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 29-SEP-2021, entry version 134. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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., 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]. 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-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP SUBUNIT, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=21472142; DOI=10.1593/neo.101630; RA De Smaele E., Di Marcotullio L., Moretti M., Pelloni M., Occhione M.A., RA Infante P., Cucchi D., Greco A., Pietrosanti L., Todorovic J., Coni S., RA Canettieri G., Ferretti E., Bei R., Maroder M., Screpanti I., Gulino A.; RT "Identification and characterization of KCASH2 and KCASH3, 2 novel Cullin3 RT adaptors suppressing histone deacetylase and Hedgehog activity in RT 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 (sAnk1.5) RT 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 KCTD RT 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 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 proteins RT 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., Prive G.G.; RT "Structural insights into KCTD protein assembly and CULLIN3 recognition."; RL J. Mol. Biol. 428:92-107(2016). RN [12] RP INTERACTION WITH USP11. RX PubMed=29293652; DOI=10.1371/journal.pone.0190513; RA Stockum A., Snijders A.P., Maertens G.N.; RT "USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle RT formation."; RL PLoS ONE 13:e0190513-e0190513(2018). CC -!- FUNCTION: Probable substrate-specific adapter of a BCR (BTB-CUL3-RBX1) CC E3 ubiquitin-protein ligase complex mediating the ubiquitination and CC subsequent proteasomal degradation of target proteins. Promotes the CC ubiquitination of HDAC1; the function seems to depend on KCTD11:KCTD6 CC oligomerization. Can function as antagonist of the Hedgehog pathway by CC affecting the nuclear transfer of transcription factor GLI1; the CC function probably occurs via HDAC1 down-regulation, keeping GLI1 CC acetylated and inactive. Inhibits cell growth and tumorigenicity of CC medulloblastoma (MDB) (PubMed:21472142). Involved in regulating protein CC levels of ANK1 isoform Mu17 probably implicating CUL3-dependent CC 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) with CC CUL3; initially a 4:4 stoichiometry has been reported, however, CC electron microscopy revealed pentameric states with a five-pointed CC pinwheel shape. The interaction with CUL3 is indicative for a CC participation in a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase CC complex. Interacts with HDAC1; probably indirect as the interaction is CC requires the presence of KCTD11 (PubMed:21472142, PubMed:24307990, CC PubMed:25974686, PubMed:27152988). Interacts with USP21 (preferentially CC catalytic inactive form) (PubMed:27621083). Interacts with ANK1 isoform CC Mu17; detected in striated muscle (PubMed:22573887). Interacts with CC USP11 (PubMed:29293652). {ECO:0000269|PubMed:21472142, CC ECO:0000269|PubMed:22573887, ECO:0000269|PubMed:24307990, CC ECO:0000269|PubMed:25974686, ECO:0000269|PubMed:26334369, CC ECO:0000269|PubMed:27152988, ECO:0000269|PubMed:27621083, CC ECO:0000269|PubMed:29293652}. CC -!- INTERACTION: CC Q8NC69; P12814: ACTN1; NbExp=3; IntAct=EBI-2511344, EBI-351710; CC Q8NC69; O95429: BAG4; NbExp=3; IntAct=EBI-2511344, EBI-2949658; CC Q8NC69; Q9H7E9: C8orf33; NbExp=3; IntAct=EBI-2511344, EBI-715389; CC Q8NC69; Q9UJX2: CDC23; NbExp=6; IntAct=EBI-2511344, EBI-396137; CC Q8NC69; O60716-5: CTNND1; NbExp=3; IntAct=EBI-2511344, EBI-701963; CC Q8NC69; O60716-29: CTNND1; NbExp=3; IntAct=EBI-2511344, EBI-702059; CC Q8NC69; Q13618: CUL3; NbExp=11; IntAct=EBI-2511344, EBI-456129; CC Q8NC69; Q08426: EHHADH; NbExp=5; IntAct=EBI-2511344, EBI-2339219; CC Q8NC69; Q9H5Z6: FAM124B; NbExp=3; IntAct=EBI-2511344, EBI-741626; CC Q8NC69; Q0D2H9: GOLGA8DP; NbExp=3; IntAct=EBI-2511344, EBI-10181276; CC Q8NC69; Q08AF8: GOLGA8G; NbExp=3; IntAct=EBI-2511344, EBI-10181260; CC Q8NC69; Q14451: GRB7; NbExp=3; IntAct=EBI-2511344, EBI-970191; CC Q8NC69; Q14451-3: GRB7; NbExp=3; IntAct=EBI-2511344, EBI-11991632; CC Q8NC69; P57764: GSDMD; NbExp=7; IntAct=EBI-2511344, EBI-2798865; CC Q8NC69; Q8NC69: KCTD6; NbExp=9; IntAct=EBI-2511344, EBI-2511344; CC Q8NC69; Q8TBB1: LNX1; NbExp=4; IntAct=EBI-2511344, EBI-739832; CC Q8NC69; P00540: MOS; NbExp=3; IntAct=EBI-2511344, EBI-1757866; CC Q8NC69; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-2511344, EBI-741158; CC Q8NC69; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-2511344, EBI-79165; CC Q8NC69; Q13427: PPIG; NbExp=3; IntAct=EBI-2511344, EBI-396072; CC Q8NC69; Q8WWY3: PRPF31; NbExp=10; IntAct=EBI-2511344, EBI-1567797; CC Q8NC69; P25786: PSMA1; NbExp=6; IntAct=EBI-2511344, EBI-359352; CC Q8NC69; Q04864-2: REL; NbExp=3; IntAct=EBI-2511344, EBI-10829018; CC Q8NC69; O00560: SDCBP; NbExp=6; IntAct=EBI-2511344, EBI-727004; CC Q8NC69; Q9BYX2-5: TBC1D2; NbExp=3; IntAct=EBI-2511344, EBI-13560915; CC Q8NC69; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-2511344, EBI-11955057; CC Q8NC69; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-2511344, EBI-11139477; CC Q8NC69; Q8TBK6: ZCCHC10; NbExp=3; IntAct=EBI-2511344, EBI-597063; CC Q8NC69; B2R8Y4; NbExp=3; IntAct=EBI-2511344, EBI-10175581; CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, M line CC {ECO:0000269|PubMed:22573887}. Note=Colocalizes with ANK1 isoform Mu17 CC at the M line in differentiated skeletal muscle cells and heart. CC {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 SMR; Q8NC69; -. DR BioGRID; 128350; 55. DR CORUM; Q8NC69; -. DR IntAct; Q8NC69; 43. DR STRING; 9606.ENSP00000347188; -. DR iPTMnet; Q8NC69; -. DR PhosphoSitePlus; Q8NC69; -. DR BioMuta; KCTD6; -. DR DMDM; 115502243; -. DR EPD; Q8NC69; -. DR MassIVE; Q8NC69; -. DR MaxQB; Q8NC69; -. DR PaxDb; Q8NC69; -. DR PeptideAtlas; Q8NC69; -. DR PRIDE; Q8NC69; -. DR ProteomicsDB; 72859; -. DR Antibodypedia; 15221; 146 antibodies. 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 GeneCards; KCTD6; -. DR HGNC; HGNC:22235; KCTD6. DR HPA; ENSG00000168301; Low tissue specificity. DR MIM; 618791; gene. DR neXtProt; NX_Q8NC69; -. DR OpenTargets; ENSG00000168301; -. DR PharmGKB; PA134918095; -. DR VEuPathDB; HostDB:ENSG00000168301; -. DR eggNOG; KOG2723; Eukaryota. DR GeneTree; ENSGT00940000157869; -. DR HOGENOM; CLU_070345_1_0_1; -. DR InParanoid; Q8NC69; -. DR OMA; THPVTLN; -. DR OrthoDB; 1426852at2759; -. DR PhylomeDB; Q8NC69; -. DR TreeFam; TF315332; -. DR PathwayCommons; Q8NC69; -. 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 BioGRID-ORCS; 200845; 14 hits in 1017 CRISPR screens. DR ChiTaRS; KCTD6; human. DR GenomeRNAi; 200845; -. DR Pharos; Q8NC69; Tbio. DR PRO; PR:Q8NC69; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q8NC69; protein. DR Bgee; ENSG00000168301; Expressed in female gonad and 215 other tissues. 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: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:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR Gene3D; 3.30.710.10; -; 1. 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 Cytoplasm; Growth regulation; Reference proteome; Tumor suppressor; KW Ubl conjugation pathway. FT CHAIN 1..237 FT /note="BTB/POZ domain-containing protein KCTD6" FT /id="PRO_0000251248" FT DOMAIN 12..81 FT /note="BTB" FT REGION 1..104 FT /note="Interaction with ANK1 isoform Mu17" FT /evidence="ECO:0000269|PubMed:22573887" FT REGION 10..110 FT /note="Interaction with CUL3" FT /evidence="ECO:0000269|PubMed:25974686" FT REGION 113..187 FT /note="Interaction with USP21" FT /evidence="ECO:0000269|PubMed:27621083" FT CONFLICT 49 FT /note="A -> T (in Ref. 2; BAC11531)" FT /evidence="ECO:0000305" FT CONFLICT 59 FT /note="D -> N (in Ref. 2; BAC11531)" FT /evidence="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 //