KCTD6_HUMAN
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 03-AUG-2022, entry version 137.
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}.
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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 AlphaFoldDB; Q8NC69; -.
DR SMR; Q8NC69; -.
DR BioGRID; 128350; 69.
DR CORUM; Q8NC69; -.
DR IntAct; Q8NC69; 43.
DR MINT; Q8NC69; -.
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 from 20 providers.
DR DNASU; 200845; -.
DR Ensembl; ENST00000355076.6; ENSP00000347188.6; ENSG00000168301.13.
DR Ensembl; ENST00000404589.8; ENSP00000384948.3; ENSG00000168301.13.
DR Ensembl; ENST00000490264.1; ENSP00000417490.1; ENSG00000168301.13.
DR GeneID; 200845; -.
DR KEGG; hsa:200845; -.
DR MANE-Select; ENST00000404589.8; ENSP00000384948.3; NM_001128214.2; NP_001121686.1.
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; PMDFTET; -.
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 SignaLink; Q8NC69; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 200845; 21 hits in 1081 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 pigmented layer of retina and 190 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
