ID WDR6_HUMAN Reviewed; 1121 AA. AC Q9NNW5; B4DHK2; Q3MIT1; Q9UF63; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 187. DE RecName: Full=tRNA (34-2'-O)-methyltransferase regulator WDR6 {ECO:0000305}; DE AltName: Full=WD repeat-containing protein 6; GN Name=WDR6; 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], AND TISSUE SPECIFICITY. RC TISSUE=Heart atrium; RX PubMed=10903905; DOI=10.1006/bbrc.2000.3012; RA Li D., Burch P., Gonzalez O., Kashork C.D., Shaffer L.G., Bachinski L.L., RA Roberts R.; RT "Molecular cloning, expression analysis, and chromosome mapping of WDR6, a RT novel human WD-repeat gene."; RL Biochem. Biophys. Res. Commun. 274:117-123(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 618-1121. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP FUNCTION, INTERACTION WITH STK11/LKB1, AND SUBCELLULAR LOCATION. RX PubMed=17216128; DOI=10.1007/s11010-006-9402-5; RA Xie X., Wang Z., Chen Y.; RT "Association of LKB1 with a WD-repeat protein WDR6 is implicated in cell RT growth arrest and p27(Kip1) induction."; RL Mol. Cell. Biochem. 301:115-122(2007). RN [7] RP FUNCTION. RX PubMed=22354037; DOI=10.1038/emboj.2012.36; RA McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M., RA Johansen T., Tooze S.A.; RT "Genome-wide siRNA screen reveals amino acid starvation-induced autophagy RT requires SCOC and WAC."; RL EMBO J. 31:1931-1946(2012). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [9] RP FUNCTION, AND INTERACTION WITH FTSJ1. RX PubMed=32558197; DOI=10.15252/embr.202050095; RA Li J., Wang Y.N., Xu B.S., Liu Y.P., Zhou M., Long T., Li H., Dong H., RA Nie Y., Chen P.R., Wang E.D., Liu R.J.; RT "Intellectual disability-associated gene ftsj1 is responsible for 2'-O- RT methylation of specific tRNAs."; RL EMBO Rep. 21:e50095-e50095(2020). RN [10] RP FUNCTION, AND INTERACTION WITH FTSJ1. RX PubMed=33771871; DOI=10.1126/sciadv.abf3072; RA Nagayoshi Y., Chujo T., Hirata S., Nakatsuka H., Chen C.W., Takakura M., RA Miyauchi K., Ikeuchi Y., Carlyle B.C., Kitchen R.R., Suzuki T., RA Katsuoka F., Yamamoto M., Goto Y., Tanaka M., Natsume K., Nairn A.C., RA Suzuki T., Tomizawa K., Wei F.Y.; RT "Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain RT and is associated with X-linked intellectual disability."; RL Sci. Adv. 7:eabf3072-eabf3072(2021). CC -!- FUNCTION: Together with methyltransferase FTSJ1, methylates the 2'-O- CC ribose of nucleotides at position 34 of the tRNA anticodon loop of CC substrate tRNAs (PubMed:32558197, PubMed:33771871). Required for the CC correct positioning of the substrate tRNA for methylation CC (PubMed:32558197). Required to suppress amino acid starvation-induced CC autophagy (PubMed:22354037). Enhances the STK11/LKB1-induced cell CC growth suppression activity (PubMed:17216128). CC {ECO:0000269|PubMed:17216128, ECO:0000269|PubMed:22354037, CC ECO:0000269|PubMed:32558197, ECO:0000269|PubMed:33771871}. CC -!- SUBUNIT: Interacts with FTSJ1; the interaction is direct, and required CC for 2'-O-methylation of position 34 in substrate tRNAs CC (PubMed:32558197, PubMed:33771871). Interacts with IRS4 (By CC similarity). Interacts with STK11/LKB1 (PubMed:17216128). CC {ECO:0000250|UniProtKB:Q5XFW6, ECO:0000269|PubMed:17216128, CC ECO:0000269|PubMed:32558197, ECO:0000269|PubMed:33771871}. CC -!- INTERACTION: CC Q9NNW5; Q9Y3R0-3: GRIP1; NbExp=3; IntAct=EBI-1568315, EBI-12193965; CC Q9NNW5; P26045: PTPN3; NbExp=6; IntAct=EBI-1568315, EBI-1047946; CC Q9NNW5; Q15831: STK11; NbExp=3; IntAct=EBI-1568315, EBI-306838; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17216128}. CC Note=Colocalizes in the cytoplasm with STK11/LKB1. CC {ECO:0000269|PubMed:17216128}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10903905}. CC -!- SIMILARITY: Belongs to the WD repeat WDR6 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG58164.1; 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; AF099100; AAF80244.1; -; mRNA. DR EMBL; AK295145; BAG58164.1; ALT_INIT; mRNA. DR EMBL; AC137630; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC101707; AAI01708.1; -; mRNA. DR EMBL; BC113467; AAI13468.1; -; mRNA. DR EMBL; AL133589; CAB63730.1; -; mRNA. DR CCDS; CCDS2782.3; -. DR PIR; JC7329; JC7329. DR PIR; T43496; T43496. DR RefSeq; NP_001307475.1; NM_001320546.1. DR RefSeq; NP_001307476.1; NM_001320547.1. DR RefSeq; NP_060501.3; NM_018031.4. DR AlphaFoldDB; Q9NNW5; -. DR BioGRID; 116350; 324. DR IntAct; Q9NNW5; 105. DR MINT; Q9NNW5; -. DR STRING; 9606.ENSP00000378857; -. DR GlyGen; Q9NNW5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NNW5; -. DR PhosphoSitePlus; Q9NNW5; -. DR SwissPalm; Q9NNW5; -. DR BioMuta; WDR6; -. DR DMDM; 12643813; -. DR EPD; Q9NNW5; -. DR jPOST; Q9NNW5; -. DR MassIVE; Q9NNW5; -. DR MaxQB; Q9NNW5; -. DR PaxDb; 9606-ENSP00000378857; -. DR PeptideAtlas; Q9NNW5; -. DR ProteomicsDB; 81856; -. DR Pumba; Q9NNW5; -. DR Antibodypedia; 13436; 119 antibodies from 26 providers. DR DNASU; 11180; -. DR Ensembl; ENST00000608424.6; ENSP00000477389.1; ENSG00000178252.19. DR GeneID; 11180; -. DR KEGG; hsa:11180; -. DR MANE-Select; ENST00000608424.6; ENSP00000477389.1; NM_018031.6; NP_060501.4. DR UCSC; uc062job.1; human. DR AGR; HGNC:12758; -. DR CTD; 11180; -. DR DisGeNET; 11180; -. DR GeneCards; WDR6; -. DR HGNC; HGNC:12758; WDR6. DR HPA; ENSG00000178252; Low tissue specificity. DR MIM; 606031; gene. DR neXtProt; NX_Q9NNW5; -. DR OpenTargets; ENSG00000178252; -. DR PharmGKB; PA37362; -. DR VEuPathDB; HostDB:ENSG00000178252; -. DR eggNOG; KOG0974; Eukaryota. DR GeneTree; ENSGT00420000029923; -. DR HOGENOM; CLU_002615_0_0_1; -. DR InParanoid; Q9NNW5; -. DR OrthoDB; 1935601at2759; -. DR PhylomeDB; Q9NNW5; -. DR TreeFam; TF313984; -. DR PathwayCommons; Q9NNW5; -. DR Reactome; R-HSA-9013420; RHOU GTPase cycle. DR Reactome; R-HSA-9013424; RHOV GTPase cycle. DR Reactome; R-HSA-9696264; RND3 GTPase cycle. DR Reactome; R-HSA-9696270; RND2 GTPase cycle. DR Reactome; R-HSA-9696273; RND1 GTPase cycle. DR SignaLink; Q9NNW5; -. DR BioGRID-ORCS; 11180; 24 hits in 1164 CRISPR screens. DR ChiTaRS; WDR6; human. DR GeneWiki; WDR6; -. DR GenomeRNAi; 11180; -. DR Pharos; Q9NNW5; Tbio. DR PRO; PR:Q9NNW5; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9NNW5; Protein. DR Bgee; ENSG00000178252; Expressed in right uterine tube and 197 other cell types or tissues. DR ExpressionAtlas; Q9NNW5; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0030234; F:enzyme regulator activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB. DR GO; GO:0070314; P:G1 to G0 transition; IPI:UniProtKB. DR GO; GO:0010507; P:negative regulation of autophagy; IMP:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central. DR GO; GO:0002130; P:wobble position ribose methylation; IDA:UniProtKB. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 3. DR InterPro; IPR011043; Gal_Oxase/kelch_b-propeller. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR14344; WD REPEAT PROTEIN; 1. DR PANTHER; PTHR14344:SF3; WD REPEAT-CONTAINING PROTEIN 6; 1. DR Pfam; PF00400; WD40; 3. DR SMART; SM00320; WD40; 7. DR SUPFAM; SSF50965; Galactose oxidase, central domain; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 2. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q9NNW5; HS. PE 1: Evidence at protein level; KW Acetylation; Cell cycle; Cytoplasm; Reference proteome; Repeat; KW tRNA processing; WD repeat. FT CHAIN 1..1121 FT /note="tRNA (34-2'-O)-methyltransferase regulator WDR6" FT /id="PRO_0000051352" FT REPEAT 53..97 FT /note="WD 1" FT REPEAT 105..143 FT /note="WD 2" FT REPEAT 147..189 FT /note="WD 3" FT REPEAT 200..238 FT /note="WD 4" FT REPEAT 247..285 FT /note="WD 5" FT REPEAT 289..327 FT /note="WD 6" FT REPEAT 335..376 FT /note="WD 7" FT REPEAT 381..422 FT /note="WD 8" FT REPEAT 425..470 FT /note="WD 9" FT REPEAT 476..520 FT /note="WD 10" FT REPEAT 559..598 FT /note="WD 11" FT REPEAT 604..642 FT /note="WD 12" FT REPEAT 645..684 FT /note="WD 13" FT REPEAT 739..785 FT /note="WD 14" FT REPEAT 848..893 FT /note="WD 15" FT REPEAT 901..946 FT /note="WD 16" FT REPEAT 970..1012 FT /note="WD 17" FT REPEAT 1036..1073 FT /note="WD 18" FT REPEAT 1079..1121 FT /note="WD 19" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895" FT CONFLICT 38 FT /note="D -> N (in Ref. 2; BAG58164)" FT /evidence="ECO:0000305" FT CONFLICT 545 FT /note="S -> R (in Ref. 2; BAG58164)" FT /evidence="ECO:0000305" FT CONFLICT 651 FT /note="V -> I (in Ref. 2; BAG58164)" FT /evidence="ECO:0000305" SQ SEQUENCE 1121 AA; 121725 MW; 4E408D5D893FF005 CRC64; MDALEDYVWP RATSELILLP VTGLECVGDR LLAGEGPDVL VYSLDFGGHL RMIKRVQNLL GHYLIHGFRV RPEPNGDLDL EAMVAVFGSK GLRVVKISWG QGHFWELWRS GLWNMSDWIW DARWLEGNIA LALGHNSVVL YDPVVGCILQ EVPCTDRCTL SSACLIGDAW KELTIVAGAV SNQLLVWYPA TALADNKPVA PDRRISGHVG IIFSMSYLES KGLLATASED RSVRIWKVGD LRVPGGRVQN IGHCFGHSAR VWQVKLLENY LISAGEDCVC LVWSHEGEIL QAFRGHQGRG IRAIAAHERQ AWVITGGDDS GIRLWHLVGR GYRGLGVSAL CFKSRSRPGT LKAVTLAGSW RLLAVTDTGA LYLYDVEVKC WEQLLEDKHF QSYCLLEAAP GPEGFGLCAM ANGEGRVKVV PINTPTAAVD QTLFPGKVHS LSWALRGYEE LLLLASGPGG VVACLEISAA PSGKAIFVKE RCRYLLPPSK QRWHTCSAFL PPGDFLVCGD RRGSVLLFPS RPGLLKDPGV GGKARAGAGA PVVGSGSSGG GNAFTGLGPV STLPSLHGKQ GVTSVTCHGG YVYTTGRDGA YYQLFVRDGQ LQPVLRQKSC RGMNWLAGLR IVPDGSMVIL GFHANEFVVW NPRSHEKLHI VNCGGGHRSW AFSDTEAAMA FAYLKDGDVM LYRALGGCTR PHVILREGLH GREITCVKRV GTITLGPEYG VPSFMQPDDL EPGSEGPDLT DIVITCSEDT TVCVLALPTT TGSAHALTAV CNHISSVRAV AVWGIGTPGG PQDPQPGLTA HVVSAGGRAE MHCFSIMVTP DPSTPSRLAC HVMHLSSHRL DEYWDRQRNR HRMVKVDPET RYMSLAVCEL DQPGLGPLVA AACSDGAVRL FLLQDSGRIL QLLAETFHHK RCVLKVHSFT HEAPNQRRRL LLCSAATDGS LAFWDLTTML DHDSTVLEPP VDPGLPYRLG TPSLTLQAHS CGINSLHTLP TREGHHLVAS GSEDGSLHVF VLAVEMLQLE EAVGEAGLVP QLRVLEEYSV PCAHAAHVTG LKILSPSIMV SASIDQRLTF WRLGHGEPTF MNSTVFHVPD VADMDCWPVS PEFGHRCALG GQGLEVYNWY D //