ID THOC6_HUMAN Reviewed; 341 AA. AC Q86W42; B2RA85; Q8NBR1; Q9BTV9; DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 10-FEB-2021, entry version 156. DE RecName: Full=THO complex subunit 6 homolog; DE AltName: Full=Functional spliceosome-associated protein 35; DE Short=fSAP35; DE AltName: Full=WD repeat-containing protein 58; GN Name=THOC6; Synonyms=WDR58; ORFNames=PSEC0006; 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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Neuroblastoma, and Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung, and Testis; 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 [3] RP IDENTIFICATION IN THE TREX COMPLEX, FUNCTION OF THE TREX COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15833825; DOI=10.1158/0008-5472.can-04-3624; RA Guo S., Hakimi M.A., Baillat D., Chen X., Farber M.J., Klein-Szanto A.J., RA Cooch N.S., Godwin A.K., Shiekhattar R.; RT "Linking transcriptional elongation and messenger RNA export to metastatic RT breast cancers."; RL Cancer Res. 65:3011-3016(2005). RN [4] RP IDENTIFICATION IN THE THO AND TREX COMPLEX, FUNCTION OF THE TREX COMPLEX, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15998806; DOI=10.1101/gad.1302205; RA Masuda S., Das R., Cheng H., Hurt E., Dorman N., Reed R.; RT "Recruitment of the human TREX complex to mRNA during splicing."; RL Genes Dev. 19:1512-1517(2005). RN [5] RP FUNCTION OF THE TREX COMPLEX. RX PubMed=17190602; DOI=10.1016/j.cell.2006.10.044; RA Cheng H., Dufu K., Lee C.-S., Hsu J.L., Dias A., Reed R.; RT "Human mRNA export machinery recruited to the 5' end of mRNA."; RL Cell 127:1389-1400(2006). RN [6] RP FUNCTION OF THE TREX COMPLEX. RX PubMed=18974867; DOI=10.1371/journal.ppat.1000194; RA Boyne J.R., Colgan K.J., Whitehouse A.; RT "Recruitment of the complete hTREX complex is required for Kaposi's RT sarcoma-associated herpesvirus intronless mRNA nuclear export and virus RT replication."; RL PLoS Pathog. 4:E1000194-E1000194(2008). RN [7] 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, VARIANT BBIS ARG-46, AND CHARACTERIZATION RP OF VARIANT BBIS ARG-46. RX PubMed=23621916; DOI=10.1186/1750-1172-8-62; RA Beaulieu C.L., Huang L., Innes A.M., Akimenko M.A., Puffenberger E.G., RA Schwartz C., Jerry P., Ober C., Hegele R.A., McLeod D.R., RA Schwartzentruber J., Majewski J., Bulman D.E., Parboosingh J.S., RA Boycott K.M.; RT "Intellectual disability associated with a homozygous missense mutation in RT THOC6."; RL Orphanet J. Rare Dis. 8:62-62(2013). CC -!- FUNCTION: Acts as component of the THO subcomplex of the TREX complex CC which is thought to couple mRNA transcription, processing and nuclear CC export, and which specifically associates with spliced mRNA and not CC with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a CC transcription-independent mechanism, binds to mRNA upstream of the CC exon-junction complex (EJC) and is recruited in a splicing- and cap- CC dependent manner to a region near the 5' end of the mRNA where it CC functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. The CC TREX complex is essential for the export of Kaposi's sarcoma-associated CC herpesvirus (KSHV) intronless mRNAs and infectious virus production. CC Plays a role in apoptosis negative control involved in brain CC development. {ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, CC ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:18974867, CC ECO:0000269|PubMed:23621916}. CC -!- SUBUNIT: Component of the THO complex, which is composed of THOC1, CC THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least CC ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the CC transcription/export (TREX) complex which seems to have a dynamic CC structure involving ATP-dependent remodeling. CC {ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23621916}. Nucleus CC speckle {ECO:0000305|PubMed:23621916}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q86W42-1; Sequence=Displayed; CC Name=2; Synonyms=hTREX40; CC IsoId=Q86W42-2; Sequence=VSP_018079; CC Name=3; CC IsoId=Q86W42-3; Sequence=VSP_018078; CC -!- DISEASE: Beaulieu-Boycott-Innes syndrome (BBIS) [MIM:613680]: An CC autosomal recessive neurodevelopmental disorder characterized by CC delayed development, moderate intellectual disability, and dysmorphic CC facial features. Other developmental anomalies, such as cardiac and CC renal defects, may also occur. {ECO:0000269|PubMed:23621916}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the WD repeat THOC6 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG36782.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AK075330; BAC11552.1; -; mRNA. DR EMBL; AK314086; BAG36782.1; ALT_INIT; mRNA. DR EMBL; BC003118; AAH03118.1; -; mRNA. DR EMBL; BC050674; AAH50674.1; -; mRNA. DR CCDS; CCDS10491.1; -. [Q86W42-1] DR CCDS; CCDS45392.1; -. [Q86W42-3] DR CCDS; CCDS86500.1; -. [Q86W42-2] DR RefSeq; NP_001135822.1; NM_001142350.2. [Q86W42-3] DR RefSeq; NP_001334632.1; NM_001347703.1. [Q86W42-2] DR RefSeq; NP_001334633.1; NM_001347704.1. [Q86W42-1] DR RefSeq; NP_077315.2; NM_024339.4. [Q86W42-1] DR BioGRID; 122605; 56. DR CORUM; Q86W42; -. DR IntAct; Q86W42; 21. DR MINT; Q86W42; -. DR STRING; 9606.ENSP00000326531; -. DR iPTMnet; Q86W42; -. DR PhosphoSitePlus; Q86W42; -. DR SwissPalm; Q86W42; -. DR BioMuta; THOC6; -. DR DMDM; 74759455; -. DR EPD; Q86W42; -. DR jPOST; Q86W42; -. DR MassIVE; Q86W42; -. DR MaxQB; Q86W42; -. DR PaxDb; Q86W42; -. DR PeptideAtlas; Q86W42; -. DR PRIDE; Q86W42; -. DR ProteomicsDB; 70112; -. [Q86W42-1] DR ProteomicsDB; 70113; -. [Q86W42-2] DR ProteomicsDB; 70114; -. [Q86W42-3] DR Antibodypedia; 23992; 155 antibodies. DR DNASU; 79228; -. DR Ensembl; ENST00000253952; ENSP00000253952; ENSG00000131652. [Q86W42-3] DR Ensembl; ENST00000326266; ENSP00000326531; ENSG00000131652. [Q86W42-1] DR Ensembl; ENST00000574549; ENSP00000458295; ENSG00000131652. [Q86W42-2] DR Ensembl; ENST00000575576; ENSP00000460015; ENSG00000131652. [Q86W42-2] DR GeneID; 79228; -. DR KEGG; hsa:79228; -. DR UCSC; uc002cta.2; human. [Q86W42-1] DR CTD; 79228; -. DR DisGeNET; 79228; -. DR GeneCards; THOC6; -. DR HGNC; HGNC:28369; THOC6. DR HPA; ENSG00000131652; Low tissue specificity. DR MalaCards; THOC6; -. DR MIM; 613680; phenotype. DR MIM; 615403; gene. DR neXtProt; NX_Q86W42; -. DR OpenTargets; ENSG00000131652; -. DR Orphanet; 363444; THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome. DR PharmGKB; PA142670592; -. DR VEuPathDB; HostDB:ENSG00000131652.13; -. DR eggNOG; KOG0649; Eukaryota. DR GeneTree; ENSGT00390000015278; -. DR HOGENOM; CLU_060667_0_0_1; -. DR InParanoid; Q86W42; -. DR OMA; WEVKIPM; -. DR OrthoDB; 760323at2759; -. DR PhylomeDB; Q86W42; -. DR TreeFam; TF324760; -. DR PathwayCommons; Q86W42; -. DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript. DR Reactome; R-HSA-72187; mRNA 3'-end processing. DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination. DR SignaLink; Q86W42; -. DR BioGRID-ORCS; 79228; 196 hits in 878 CRISPR screens. DR ChiTaRS; THOC6; human. DR GenomeRNAi; 79228; -. DR Pharos; Q86W42; Tbio. DR PRO; PR:Q86W42; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q86W42; protein. DR Bgee; ENSG00000131652; Expressed in stomach and 148 other tissues. DR Genevisible; Q86W42; HS. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000347; C:THO complex; IDA:UniProtKB. DR GO; GO:0000445; C:THO complex part of transcription export complex; IDA:UniProtKB. DR GO; GO:0000346; C:transcription export complex; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007417; P:central nervous system development; IMP:UniProtKB. DR GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome. DR GO; GO:0006406; P:mRNA export from nucleus; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0006405; P:RNA export from nucleus; TAS:Reactome. DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW. DR GO; GO:0046784; P:viral mRNA export from host cell nucleus; IDA:UniProtKB. DR Gene3D; 2.130.10.10; -; 1. DR InterPro; IPR042626; THOC6. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR017986; WD40_repeat_dom. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR PANTHER; PTHR44411; PTHR44411; 1. DR Pfam; PF00400; WD40; 1. DR SMART; SM00320; WD40; 3. DR SUPFAM; SSF50978; SSF50978; 1. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Developmental protein; Disease variant; KW Mental retardation; mRNA processing; mRNA splicing; mRNA transport; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; RNA-binding; KW Transport; WD repeat. FT CHAIN 1..341 FT /note="THO complex subunit 6 homolog" FT /id="PRO_0000233158" FT REPEAT 22..61 FT /note="WD 1" FT REPEAT 74..112 FT /note="WD 2" FT REPEAT 124..165 FT /note="WD 3" FT REPEAT 166..205 FT /note="WD 4" FT REPEAT 215..254 FT /note="WD 5" FT REPEAT 256..293 FT /note="WD 6" FT REPEAT 295..339 FT /note="WD 7" FT MOD_RES 180 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT VAR_SEQ 1..24 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_018079" FT VAR_SEQ 271..315 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_018078" FT VARIANT 46 FT /note="G -> R (in BBIS; localizes to the cytoplasm and not FT to the nucleus; dbSNP:rs587777030)" FT /evidence="ECO:0000269|PubMed:23621916" FT /id="VAR_069779" FT CONFLICT 97 FT /note="V -> E (in Ref. 1; BAC11552)" FT /evidence="ECO:0000305" FT CONFLICT 121 FT /note="R -> S (in Ref. 1; BAG36782)" FT /evidence="ECO:0000305" SQ SEQUENCE 341 AA; 37535 MW; E854A8959F245FA9 CRC64; MERAVPLAVP LGQTEVFQAL QRLHMTIFSQ SVSPCGKFLA AGNNYGQIAI FSLSSALSSE AKEESKKPVV TFQAHDGPVY SMVSTDRHLL SAGDGEVKAW LWAEMLKKGC KELWRRQPPY RTSLEVPEIN ALLLVPKENS LILAGGDCQL HTMDLETGTF TRVLRGHTDY IHCLALRERS PEVLSGGEDG AVRLWDLRTA KEVQTIEVYK HEECSRPHNG RWIGCLATDS DWMVCGGGPA LTLWHLRSST PTTIFPIRAP QKHVTFYQDL ILSAGQGRCV NQWQLSGELK AQVPGSSPGL LSLSLNQQPA APECKVLTAA GNSCRVDVFT NLGYRAFSLS F //