAL Reactome DB_ID: 71907 1 UniProt:P62306 SNRPF SNRPF PBSCF SNRPF FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077). As part of the U7 snRNP it is involved in histone 3'-end processing (PubMed:12975319).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:11574479). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:18984161, PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP (PubMed:18984161, PubMed:23333303). Interacts with GEMIN2 (via N-terminus); the interaction is direct (PubMed:21816274, PubMed:31799625). Interacts with SNRPD2; the interaction is direct (PubMed:21816274, PubMed:31799625). Interacts with SNRPE; the interaction is direct (PubMed:21816274, PubMed:31799625).SIMILARITY Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily. UniProt P62306 2 EQUAL 86 EQUAL Reactome DB_ID: 71905 1 UniProt:P62304 SNRPE SNRPE SNRPE FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:23246290, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077). As part of the U7 snRNP it is involved in histone 3'-end processing (PubMed:12975319).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:23246290, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:11574479). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:18984161, PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP (PubMed:18984161, PubMed:23333303). Interacts with SMN1; the interaction is direct (PubMed:10500148). Interacts with GEMIN2 (via N-terminus); the interaction is direct (PubMed:21816274, PubMed:31799625). Interacts with SNRPF; the interaction is direct (PubMed:21816274, PubMed:31799625). Interacts with SNRPG; the interaction is direct (PubMed:21816274, PubMed:31799625).TISSUE SPECIFICITY Widely expressed. In scalp skin, it is present in the hair follicle, the epidermis, and the dermis.MISCELLANEOUS Patients with systemic lupus erythematosus produce antibodies which interact with snRNP proteins.SIMILARITY Belongs to the snRNP Sm proteins family. UniProt P62304 1 EQUAL 92 EQUAL Reactome DB_ID: 71901 1 UniProt:P62316 SNRPD2 SNRPD2 SNRPD2 SNRPD1 FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts with SMN1; the interaction is direct (PubMed:21816274). Interacts with GEMIN2; the interaction is direct (PubMed:21816274, PubMed:31799625). Interacts with SNRPD1; the interaction is direct (PubMed:21816274, PubMed:31799625). Interacts with SNRPF; the interaction is direct (PubMed:21816274, PubMed:31799625).MISCELLANEOUS In the autoimmune disease systemic lupus erythematosus, antinuclear antibodies are developed with Sm specificity.SIMILARITY Belongs to the snRNP core protein family. UniProt P62316 2 EQUAL 118 EQUAL Reactome DB_ID: 192213 1 UniProt:P14678 SNRPB SNRPB COD SNRPB1 SNRPB FUNCTION Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Is also a component of the minor U12 spliceosome (PubMed:15146077). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (PubMed:12975319).SUBUNIT Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:11574479, PubMed:12975319). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:12095920, PubMed:18984161, PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP (PubMed:18984161). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (By similarity). Interacts with TDRD3 and SNUPN (PubMed:12095920, PubMed:15955813). Interacts with PRMT5; interaction leads to its symmetric arginine dimethylation (By similarity). Interacts with TDRD6; interaction promotes association with PRMT5 (By similarity). Interacts with SMN1; the interaction is direct (PubMed:10500148).PTM Methylated by PRMT5 (By similarity). Arg-108 and Arg-112 are dimethylated, probably to asymmetric dimethylarginine (PubMed:16087681, Ref.10).MISCELLANEOUS Patients with the autoimmune disease systemic lupus erythematosus (SLE) have autoantibodies directed against some of the individual snRNP polypeptides. The most common autoantigen is called Sm. B/b' bear Sm epitopes.SIMILARITY Belongs to the snRNP SmB/SmN family. UniProt P14678 symmetric dimethyl-L-arginine at 108 108 EQUAL symmetric dimethyl-L-arginine symmetric dimethyl-L-arginine at 112 112 EQUAL 1 EQUAL 240 EQUAL Reactome Database ID Release 82 71910 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71910 Reactome R-HSA-71910 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71910.3 Reactome DB_ID: 8865876 1 UniProt:P09234 SNRPC SNRPC SNRPC FUNCTION Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. SNRPC/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.SUBUNIT Component of the U1 snRNP (PubMed:2136774). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. SNRPC/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA. Interacts (via N-terminus) with TIA1 (via C-terminus); thereby promoting spliceosomal U1 snRNP recruitment to 5' splice sites (PubMed:12486009).SIMILARITY Belongs to the U1 small nuclear ribonucleoprotein C family. UniProt P09234 1 EQUAL 159 EQUAL Reactome DB_ID: 71913 1 UniProt:P08621 SNRNP70 SNRNP70 SNRP70 U1AP1 RNPU1Z SNRNP70 RPU1 FUNCTION Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome (PubMed:19325628, PubMed:25555158). SNRNP70 binds to the loop I region of U1-snRNA (PubMed:2467746, PubMed:19325628, PubMed:25555158).SUBUNIT Component of the U1 snRNP (PubMed:19325628, PubMed:21113136, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:21113136, PubMed:25555158). Interacts with SCNM1 (By similarity). Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2 (PubMed:9531537). Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRNP70, SNRPA1, SRRM1 and TRA2B/SFRS10 (PubMed:10339552). Interacts with dephosphorylated SFRS13A and SFPQ (PubMed:11514619, PubMed:14765198). Interacts with NUDT21/CPSF5, CPSF6, SCAF11, and ZRANB2 (PubMed:14561889, PubMed:11448987, PubMed:9447963). Interacts with GEMIN5 (PubMed:25911097). Interacts with FUS.DOMAIN The RRM domain mediates interaction with U1 RNA.PTM The N-terminus is blocked.PTM Extensively phosphorylated on serine residues in the C-terminal region.MISCELLANEOUS Major ribonucleoprotein antigen recognized by the sera from patients with autoimmune diseases, such as systemic lupus erythematosus. UniProt P08621 1 EQUAL 437 EQUAL Reactome Database ID Release 82 71917 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71917 Reactome R-HSA-71917 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71917.2 Reactome DB_ID: 72054 1 UniProt:O95400 CD2BP2 CD2BP2 CD2BP2 KIAA1178 FUNCTION Involved in pre-mRNA splicing as component of the U5 snRNP complex that is involved in spliceosome assembly.SUBUNIT Component of the U5 snRNP complex composed of the U5 snRNA and at least PRPF6, PRPF8, SNRNP200, EFTUD2, SNRNP40, DDX23, TXNL4A and CD2BP2. Interacts directly with TXNL4A and PRPF6. Interacts (via GYF domain) with CD2 (via Pro-rich sequence in the cytoplasmic domain). Interacts with PQBP1. UniProt O95400 1 EQUAL 341 EQUAL Reactome DB_ID: 71935 1 UniProt:Q14103 HNRNPD HNRNPD AUF1 HNRNPD HNRPD FUNCTION Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation.SUBUNIT Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR and SYNCRIP. Interacts with IGF2BP2. Interacts with GTPBP1. Interacts with EIF4G1; the interaction requires RNA. Interacts with EIF3B and RPS3.PTM Arg-345 is dimethylated, probably to asymmetric dimethylarginine.PTM Methylated by PRMT1, in an insulin-dependent manner. The PRMT1-mediated methylation regulates tyrosine phosphorylation (By similarity). UniProt Q14103 1 EQUAL 355 EQUAL Reactome DB_ID: 5420896 1 PRP19-CDC5L complex [nucleoplasm] PRP19-CDC5L complex NTC complex NineTeen Complex Reactome DB_ID: 5420902 1 UniProt:O75934 BCAS2 BCAS2 BCAS2 DAM1 FUNCTION Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR).SUBUNIT Component of the pre-catalytic and catalytic spliceosome complexes (PubMed:9731529, PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961). Component of the postcatalytic spliceosome P complex (PubMed:30705154). Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly in the complex with PRPF19, CDC5L and PLRG1 (PubMed:20176811).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the SPF27 family. UniProt O75934 2 EQUAL 225 EQUAL Reactome DB_ID: 5082380 1 UniProt:P11142 HSPA8 HSPA8 HSPA8 HSPA10 HSC70 HSP73 FUNCTION Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). Interacts with VGF-derived peptide TLQP-21 (PubMed:28934328).SUBUNIT Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7. Interacts with DNAJB12 (via J domain) (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661). Interacts with DNAJB14 (via J domain) (PubMed:23018488, PubMed:24732912, PubMed:27916661). Interacts (via C-terminus) with the E3 ligase CHIP forming a 210 kDa complex of one CHIP and two HSPA8 molecules. Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts with TRIM5. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with METTL21A. Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts with PRKN. Interacts with FOXP3. Interacts with DNAJC9 (via J domain) (PubMed:17182002). Interacts with MLLT11 (PubMed:24880125). Interacts with RNF207 (PubMed:25281747). Interacts with DNAJC21 (PubMed:27346687). Interacts with DNAJB2 (PubMed:15936278). Interacts with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with SGTA (via TPR repeats) (By similarity). Interacts with HSF1 (via transactivation domain) (PubMed:9499401). Interacts with HOPX, HSP40 and HSP90 (PubMed:27708256). Interacts with STUB1 (PubMed:27708256). Interacts with BAG2 (PubMed:24318877). Interacts with BAG3 (PubMed:27474739, PubMed:24318877). Interacts with DNAJC12 (PubMed:24122553). Interacts with ZMYND10 (PubMed:29601588). Interacts with HSPC138 (PubMed:25760597). Interacts with BCL2L1, GIMAP5 and MCL1; the interaction with BCL2L1 or MCL1 is impaired in the absence of GIMAP5 (By similarity). Interacts with NLPR12 (PubMed:17947705). Interacts with TTC4 (PubMed:18320024). Interacts with TOMM70; the interaction is required for preprotein mitochondrial import (PubMed:12526792). May interact with DNJC9; the interaction seems to be histone-dependent (PubMed:33857403).SUBUNIT (Microbial infection) Interacts with SV40 VP1.TISSUE SPECIFICITY Ubiquitous.INDUCTION Constitutively synthesized.DOMAIN The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.PTM Acetylated.PTM ISGylated.PTM Trimethylation at Lys-561 reduces fibrillar SNCA binding.SIMILARITY Belongs to the heat shock protein 70 family. UniProt P11142 2 EQUAL 646 EQUAL Reactome DB_ID: 5420890 1 UniProt:O43660 PLRG1 PLRG1 PLRG1 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:28076346). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing (PubMed:11101529, PubMed:11544257).SUBUNIT Identified in the spliceosome C complex (PubMed:12176931, PubMed:28502770, PubMed:28076346). Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 (PubMed:11101529, PubMed:20176811). Interacts (via its WD40 repeat domain) directly with CDC5L (via its C-terminal); the interaction is required for mRNA splicing but not for spliceosome assembly (PubMed:11544257). Also interacts directly in the complex with BCAS2 and PRPF19 (PubMed:20176811). Interacts with USB1 (PubMed:23022480).SIMILARITY Belongs to the WD repeat PRL1/PRL2 family. UniProt O43660 1 EQUAL 514 EQUAL Reactome DB_ID: 5420895 1 UniProt:Q8WYA6 CTNNBL1 CTNNBL1 C20orf33 PP8304 CTNNBL1 FUNCTION Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. Participates in AID/AICDA-mediated Ig class switching recombination (CSR). May induce apoptosis.SUBUNIT Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly with CWC15 and CDC5L in the complex. Interacts with AICDA; the interaction is important for the antibody diversification activity of AICDA. Interacts with PRPF31 (via its NLS). Interacts (via its N-terminal NLS) with KPNA1 and KPNA2.TISSUE SPECIFICITY Widely expressed with highest levels in skeletal muscle, placenta, heart, spleen, testis and thyroid.DOMAIN The surface residues of the concave side of the superhelical ARM repeat region contribute to, but are not essential for NLS binding. UniProt Q8WYA6 1 EQUAL 563 EQUAL Reactome DB_ID: 5420887 1 UniProt:Q99459 CDC5L CDC5L KIAA0432 PCDC5RP CDC5L FUNCTION DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811).SUBUNIT Homodimer. Interacts with DAPK3 (By similarity). Component of the precatalytic, catalytic and postcatalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Part of a spliceosomal 'core' complex consisting of CDC5L, PLRG1, SPF27, CCAP1, CCAP3 and CCAP6. Interacts with PLRG1, Lodestar/TTF2, and NIPP1/PPP1R8. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts (via its C-terminus) directly in the complex with PRPF19 and BCAS2. Interacts (via its C-terminus) directly with PRGL1 (via its WD40 repeat domain); the interaction is required for mRNA splicing but not for spliceosome assembly. Also interacts with CTNNBL1. Interacts with PRPF19 (via N-terminus) (By similarity). Interacts with USB1 (PubMed:23022480).TISSUE SPECIFICITY Ubiquitously expressed in both fetal and adult tissues.PTM Phosphorylated on serine and threonine residues. Phosphorylation on Thr-411 and Thr-438 is required for CDC5L-mediated mRNA splicing. Has no effect on subcellular location nor on homodimerization. Phosphorylated in vitro by CDK2. Phosphorylation enhances interaction with PPP1R8.DISEASE A chromosomal aberration involving CDC5L is found in multicystic renal dysplasia. Translocation t(6;19)(p21;q13.1) with USF2.SIMILARITY Belongs to the CEF1 family. UniProt Q99459 1 EQUAL 802 EQUAL Reactome DB_ID: 5420897 1 UniProt:Q9P013 CWC15 CWC15 C11orf5 AD-002 CWC15 HSPC148 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:28076346). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing.SUBUNIT Identified in the spliceosome C complex (PubMed:28502770, PubMed:28076346). Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 (PubMed:20176811). Interacts directly with CTNNBL1 in the complex (PubMed:20176811).SIMILARITY Belongs to the CWC15 family.CAUTION Has been termed C11orf5, but is not the official C11orf5 as defined by HGNC. UniProt Q9P013 2 EQUAL 229 EQUAL Reactome DB_ID: 5420907 4 UniProt:Q9UMS4 PRPF19 PRPF19 SNEV PRP19 PRPF19 NMP200 FUNCTION Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961, PubMed:30705154). Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex (PubMed:20595234). Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries (PubMed:21536736). The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair (PubMed:17981804). Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response (PubMed:24332808). May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA (PubMed:18263876). As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process (PubMed:16223718). In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:11435423). May play a role in the biogenesis of lipid droplets (By similarity). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Homotetramer. Component of activated, catalytic and post-catalytic spliceosomes (PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961, PubMed:30705154). Component of the Prp19 complex/PRP19C/Nineteen complex/NTC and related complexes described as PRP19-CDC5L splicing complex and PSO4 complex. A homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2 constitute the core of those complexes. The interaction with CDC5L, PLRG1 and BCAS2 is direct within this core complex. At least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 are found in the Prp19 complex. The Prp19 complex associates with the spliceosome during its assembly and remodeling recruiting additional proteins. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Interacts with CWC22 and EIF4A3 in an RNA-independent manner. Interacts with RPA1 and RPA2; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it interacts with the replication protein A complex (RPA). Interacts with SETMAR; required for SETMAR recruitment to site of DNA damage. Interacts with U2AF2; the interaction is direct and recruits the Prp19 complex to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA. Interacts with PRPF3. Interacts with APEX1, DNTT and PSMB4. Interacts with PSMC5 (By similarity). Interacts with KNSTRN (PubMed:24718257). Interacts (via N-terminus) with CDC5L (By similarity). Interacts with KHDC4 (PubMed:19641227). Interacts with USB1 (PubMed:23022480).TISSUE SPECIFICITY Ubiquitous. Weakly expressed in senescent cells of different tissue origins. Highly expressed in tumor cell lines.INDUCTION By gamma irradiation and chemical mutagens but not by UV irradiation.DOMAIN The 7 WD repeats are necessary and sufficient to support interaction with the RPA complex.SIMILARITY Belongs to the WD repeat PRP19 family. UniProt Q9UMS4 2 EQUAL 504 EQUAL Reactome DB_ID: 8867889 1 UniProt:O60828 PQBP1 PQBP1 JM26 NPW38 PQBP1 FUNCTION Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development (PubMed:10198427, PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:10332029, PubMed:12062018, PubMed:23512658, PubMed:20410308). May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery (PubMed:10198427). May be involved in ATXN1 mutant-induced cell death (PubMed:12062018). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (PubMed:12062018). Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules (PubMed:21933836). Also acts as an innate immune sensor of infection by retroviruses, such as HIV, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:26046437). Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production (PubMed:26046437).SUBUNIT Interacts with POU3F2/Brn-2, ATXN1, TXNL4A, HTT and AR (PubMed:10332029, PubMed:10873650, PubMed:19303059, PubMed:24781215). Interaction with ATXN1 correlates positively with the length of the polyglutamine tract (PubMed:12062018). Interacts with RNA polymerase II large subunit in a phosphorylation-dependent manner (PubMed:12062018). Forms a ternary complex with ATXN1 mutant and phosphorylated RNA polymerase II (PubMed:12062018). Interacts (via C-terminus) with TXNL4A and CD2BP2 (PubMed:10873650, PubMed:19303059, PubMed:24781215). Interacts (via WW domain) with ATN1 and SF3B1, and may interact with additional splice factors (PubMed:23512658, PubMed:20410308). Interacts (via WW domain) with WBP11; Leading to reduce interaction between PQBP1 and TXNL4A (PubMed:23512658, PubMed:20410308, PubMed:27314904). Interacts with CAPRIN1 (PubMed:21933836). Interacts with DDX1 (PubMed:21933836). Interacts with SFPQ (PubMed:21933836). Interacts with KHSRP (PubMed:21933836).TISSUE SPECIFICITY Widely expressed with high level in heart, skeletal muscle, pancreas, spleen, thymus, prostate, ovary, small intestine and peripheral blood leukocytes.DOMAIN The WW domain may play a role as a transcriptional activator directly or via association with the transcription machinery. The WW domain mediates interaction with WBP11, ATN1, SF3B1 and the C-terminal domain of the RNA polymerase II large subunit.DOMAIN Except for the WW domain, the protein is intrinsically disordered. UniProt O60828 2 EQUAL 265 EQUAL Reactome DB_ID: 8867887 1 UniProt:Q9Y2W2 WBP11 WBP11 NPWBP SNP70 WBP11 SIPP1 FUNCTION Activates pre-mRNA splicing. May inhibit PP1 phosphatase activity.SUBUNIT Interacts with PPP1CA, PPP1CB and PPP1CC (By similarity). Interacts via the PGR motif with PQBP1 in the nucleus. Interacts with the WW domains of WBP4.TISSUE SPECIFICITY Ubiquitous. Highly expressed in the heart, pancreas, kidney skeletal muscle, placenta and brain (at protein level). Weakly expressed in liver and lung. UniProt Q9Y2W2 1 EQUAL 641 EQUAL Reactome Database ID Release 82 5420896 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5420896 Reactome R-HSA-5420896 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5420896.3 Reactome DB_ID: 71953 1 UniProt:Q00839 HNRNPU HNRNPU U21.1 C1orf199 HNRNPU HNRPU SAFA FUNCTION 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:10490622, PubMed:18082603, PubMed:19029303, PubMed:22325991, PubMed:25986610, PubMed:28622508). 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 (PubMed:1324173, PubMed:8174554, PubMed:28622508). 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 (By similarity). Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator (PubMed:8174554, PubMed:9353307, PubMed:10490622, PubMed:15711563, PubMed:19617346, PubMed:23811339). 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 (PubMed:10490622, PubMed:15711563). 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 (PubMed:10490622). Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus (PubMed:19617346). Negatively regulates glucocorticoid-mediated transcriptional activation (PubMed:9353307). Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling (By similarity). Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression (PubMed:23811339). Participates in the circadian regulation of the core clock component ARNTL/BMAL1 transcription (By similarity). Plays a role in the regulation of telomere length (PubMed:18082603). Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis (PubMed:22325991). Plays a role in mRNA stability (PubMed:17174306, PubMed:17289661, PubMed:19029303). Component of the CRD-mediated complex that promotes MYC mRNA stabilization (PubMed:19029303). 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) (PubMed:17174306). Plays a role in mitotic cell cycle regulation (PubMed:21242313, PubMed:25986610). Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression (PubMed:21242313). Phosphorylation at Ser-59 by PLK1 is required for chromosome alignement and segregation and progression through mitosis (PubMed:25986610). Contributes also to the targeting of AURKA to mitotic spindle MTs (PubMed:21242313). Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides (PubMed:1628625, PubMed:8068679, PubMed:8174554, PubMed:9204873, PubMed:9405365). Binds to chromatin-associated RNAs (caRNAs) (PubMed:28622508). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner (PubMed:7509195, PubMed:1324173, PubMed:9204873, PubMed:9405365, PubMed:10671544, PubMed:11003645, PubMed:11909954, PubMed:28622508). Binds to the Xist RNA (PubMed:26244333). Binds the long non-coding H19 RNA (PubMed:23811339). Binds to SMN1/2 pre-mRNAs at G/U-rich regions (PubMed:22325991). Binds to small nuclear RNAs (snRNAs) (PubMed:22325991). Binds to the 3'-UTR of TNFA mRNA (PubMed:17174306). 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) (By similarity). Also negatively regulates embryonic stem cell differentiation upon LIF signaling (By similarity). Required for embryonic development (By similarity). Binds to brown fat long non-coding RNA 1 (Blnc1); facilitates the recruitment of Blnc1 by ZBTB7B required to drive brown and beige fat development and thermogenesis (By similarity).FUNCTION (Microbial infection) Negatively regulates immunodeficiency virus type 1 (HIV-1) replication by preventing the accumulation of viral mRNA transcripts in the cytoplasm.SUBUNIT 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 (PubMed:28622508). ATP hydrolysis is required to cycle from an oligomeric to monomeric state to compact chromatin (PubMed:28622508). Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (PubMed:19029303). Identified in the spliceosome C complex (PubMed:11991638). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661, PubMed:19029303). Associates with heterogeneous nuclear ribonucleoprotein (hnRNP) particles (PubMed:8174554, PubMed:9204873, PubMed:9405365, PubMed:11909954). 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:10490622). Associates (via middle region) with the core-TFIIH basal transcription factor complex; this association inhibits the CTD phosphorylation of RNA polymerase II holoenzyme by down-regulating TFIIH kinase activity (PubMed:10490622). Associates with the telomerase holoenzyme complex (PubMed:18082603). Associates with spindle microtubules (MTs) in a TPX2-dependent manner (PubMed:21242313). 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 (PubMed:15711563, PubMed:23811339). Interacts with AURKA (PubMed:21242313, PubMed:25986610). Interacts (via C-terminus) with CBX5; this interaction is, at least in part, RNA-dependent (PubMed:19617346). Interacts with CR2 (PubMed:7753047). Interacts with CRY1 (By similarity). Interacts (via C-terminus) with EP300; this interaction enhances DNA-binding to nuclear scaffold/matrix attachment region (S/MAR) elements (PubMed:11909954). Interacts with ERBB4 (PubMed:20858735). Interacts with GEMIN5 (PubMed:25911097). Interacts with IGF2BP1 (PubMed:17289661, PubMed:23640942). Interacts with IGF2BP2 and IGF2BP3 (PubMed:23640942). Interacts with NCL; this interaction occurs during mitosis (PubMed:21242313). Interacts (via C-terminus) with NR3C1 (via C-terminus) (PubMed:9353307). Interacts with PLK1; this interaction induces phosphorylation of HNRNPU at Ser-59 in mitosis (PubMed:25986610). Interacts with POU3F4 (PubMed:9105675). Interacts with SMARCA4; this interaction occurs in embryonic stem cells and stimulates global Pol II-mediated transcription. 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 (By similarity). Interacts with TPX2; this interaction recruits HNRNPU to spindle microtubules (MTs) (PubMed:21242313, PubMed:25986610). Interacts with UBQLN2 (PubMed:25616961). Interacts (via RNA-binding RGG-box region) with ZBTB7B; the interaction facilitates the recruitment of long non-coding RNA Blnc1 by ZBTB7B (By similarity). Interacts with ERCC6 (PubMed:26030138).SUBUNIT (Microbial infection) Interacts with HIV-1 protein Rev.TISSUE SPECIFICITY Widely expressed.DOMAIN The SAP domain is necessary for specific binding to nuclear scaffold/matrix attachment region (S/MAR) elements in DNA (PubMed:9405365, PubMed:11003645). The RNA-binding RGG-box region is necessary for its association with inactive X chromosome (Xi) regions and to chromatin-associated RNAs (caRNAs) (PubMed:14608463, PubMed:28622508). Both the DNA-binding domain SAP and the RNA-binding RGG-box region are necessary for the localization of Xist RNA on the Xi (By similarity). The ATPase and RNA-binding RGG-box regions are necessary for oligomerization (PubMed:28622508).PTM Cleaved at Asp-100 by CASP3 during T-cell apoptosis, resulting in a loss of DNA- and chromatin-binding activities (PubMed:9405365, PubMed:10671544).PTM Extensively phosphorylated (PubMed:7993898). Phosphorylated on Ser-59 by PLK1 and dephosphorylated by protein phosphatase 2A (PP2A) in mitosis (PubMed:25986610).PTM Arg-739 is dimethylated, probably to asymmetric dimethylarginine (Ref.8). Arg-733 is dimethylated, probably to asymmetric dimethylarginine (By similarity).PTM Citrullinated by PADI4. UniProt Q00839 2 EQUAL 825 EQUAL Reactome DB_ID: 3900136 1 UniProt:P17844 DDX5 DDX5 G17P1 DDX5 HELR HLR1 FUNCTION Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638). Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF (PubMed:24644279). Interacts with RBM4; the interaction occurs in an RNA-independent manner. Interacts with AGO1 and AGO2. Interacts with ESR1, AR, EP300, CREBBP, POLR2A, TP53, RUNX2 and HDAC1. Self-associates. Interacts with DDX17. Interacts with BRDT. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with NUPR1 (By similarity). Interacts with ERCC6 (PubMed:26030138). Interacts with DDX3X in the cytoplasm; this interaction may be more efficient when both proteins are unphosphorylated (PubMed:22034099).PTM Arg-502 is dimethylated, probably to asymmetric dimethylarginine.PTM Sumoylated; sumoylation, promoted by PIAS1, promotes interaction with HDAC1 and transcriptional repression activity. Sumoylation also significantly increases stability, and reduces polyubiquitination.PTM Polyubiquitinated, leading to proteasomal degradation.PTM Weakly phosphorylated in the G1/S phase of the cell cycle and much more at G2/M, especially at Thr and Tyr residues.SIMILARITY Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.CAUTION DDX5 was reported to be a transcriptional coactivator of ESR1. However, this study has been retracted due to concerns of image manipulation. UniProt P17844 1 EQUAL 614 EQUAL Reactome DB_ID: 71931 1 UniProt:P51991 HNRNPA3 HNRNPA3 HNRNPA3 HNRPA3 FUNCTION Plays a role in cytoplasmic trafficking of RNA. Binds to the cis-acting response element, A2RE. May be involved in pre-mRNA splicing.SUBUNIT Identified in the spliceosome C complex.CAUTION An older version of this entry represented the conceptual translation of what was thought to be HNRNPA3 but which was in fact a pseudogene (HNRPA3P1/FBRNP) located on chromosome 10. UniProt P51991 1 EQUAL 378 EQUAL Reactome DB_ID: 71927 1 UniProt:P09651 HNRNPA1 HNRNPA1 HNRPA1 HNRNPA1 FUNCTION Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection (PubMed:17371836). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1 (PubMed:31498791). May bind to specific miRNA hairpins (PubMed:28431233).FUNCTION (Microbial infection) May play a role in HCV RNA replication.FUNCTION (Microbial infection) Cleavage by Enterovirus 71 protease 3C results in increased translation of apoptosis protease activating factor APAF1, leading to apoptosis.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with SEPT6 (PubMed:17229681). Interacts with C9orf72 (PubMed:24549040). Interacts with KHDRBS1 (PubMed:17371836). Interacts with UBQLN2 (PubMed:25616961). Interacts with PPIA/CYPA (PubMed:25678563). Interacts (via the RGG-box) with the HOXB-AS3 peptide; the interaction inhibits binding of HNRNPA1 to the intronic sequences flanking exon 9 of the PKM gene, preventing inclusion of exon 9 and promoting inclusion of exon 10 which suppresses formation of the PKM M2 isoform and promotes production of the M1 isoform (PubMed:28985503).SUBUNIT (Microbial infection) Interacts with HCV NS5B and with the 5'-UTR and 3'-UTR of HCV RNA.SUBUNIT (Microbial infection) May interact with SARS-CoV Nucleoprotein.PTM Arg-194, Arg-206 and Arg-225 are dimethylated, probably to asymmetric dimethylarginine.PTM Sumoylated.CAUTION Variant Val-314 has been originally associated with IBMPFD3 and variant Asn-314 with ALS20 (PubMed:25616961). However in another report, variant Val-314 is associated with amyotrophic lateral sclerosis (ALS) but this variant is not supported by clinical data in this publication (PubMed:25616961). UniProt P09651 2 EQUAL 372 EQUAL Reactome DB_ID: 71943 1 UniProt:P55795 HNRNPH2 HNRNPH2 FTP3 HNRPH2 HNRNPH2 FUNCTION This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Binds poly(RG).SUBUNIT Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF (PubMed:24644279). Interacts with TXNL4/DIM1 (PubMed:11054566).TISSUE SPECIFICITY Expressed ubiquitously. UniProt P55795 1 EQUAL 449 EQUAL Reactome DB_ID: 72049 1 UniProt:P52756 RBM5 RBM5 LUCA15 H37 RBM5 FUNCTION Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate apoptosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis.SUBUNIT Component of the spliceosome A complex (also known as the prespliceosome). Appears to dissociate from the spliceosome upon formation of the spliceosome B complex (also known as the precatalytic spliceosome), in which the heterotrimeric U4/U6.U5 snRNPs are bound. Interacts with U2AF2; this interaction is direct. Also interacts with ACIN1, PRPF8, SFRS3, SNRPB, SNRPN, SNRNP70 and SNRNP200; these interactions may be indirect.TISSUE SPECIFICITY Isoform 5 is widely expressed in normal tissues and is expressed at increased levels in T-leukemic cell lines.SIMILARITY Belongs to the RBM5/RBM10 family. UniProt P52756 1 EQUAL 815 EQUAL Reactome DB_ID: 71949 1 UniProt:P52272 HNRNPM HNRNPM HNRNPM HNRPM NAGR1 FUNCTION Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638). Interacts with PPIA/CYPA (PubMed:25678563).PTM Sumoylated. UniProt P52272 2 EQUAL 730 EQUAL Reactome DB_ID: 71925 1 UniProt:Q13151 HNRNPA0 HNRNPA0 HNRPA0 HNRNPA0 FUNCTION mRNA-binding component of ribonucleosomes. Specifically binds AU-rich element (ARE)-containing mRNAs. Involved in post-transcriptional regulation of cytokines mRNAs.PTM Phosphorylated at Ser-84 by MAPKAPK2 in response to LPS treatment, promoting stabilization of GADD45A mRNA.PTM Arg-291 is dimethylated, probably to asymmetric dimethylarginine. UniProt Q13151 1 EQUAL 305 EQUAL Reactome DB_ID: 72058 1 UniProt:Q05519 SRSF11 SRSF11 SFRS11 SRSF11 FUNCTION May function in pre-mRNA splicing.SUBUNIT Interacts with PUF60.SIMILARITY Belongs to the splicing factor SR family. UniProt Q05519 1 EQUAL 484 EQUAL Reactome DB_ID: 72062 1 UniProt:O60508 CDC40 CDC40 PRPF17 EHB3 PRP17 CDC40 FUNCTION Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:33220177). Plays an important role in embryonic brain development; this function does not require proline isomerization (PubMed:33220177).SUBUNIT Component of the pre-catalytic and catalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961). Component of the postcatalytic spliceosome P complex (PubMed:30705154). Interacts with PPIL1; this interaction leads to CDC40 isomerization (PubMed:33220177).PTM Undergoes isomerization of the peptide bond between Gly-94 and Pro-95. The reaction is catalyzed by PPIL1. UniProt O60508 1 EQUAL 579 EQUAL Reactome DB_ID: 53517 1 UniProt:Q08211 DHX9 DHX9 LKP NDH2 DHX9 DDX9 FUNCTION Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:9111062, PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:25062910, PubMed:24990949, PubMed:28221134). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:9111062, PubMed:10198287). Binds also to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11149922, PubMed:9323138, PubMed:9662397, PubMed:11038348, PubMed:11416126, PubMed:15355351, PubMed:28221134). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Acts also as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:9162007, PubMed:10924507, PubMed:11402034). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588).FUNCTION (Microbial infection) Plays a role in HIV-1 replication and virion infectivity (PubMed:11096080, PubMed:19229320, PubMed:25149208, PubMed:27107641). Enhances HIV-1 transcription by facilitating the binding of RNA polymerase II holoenzyme to the proviral DNA (PubMed:11096080, PubMed:25149208). Binds (via DRBM domain 2) to the HIV-1 TAR RNA and stimulates HIV-1 transcription of transactivation response element (TAR)-containing mRNAs (PubMed:9892698, PubMed:11096080). Involved also in HIV-1 mRNA splicing and transport (PubMed:25149208). Positively regulates HIV-1 gag mRNA translation, through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Binds (via DRBM domains) to a HIV-1 double-stranded RNA region of the primer binding site (PBS)-segment of the 5'-UTR, and hence stimulates DHX9 incorporation into virions and virion infectivity (PubMed:27107641). Also plays a role as a cytosolic viral MyD88-dependent DNA and RNA sensors in plasmacytoid dendritic cells (pDCs), and hence induce antiviral innate immune responses (PubMed:20696886, PubMed:21957149). Binds (via the OB-fold region) to viral single-stranded DNA unmethylated C-phosphate-G (CpG) oligonucleotide (PubMed:20696886).SUBUNIT Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (PubMed:19029303). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 (PubMed:19029303). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active) (By similarity). Associates (via DRBM domains) with the RISC complex; this association occurs in a small interfering (siRNA)-dependent manner (PubMed:17531811, PubMed:23361462). Associates with the SMN complex; this association induces recruitment of DHX9 to the RNA polymerase II (ref.8). Associates with polysomes in a LIN28A-dependent manner (PubMed:16680162, PubMed:21247876). Interacts (via C-terminus) with ACTB; this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes (PubMed:11687588). Interacts with ADAR isoform 1; this interaction occurs in a RNA-independent manner (PubMed:28355180). Interacts (via DRBM domains) with AGO2 (via middle region); this interaction promotes active RISC assembly by promoting the association of siRNA with AGO2 (PubMed:17531811, PubMed:23361462). Interacts (via RGG region) with AKAP8L (via N-terminus) (PubMed:11402034). Interacts with BRCA1 (via C-terminus); this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme (PubMed:9662397). Interacts (via N-terminus) with CREBBP; this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation (PubMed:9323138). Interacts (via N-terminus) with EIF2AK2/PKR; this interaction is dependent upon the activation of the kinase (PubMed:19229320). Interacts (via DRBM domains) with DICER1 (PubMed:17531811). Interacts with H2AX; this interaction is direct, requires phosphorylation of histone H2AX on 'Ser-140' by PRKDC and promotes binding of DHX9 to transcriptionally stalled sites on chromosomal DNA in response to genotoxic stress (PubMed:15613478, PubMed:17498979). Interacts with HNRNPC; this interaction is direct, enhanced probably by their concomitant binding to RNA and mediates the attachment to actin filaments (PubMed:11687588). Interacts (via RGG region) with PRMT1 (PubMed:15084609). Interacts with IGF2BP1 (PubMed:17289661, PubMed:23640942). Interacts with IGF2BP2, IGF2BP3 (PubMed:23640942). Interacts (via DRBM domains) with ILF3; this interaction occurs in a RNA-independent manner (PubMed:12946349). Interacts with Importin alpha/Importin beta receptor (PubMed:16375861). Interacts with LARP6 (via C-terminus); this interaction occurs in a mRNA-independent manner (PubMed:22190748). Interacts (via N- and C-terminus) with LIN28A (via C-terminus); this interaction occurs in a RNA-independent manner (PubMed:21247876). Interacts with LMX1B (PubMed:23308148). Interacts (via helicase C-terminal domain, HA2 and OB-fold regions) with MAVS (via CARD domain); this interaction occurs in both resting and double-stranded RNA poly(I:C)-induced cells (PubMed:21957149). Interacts with MBD2; this interaction stimulates transcriptional activation in a CREB-dependent manner (PubMed:12665568). Interacts (via H2A and OB-fold regions) with MYD88 (via TIR domain); this interaction is direct (PubMed:20696886). Interacts with NLRP9 upon rotavirus infection; this interaction may trigger NLRP9 inflammasome activation and inflammatory response (PubMed:28636595). Interacts (via DRBM, OB-fold and RGG regions) with NUP98 (via N-terminus); this interaction occurs in a RNA-dependent manner and stimulates DHX9-mediated ATPase activity and regulates transcription and splicing of a subset of genes (PubMed:28221134). Interacts (via N-terminus) with NXF1 (via N-terminus); this interaction is direct and negatively regulates NXF1-mediated nuclear export of constitutive transport element (CTE)-containing cellular mRNAs (PubMed:10924507). Interacts with RELA; this interaction is direct and activates NF-kappa-B-mediated transcription (PubMed:15355351). Interacts (via MTAD region) with RNA polymerase II holoenzyme; this interaction stimulates transcription activation in a CREB-dependent manner (PubMed:11149922, PubMed:9323138, PubMed:11416126). Interacts (via RGG region) with SMN1; this interaction links SMN1 to the RNA polymerase II holoenzyme (PubMed:11149922). Interacts with SP7 (PubMed:17303075). Interacts (via DRBM domains) with TARBP2 (via DRBM first and second domains); this interaction occurs in a small interfering (siRNA)-dependent manner (PubMed:17531811, PubMed:23361462). Interacts with TOP2A; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity (PubMed:12711669). Interacts (via DRBM domains and C-terminus) with WRN (via 3'-5' exonuclease domain); this interaction inhibits the DNA-dependent NTPase and DNA helicase activities of DHX9 and stimulates the 3'-5' exonuclease activity of WRN (PubMed:15995249). Interacts with XRCC5; this interaction occurs in a RNA-dependent manner (PubMed:14704337). Interacts with ZIC2 (via C2H2-type domain 3) (PubMed:17251188). Interacts with MCM3AP isoform GANP (PubMed:23652018).SUBUNIT (Microbial infection) Interacts with Chikungunya virus non-structural protein 3 (via C-terminus); this interaction allows the recruitment of DHX9 to the plasma membrane, where it associates with viral replication complexes and may play a role in the translation-to-replication switch.DOMAIN DRBM domains cooperate for the binding to nucleic acid but not for unwinding helicase activity (PubMed:9111062, PubMed:25062910). The helicase-associated domain-2 (HA2) region is essential for the duplex RNA unwinding helicase activity (PubMed:25062910). The minimal transactivation region (MTAD) mediates interaction with the RNA polymerase II holoenzyme and stimulates transcriptional activation in a CREB-dependent manner (PubMed:11416126). The oligonucleotide- or oligosaccharide-binding (OB-fold) and the repeated arginine and glycine-glycine (RGG) regions are dispensable for both RNA-binding and unwinding helicase activities (PubMed:25062910). The RGG region contains both nuclear localization signal (NLS) and nuclear export signal (NES) and is necessary and sufficient for nucleocytoplasmic shuttling in a RNA-independent manner (PubMed:10207077, PubMed:11149922).PTM Methylated (PubMed:15084609). PRMT1-mediated methylation of undefined Arg residues in the RGG region is required for nuclear import of DHX9 (PubMed:15084609).PTM Phosphorylated by PRKDC; phosphorylation occurs in a RNA-dependent manner (PubMed:14704337). Phosphorylated by EIF2AK2/PKR; this phosphorylation reduces its association with double-stranded RNA (PubMed:19229320).SIMILARITY Belongs to the DEAD box helicase family. DEAH subfamily. UniProt Q08211 1 EQUAL 1270 EQUAL Reactome DB_ID: 72037 1 UniProt:Q13242 SRSF9 SRSF9 SFRS9 SRSF9 SRP30C FUNCTION Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10.SUBUNIT Interacts with KHDRBS3 (By similarity). Interacts with HABP4 (PubMed:19523114). Interacts with NOL3/ARC/NOP30 (PubMed:10196175). Interacts with NSEP1/YB-1/YB1 (PubMed:12604611). Interacts with SAFB/SAFB1 (PubMed:9671816, PubMed:11694584). Interacts with SRSF6/SFRS6 (PubMed:15695522). Interacts with TRA2B/SFRS10 (PubMed:11875052, PubMed:15695522). Interacts with C1QBP (PubMed:10022843). May also interact with DUSP11/PIR1(PubMed:11694584).TISSUE SPECIFICITY Expressed at high levels in the heart, kidney, pancreas and placenta, and at lower levels in the brain, liver, lung and skeletal muscle.PTM Extensively phosphorylated on serine residues in the RS domain.SIMILARITY Belongs to the splicing factor SR family. UniProt Q13242 1 EQUAL 221 EQUAL Reactome DB_ID: 71951 1 UniProt:O43390 HNRNPR HNRNPR HNRPR HNRNPR FUNCTION Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus.SUBUNIT Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with GTPBP1. UniProt O43390 2 EQUAL 633 EQUAL Reactome DB_ID: 8865956 1 UniProt:Q9HCG8 CWC22 CWC22 KIAA1604 CWC22 NCM FUNCTION Required for pre-mRNA splicing as component of the spliceosome (PubMed:12226669, PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961). Promotes exon-junction complex (EJC) assembly (PubMed:22959432, PubMed:22961380). Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.SUBUNIT Component of the pre-catalytic spliceosome B and the catalytic spliceosome C complexes (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29360106, PubMed:29301961). Interacts with EIF4A3 and PRPF19 in an RNA-independent manner. Direct interaction with EIF4A3 is mediated by the MIF4G domain (PubMed:24218557). Full interaction with EIF4A3 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA.SIMILARITY Belongs to the CWC22 family. UniProt Q9HCG8 1 EQUAL 908 EQUAL Reactome DB_ID: 8867890 1 UniProt:O75400 PRPF40A PRPF40A HYPA FNBP3 HIP10 PRPF40A FLAF1 FBP11 HSPC225 FUNCTION Binds to WASL/N-WASP and suppresses its translocation from the nucleus to the cytoplasm, thereby inhibiting its cytoplasmic function (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. May play a role in cytokinesis. May be involved in pre-mRNA splicing.SUBUNIT Interacts with the N-terminus of HTT. Interacts with the phosphorylated C-terminal domain of POLR2A. Interacts with AKAP8L, SF1, SRPK1, ENAH, ATBF1 and MECP2 (By similarity). Interacts through the WW domains with formin proline-rich regions and with WASL/N-WASP (By similarity).TISSUE SPECIFICITY Expressed in the brain cortex (at protein level). Widely expressed.DOMAIN The WW domains are essential for localization to nuclear speckles.SIMILARITY Belongs to the PRPF40 family. UniProt O75400 1 EQUAL 957 EQUAL Reactome DB_ID: 71933 1 UniProt:P07910 HNRNPC HNRNPC HNRPC HNRNPC FUNCTION Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671).SUBUNIT Tetramer composed of 3 copies of isoform C1 and 1 copy of isoform C2. Assembly of 3 tetramers with bound pre-mRNA gives rise to a 19S complex that interacts with HNRNPA2B1 tetramers. Component of the 40S hnRNP particle. Identified in the spliceosome C complex. Interacts with IGF2BP1. Interacts with DHX9; this interaction is direct, enhanced probably by their concomitant binding to RNA and mediates the attachment to actin filaments (PubMed:11687588). Interacts with PPIA/CYPA (PubMed:25678563).PTM Phosphorylated on Ser-260 and Ser-299 in resting cells. Phosphorylated on Ser-253 and on 1 serine residue in the poly-Ser stretch at position 238 in response to hydrogen peroxide.PTM Sumoylated. Sumoylation reduces affinity for mRNA.SIMILARITY Belongs to the RRM HNRPC family. RALY subfamily. UniProt P07910 2 EQUAL 306 EQUAL Reactome DB_ID: 156778 1 UniProt:Q15287 RNPS1 RNPS1 LDC2 RNPS1 FUNCTION Part of pre- and post-splicing multiprotein mRNP complexes. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Enhances the formation of the ATP-dependent A complex of the spliceosome. Involved in both constitutive splicing and, in association with SRP54 and TRA2B/SFRS10, in distinctive modulation of alternative splicing in a substrate-dependent manner. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Participates in mRNA 3'-end cleavage. Involved in UPF2-dependent nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Also mediates increase of mRNA abundance and translational efficiency. Binds spliced mRNA 20-25 nt upstream of exon-exon junctions.SUBUNIT Found in mRNA splicing-dependent exon junction complexes (EJC). Found in a post-splicing complex with NXF1, RBM8A, UPF1, UPF2, UPF3A, UPF3B and RNPS1. Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) and PSAP complexes consisting of RNPS1, SAP18 and either ACIN1 or PNN, respectively; the ASAP and PSAP complexes probably are formed mutually exclusive. Component of the active spliceosome. Associates with polysomes. Interacts with the cleaved p110 isoform of CDC2L1, CSNK2A1, PNN, SART3, SRP54, SRRM1 and TRA2B/SFRS10.TISSUE SPECIFICITY Ubiquitous.DOMAIN The RRM domain is required for the formation of the ASAP complex.PTM Phosphorylated on one or more of the four Ser/Thr residues (Ser-43, Thr-49, Ser-52 or Ser-53). Ser-53 phosphorylation site is important for splicing and translation stimulation activity in vitro.SIMILARITY Belongs to the splicing factor SR family. UniProt Q15287 1 EQUAL 305 EQUAL Reactome DB_ID: 72060 1 UniProt:Q92620 DHX38 DHX38 DDX38 KIAA0224 DHX38 PRP16 FUNCTION Probable ATP-binding RNA helicase (Probable). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:29301961, PubMed:9524131).SUBUNIT Identified in the spliceosome C complex.SIMILARITY Belongs to the DEAD box helicase family. DEAH subfamily. PRP16 sub-subfamily. UniProt Q92620 2 EQUAL 1227 EQUAL Reactome DB_ID: 71941 1 UniProt:P31943 HNRNPH1 HNRNPH1 HNRPH1 HNRNPH1 HNRPH FUNCTION This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG).SUBUNIT Part of a ternary complex containing FUBP2, PTBP1, PTBP2 and HNRNPH1. Identified in the spliceosome C complex. Interacts with IGF2BP1. Interacts with CUGBP1; the interaction is RNA-dependent. Interacts with MBNL1; the interaction in RNA-independent.TISSUE SPECIFICITY Expressed ubiquitously.INDUCTION Up-regulated in myotonic dystrophy pathophysiology (DM).DOMAIN Each quasi-RRM repeat bound poly(RG), while only the N-terminal QRRM bound poly(RC) and poly(RU). None of the repeats bound detectable amounts of poly(RA). UniProt P31943 1 EQUAL 449 EQUAL Reactome DB_ID: 72033 1 UniProt:Q01130 SRSF2 SRSF2 SRSF2 SFRS2 FUNCTION Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment.SUBUNIT Interacts with BRDT (By similarity). In vitro, self-associates and binds SRSF1/SFRS1 (ASF/SF2), SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with CCNL1 and CCNL2. Interacts with SCAF11. Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus).INDUCTION Accumulates in a hypoacetylated/phosphorylated form in response to cisplatin treatment.PTM Extensively phosphorylated on serine residues in the RS domain. Phosphorylated by SRPK2 and this causes its redistribution from the nuclear speckle to nucleoplasm and controls cell fate decision in response to cisplatin treatment. KAT5/TIP60 inhibits its phosphorylation by preventing SRPK2 nuclear translocation.PTM Acetylation on Lys-52 by KAT5/TIP60 promotes its proteasomal degradation. This effect is counterbalanced by HDAC6, which positively controls SRSF2 protein level by deacetylating it and preventing its proteasomal degradation.SIMILARITY Belongs to the splicing factor SR family. UniProt Q01130 2 EQUAL 221 EQUAL Reactome DB_ID: 71980 1 U2 snRNP [nucleoplasm] U2 snRNP Reactome DB_ID: 8871336 1 U2 Sm core complex [nucleoplasm] U2 Sm core complex Reactome DB_ID: 71909 1 1 EQUAL 76 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 8865952 1 Me2-R108,R112-SNRPB,SNRPN [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Me2-R108,R112-SNRPN [nucleoplasm] Me2-R108,R112-SNRPB [nucleoplasm] UniProt P63162 Reactome DB_ID: 192215 1 monomethylated residue at unknown position monomethylated residue at unknown position 1 EQUAL 119 EQUAL Reactome DB_ID: 192219 1 monomethylated residue at unknown position monomethylated residue at unknown position 1 EQUAL 126 EQUAL Reactome DB_ID: 71907 1 2 EQUAL 86 EQUAL Reactome DB_ID: 71905 1 1 EQUAL 92 EQUAL Reactome DB_ID: 71901 1 2 EQUAL 118 EQUAL Reactome Database ID Release 82 8871336 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8871336 Reactome R-HSA-8871336 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8871336.2 Reactome DB_ID: 5688096 1 UniProt:Q7L014 DDX46 DDX46 KIAA0801 DDX46 FUNCTION Plays an essential role in splicing, either prior to, or during splicing A complex formation.SUBUNIT Integral component of the 17S U2 snRNP.SIMILARITY Belongs to the DEAD box helicase family. DDX46/PRP5 subfamily. UniProt Q7L014 1 EQUAL 1031 EQUAL Reactome DB_ID: 66652 1 UniProt:Q7RTV0 PHF5A PHF5A PHF5A FUNCTION Involved with the PAF1 complex (PAF1C) in transcriptional elongation by RNA polymerase II, and in regulation of development and maintenance of embryonic stem cell (ESC) pluripotency. Required for maintenance of ESCs self-renewal and cellular reprogramming of stem cells. Maintains pluripotency by recruiting and stabilizing PAF1C on pluripotency genes loci, and by regulating the expression of the pluripotency genes. Regulates the deposition of elongation-associated histone modifications, including dimethylated histone H3 'Lys-79' (H3K79me2) and trimethylated histone H3 'Lys-36' (H3K36me3), on PAF1C targets, self-renewal and pluripotency genes. Regulates RNA polymerase II promoter-proximal pause release of the PAF1C targets and self-renewal genes, and the levels of elongating ('Ser-2' phosphorylated) RNA polymerase II in their gene bodies. Regulates muscle specification in adult stem cells by stabilizing PAF1C in chromatin to promote myogenic differentiation (By similarity). Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643, PubMed:28541300). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha (By similarity).SUBUNIT Interacts (via N-terminus) with U2AF1 and SRSF5; acts to bridge the two. Interacts (via C-terminus) with EP400 and DDX1; acts to bridge the two (By similarity). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:27720643, PubMed:28541300). Within the SF3B complex interacts directly with SF3B1 and SF3B3 (PubMed:27720643). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP) (PubMed:12234937). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Interacts with the PAF1 complex (PAF1C) composed of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61. Within the PAF1C interacts directly with CDC73 and WDR61. Interacts with RNA polymerase II (By similarity).SIMILARITY Belongs to the PHF5 family. UniProt Q7RTV0 2 EQUAL 110 EQUAL Reactome DB_ID: 71976 1 SF3B [nucleoplasm] SF3B Splicing Factor 3B Reactome DB_ID: 8867894 1 UniProt:Q86XP3 DDX42 DDX42 DDX42 FUNCTION ATP-dependent RNA helicase. Binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. Unwinding is promoted in the presence of single-strand binding proteins. Mediates also RNA duplex formation thereby displacing the single-strand RNA binding protein. ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands. Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2. Relocalizes TP53BP2 to the cytoplasm.SUBUNIT Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A/SF3B14B, and DDX42/SF3B125. Interacts (via the C-terminus) with TP53BP2; the interaction is not inhibitied by TP53BP2 ubiquitination and is independent of p53/TP53.TISSUE SPECIFICITY Expressed in several cell lines (at protein level). Expressed in liver, lung, tonsil, thymus, muscle and pancreatic islets.SIMILARITY Belongs to the DEAD box helicase family. DDX42 subfamily. UniProt Q86XP3 1 EQUAL 938 EQUAL Reactome DB_ID: 71971 1 UniProt:Q13435 SF3B2 SF3B2 SF3B2 SAP145 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077).SUBUNIT Identified in the spliceosome C complex (PubMed:11991638). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Component of splicing factor SF3B which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:27720643, PubMed:28541300). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP) (PubMed:12234937). Interacts directly with SF3B4 (PubMed:25737013). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). Found in a complex with PRMT9, SF3B2 and SF3B4 (PubMed:25737013). Interacts (Arg-508-methylated form) with SMN1 (via Tudor domain) (PubMed:25737013). Interacts with RBM7 (PubMed:27905398). Interacts with ERCC6 (PubMed:26030138).SUBUNIT (Microbial infection) Interacts with HIV-1 Vpr.PTM Methylation at Arg-508 by PRMT9 is required for the interaction with SMN1. UniProt Q13435 1 EQUAL 895 EQUAL Reactome DB_ID: 71968 1 UniProt:O75533 SF3B1 SF3B1 SAP155 SF3B1 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92 (By similarity). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077).SUBUNIT Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (PubMed:16603771). Identified in the spliceosome C complex (PubMed:11991638). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:28541300, PubMed:27720643). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Interacts directly with the splicing factor U2AF (PubMed:12234937). Within the SF3B complex interacts directly (via HEAT domain) with SF3B3, SF3B5 and (via HEAT domain) with PHF5A (PubMed:27720643). Interacts directly with SF3B6 (PubMed:16432215, Ref.37, PubMed:21062891). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). Phosphorylated form interacts with PPP1R8 (PubMed:12105215). Interacts with PQBP1 (PubMed:23512658). Interacts with RBM17 (PubMed:17589525). Interacts with RBM39 (PubMed:24795046). Interacts with SETX (PubMed:21700224). Interacts with RBM15 (PubMed:26575292). Interacts with USH1G (PubMed:34023904).PTM Phosphorylated. Phosphorylation occurs concomitantly with the splicing catalytic steps. Phosphorylation on Thr-244, Thr-248 and Thr-313 by cyclin-dependent kinases promotes interaction with PPP1R8 during mitosis.PTM Citrullinated by PADI4.SIMILARITY Belongs to the SF3B1 family. UniProt O75533 1 EQUAL 1304 EQUAL Reactome DB_ID: 71973 1 UniProt:Q15393 SF3B3 SF3B3 KIAA0017 SF3B3 SAP130 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex, a constituent of the spliceosome (PubMed:10490618, PubMed:10882114, PubMed:27720643, PubMed:28781166). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077).SUBUNIT Identified in the spliceosome A complex; remains associated with the spliceosome throughout the splicing process (PubMed:10490618). Component of the spliceosome B complex (PubMed:28781166). Identified in the spliceosome C complex (PubMed:11991638). Identified in the spliceosome E complex (PubMed:10882114). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:28541300, PubMed:27720643). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Interaction between SF3B3 and SF3B1 is tighter than the interaction between SF3B3 and SF3B2 (PubMed:12234937). Within the SF3B complex interacts directly with SF3B1 (via HEAT domain), SF3B5 and PHF5A (PubMed:27720643). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). Associates with the STAGA transcription coactivator-HAT complex. Interacts with SUPT3H (PubMed:11564863). Interacts with TAF3 (PubMed:11438666).DOMAIN The core of the protein consists of three beta-propeller domains.SIMILARITY Belongs to the RSE1 family. UniProt Q15393 1 EQUAL 1217 EQUAL Reactome DB_ID: 71975 1 UniProt:Q15427 SF3B4 SF3B4 SF3B4 SAP49 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex. SF3B4 has been found in complex 'B' and 'C' as well (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077).SUBUNIT Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:27720643, PubMed:28541300). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP) (PubMed:12234937). Interacts directly with SF3B2. Found in a complex with PRMT9, SF3B2 and SF3B4 (PubMed:25737013). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077).SIMILARITY Belongs to the SF3B4 family. UniProt Q15427 2 EQUAL 424 EQUAL Reactome DB_ID: 71979 1 UniProt:Q9BWJ5 SF3B5 SF3B5 SF3B5 SF3B10 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex, a constituent of the spliceosome (PubMed:27720643, PubMed:28781166). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937).SUBUNIT Component of the spliceosome B complex (PubMed:28781166). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:28541300, PubMed:27720643). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP) (PubMed:12234937). Within the SF3B complex interacts directly with SF3B1 (via HEAT domain) and SF3B3 (PubMed:27720643). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077).SIMILARITY Belongs to the SF3B5 family. UniProt Q9BWJ5 1 EQUAL 86 EQUAL Reactome DB_ID: 83808 1 UniProt:Q9Y3B4 SF3B6 SF3B6 SF3B14 SAP14 SF3B6 HT006 HSPC175 SF3B14A CGI-110 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA (PubMed:12234937). Directly contacts the pre-mRNA branch site adenosine for the first catalytic step of splicing (PubMed:16432215). Enters the spliceosome and associates with the pre-mRNA branch site as part of the 17S U2 or, in the case of the minor spliceosome, as part of the 18S U11/U12 snRNP complex, and thus may facilitate the interaction of these snRNP with the branch sites of U2 and U12 respectively (PubMed:16432215).SUBUNIT Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:16432215, PubMed:27720643, PubMed:28541300). Within the SF3B complex interacts directly with SF3B1 (PubMed:21062891, PubMed:16432215, Ref.20). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077).SIMILARITY Belongs to the SF3B6 family. UniProt Q9Y3B4 1 EQUAL 125 EQUAL Reactome Database ID Release 82 71976 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71976 Reactome R-HSA-71976 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71976.3 Reactome DB_ID: 8865901 1 UniProt:Q8IWX8 CHERP CHERP SCAF6 DAN26 CHERP FUNCTION Involved in calcium homeostasis, growth and proliferation.TISSUE SPECIFICITY Expressed in brain, placenta, lung, liver, kidney, pancreas, cardiac and skeletal muscle, and in cultured HEL and Dami cells. UniProt Q8IWX8 1 EQUAL 916 EQUAL Reactome DB_ID: 8865958 1 UniProt:O75940 SMNDC1 SMNDC1 SPF30 SMNR SMNDC1 FUNCTION Involved in spliceosome assembly.SUBUNIT Associates with spliceosomes (PubMed:11331295). Associates with U4/U5/U6 tri-snRNP and with U2 snRNP (PubMed:11331295). Interacts (via Tudor domain) with SNRPD3 (via C-terminus); the interaction is direct (PubMed:22101937).TISSUE SPECIFICITY Detected at intermediate levels in skeletal muscle, and at low levels in heart and pancreas.DOMAIN The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.SIMILARITY Belongs to the SMN family. UniProt O75940 1 EQUAL 238 EQUAL Reactome DB_ID: 5688097 1 UniProt:O43143 DHX15 DHX15 DBP1 DDX15 DHX15 FUNCTION RNA helicase involved in mRNA processing and antiviral innate immunity (PubMed:19432882, PubMed:19103666, PubMed:32179686, PubMed:24990078, PubMed:24782566, PubMed:34161762). Pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA (PubMed:19103666). In cooperation with TFIP11 seem to be involved in the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns (PubMed:19103666). Plays a key role in antiviral innate immunity by promoting both MAVS-dependent signaling and NLRP6 inflammasome (PubMed:24990078, PubMed:24782566, PubMed:34161762). Acts as an RNA virus sensor: recognizes and binds viral double stranded RNA (dsRNA) and activates the MAVS-dependent signaling to produce interferon-beta and interferon lambda-3 (IFNL3) (PubMed:24990078, PubMed:24782566, PubMed:34161762). Involved in intestinal antiviral innate immunity together with NLRP6: recognizes and binds viral dsRNA and promotes activation of the NLRP6 inflammasome in intestinal epithelial cells to restrict infection by enteric viruses (PubMed:34161762). The NLRP6 inflammasome acts by promoting maturation and secretion of IL18 in the extracellular milieu (PubMed:34161762). Also involved in antibacterial innate immunity by promoting Wnt-induced antimicrobial protein expression in Paneth cells (By similarity).ACTIVITY REGULATION ATPase activity is enhanced upon binding to G-patch domain-containing proteins (PubMed:32179686). G-patch domain-containing proteins act like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity, thereby promoting the ATPase activity (PubMed:32179686).SUBUNIT Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (PubMed:15146077). Identified in the Intron Large spliceosome complex (IL, also named intron lariat spliceosome), a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors; the association may be transient (PubMed:19103666, PubMed:30728453). The IL complex exists in two distinct conformations, one with the DHX15 (ILS2) and one without (ILS1) (PubMed:30728453). Interacts with TFIP11 (via G-patch domain); indicative for a recruitment to the IL complex (PubMed:19103666). Interacts with SSB/La (PubMed:12458796). Interacts with GPATCH2 (via G-patch domain); promoting the RNA helicase activity (PubMed:19432882). Interacts with NKRF (via G-patch domain); promoting the RNA helicase activity (PubMed:32179686). Interacts with NLRP6 (PubMed:34161762).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily. UniProt O43143 1 EQUAL 795 EQUAL Reactome DB_ID: 71958 1 UniProt:P09661 SNRPA1 SNRPA1 SNRPA1 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:27035939). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (PubMed:9716128, PubMed:27035939).SUBUNIT Identified in the spliceosome B complex (PubMed:28781166). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2 (PubMed:9531537). Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRNP70, SNRPA1, SRRM1 and TRA2B (PubMed:10339552). Contributes to the binding of stem loop IV of U2 snRNA with SNRPB2 (PubMed:9716128, PubMed:27035939).SIMILARITY Belongs to the U2 small nuclear ribonucleoprotein A family. UniProt P09661 2 EQUAL 255 EQUAL Reactome DB_ID: 71967 1 SF3A [nucleoplasm] SF3A Reactome DB_ID: 71964 1 UniProt:Q15428 SF3A2 SF3A2 SF3A2 SAP62 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3A complex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes, including the Bact complex (PubMed:29361316, PubMed:29360106, PubMed:30315277). Interacts directly with the duplex formed by U2 snRNA and the intron (PubMed:29360106).SUBUNIT Component of splicing factor SF3A which is composed of three subunits; SF3A3/SAP61, SF3A2/SAP62 and SF3A1/SAP114 (PubMed:10882114, PubMed:11533230, PubMed:21349847). SF3A1 functions as scaffold that interacts directly with both SF3A2 and SF3A3 (PubMed:11533230, PubMed:21349847). SF3A associates with the splicing factor SF3B and a 12S RNA unit to form the mature 17S U2 small nuclear ribonucleoprotein complex (17S U2 snRNP) (PubMed:10882114, PubMed:11533230). Identified in the spliceosome 'E' complex, a precursor of the spliceosome 'A' complex (PubMed:10882114). Identified in the spliceosome 'A' and 'B' complexes (PubMed:10882114, PubMed:29361316, PubMed:29360106, PubMed:30315277). Identified in the spliceosome 'C' complex (PubMed:11991638). Interacts with HTATSF1 (PubMed:9710584).SIMILARITY Belongs to the SF3A2 family. UniProt Q15428 1 EQUAL 464 EQUAL Reactome DB_ID: 71962 1 UniProt:Q15459 SF3A1 SF3A1 SF3A1 SAP114 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3A complex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes (PubMed:29360106, PubMed:30315277).SUBUNIT Component of splicing factor SF3A which is composed of three subunits; SF3A3/SAP61, SF3A2/SAP62 and SF3A1/SAP114 (PubMed:10882114, PubMed:11533230, PubMed:21349847). SF3A1 functions as scaffold that interacts directly with both SF3A2 and SF3A3 (PubMed:11533230, PubMed:21349847, PubMed:17098193). SF3A associates with the splicing factor SF3B and a 12S RNA unit to form the mature 17S U2 small nuclear ribonucleoprotein complex (17S U2 snRNP) (PubMed:10882114, PubMed:11533230). Identified in the spliceosome 'E' complex, a precursor of the spliceosome 'A' complex (PubMed:10882114). Identified in the spliceosome 'A' and 'B' complexes (PubMed:10882114, PubMed:29360106, PubMed:30315277). Identified in the spliceosome 'C' complex (PubMed:11991638).TISSUE SPECIFICITY Ubiquitously expressed.DOMAIN SURP motif 2 mediates direct binding to SF3A3. UniProt Q15459 1 EQUAL 793 EQUAL Reactome DB_ID: 71966 1 UniProt:Q12874 SF3A3 SF3A3 SF3A3 SAP61 FUNCTION Involved in pre-mRNA splicing as a component of the splicing factor SF3A complex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:8022796, PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes (PubMed:29360106, PubMed:30315277).SUBUNIT Component of splicing factor SF3A which is composed of three subunits; SF3A3/SAP61, SF3A2/SAP62 and SF3A1/SAP114 (PubMed:8022796, PubMed:10882114, PubMed:11533230, PubMed:21349847). SF3A1 functions as scaffold that interacts directly with both SF3A2 and SF3A3 (PubMed:11533230, PubMed:21349847, PubMed:17098193). SF3A associates with the splicing factor SF3B and a 12S RNA unit to form the mature 17S U2 small nuclear ribonucleoprotein complex (17S U2 snRNP) (PubMed:10882114, PubMed:11533230, PubMed:17098193). Identified in the spliceosome 'E' complex, a precursor of the spliceosome 'A' complex (PubMed:10882114). Identified in the spliceosome 'A' and 'B' complexes (PubMed:8022796, PubMed:10882114, PubMed:29360106, PubMed:30315277). Identified in the spliceosome 'C' complex (PubMed:11991638).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the SF3A3 family. UniProt Q12874 1 EQUAL 501 EQUAL Reactome Database ID Release 82 71967 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71967 Reactome R-HSA-71967 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71967.1 Reactome DB_ID: 71960 1 UniProt:P08579 SNRPB2 SNRPB2 SNRPB2 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (PubMed:9716128).SUBUNIT Identified in the spliceosome B complex (PubMed:28781166). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Present in a spliceosome complex assembled in vitro, and composed of SNRPB2, HPRP8BP and CRNKL1 (PubMed:12084575). Contributes to the binding of stem loop IV of U2 snRNA with SNRPP1 (PubMed:9716128).MISCELLANEOUS Patients with systemic lupus erythematosus produce antibodies which interact with snRNP proteins.SIMILARITY Belongs to the RRM U1 A/B'' family. UniProt P08579 1 EQUAL 225 EQUAL Reactome DB_ID: 8865910 1 UniProt:Q9UHX1 PUF60 PUF60 PUF60 ROBPI SIAHBP1 FIR FUNCTION DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with RO60. Binds to poly(U) RNA.SUBUNIT Homodimer (PubMed:10606266). Associates with the spliceosome (PubMed:17579712). Found in a complex with RO60 and Y5 RNA (PubMed:10668799). Found in a complex with FUBP1 and far upstream element (FUSE) DNA segment (PubMed:10882074). Interacts directly with ERCC3 (PubMed:11239393). Interacts with CDK7 and GTF2H1 (PubMed:10882074). Interacts with SRSF11/P54 (PubMed:10606266). Does not interact with ERCC3 in xeroderma pigmentosum complementation group B (XPB) cells (PubMed:11239393).TISSUE SPECIFICITY Isoform 2 is expressed in colonic epithelium and colorectal epithelium cancer (at protein level). Isoform 6 is expressed in colorectal epithelial cancer but below detection level in colonic epithelium. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.DOMAIN The third RNA recognition motif, called PUMP domain, is atypical and may rather mediate homodimerization and/or protein-protein interactions.MISCELLANEOUS Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells.SIMILARITY Belongs to the RRM half pint family. UniProt Q9UHX1 1 EQUAL 559 EQUAL Reactome DB_ID: 71956 1 EMBL:X59360 U2 snRNA U2 snRNA EMBL X59360 Reactome DB_ID: 8865950 1 UniProt:O15042 U2SURP U2SURP KIAA0332 SR140 U2SURP SUBUNIT Interacts with ERBB4.SIMILARITY Belongs to the splicing factor SR family. UniProt O15042 2 EQUAL 1029 EQUAL Reactome DB_ID: 8865891 1 UniProt:Q96I25 RBM17 RBM17 RBM17 SPF45 FUNCTION Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia.SUBUNIT Binds SXL. Associates with the spliceosome. Interacts with SF3B1, SF1 and U2AF2. UniProt Q96I25 2 EQUAL 401 EQUAL Reactome Database ID Release 82 71980 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71980 Reactome R-HSA-71980 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71980.2 Converted from EntitySet in Reactome Reactome DB_ID: 8865886 1 U2AF1,U2AF1L4 [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity U2AF1 [nucleoplasm] U2AF1L4 [nucleoplasm] UniProt Q01081 UniProt Q8WU68 Reactome DB_ID: 8850864 1 UniProt:Q12926 ELAVL2 ELAVL2 HUB ELAVL2 FUNCTION RNA-binding protein that binds to the 3' untranslated region (3'UTR) of target mRNAs (By similarity). Seems to recognize a GAAA motif (By similarity). Can bind to its own 3'UTR, the FOS 3'UTR and the ID 3'UTR (By similarity).SUBUNIT Interacts with IGF2BP1 (PubMed:17289661). Interacts with MAP1B light chain LC1 (By similarity).TISSUE SPECIFICITY Brain; neural-specific.SIMILARITY Belongs to the RRM elav family. UniProt Q12926 1 EQUAL 359 EQUAL Reactome DB_ID: 72048 1 UniProt:Q8IX12 CCAR1 CCAR1 CARP1 CCAR1 DIS FUNCTION Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation (By similarity). May be involved in apoptosis signaling in the presence of the reinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation (PubMed:12816952). In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells (PubMed:23887938).SUBUNIT Directly interacts with ESR1, NR3C1 and p53/TP53 (By similarity). Interacts (via N-terminus) with CALCOCO1. Interacts with MED1 (By similarity). Interacts with GATA1. Interacts with AR and GATA2.TISSUE SPECIFICITY Expressed in various epithelial cancer cell lines, including breast, colon, prostate, pancreatic and leukemia. Expression is regulated by growth factors. UniProt Q8IX12 1 EQUAL 1150 EQUAL Reactome DB_ID: 72043 1 UniProt:Q8IWZ8 SUGP1 SUGP1 SF4 SUGP1 FUNCTION Plays a role in pre-mRNA splicing.SUBUNIT Component of the spliceosome.TISSUE SPECIFICITY Detected in adult testis and heart, and in adult and fetal brain, kidney and skeletal muscle. UniProt Q8IWZ8 1 EQUAL 645 EQUAL Reactome DB_ID: 72024 1 UniProt:Q08170 SRSF4 SRSF4 SFRS4 SRP75 SRSF4 FUNCTION Plays a role in alternative splice site selection during pre-mRNA splicing. Represses the splicing of MAPT/Tau exon 10.SUBUNIT Found in a pre-mRNA splicing complex with SRSF4/SFRS4, SRSF5/SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2. Interacts with PNN.PTM Extensively phosphorylated on serine residues in the RS domain.SIMILARITY Belongs to the splicing factor SR family. UniProt Q08170 1 EQUAL 494 EQUAL Reactome DB_ID: 72035 1 UniProt:P84103 SRSF3 SRSF3 SRP20 SRSF3 SFRS3 FUNCTION Splicing factor that specifically promotes exon-inclusion during alternative splicing (PubMed:26876937). Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). Also functions as export adapter involved in mRNA nuclear export (PubMed:11336712, PubMed:18364396, PubMed:28984244). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity (PubMed:11336712, PubMed:18364396). Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). RNA-binding is semi-sequence specific (PubMed:17036044).SUBUNIT Interacts with CPSF6 (PubMed:15169763). Interacts with RBMY1A1 (PubMed:15595951). Interacts with SREK1/SFRS12 (PubMed:10757789). Interacts with NXF1 (PubMed:12667464, PubMed:17036044). Interacts with YTHDC1, leading to recruitment to RNA elements adjacent to m6A sites (PubMed:26876937, PubMed:28984244).PTM Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Extensively phosphorylated on serine residues in the RS domain.SIMILARITY Belongs to the splicing factor SR family. UniProt P84103 1 EQUAL 164 EQUAL Reactome DB_ID: 6814858 1 UniProt:Q9BXP5 SRRT SRRT SRRT ASR2 ARS2 FUNCTION Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped RNA); however interaction is probably mediated via its interaction with NCBP1/CBP80 component of the CBC complex. Involved in cell cycle progression at S phase. Does not directly confer arsenite resistance but rather modulates arsenic sensitivity. Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription (By similarity).SUBUNIT Interacts with NCBP1 and DROSHA (By similarity). Interacts with CASP8AP2 and ERBB4. Interacts with LUZP4. Interacts with NCBP2/CBP20 and NCBP3 (PubMed:26382858). Interacts with MTREX (PubMed:30842217).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the ARS2 family. UniProt Q9BXP5 2 EQUAL 876 EQUAL Reactome DB_ID: 71954 1 capped, methylated pre-mRNA:CBC Complex [nucleoplasm] capped, methylated pre-mRNA:CBC Complex Reactome DB_ID: 77088 1 Cap Binding Complex (CBC) [nucleoplasm] Cap Binding Complex (CBC) Reactome DB_ID: 51469 1 UniProt:Q09161 NCBP1 NCBP1 NCBP1 CBP80 NCBP FUNCTION Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability (PubMed:26382858).SUBUNIT Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA. Found in a U snRNA export complex containing PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PHAX/RNUXA, SRRT/ARS2, EIF4G2, IGF2BP1, HNRNPF, HNRNPH1, KIAA0427/CTIF, PARN, DROSHA, UPF1 and ALYREF/THOC4. May interact with EIF4G1; the interaction is however controversial since it is reported by PubMed:11340157, PubMed:15059963 and PubMed:15361857, but is not observed by PubMed:19648179. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1/CBP80 and POLR2A. Component of an alternative nuclear cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3 (PubMed:26382858). Interacts with METTL3 (PubMed:27117702). Interacts with ZFC3H1 in a RNase-insensitive manner (PubMed:27871484). Interacts with MTREX (PubMed:30842217). Interacts with TASOR (By similarity). Interacts with DHX34; the interaction is RNA-dependent (PubMed:25220460).SIMILARITY Belongs to the NCBP1 family. UniProt Q09161 1 EQUAL 790 EQUAL Reactome DB_ID: 51463 1 UniProt:P52298 NCBP2 NCBP2 CBP20 NCBP2 PIG55 FUNCTION Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus (PubMed:26382858).SUBUNIT Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA (PubMed:26382858). Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Interacts with PHAX/RNUXA, EIF4G1, HNRNPF, HNRNPH1 and ALYREF/THOC4/ALY. Interacts with SRRT/ARS2 and KPNA3 (PubMed:26382858).SIMILARITY Belongs to the RRM NCBP2 family. UniProt P52298 1 EQUAL 156 EQUAL Reactome Database ID Release 82 77088 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77088 Reactome R-HSA-77088 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-77088.1 Reactome DB_ID: 71307 1 RNA Polymerase II (unphosphorylated):TFIIF complex [nucleoplasm] RNA Polymerase II (unphosphorylated):TFIIF complex Reactome DB_ID: 109631 1 TFIIF [nucleoplasm] TFIIF Reactome DB_ID: 65567 1 UniProt:P13984 GTF2F2 GTF2F2 RAP30 GTF2F2 FUNCTION TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB.SUBUNIT Heterodimer of an alpha and a beta subunit. Interacts with HTATSF1 and GPBP1 (By similarity). Interacts with URI1. Interacts with GTF2B (via N-terminus); this interaction is inhibited in presence of GTF2F1 (PubMed:8504927, PubMed:8662660).SIMILARITY Belongs to the TFIIF beta subunit family.CAUTION GTF2F2 appears to have ATP-dependent DNA-helicase activity; however this is probably an artifact that happened during the protein purification. UniProt P13984 2 EQUAL 249 EQUAL Reactome DB_ID: 65565 1 UniProt:P35269 GTF2F1 GTF2F1 GTF2F1 RAP74 FUNCTION TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation.SUBUNIT Heterodimer of an alpha and a beta subunit. Interacts with GTF2F2, CTDP1, TAF6/TAFII80 and URI1. Interacts with GTF2B (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2 (PubMed:8662660, PubMed:12931194).INDUCTION Up-regulated in response to enterovirus 71 (EV71) infection.PTM Phosphorylated on Ser and other residues by TAF1 and casein kinase II-like kinases.SIMILARITY Belongs to the TFIIF alpha subunit family.CAUTION Was reported to have a protein kinase activity and to autophosphorylates on Ser-385 and Thr-389. UniProt P35269 2 EQUAL 517 EQUAL Reactome Database ID Release 82 109631 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109631 Reactome R-HSA-109631 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-109631.1 Reactome DB_ID: 113401 1 RNA Polymerase II holoenzyme complex (unphosphorylated) [nucleoplasm] RNA Polymerase II holoenzyme complex (unphosphorylated) Reactome DB_ID: 63502 1 UniProt:P24928 POLR2A POLR2A POLR2 POLR2A FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (By similarity). Initiation or early elongation steps of transcription of growth-factors-induced immediate early genes are regulated by the acetylation status of the CTD (PubMed:24207025). Methylation and dimethylation have a repressive effect on target genes expression (By similarity).FUNCTION (Microbial infection) Acts as an RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicate and transcriptase for the viral RNA circular genome.SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 complex to the pre-mRNA and may couple transcription to pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes. Interacts via the phosphorylated C-terminal domain with WDR82 and with SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at 'Ser-5', interacts with MEN1; the unphosphorylated form, or phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5 and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated C-terminal domain interacts with FNBP3 and SYNCRIP. Interacts with ATF7IP. Interacts with DDX5. Interacts with WWP2. Interacts with SETX. Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2. Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CCNL2, MYO1C, PAF1 and SFRS19. Interacts (via C-terminus) with CMTR1, CTDSP1 and SCAF8. Interacts (via the C-terminal domain (CTD)) with CCNT2 (PubMed:15563843). Interacts with FUS. Interacts with MCM3AP isoform GANP (PubMed:23652018). Interacts with kinase SRPK2; the interaction occurs during the co-transcriptional formation of inappropriate R-loops (PubMed:28076779).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 protein ICP22; this interaction causes loss of CTD 'Ser-2' phosphorylation from pol II engaged in transcription (PubMed:23029222).DOMAIN The C-terminal domain (CTD) serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing.PTM The tandem heptapeptide repeats in the C-terminal domain (CTD) can be highly phosphorylated (PubMed:28076779). The phosphorylation activates Pol II. Phosphorylation occurs mainly at residues 'Ser-2' and 'Ser-5' of the heptapeptide repeat and is mediated, at least, by CDK7 and CDK9. CDK7 phosphorylation of POLR2A associated with DNA promotes transcription initiation by triggering dissociation from DNA. Phosphorylation also takes place at 'Ser-7' of the heptapeptide repeat, which is required for efficient transcription of snRNA genes and processing of the transcripts. The phosphorylation state is believed to result from the balanced action of site-specific CTD kinases and phosphatases, and a 'CTD code' that specifies the position of Pol II within the transcription cycle has been proposed. Dephosphorylated by the protein phosphatase CTDSP1.PTM Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated and dimethylated. EP300 is one of the enzyme able to acetylate 'Lys-7'. Acetylation at 'Lys-7' of non-consensus heptapeptide repeats is associated with 'Ser-2' phosphorylation and active transcription. Regulates initiation or early elongation steps of transcription specially for inducible genes.PTM Methylated at Arg-1810 prior to transcription initiation when the CTD is hypophosphorylated, phosphorylation at Ser-1805 and Ser-1808 preventing this methylation. Symmetrically or asymmetrically dimethylated at Arg-1810 by PRMT5 and CARM1 respectively. Symmetric or asymmetric dimethylation modulates interactions with CTD-binding proteins like SMN1/SMN2 and TDRD3. SMN1/SMN2 interacts preferentially with the symmetrically dimethylated form while TDRD3 interacts with the asymmetric form. Through the recruitment of SMN1/SMN2, symmetric dimethylation is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. CTD dimethylation may also facilitate the expression of select RNAs. Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated, dimethylated and trimethylated. Methylation occurs in the earliest transcription stages and precedes or is concomitant to 'Ser-5' and 'Ser-7' phosphorylation. Dimethylation and trimehtylation at 'Lys-7' of non-consensus heptapeptide repeats are exclusively associated with phosphorylated CTD.PTM Ubiquitinated by WWP2 leading to proteasomal degradation (By similarity). Following UV treatment, the elongating form of RNA polymerase II (RNA pol IIo) is ubiquitinated on UV damage sites without leading to degradation: ubiquitination is facilitated by KIAA1530/UVSSA and promotes RNA pol IIo backtracking to allow access to the nucleotide excision repair machinery.MISCELLANEOUS The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion temporarily coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits. The ribonucleoside triphosphate is transferred by a rotation to the nucleotide addition (A) site for pairing with the template DNA. The catalytic A site involves three conserved aspartate residues of the RNA Pol II largest subunit which permanently coordinate a second magnesium ion.SIMILARITY Belongs to the RNA polymerase beta' chain family. UniProt P24928 1 EQUAL 1970 EQUAL Reactome DB_ID: 63531 1 UniProt:P52435 POLR2J POLR2J POLR2J1 POLR2J FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with AATF.TISSUE SPECIFICITY Ubiquitously expressed. High expression was found in heart and skeletal muscle.SIMILARITY Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family. UniProt P52435 1 EQUAL 117 EQUAL Reactome DB_ID: 63517 1 UniProt:P62487 POLR2G POLR2G RPB7 POLR2G FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB7 is part of a subcomplex with RPB4 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity). Binds RNA.SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.SIMILARITY Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family. UniProt P62487 1 EQUAL 172 EQUAL Reactome DB_ID: 63506 1 UniProt:P19387 POLR2C POLR2C A-152E5.7 POLR2C FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB11/POLR2J and RPB3/POLR2C subunits interact with each other.SIMILARITY Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family. UniProt P19387 2 EQUAL 275 EQUAL Reactome DB_ID: 63537 1 UniProt:P53803 POLR2K POLR2K POLR2K FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively.SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal Rpo12/eukaryotic RPC10 RNA polymerase subunit family. UniProt P53803 1 EQUAL 58 EQUAL Reactome DB_ID: 63504 1 UniProt:P30876 POLR2B POLR2B POLR2B FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB2 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with WDR82. Interacts with MEN1.MISCELLANEOUS The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits (By similarity).SIMILARITY Belongs to the RNA polymerase beta chain family. UniProt P30876 1 EQUAL 1174 EQUAL Reactome DB_ID: 83714 1 UniProt:P61218 POLR2F POLR2F POLR2F POLRF FUNCTION DNA-dependent RNA polymerases catalyze the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II, and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2F/RPB6 is part of the clamp element and together with parts of RPB1 and RPB2 forms a pocket to which the RPB4-RPB7 subcomplex binds (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal Rpo6/eukaryotic RPB6 RNA polymerase subunit family. UniProt P61218 2 EQUAL 127 EQUAL Reactome DB_ID: 63525 1 UniProt:P36954 POLR2I POLR2I POLR2I FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.SIMILARITY Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family. UniProt P36954 1 EQUAL 125 EQUAL Reactome DB_ID: 63508 1 UniProt:O15514 POLR2D POLR2D POLR2D FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB4 is part of a subcomplex with RPB7 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.SIMILARITY Belongs to the eukaryotic RPB4 RNA polymerase subunit family. UniProt O15514 1 EQUAL 142 EQUAL Reactome DB_ID: 83715 1 UniProt:P62875 POLR2L POLR2L POLR2L FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2L/RBP10 is part of the core element with the central large cleft (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family. UniProt P62875 1 EQUAL 67 EQUAL Reactome DB_ID: 63523 1 UniProt:P52434 POLR2H POLR2H POLR2H FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively.SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively. Directly interacts with POLR2A.SIMILARITY Belongs to the eukaryotic RPB8 RNA polymerase subunit family. UniProt P52434 2 EQUAL 150 EQUAL Reactome DB_ID: 83713 1 UniProt:P19388 POLR2E POLR2E POLR2E FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively (PubMed:9852112, PubMed:16809778). In RNA Pol II, this subunit is present in 2-fold molar excess over the other subunits (PubMed:9852112). Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (PubMed:31738558). Interacts with URI1 (PubMed:9819440).SUBUNIT (Microbial infection) Interacts with HBV protein X.SIMILARITY Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family. UniProt P19388 1 EQUAL 210 EQUAL Reactome Database ID Release 82 113401 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113401 Reactome R-HSA-113401 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-113401.1 Reactome Database ID Release 82 71307 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71307 Reactome R-HSA-71307 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71307.1 Reactome DB_ID: 77507 1 capped, methylated pre-mRNA [nucleoplasm] capped, methylated pre-mRNA Reactome Database ID Release 82 71954 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71954 Reactome R-HSA-71954 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71954.2 Reactome DB_ID: 71939 1 UniProt:P38159 RBMX RBMX HNRPG RBMX RBMXP1 FUNCTION RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Also plays a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment.SUBUNIT Homomultimer. Interacts with SAFB/SAFB1 (By similarity). Found in the supraspliceosome complex. Identified in the spliceosome C complex. Interacts with KHDRBS3. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, NCOA5 and PPP1CA. Interacts with CLK2, KHDRBS2, SAFB, TRA2B and YTHDC1. Interacts with ERAP1; the interaction is RNA-independent (PubMed:18445477). Interacts with PPIA/CYPA (PubMed:25678563).TISSUE SPECIFICITY Expressed strongly in oral keratinocytes, but only weakly detected in oral squamous cell carcinomas (at protein level).DOMAIN The RRM domain is necessary for RNA-binding, but not for splice site selection, indicating that its splicing activity does not require direct binding to RNA.PTM O-glycosylated.PTM Arg-185 is dimethylated, probably to asymmetric dimethylarginine.PTM Cleavage of initiator Met is partial. If Met-1 is not removed, it is acetylated. If it is removed, Val-2 is acetylated. UniProt P38159 1 EQUAL 391 EQUAL Reactome Database ID Release 82 72068 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72068 Reactome R-HSA-72068 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72068.3 Reactome DB_ID: 6781959 1 UniProt:Q9UNP9 PPIE PPIE CYP33 PPIE FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346). Combines RNA-binding and PPIase activities (PubMed:8977107, PubMed:18258190, PubMed:20677832, PubMed:20460131). Binds mRNA and has a preference for single-stranded RNA molecules with poly-A and poly-U stretches, suggesting it binds to the poly(A)-region in the 3'-UTR of mRNA molecules (PubMed:8977107, PubMed:18258190, PubMed:20460131). Catalyzes the cis-trans isomerization of proline imidic peptide bonds in proteins (PubMed:8977107, PubMed:18258190, PubMed:20677832, PubMed:20541251). Inhibits KMT2A activity; this requires proline isomerase activity (PubMed:20677832, PubMed:20541251, PubMed:20460131).ACTIVITY REGULATION Enzyme activity is inhibited by cyclosporin A.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:28076346). Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE (PubMed:17981804). Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex (PubMed:25599396). The IB complex does not contain PRPF19 (PubMed:25599396). Interacts (via RNA-binding domain) with KMT2A (via the third PHD-type zinc-finger) (PubMed:20677832, PubMed:20541251, PubMed:20460131).TISSUE SPECIFICITY Found in all the examined tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.DOMAIN The RRM domain mediates both interaction with RNA and with KMT2A (via the third PHD-type zinc-finger), but has much higher affinity for the KMT2A PHD-type zinc-finger.SIMILARITY Belongs to the cyclophilin-type PPIase family. PPIase E subfamily. UniProt Q9UNP9 1 EQUAL 301 EQUAL Reactome DB_ID: 67411 1 UniProt:Q9HCS7 XAB2 XAB2 XAB2 SYF1 PP3898 KIAA1177 HCNP FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346). Involved in transcription-coupled repair (TCR), transcription and pre-mRNA splicing (PubMed:10944529, PubMed:17981804).SUBUNIT Associates with RNA polymerase II, the TCR-specific proteins CKN1/CSA and ERCC6/CSB, and XPA (PubMed:10944529). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE (PubMed:17981804). Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex (PubMed:25599396). The IB complex does not contain PRPF19 (PubMed:25599396).SIMILARITY Belongs to the crooked-neck family. UniProt Q9HCS7 1 EQUAL 855 EQUAL Reactome DB_ID: 77506 1 U4:U5:U6 tri-snRNP complex [nucleoplasm] U4:U5:U6 tri-snRNP complex Reactome DB_ID: 71981 1 U5 snRNP [nucleoplasm] U5 snRNP Reactome DB_ID: 71881 1 UniProt:O94906 PRPF6 PRPF6 PRPF6 C20orf14 FUNCTION Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:28781166, PubMed:21549338). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation.SUBUNIT Identified in the spliceosome B complex (PubMed:28781166). Identified in the spliceosome C complex (PubMed:11991638). Associates with the U5 snRNP particle (PubMed:10788320). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, LSm proteins LSm2-8 and Sm proteins (PubMed:16723661, PubMed:26912367, PubMed:28781166). Interacts with ARAF (PubMed:10848612). Interacts with AR and NR3C1, but not ESR1, independently of the presence of hormones (PubMed:12039962). Interacts with USH1G (PubMed:34023904).TISSUE SPECIFICITY Widely expressed. UniProt O94906 1 EQUAL 941 EQUAL Reactome DB_ID: 71875 1 UniProt:P83876 TXNL4A TXNL4A DIM1 TXNL4 TXNL4A FUNCTION Plays role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes that are involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U5 snRNP complex (PubMed:10610776). Component of the U4/U6-U5 tri-snRNP complex (PubMed:26912367). The U4/U6-U5 tri-snRNP complex is a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:26912367, PubMed:28781166). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:16723661, PubMed:26912367, PubMed:28781166). Directly interacts with CD2BP2 (PubMed:17467737, PubMed:24781215). Interacts with HNRPF, HNRPH2, NEDD9 and PQBP1 (PubMed:11054566). Interacts with ERBB4 (PubMed:20858735).PTM The disulfide bond seen in structures determined by X-ray crystallography (PubMed:10610776) and NMR (PubMed:12911302) is not essential for protein folding and function (PubMed:12911302 and PubMed:17467737).SIMILARITY Belongs to the DIM1 family. UniProt P83876 1 EQUAL 142 EQUAL Reactome DB_ID: 71877 1 UniProt:Q96DI7 SNRNP40 SNRNP40 SFP38 SNRNP40 PRP8BP WDR57 FUNCTION Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30705154). Component of the U5 small nuclear ribonucleoprotein (snRNP) complex and the U4/U6-U5 tri-snRNP complex, building blocks of the spliceosome (PubMed:9774689, PubMed:16723661, PubMed:26912367).SUBUNIT Component of the pre-catalytic and catalytic spliceosome complexes (PubMed:9731529, PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:30315277, PubMed:29360106, PubMed:29301961). Component of the postcatalytic spliceosome P complex (PubMed:30705154). Part of the U5 snRNP complex. Interacts with PRPF8. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (PubMed:16723661). UniProt Q96DI7 1 EQUAL 357 EQUAL Reactome DB_ID: 71883 1 UniProt:Q15029 EFTUD2 EFTUD2 EFTUD2 KIAA0031 SNRP116 FUNCTION Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes (PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30705154). Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (PubMed:16723661).SUBUNIT Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (PubMed:26912367, PubMed:16723661). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (PubMed:16723661, PubMed:26912367). Component of the pre-catalytic, catalytic and post-catalytic spliceosome complexes (PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30705154). Interacts with ERBB4 and PRPF8. Interacts with PIH1D1 (PubMed:24656813). Interacts with RPAP3 and URI1 in a ZNHIT2-dependent manner (PubMed:28561026). Interacts with NRDE2 (PubMed:30538148). Interacts with FAM50A (PubMed:32703943).SIMILARITY Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily. UniProt Q15029 1 EQUAL 972 EQUAL Reactome DB_ID: 83810 1 UniProt:Q6P2Q9 PRPF8 PRPF8 PRPF8 PRPC8 FUNCTION Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome (PubMed:10411133, PubMed:11971955, PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site.SUBUNIT Part of the U5 snRNP complex (PubMed:2532307, PubMed:2527369). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (PubMed:2479028, PubMed:16723661, PubMed:26912367). Component of the U5.U4atac/U6atac snRNP complexes in U12-dependent spliceosomes (PubMed:11971955). Core component of U2-type precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:10411133, PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Found in a mRNA splicing-dependent exon junction complex (EJC) with SRRM1. Interacts with U5 snRNP proteins SNRP116 and SNRNP40. Interacts with EFTUD2 and SNRNP200. Interacts (via the MPN (JAB/Mov34) domain) with PRPF3 ('Lys-63'-linked polyubiquitinated); may stabilize the U4/U6-U5 tri-snRNP complex. Interacts (via RNase H homology domain) with AAR2 (PubMed:26527271). Interacts with RPAP3 and URI1 in a ZNHIT2-dependent manner (PubMed:28561026).TISSUE SPECIFICITY Widely expressed.DOMAIN The MPN (JAB/Mov34) domain has structural similarity with deubiquitinating enzymes, but lacks the residues that would bind the catalytic metal ion.DOMAIN Contains a region with structural similarity to reverse transcripase, presenting the classical thumb, fingers and palm architecture, but lacks enzyme activity, since the essential metal-binding residues are not conserved.DOMAIN Contains a region with structural similarity to type-2 restriction endonucleases, but the residues that would bind catalytic metal ions in endonucleases are instead involved in hydrogen bonds that stabilize the protein structure.DOMAIN Contains a region with structural similarity to RNase H, but lacks RNase H activity. UniProt Q6P2Q9 2 EQUAL 2335 EQUAL Reactome DB_ID: 71910 1 Reactome DB_ID: 71874 1 EMBL:X04293 U5 snRNA U5 snRNA EMBL X04293 Reactome DB_ID: 71879 1 UniProt:Q9BUQ8 DDX23 DDX23 DDX23 FUNCTION Involved in pre-mRNA splicing and its phosphorylated form (by SRPK2) is required for spliceosomal B complex formation (PubMed:18425142). Independently of its spliceosome formation function, required for the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:28076779).SUBUNIT The phosphorylated form (by SRPK2) is a component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (PubMed:16723661, PubMed:9409622). Identified in the spliceosome C complex (PubMed:11991638). Interacts with ERBB4 (PubMed:20858735). Interacts with ERCC6 (PubMed:26030138).PTM In vitro phosphorylated by CLK1 and U1 snRNP-associated protein kinase (PubMed:9409622). Phosphorylated by SRPK2 and this phosphorylation is required for its association with the tri-snRNP (U4/U6-U5 tri-small nuclear ribonucleoproteins) and subsequent spliceosomal B complex formation (PubMed:18425142). May be phosphorylated by SRPK2 on Ser residues in the SR domain; the phosphorylation is required for the removal of inappropriate R-loops during transcription (PubMed:28076779).SIMILARITY Belongs to the DEAD box helicase family. DDX23/PRP28 subfamily. UniProt Q9BUQ8 1 EQUAL 820 EQUAL Reactome DB_ID: 71885 1 UniProt:O75643 SNRNP200 SNRNP200 ASCC3L1 KIAA0788 HELIC2 SNRNP200 FUNCTION Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:28502770, PubMed:28781166, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.SUBUNIT Component of a core complex containing at least PRPF8, SNRNP200, EFTUD2 and SNRNP40. Component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes, building blocks of the spliceosome. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (PubMed:16723661, PubMed:8670905, PubMed:26912367). Component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154).TISSUE SPECIFICITY Widely expressed.DOMAIN Contains two helicase domains. The N-terminal helicase domain has catalytic activity by itself, contrary to the C-terminal helicase domain that may have a regulatory role and enhance the activity of the first helicase domain.SIMILARITY Belongs to the helicase family. SKI2 subfamily. UniProt O75643 1 EQUAL 2136 EQUAL Reactome Database ID Release 82 71981 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71981 Reactome R-HSA-71981 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71981.2 Reactome DB_ID: 4615999 1 UniProt:O43290 SART1 SART1 SART1 FUNCTION Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA.SUBUNIT Identified in the spliceosome C complex. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39.TISSUE SPECIFICITY Ubiquitously expressed.PTM Sumoylated with SUMO2.ALLERGEN Causes an allergic reaction in human. Binds to IgE from atopic dermatitis (AD) patients. Identified as an IgE autoantigen in atopic dermatitis (AD) patients with severe skin manifestations.SIMILARITY Belongs to the SNU66/SART1 family. UniProt O43290 1 EQUAL 800 EQUAL Reactome DB_ID: 6806793 1 UniProt:Q53GS9 USP39 USP39 PRO2855 CGI-21 USP39 HSPC332 FUNCTION Plays a role in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the precatalytic spliceosome (PubMed:11350945, PubMed:26912367). Regulates AURKB mRNA levels, and thereby plays a role in cytokinesis and in the spindle checkpoint. Does not have ubiquitin-specific peptidase activity (PubMed:18728397).SUBUNIT The U4/U6-U5 tri-snRNP complex is a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:11350945, PubMed:26912367). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:16723661, PubMed:26912367).SIMILARITY Belongs to the peptidase C19 family.CAUTION Lacks the conserved His and Cys residues that are essential for the activity of de-ubiquitinating enzymes. Lacks ubiquitin C-terminal hydrolase activity (PubMed:18728397). UniProt Q53GS9 1 EQUAL 565 EQUAL Reactome DB_ID: 9769526 1 UniProt:Q9BTD8 RBM42 RBM42 RBM42 FUNCTION Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA.SUBUNIT Interacts with HNRNPK.SIMILARITY Belongs to the RRM RBM42 family. UniProt Q9BTD8 2 EQUAL 480 EQUAL Reactome DB_ID: 6806778 1 UniProt:Q8WVK2 SNRNP27 SNRNP27 SNRNP27 FUNCTION May play a role in mRNA splicing.SUBUNIT Part of a tri-snRNP complex.PTM Phosphorylated in vitro by snRNP-associated protein kinase.SIMILARITY Belongs to the SNUT3 family. UniProt Q8WVK2 1 EQUAL 155 EQUAL Reactome DB_ID: 71983 1 U4 snRNP:U6 snRNP complex [nucleoplasm] U4 snRNP:U6 snRNP complex Reactome DB_ID: 71982 1 U6 snRNP [nucleoplasm] U6 snRNP Reactome DB_ID: 6806791 1 LSM2-8 complex [nucleoplasm] LSM2-8 complex LSM2:LSM3:LSM4:LSM5:LSM6:LSM7:LSM8 Reactome DB_ID: 6806802 1 UniProt:Q9UK45 LSM7 LSM7 LSM7 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166). Interacts with TACC1 (PubMed:12165861).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt Q9UK45 2 EQUAL 103 EQUAL Reactome DB_ID: 6806807 1 UniProt:P62310 LSM3 LSM3 MDS017 LSM3 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:11991638, PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt P62310 2 EQUAL 102 EQUAL Reactome DB_ID: 6806804 1 UniProt:Q9Y4Z0 LSM4 LSM4 LSM4 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt Q9Y4Z0 1 EQUAL 139 EQUAL Reactome DB_ID: 6806795 1 UniProt:Q9Y4Y9 LSM5 LSM5 LSM5 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt Q9Y4Y9 2 EQUAL 91 EQUAL Reactome DB_ID: 6806779 1 UniProt:O95777 LSM8 LSM8 LSM8 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt O95777 2 EQUAL 96 EQUAL Reactome DB_ID: 71894 1 UniProt:Q9Y333 LSM2 LSM2 G7B C6orf28 LSM2 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:11991638, PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166).SIMILARITY Belongs to the snRNP Sm proteins family. UniProt Q9Y333 1 EQUAL 95 EQUAL Reactome DB_ID: 6806794 1 UniProt:P62312 LSM6 LSM6 LSM6 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320). Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner, facilitating the efficient association of RNA processing factors with their substrates. Component of the cytoplasmic LSM1-LSM7 complex, which is thought to be involved in mRNA degradation by activating the decapping step in the 5'-to-3' mRNA decay pathway (Probable).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166). Component of the heptameric LSM1-LSM7 complex, which consists of LSM1, LSM2, LSM3, LSM4, LSM5, LSM6 and LSM7 (PubMed:12515382).SIMILARITY Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily. UniProt P62312 1 EQUAL 80 EQUAL Reactome Database ID Release 82 6806791 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6806791 Reactome R-HSA-6806791 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6806791.1 Reactome DB_ID: 71892 1 EMBL:X59362 U6 snRNA U6 snRNA EMBL X59362 Reactome Database ID Release 82 71982 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71982 Reactome R-HSA-71982 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71982.2 Reactome DB_ID: 71891 1 U4 snRNP [nucleoplasm] U4 snRNP Reactome DB_ID: 71888 1 EMBL:X59361 U4 snRNA U4 snRNA EMBL X59361 Reactome DB_ID: 6806772 1 UniProt:Q8WWY3 PRPF31 PRPF31 PRP31 PRPF31 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11867543, PubMed:28781166). Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:11867543).SUBUNIT Identified in the spliceosome B complex (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (PubMed:11867543, PubMed:16723661, PubMed:26912367). Interacts with a complex formed by SNU13 and U4 snRNA, but not with SNU13 or U4 snRNA alone (PubMed:17412961, PubMed:21784869). The complex formed by SNU13 and PRPF31 binds also U4atac snRNA, a characteristic component of specific, less abundant spliceosomal complexes (PubMed:21784869). Interacts with PRPF6/U5 snRNP-associated 102 kDa protein (PubMed:11867543, PubMed:17412961, PubMed:26912367). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15960975). Interacts (via its NLS) with CTNNBL1 (PubMed:21385873). Interacts with USH1G (PubMed:34023904).TISSUE SPECIFICITY Ubiquitously expressed.DOMAIN Interacts with the snRNP via the Nop domain.DOMAIN The coiled coil domain is formed by two non-contiguous helices.SIMILARITY Belongs to the PRP31 family. UniProt Q8WWY3 1 EQUAL 499 EQUAL Reactome DB_ID: 71910 1 Reactome DB_ID: 6806775 1 PPIH:PRPF4:PRPF3 [nucleoplasm] PPIH:PRPF4:PRPF3 20K:60K:90K Reactome DB_ID: 71890 1 UniProt:O43172 PRPF4 PRPF4 PRPF4 PRP4 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:9257651, PubMed:9404889, PubMed:9328476, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:16723661, PubMed:26912367). Interacts directly with PRPF18, PPIH and PRPF3 (PubMed:9404889, PubMed:9328476, PubMed:9000057, PubMed:12875835, PubMed:25383878). Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA (PubMed:9404889). Interacts with ERCC6 (PubMed:26030138). UniProt O43172 1 EQUAL 522 EQUAL Reactome DB_ID: 6806776 1 UniProt:O43447 PPIH PPIH CYP20 CYPH PPIH FUNCTION PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome. May act as a chaperone.ACTIVITY REGULATION Inhibited by cyclosporin A.SUBUNIT Interacts directly with PRPF4. Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Heterodimer with PRPF18.SIMILARITY Belongs to the cyclophilin-type PPIase family. PPIase H subfamily. UniProt O43447 2 EQUAL 177 EQUAL Reactome DB_ID: 6806806 1 UniProt:O43395 PRPF3 PRPF3 PRP3 HPRP3 PRPF3 FUNCTION Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).SUBUNIT Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:9328476, PubMed:9404889, PubMed:28781166, PubMed:26912367, PubMed:17932117). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:16723661, PubMed:26912367). Interacts directly with PRPF4 (PubMed:9328476, PubMed:9404889, PubMed:17932117). Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA (PubMed:9404889). Interacts with SART3; the interaction is direct and recruits the deubiquitinase USP4 to PRPF3 (PubMed:15314151, PubMed:20595234). Interacts with PRPF19. Interacts ('Lys-63'-linked polyubiquitinated) with PRPF8 (via the MPN (JAB/Mov34) domain); may stabilize the U4/U6-U5 tri-snRNP complex (PubMed:20595234). Interacts with ERCC6 (PubMed:26030138).TISSUE SPECIFICITY Highly expressed in retina, liver, kidney and blood. Detected at lower levels in heart and brain.PTM Ubiquitinated. Undergoes 'Lys-63'-linked polyubiquitination by PRPF19 and deubiquitination by USP4. 'Lys-63'-linked ubiquitination increases the affinity for PRPF8 and may regulate the assembly of the U4/U6-U5 tri-snRNP complex. UniProt O43395 1 EQUAL 683 EQUAL Reactome Database ID Release 82 6806775 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6806775 Reactome R-HSA-6806775 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6806775.1 Reactome DB_ID: 71887 1 UniProt:P55769 SNU13 SNU13 NHP2L1 SNU13 FUNCTION Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28781166). Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly (PubMed:10545122, PubMed:17412961). The protein undergoes a conformational change upon RNA-binding (PubMed:17412961).SUBUNIT Identified in the spliceosome B complex (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, NHP2L1, EFTUD2, SART1 and USP39 (PubMed:16723661, PubMed:26912367). Interacts with RAD17 and PRPF31 (PubMed:10593953, PubMed:17412961, PubMed:21784869). The complex formed by SNU13 and PRPF31 binds U4 snRNA (PubMed:17412961). The complex formed by SNU13 and PRPF31 binds also U4atac snRNA, a characteristic component of specific, less abundant spliceosomal complexes (PubMed:21784869).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the eukaryotic ribosomal protein eL8 family. UniProt P55769 2 EQUAL 128 EQUAL Reactome Database ID Release 82 71891 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71891 Reactome R-HSA-71891 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71891.2 Reactome Database ID Release 82 71983 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71983 Reactome R-HSA-71983 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71983.1 Reactome Database ID Release 82 77506 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77506 Reactome R-HSA-77506 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-77506.3 Reactome DB_ID: 72069 1 Spliceosomal B Complex [nucleoplasm] Spliceosomal B Complex Reactome DB_ID: 156649 1 2 EQUAL 257 EQUAL Reactome DB_ID: 8867896 1 1 EQUAL 491 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 8952109 1 Reactome DB_ID: 72028 1 1 EQUAL 272 EQUAL Reactome DB_ID: 71929 1 1 EQUAL 353 EQUAL Reactome DB_ID: 8867895 1 1 EQUAL 376 EQUAL Reactome DB_ID: 71987 1 2 EQUAL 475 EQUAL Reactome DB_ID: 53703 1 2 EQUAL 253 EQUAL Reactome DB_ID: 72040 1 1 EQUAL 526 EQUAL Reactome DB_ID: 72106 1 1 EQUAL 856 EQUAL Reactome DB_ID: 71919 1 1 EQUAL 356 EQUAL Reactome DB_ID: 71937 1 1 EQUAL 415 EQUAL Reactome DB_ID: 71923 1 1 EQUAL 531 EQUAL Reactome DB_ID: 71921 1 1 EQUAL 365 EQUAL Reactome DB_ID: 8865911 1 Reactome DB_ID: 67411 1 1 EQUAL 855 EQUAL Reactome DB_ID: 71945 1 1 EQUAL 463 EQUAL Reactome DB_ID: 72029 1 1 EQUAL 238 EQUAL Reactome DB_ID: 72031 1 2 EQUAL 248 EQUAL Reactome DB_ID: 450601 1 2 EQUAL 326 EQUAL Reactome DB_ID: 71947 1 1 EQUAL 589 EQUAL Reactome DB_ID: 8867891 1 1 EQUAL 144 EQUAL Reactome DB_ID: 72041 1 2 EQUAL 324 EQUAL Reactome DB_ID: 72026 1 1 EQUAL 344 EQUAL Reactome DB_ID: 71917 1 Reactome DB_ID: 8867897 1 1 EQUAL 312 EQUAL Reactome DB_ID: 72054 1 1 EQUAL 341 EQUAL Reactome DB_ID: 71935 1 1 EQUAL 355 EQUAL Reactome DB_ID: 71953 1 2 EQUAL 825 EQUAL Reactome DB_ID: 5420896 1 Reactome DB_ID: 6781959 1 1 EQUAL 301 EQUAL Reactome DB_ID: 3900136 1 1 EQUAL 614 EQUAL Reactome DB_ID: 71931 1 1 EQUAL 378 EQUAL Reactome DB_ID: 71927 1 2 EQUAL 372 EQUAL Reactome DB_ID: 71943 1 1 EQUAL 449 EQUAL Reactome DB_ID: 72049 1 1 EQUAL 815 EQUAL Reactome DB_ID: 71949 1 2 EQUAL 730 EQUAL Reactome DB_ID: 351663 1 2 EQUAL 536 EQUAL Reactome DB_ID: 71925 1 1 EQUAL 305 EQUAL Reactome DB_ID: 72062 1 1 EQUAL 579 EQUAL Reactome DB_ID: 72058 1 1 EQUAL 484 EQUAL Reactome DB_ID: 53517 1 1 EQUAL 1270 EQUAL Reactome DB_ID: 72037 1 1 EQUAL 221 EQUAL Reactome DB_ID: 6781963 1 1 EQUAL 285 EQUAL Reactome DB_ID: 71951 1 2 EQUAL 633 EQUAL Reactome DB_ID: 8865956 1 1 EQUAL 908 EQUAL Reactome DB_ID: 5215975 1 2 EQUAL 420 EQUAL Reactome DB_ID: 71933 1 2 EQUAL 306 EQUAL Reactome DB_ID: 156778 1 1 EQUAL 305 EQUAL Reactome DB_ID: 72060 1 2 EQUAL 1227 EQUAL Reactome DB_ID: 71941 1 1 EQUAL 449 EQUAL Reactome DB_ID: 72033 1 2 EQUAL 221 EQUAL Reactome DB_ID: 77506 1 Reactome DB_ID: 6781960 1 1 EQUAL 1485 EQUAL Reactome DB_ID: 71980 1 Converted from EntitySet in Reactome Reactome DB_ID: 8865886 1 Reactome DB_ID: 8867899 1 1 EQUAL 848 EQUAL Reactome DB_ID: 72048 1 1 EQUAL 1150 EQUAL Reactome DB_ID: 8850864 1 1 EQUAL 359 EQUAL Reactome DB_ID: 72043 1 1 EQUAL 645 EQUAL Reactome DB_ID: 72024 1 1 EQUAL 494 EQUAL Reactome DB_ID: 72035 1 1 EQUAL 164 EQUAL Reactome DB_ID: 6814858 1 2 EQUAL 876 EQUAL Reactome DB_ID: 71954 1 Reactome DB_ID: 71939 1 1 EQUAL 391 EQUAL Reactome Database ID Release 82 72069 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72069 Reactome R-HSA-72069 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72069.4 Reactome DB_ID: 8867890 1 1 EQUAL 957 EQUAL Reactome Database ID Release 82 72127 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72127 Reactome R-HSA-72127 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72127.4 12477934 Pubmed 2002 Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method. Hartmuth, K Urlaub, H Vornlocher, HP Will, CL Gentzel, M Wilm, M Lührmann, Reinhard Proc Natl Acad Sci U S A 99:16719-24 16809785 Pubmed 2006 Protein composition and electron microscopy structure of affinity-purified human spliceosomal B complexes isolated under physiological conditions Deckert, Jochen Hartmuth, Klaus Boehringer, Daniel Behzadnia, Nastaran Will, Cindy L Kastner, Berthold Stark, Holger Urlaub, Henning Lührmann, Reinhard Mol. Cell. Biol. 26:5528-43 12176931 Pubmed 2002 Large-scale proteomic analysis of the human spliceosome. Rappsilber, J Ryder, U Lamond, AI Mann, M Genome Res 12:1231-45