THOC6_HUMAN
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 03-AUG-2022, entry version 162.
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};
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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 PDB; 7APK; EM; 3.30 A; F/N/f/n=1-341.
DR PDBsum; 7APK; -.
DR AlphaFoldDB; Q86W42; -.
DR SMR; Q86W42; -.
DR BioGRID; 122605; 65.
DR CORUM; Q86W42; -.
DR IntAct; Q86W42; 23.
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; 162 antibodies from 26 providers.
DR DNASU; 79228; -.
DR Ensembl; ENST00000253952.9; ENSP00000253952.9; ENSG00000131652.14. [Q86W42-3]
DR Ensembl; ENST00000326266.13; ENSP00000326531.8; ENSG00000131652.14. [Q86W42-1]
DR Ensembl; ENST00000574549.5; ENSP00000458295.1; ENSG00000131652.14. [Q86W42-2]
DR Ensembl; ENST00000575576.5; ENSP00000460015.1; ENSG00000131652.14. [Q86W42-2]
DR GeneID; 79228; -.
DR KEGG; hsa:79228; -.
DR MANE-Select; ENST00000326266.13; ENSP00000326531.8; NM_024339.5; NP_077315.2.
DR UCSC; uc002cta.2; human. [Q86W42-1]
DR CTD; 79228; -.
DR DisGeNET; 79228; -.
DR GeneCards; THOC6; -.
DR GeneReviews; 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; -.
DR eggNOG; KOG0649; Eukaryota.
DR GeneTree; ENSGT00390000015278; -.
DR HOGENOM; CLU_060667_0_0_1; -.
DR InParanoid; Q86W42; -.
DR OMA; HLRSMEC; -.
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 SIGNOR; Q86W42; -.
DR BioGRID-ORCS; 79228; 219 hits in 1080 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 granulocyte and 108 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:0006406; P:mRNA export from nucleus; IDA:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
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; 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 3D-structure; Alternative splicing; Apoptosis; Developmental protein;
KW Disease variant; Intellectual disability; mRNA processing; mRNA splicing;
KW mRNA transport; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; 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:0007744|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"
FT HELIX 13..23
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 34..42
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:7APK"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 136..139
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 148..157
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 197..200
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 230..239
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:7APK"
FT TURN 246..249
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 261..266
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 268..284
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 289..294
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 296..305
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 317..331
FT /evidence="ECO:0007829|PDB:7APK"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:7APK"
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
