ID KCTD6_HUMAN Reviewed; 237 AA. AC Q8NC69; B3KNI5; Q8NBS6; Q8TCA6; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2006, sequence version 2. DT 12-SEP-2018, entry version 117. DE RecName: Full=BTB/POZ domain-containing protein KCTD6; DE AltName: Full=KCASH3 protein {ECO:0000303|PubMed:21472142}; DE AltName: Full=Potassium channel tetramerization domain-containing protein 6; GN Name=KCTD6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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]. RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full- RT length human cDNAs encoding secretion or membrane proteins from oligo- RT capped cDNA libraries."; RL DNA Res. 12:117-126(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP SUBUNIT, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=21472142; RA De Smaele E., Di Marcotullio L., Moretti M., Pelloni M., RA Occhione M.A., Infante P., Cucchi D., Greco A., Pietrosanti L., RA Todorovic J., Coni S., Canettieri G., Ferretti E., Bei R., Maroder M., RA Screpanti I., Gulino A.; RT "Identification and characterization of KCASH2 and KCASH3, 2 novel RT Cullin3 adaptors suppressing histone deacetylase and Hedgehog activity RT in medulloblastoma."; RL Neoplasia 13:374-385(2011). RN [6] RP INTERACTION WITH ANK1, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22573887; DOI=10.1091/mbc.E12-01-0052; RA Lange S., Perera S., Teh P., Chen J.; RT "Obscurin and KCTD6 regulate cullin-dependent small ankyrin-1 RT (sAnk1.5) protein turnover."; RL Mol. Biol. Cell 23:2490-2504(2012). RN [7] RP SUBUNIT. RX PubMed=24307990; DOI=10.1155/2013/162674; RA Pirone L., Esposito C., Correale S., Graziano G., Di Gaetano S., RA Vitagliano L., Pedone E.; RT "Thermal and chemical stability of two homologous POZ/BTB domains of RT KCTD proteins characterized by a different oligomeric organization."; RL Biomed. Res. Int. 2013:162674-162674(2013). RN [8] RP INTERACTION WITH CUL3. RX PubMed=25974686; DOI=10.1371/journal.pone.0126808; RA Smaldone G., Pirone L., Balasco N., Di Gaetano S., Pedone E.M., RA Vitagliano L.; RT "Cullin 3 recognition is not a universal property among KCTD RT proteins."; RL PLoS ONE 10:E0126808-E0126808(2015). RN [9] RP PENTAMERIZATION, AND ELECTRON MICROSCOPY OF THE KCTD6:CUL3 COMPLEX. RX PubMed=27152988; DOI=10.1002/1873-3468.12203; RA Smaldone G., Pirone L., Pedone E., Marlovits T., Vitagliano L., RA Ciccarelli L.; RT "The BTB domains of the potassium channel tetramerization domain RT proteins prevalently assume pentameric states."; RL FEBS Lett. 590:1663-1671(2016). RN [10] RP INTERACTION WITH USP21. RX PubMed=27621083; DOI=10.1242/jcs.188516; RA Heride C., Rigden D.J., Bertsoulaki E., Cucchi D., De Smaele E., RA Clague M.J., Urbe S.; RT "The centrosomal deubiquitylase USP21 regulates Gli1 transcriptional RT activity and stability."; RL J. Cell Sci. 129:4001-4013(2016). RN [11] RP INTERACTION WITH CUL3, AND PENTAMERIZATION. RX PubMed=26334369; DOI=10.1016/j.jmb.2015.08.019; RA Ji A.X., Chu A., Nielsen T.K., Benlekbir S., Rubinstein J.L., RA Prive G.G.; RT "Structural insights into KCTD protein assembly and CULLIN3 RT recognition."; RL J. Mol. Biol. 428:92-107(2016). CC -!- FUNCTION: Probable substrate-specific adapter of a BCR (BTB-CUL3- CC RBX1) E3 ubiquitin-protein ligase complex mediating the CC ubiquitination and subsequent proteasomal degradation of target CC proteins. Promotes the ubiquitination of HDAC1; the function seems CC to depend on KCTD11:KCTD6 oligomerization. Can function as CC antagonist of the Hedgehog pathway by affecting the nuclear CC transfer of transcription factor GLI1; the function probably CC occurs via HDAC1 down-regulation, keeping GLI1 acetylated and CC inactive. Inhibits cell growth and tumorigenicity of CC medulloblastoma (MDB) (PubMed:21472142). Involved in regulating CC protein levels of ANK1 isoform Mu17 probably implicating CUL3- CC dependent proteasomal degradation (PubMed:22573887). CC {ECO:0000269|PubMed:21472142, ECO:0000269|PubMed:22573887}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Homopentamer. Interacts with KCTD11; KCTD6 and KCTD11 may CC associate in pentameric assemblies. Interacts (via BTB domain) CC with CUL3; initially a 4:4 stoichiometry has been reported, CC however, electron microscopy revealed pentameric states with a CC five-pointed pinwheel shape. The interaction with CUL3 is CC indicative for a participation in a BCR (BTB-CUL3-RBX1) E3 CC ubiquitin-protein ligase complex. Interacts with HDAC1; probably CC indirect as the interaction is requiring the presence of KCTD11 CC (PubMed:21472142, PubMed:24307990, PubMed:25974686, CC PubMed:27152988). Interacts with USP21 (preferentially catalytic CC inactive form) (PubMed:27621083). Interacts with ANK1 isoform CC Mu17; detected in striated muscle (PubMed:22573887). CC {ECO:0000269|PubMed:21472142, ECO:0000269|PubMed:22573887, CC ECO:0000269|PubMed:24307990, ECO:0000269|PubMed:25974686, CC ECO:0000269|PubMed:26334369, ECO:0000269|PubMed:27152988, CC ECO:0000269|PubMed:27621083}. CC -!- INTERACTION: CC Self; NbExp=6; IntAct=EBI-2511344, EBI-2511344; CC B2R8Y4:-; NbExp=3; IntAct=EBI-2511344, EBI-10175581; CC P12814:ACTN1; NbExp=3; IntAct=EBI-2511344, EBI-351710; CC Q9H7E9:C8orf33; NbExp=3; IntAct=EBI-2511344, EBI-715389; CC Q9UJX2:CDC23; NbExp=5; IntAct=EBI-2511344, EBI-396137; CC O60716-29:CTNND1; NbExp=3; IntAct=EBI-2511344, EBI-702059; CC Q13618:CUL3; NbExp=6; IntAct=EBI-2511344, EBI-456129; CC Q08426:EHHADH; NbExp=3; IntAct=EBI-2511344, EBI-2339219; CC Q9H5Z6:FAM124B; NbExp=3; IntAct=EBI-2511344, EBI-741626; CC Q0D2H9:GOLGA8DP; NbExp=3; IntAct=EBI-2511344, EBI-10181276; CC Q08AF8:GOLGA8G; NbExp=3; IntAct=EBI-2511344, EBI-10181260; CC Q14451:GRB7; NbExp=3; IntAct=EBI-2511344, EBI-970191; CC P57764:GSDMD; NbExp=5; IntAct=EBI-2511344, EBI-2798865; CC Q8TBB1:LNX1; NbExp=3; IntAct=EBI-2511344, EBI-739832; CC Q13427:PPIG; NbExp=3; IntAct=EBI-2511344, EBI-396072; CC Q8WWY3:PRPF31; NbExp=8; IntAct=EBI-2511344, EBI-1567797; CC P25786:PSMA1; NbExp=4; IntAct=EBI-2511344, EBI-359352; CC O00560:SDCBP; NbExp=5; IntAct=EBI-2511344, EBI-727004; CC Q8TBK6:ZCCHC10; NbExp=3; IntAct=EBI-2511344, EBI-597063; CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, M line CC {ECO:0000269|PubMed:22573887}. Note=Colocalizes with ANK1 isoform CC Mu17 at the M line in differentiated skeletal muscle cells and CC heart. {ECO:0000269|PubMed:22573887}. CC -!- TISSUE SPECIFICITY: Highly expressed in cerebellum and brain. CC Expression is down-regulated in medulloblastoma. CC {ECO:0000269|PubMed:21472142}. 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; AK027572; BAG51347.1; -; mRNA. DR EMBL; AK074934; BAC11301.1; -; mRNA. DR EMBL; AK075297; BAC11531.1; -; mRNA. DR EMBL; CH471055; EAW65374.1; -; Genomic_DNA. DR EMBL; BC022893; AAH22893.2; -; mRNA. DR CCDS; CCDS2891.1; -. DR RefSeq; NP_001121686.1; NM_001128214.1. DR RefSeq; NP_699162.3; NM_153331.3. DR RefSeq; XP_005264994.1; XM_005264937.2. DR UniGene; Hs.13982; -. DR ProteinModelPortal; Q8NC69; -. DR SMR; Q8NC69; -. DR BioGrid; 128350; 41. DR IntAct; Q8NC69; 35. DR MINT; Q8NC69; -. DR STRING; 9606.ENSP00000347188; -. DR iPTMnet; Q8NC69; -. DR PhosphoSitePlus; Q8NC69; -. DR BioMuta; KCTD6; -. DR DMDM; 115502243; -. DR EPD; Q8NC69; -. DR MaxQB; Q8NC69; -. DR PaxDb; Q8NC69; -. DR PeptideAtlas; Q8NC69; -. DR PRIDE; Q8NC69; -. DR ProteomicsDB; 72859; -. DR DNASU; 200845; -. DR Ensembl; ENST00000355076; ENSP00000347188; ENSG00000168301. DR Ensembl; ENST00000404589; ENSP00000384948; ENSG00000168301. DR Ensembl; ENST00000490264; ENSP00000417490; ENSG00000168301. DR GeneID; 200845; -. DR KEGG; hsa:200845; -. DR UCSC; uc003dkj.5; human. DR CTD; 200845; -. DR DisGeNET; 200845; -. DR EuPathDB; HostDB:ENSG00000168301.12; -. DR GeneCards; KCTD6; -. DR HGNC; HGNC:22235; KCTD6. DR HPA; HPA036100; -. DR HPA; HPA036101; -. DR neXtProt; NX_Q8NC69; -. DR OpenTargets; ENSG00000168301; -. DR PharmGKB; PA134918095; -. DR eggNOG; KOG2723; Eukaryota. DR eggNOG; ENOG410Z155; LUCA. DR GeneTree; ENSGT00760000119013; -. DR HOGENOM; HOG000236287; -. DR HOVERGEN; HBG080695; -. DR InParanoid; Q8NC69; -. DR KO; K21916; -. DR OMA; NFTKWNK; -. DR OrthoDB; EOG091G0FYS; -. DR PhylomeDB; Q8NC69; -. DR TreeFam; TF315332; -. DR Reactome; R-HSA-8931987; RUNX1 regulates estrogen receptor mediated transcription. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR GenomeRNAi; 200845; -. DR PRO; PR:Q8NC69; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; ENSG00000168301; Expressed in 203 organ(s), highest expression level in female gonad. DR CleanEx; HS_KCTD6; -. DR ExpressionAtlas; Q8NC69; baseline and differential. DR Genevisible; Q8NC69; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0031430; C:M band; IEA:UniProtKB-SubCell. DR GO; GO:0030506; F:ankyrin binding; IDA:MGI. DR GO; GO:0097602; F:cullin family protein binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW. DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; TAS:Reactome. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR InterPro; IPR003131; T1-type_BTB. DR Pfam; PF02214; BTB_2; 1. DR SMART; SM00225; BTB; 1. DR SUPFAM; SSF54695; SSF54695; 1. PE 1: Evidence at protein level; KW Complete proteome; Cytoplasm; Growth regulation; Reference proteome; KW Tumor suppressor; Ubl conjugation pathway. FT CHAIN 1 237 BTB/POZ domain-containing protein KCTD6. FT /FTId=PRO_0000251248. FT DOMAIN 12 81 BTB. FT REGION 1 104 Interaction with ANK1 isoform Mu17. FT {ECO:0000269|PubMed:22573887}. FT REGION 10 110 Interaction with CUL3. FT {ECO:0000269|PubMed:25974686}. FT REGION 113 187 Interaction with USP21. FT {ECO:0000269|PubMed:27621083}. FT CONFLICT 49 49 A -> T (in Ref. 2; BAC11531). FT {ECO:0000305}. FT CONFLICT 59 59 D -> N (in Ref. 2; BAC11531). FT {ECO:0000305}. SQ SEQUENCE 237 AA; 27610 MW; 6358D9993DD060ED CRC64; MDNGDWGYMM TDPVTLNVGG HLYTTSLTTL TRYPDSMLGA MFGGDFPTAR DPQGNYFIDR DGPLFRYVLN FLRTSELTLP LDFKEFDLLR KEADFYQIEP LIQCLNDPKP LYPMDTFEEV VELSSTRKLS KYSNPVAVII TQLTITTKVH SLLEGISNYF TKWNKHMMDT RDCQVSFTFG PCDYHQEVSL RVHLMEYITK QGFTIRNTRV HHMSERANEN TVEHNWTFCR LARKTDD //