ID RTRAF_HUMAN Reviewed; 244 AA. AC Q9Y224; DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 24-JAN-2024, entry version 180. DE RecName: Full=RNA transcription, translation and transport factor protein {ECO:0000312|HGNC:HGNC:23169}; DE AltName: Full=CLE7 homolog; DE Short=CLE; DE Short=hCLE {ECO:0000303|PubMed:26864902}; GN Name=RTRAF {ECO:0000312|HGNC:HGNC:23169}; GN Synonyms=C14orf166 {ECO:0000312|HGNC:HGNC:23169}; ORFNames=CGI-99; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pituitary; RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G., RA Luo M., Chen J., Hu R.; RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH INFLUENZA A VIRUS PA (MICROBIAL INFECTION). RX PubMed=11507205; DOI=10.1128/jvi.75.18.8597-8604.2001; RA Huarte M., Sanz-Ezquerro J.J., Roncal F., Ortin J., Nieto A.; RT "PA subunit from influenza virus polymerase complex interacts with a RT cellular protein with homology to a family of transcriptional activators."; RL J. Virol. 75:8597-8604(2001). RN [5] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH NIN. RX PubMed=15147888; DOI=10.1016/j.febslet.2004.04.024; RA Howng S.-L., Hsu H.-C., Cheng T.-S., Lee Y.-L., Chang L.-K., Lu P.-J., RA Hong Y.-R.; RT "A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation RT by GSK3beta and is highly expressed in brain tumors."; RL FEBS Lett. 566:162-168(2004). RN [6] RP FUNCTION, AND INTERACTION WITH POLR2A. RX PubMed=16950395; DOI=10.1016/j.jmb.2006.07.085; RA Perez-Gonzalez A., Rodriguez A., Huarte M., Salanueva I.J., Nieto A.; RT "hCLE/CGI-99, a human protein that interacts with the influenza virus RT polymerase, is a mRNA transcription modulator."; RL J. Mol. Biol. 362:887-900(2006). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20; LYS-62 AND LYS-98, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP INTERACTION WITH HEPATITIS C VIRUS CORE PROTEIN P19 (MICROBIAL INFECTION). RX PubMed=21823664; DOI=10.1021/pr200338d; RA Lee J.W., Liao P.C., Young K.C., Chang C.L., Chen S.S., Chang T.T., RA Lai M.D., Wang S.W.; RT "Identification of hnRNPH1, NF45, and C14orf166 as novel host interacting RT partners of the mature hepatitis C virus core protein."; RL J. Proteome Res. 10:4522-4534(2011). RN [10] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH INFLUENZA VIRUS PA; RP PB1; PB2 AND NP (MICROBIAL INFECTION). RX PubMed=21900157; DOI=10.1128/jvi.00684-11; RA Rodriguez A., Perez-Gonzalez A., Nieto A.; RT "Cellular human CLE/C14orf166 protein interacts with influenza virus RT polymerase and is required for viral replication."; RL J. Virol. 85:12062-12066(2011). RN [11] RP IDENTIFICATION IN THE TRNA SPLICING LIGASE COMPLEX. RX PubMed=21311021; DOI=10.1126/science.1197847; RA Popow J., Englert M., Weitzer S., Schleiffer A., Mierzwa B., Mechtler K., RA Trowitzsch S., Will C.L., Luhrmann R., Soll D., Martinez J.; RT "HSPC117 is the essential subunit of a human tRNA splicing ligase RT complex."; RL Science 331:760-764(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP FUNCTION, AND IDENTIFICATION IN THE TRNA SPLICING LIGASE COMPLEX. RX PubMed=24870230; DOI=10.1038/nature13284; RA Popow J., Jurkin J., Schleiffer A., Martinez J.; RT "Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing RT factors."; RL Nature 511:104-107(2014). RN [14] RP SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH FAM98B; DDX1 AND RTCB, RP RNA-BINDING, AND FUNCTION. RX PubMed=24608264; DOI=10.1371/journal.pone.0090957; RA Perez-Gonzalez A., Pazo A., Navajas R., Ciordia S., Rodriguez-Frandsen A., RA Nieto A.; RT "hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel RT transcription-dependent shuttling RNA-transporting complex."; RL PLoS ONE 9:E90957-E90957(2014). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [16] RP ASSOCIATION WITH INFLUENZA A VIRUS RNP AND RNA POLYMERASE SUBUNITS RP (MICROBIAL INFECTION), SUBCELLULAR LOCATION (MICROBIAL INFECTION), AND RP INDUCTION (MICROBIAL INFECTION). RX PubMed=26864902; DOI=10.1038/srep20744; RA Rodriguez-Frandsen A., de Lucas S., Perez-Gonzalez A., Perez-Cidoncha M., RA Roldan-Gomendio A., Pazo A., Marcos-Villar L., Landeras-Bueno S., Ortin J., RA Nieto A.; RT "hCLE/C14orf166, a cellular protein required for viral replication, is RT incorporated into influenza virus particles."; RL Sci. Rep. 6:20744-20744(2016). RN [17] RP INTERACTION WITH FAM98A, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=28040436; DOI=10.1016/j.biocel.2016.12.013; RA Akter K.A., Mansour M.A., Hyodo T., Senga T.; RT "FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved RT in colorectal cancer progression."; RL Int. J. Biochem. Cell Biol. 84:1-13(2017). CC -!- FUNCTION: RNA-binding protein involved in modulation of mRNA CC transcription by Polymerase II (PubMed:16950395). Component of the CC tRNA-splicing ligase complex and is required for tRNA ligation CC (PubMed:24870230). May be required for RNA transport (PubMed:24608264). CC {ECO:0000269|PubMed:16950395, ECO:0000269|PubMed:24608264, CC ECO:0000269|PubMed:24870230}. CC -!- FUNCTION: (Microbial infection) In case of infection by influenza virus CC A (IVA), is involved in viral replication (PubMed:21900157). CC {ECO:0000269|PubMed:21900157}. CC -!- SUBUNIT: Homodimer (Probable). Interacts with FAM98A (via N- and C- CC terminus) (PubMed:28040436). Interacts with NIN; which may prevent CC phosphorylation of NIN (PubMed:15147888). Interacts with POLR2A CC (PubMed:16950395). Component of a tRNA-splicing ligase complex with CC FAM98B, DDX1 and RTCB (PubMed:21311021, PubMed:24870230, CC PubMed:24608264). {ECO:0000269|PubMed:15147888, CC ECO:0000269|PubMed:16950395, ECO:0000269|PubMed:21311021, CC ECO:0000269|PubMed:24608264, ECO:0000269|PubMed:24870230, CC ECO:0000269|PubMed:28040436, ECO:0000305|PubMed:24608264}. CC -!- SUBUNIT: (Microbial infection) Interacts with influenza A virus (IAV) CC RNA polymerase subunits PA, PB1 and PB2, and nucleocapsid NP CC (PubMed:21900157, PubMed:26864902). Associates with IAV polymerase CC complexes both in the nucleus and cytosol (PubMed:26864902). Associates CC with IAV ribonucleoproteins (vRNP) packaged in virions CC (PubMed:26864902). Interacts with hepatitis C virus core protein p19 CC (PubMed:21823664). {ECO:0000269|PubMed:21823664, CC ECO:0000269|PubMed:21900157, ECO:0000269|PubMed:26864902}. CC -!- INTERACTION: CC Q9Y224; Q92499: DDX1; NbExp=3; IntAct=EBI-1104547, EBI-358474; CC Q9Y224; Q8NCA5: FAM98A; NbExp=7; IntAct=EBI-1104547, EBI-1210765; CC Q9Y224; Q52LJ0: FAM98B; NbExp=2; IntAct=EBI-1104547, EBI-1043130; CC Q9Y224; Q8N4C6: NIN; NbExp=4; IntAct=EBI-1104547, EBI-1164022; CC Q9Y224; Q9UIG4: PSORS1C2; NbExp=3; IntAct=EBI-1104547, EBI-11974061; CC Q9Y224; Q9Y3I0: RTCB; NbExp=4; IntAct=EBI-1104547, EBI-2107208; CC Q9Y224; Q9Y224: RTRAF; NbExp=5; IntAct=EBI-1104547, EBI-1104547; CC Q9Y224; P31343: PA; Xeno; NbExp=4; IntAct=EBI-1104547, EBI-5800362; CC Q9Y224; Q67020: PA; Xeno; NbExp=3; IntAct=EBI-1104547, EBI-11514477; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15147888, CC ECO:0000269|PubMed:24608264}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:15147888, ECO:0000269|PubMed:24608264}. Cytoplasm, CC perinuclear region {ECO:0000269|PubMed:15147888}. Cytoplasm, CC cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:15147888}. Note=May localize at the centrosome CC during mitosis (PubMed:15147888). Shuttles between the cytosol and the CC nucleus: enters into the nucleus in case of active transcription while CC it accumulates in cytosol when transcription level is low CC (PubMed:24608264). {ECO:0000269|PubMed:15147888, CC ECO:0000269|PubMed:24608264}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26864902}. Cytoplasm CC {ECO:0000269|PubMed:26864902}. Note=(Microbial infection) Following CC influenza A virus (IAV) infection, included in influenza A virions via CC its association with packaged viral ribonucleoproteins (vRNP) in the CC nucleus and cytoplasm (PubMed:21900157, PubMed:26864902). CC {ECO:0000269|PubMed:21900157, ECO:0000269|PubMed:26864902}. CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at high level in heart CC and skeletal muscle. Expressed at intermediate level in liver, CC pancreas, fetal brain and fetal lung. Weakly expressed in adult brain, CC adult lung, placenta, fetal liver and fetal kidney. Overexpressed in CC many brain tumors. {ECO:0000269|PubMed:15147888}. CC -!- INDUCTION: (Microbial infection) Up-regulated specifically following CC influenza A virus (IAV) infection in a viral replication-dependent CC manner (at protein level) (PubMed:26864902). CC {ECO:0000269|PubMed:26864902}. CC -!- SIMILARITY: Belongs to the RTRAF family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF100755; AAD43019.1; -; mRNA. DR EMBL; AF151857; AAD34094.1; -; mRNA. DR EMBL; BC001722; AAH01722.1; -; mRNA. DR CCDS; CCDS9705.1; -. DR RefSeq; NP_057123.1; NM_016039.2. DR PDB; 7P3A; X-ray; 2.00 A; A/B=2-101. DR PDBsum; 7P3A; -. DR AlphaFoldDB; Q9Y224; -. DR SMR; Q9Y224; -. DR BioGRID; 119650; 203. DR ComplexPortal; CPX-6411; tRNA-splicing ligase complex. DR CORUM; Q9Y224; -. DR IntAct; Q9Y224; 94. DR MINT; Q9Y224; -. DR STRING; 9606.ENSP00000261700; -. DR GlyGen; Q9Y224; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y224; -. DR MetOSite; Q9Y224; -. DR PhosphoSitePlus; Q9Y224; -. DR SwissPalm; Q9Y224; -. DR BioMuta; RTRAF; -. DR DMDM; 20138086; -. DR REPRODUCTION-2DPAGE; Q9Y224; -. DR EPD; Q9Y224; -. DR jPOST; Q9Y224; -. DR MassIVE; Q9Y224; -. DR MaxQB; Q9Y224; -. DR PaxDb; 9606-ENSP00000261700; -. DR PeptideAtlas; Q9Y224; -. DR ProteomicsDB; 85609; -. DR Pumba; Q9Y224; -. DR TopDownProteomics; Q9Y224; -. DR Antibodypedia; 10723; 382 antibodies from 27 providers. DR DNASU; 51637; -. DR Ensembl; ENST00000261700.8; ENSP00000261700.3; ENSG00000087302.9. DR GeneID; 51637; -. DR KEGG; hsa:51637; -. DR MANE-Select; ENST00000261700.8; ENSP00000261700.3; NM_016039.3; NP_057123.1. DR UCSC; uc010aod.4; human. DR AGR; HGNC:23169; -. DR CTD; 51637; -. DR DisGeNET; 51637; -. DR GeneCards; RTRAF; -. DR HGNC; HGNC:23169; RTRAF. DR HPA; ENSG00000087302; Low tissue specificity. DR MIM; 610858; gene. DR neXtProt; NX_Q9Y224; -. DR OpenTargets; ENSG00000087302; -. DR PharmGKB; PA134953268; -. DR VEuPathDB; HostDB:ENSG00000087302; -. DR eggNOG; KOG4380; Eukaryota. DR GeneTree; ENSGT00390000005163; -. DR HOGENOM; CLU_075085_0_0_1; -. DR InParanoid; Q9Y224; -. DR OMA; YLKYCAD; -. DR OrthoDB; 2877202at2759; -. DR PhylomeDB; Q9Y224; -. DR TreeFam; TF323606; -. DR BioCyc; MetaCyc:ENSG00000087302-MONOMER; -. DR PathwayCommons; Q9Y224; -. DR Reactome; R-HSA-6784531; tRNA processing in the nucleus. DR SignaLink; Q9Y224; -. DR BioGRID-ORCS; 51637; 453 hits in 1126 CRISPR screens. DR ChiTaRS; C14orf166; human. DR GeneWiki; C14orf166; -. DR GenomeRNAi; 51637; -. DR Pharos; Q9Y224; Tbio. DR PRO; PR:Q9Y224; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9Y224; Protein. DR Bgee; ENSG00000087302; Expressed in secondary oocyte and 202 other cell types or tissues. DR ExpressionAtlas; Q9Y224; baseline and differential. DR Genevisible; Q9Y224; HS. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0072669; C:tRNA-splicing ligase complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB. DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB. DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0050658; P:RNA transport; TAS:UniProtKB. DR GO; GO:0006388; P:tRNA splicing, via endonucleolytic cleavage and ligation; IMP:UniProtKB. DR InterPro; IPR019265; RTRAF. DR PANTHER; PTHR15924; CLE; 1. DR PANTHER; PTHR15924:SF9; RNA TRANSCRIPTION, TRANSLATION AND TRANSPORT FACTOR PROTEIN; 1. DR Pfam; PF10036; RLL; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Cytoskeleton; Host-virus interaction; KW Nucleus; Reference proteome; RNA-binding; Transcription; KW Transcription regulation. FT CHAIN 1..244 FT /note="RNA transcription, translation and transport factor FT protein" FT /id="PRO_0000089956" FT MOD_RES 20 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 62 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 98 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT HELIX 2..11 FT /evidence="ECO:0007829|PDB:7P3A" FT HELIX 15..35 FT /evidence="ECO:0007829|PDB:7P3A" FT HELIX 42..45 FT /evidence="ECO:0007829|PDB:7P3A" FT HELIX 46..49 FT /evidence="ECO:0007829|PDB:7P3A" FT HELIX 56..66 FT /evidence="ECO:0007829|PDB:7P3A" FT HELIX 76..91 FT /evidence="ECO:0007829|PDB:7P3A" FT HELIX 97..100 FT /evidence="ECO:0007829|PDB:7P3A" SQ SEQUENCE 244 AA; 28068 MW; EB2C3C5577A09A2A CRC64; MFRRKLTALD YHNPAGFNCK DETEFRNFIV WLEDQKIRHY KIEDRGNLRN IHSSDWPKFF EKYLRDVNCP FKIQDRQEAI DWLLGLAVRL EYGDNAEKYK DLVPDNSKTA DNATKNAEPL INLDVNNPDF KAGVMALANL LQIQRHDDYL VMLKAIRILV QERLTQDAVA KANQTKEGLP VALDKHILGF DTGDAVLNEA AQILRLLHIE ELRELQTKIN EAIVAVQAII ADPKTDHRLG KVGR //