ID KCD11_HUMAN Reviewed; 232 AA.
AC Q693B1; B3KPE0;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 27-MAR-2024, entry version 146.
DE RecName: Full=BTB/POZ domain-containing protein KCTD11;
DE AltName: Full=KCASH1 protein {ECO:0000303|PubMed:21472142};
DE AltName: Full=Potassium channel tetramerization domain-containing protein 11;
DE AltName: Full=RING-type E3 ubiquitin transferase subunit KCTD11 {ECO:0000303|PubMed:20081843};
GN Name=KCTD11; Synonyms=C17orf36, REN;
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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP CHARACTERIZATION OF BTB DOMAIN, AND ROLE IN MEDULLOBLASTOMA DEVELOPMENT.
RX PubMed=15249678; DOI=10.1073/pnas.0400690101;
RA Di Marcotullio L., Ferretti E., De Smaele E., Argenti B., Mincione C.,
RA Zazzeroni F., Gallo R., Masuelli L., Napolitano M., Maroder M., Modesti A.,
RA Giangaspero F., Screpanti I., Alesse E., Gulino A.;
RT "REN(KCTD11) is a suppressor of Hedgehog signaling and is deleted in human
RT medulloblastoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10833-10838(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ALTERNATIVE INITIATION,
RP USE OF A NON-AUG INITIATOR START CODON, SUBUNIT, AND INTERACTION WITH CUL3.
RX PubMed=21237243; DOI=10.1016/j.biochi.2010.12.014;
RA Correale S., Pirone L., Di Marcotullio L., De Smaele E., Greco A.,
RA Mazza D., Moretti M., Alterio V., Vitagliano L., Di Gaetano S., Gulino A.,
RA Pedone E.M.;
RT "Molecular organization of the cullin E3 ligase adaptor KCTD11.";
RL Biochimie 93:715-724(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP FUNCTION IN UBIQUITINATION OF HDAC1.
RX PubMed=20081843; DOI=10.1038/ncb2013;
RA Canettieri G., Di Marcotullio L., Greco A., Coni S., Antonucci L.,
RA Infante P., Pietrosanti L., De Smaele E., Ferretti E., Miele E.,
RA Pelloni M., De Simone G., Pedone E.M., Gallinari P., Giorgi A.,
RA Steinkuhler C., Vitagliano L., Pedone C., Schinin M.E., Screpanti I.,
RA Gulino A.;
RT "Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay
RT regulates Hedgehog signalling through Gli acetylation.";
RL Nat. Cell Biol. 12:132-142(2010).
RN [7]
RP SUBUNIT.
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 [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 OLIGOMERIZED BTB DOMAIN.
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).
CC -!- FUNCTION: Plays a role as a marker and a regulator of neuronal
CC differentiation; Up-regulated by a variety of neurogenic signals, such
CC as retinoic acid, epidermal growth factor/EGF and NGFB/nerve growth
CC factor. Induces apoptosis, growth arrest and the expression of cyclin-
CC dependent kinase inhibitor CDKN1B. Plays a role as a tumor repressor
CC and inhibits cell growth and tumorigenicity of medulloblastoma (MDB).
CC Acts as a probable substrate-specific adapter for a BCR (BTB-CUL3-RBX1)
CC E3 ubiquitin-protein ligase complex towards HDAC1. Functions as
CC antagonist of the Hedgehog pathway on cell proliferation and
CC differentiation by affecting the nuclear transfer of transcription
CC factor GLI1, thus maintaining cerebellar granule cells in
CC undifferentiated state, this effect probably occurs via HDAC1 down-
CC regulation, keeping GLI1 acetylated and inactive. When knock-down,
CC Hedgehog antagonism is impaired and proliferation of granule cells is
CC sustained. Activates the caspase cascade. {ECO:0000269|PubMed:15249678,
CC ECO:0000269|PubMed:20081843, ECO:0000269|PubMed:21237243}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homopentamer. Interacts with KCTD6 and KCTD21; KCTD11 and
CC KCTD6 or KCTD21 may associate in pentameric assemblies. Component of
CC the BCR(KCTD11) E3 ubiquitin ligase complex, at least composed of CUL3
CC and KCTD11 and RBX1. Interacts (via BTB domain) with CUL3; initially a
CC 4:4 stoichiometry has been reported, however, electron microscopy
CC revealed pentameric states of the BTB domain.
CC {ECO:0000269|PubMed:21237243, ECO:0000269|PubMed:21472142,
CC ECO:0000269|PubMed:25974686, ECO:0000269|PubMed:27152988}.
CC -!- INTERACTION:
CC Q693B1; Q693B1: KCTD11; NbExp=2; IntAct=EBI-12552177, EBI-12552177;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=sKCTD11;
CC IsoId=Q693B1-1; Sequence=Displayed;
CC Name=2; Synonyms=lKCTD11;
CC IsoId=Q693B1-2; Sequence=VSP_044086;
CC -!- TISSUE SPECIFICITY: Higher expression in cerebellum than in whole brain
CC and lower expression in medulloblastoma. {ECO:0000269|PubMed:15249678}.
CC -!- DOMAIN: The BTB domain is required for growth-suppressing properties.
CC -!- MISCELLANEOUS: Haploinsufficiency of KCTD11 may be a cause of
CC development of medulloblastoma (MDB). MDB is a malignant, invasive
CC embryonal tumor of the cerebellum with a preferential manifestation in
CC children. An allelic deletion involving genes from chromosome region
CC 17p11.2-pter, sometimes restricted to 17p13.2-13.3, occurs in up to 50%
CC of MDB.
CC -!- MISCELLANEOUS: [Isoform 2]: Non-AUG start codon. {ECO:0000305}.
CC -!- CAUTION: A N-terminal fragment of KCTD11 isoform 2 (comprising residues
CC 15 - 115) has been used for some KCTD11:CUL3 interaction studies.
CC {ECO:0000269|PubMed:25974686}.
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; AY646650; AAT75307.1; -; mRNA.
DR EMBL; AK056227; BAG51652.1; -; mRNA.
DR EMBL; CH471108; EAW90208.1; -; Genomic_DNA.
DR EMBL; BC110598; AAI10599.1; -; mRNA.
DR CCDS; CCDS32545.1; -. [Q693B1-1]
DR CCDS; CCDS92247.1; -. [Q693B1-2]
DR RefSeq; NP_001002914.1; NM_001002914.2. [Q693B1-1]
DR AlphaFoldDB; Q693B1; -.
DR SMR; Q693B1; -.
DR BioGRID; 127031; 7.
DR CORUM; Q693B1; -.
DR IntAct; Q693B1; 2.
DR MINT; Q693B1; -.
DR STRING; 9606.ENSP00000495203; -.
DR BindingDB; Q693B1; -.
DR ChEMBL; CHEMBL4630837; -.
DR iPTMnet; Q693B1; -.
DR PhosphoSitePlus; Q693B1; -.
DR BioMuta; KCTD11; -.
DR DMDM; 74708977; -.
DR MassIVE; Q693B1; -.
DR PaxDb; 9606-ENSP00000328352; -.
DR PeptideAtlas; Q693B1; -.
DR ProteomicsDB; 66150; -. [Q693B1-1]
DR Antibodypedia; 11945; 151 antibodies from 25 providers.
DR DNASU; 147040; -.
DR Ensembl; ENST00000333751.8; ENSP00000328352.5; ENSG00000213859.8. [Q693B1-2]
DR Ensembl; ENST00000576980.2; ENSP00000495203.1; ENSG00000213859.8. [Q693B1-1]
DR Ensembl; ENST00000672140.1; ENSP00000500224.1; ENSG00000288399.2. [Q693B1-1]
DR Ensembl; ENST00000673447.2; ENSP00000500427.2; ENSG00000288399.2. [Q693B1-2]
DR GeneID; 147040; -.
DR KEGG; hsa:147040; -.
DR MANE-Select; ENST00000333751.8; ENSP00000328352.5; NM_001363642.1; NP_001350571.1. [Q693B1-2]
DR UCSC; uc002gge.5; human. [Q693B1-1]
DR AGR; HGNC:21302; -.
DR DisGeNET; 147040; -.
DR GeneCards; KCTD11; -.
DR HGNC; HGNC:21302; KCTD11.
DR HPA; ENSG00000213859; Low tissue specificity.
DR MIM; 609848; gene.
DR neXtProt; NX_Q693B1; -.
DR OpenTargets; ENSG00000213859; -.
DR PharmGKB; PA134890547; -.
DR VEuPathDB; HostDB:ENSG00000213859; -.
DR eggNOG; KOG2723; Eukaryota.
DR GeneTree; ENSGT00940000162799; -.
DR HOGENOM; CLU_088122_0_0_1; -.
DR InParanoid; Q693B1; -.
DR OMA; FRLEWAP; -.
DR OrthoDB; 2912088at2759; -.
DR PhylomeDB; Q693B1; -.
DR TreeFam; TF315332; -.
DR PathwayCommons; Q693B1; -.
DR SignaLink; Q693B1; -.
DR SIGNOR; Q693B1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 147040; 13 hits in 1155 CRISPR screens.
DR GenomeRNAi; 147040; -.
DR Pharos; Q693B1; Tchem.
DR PRO; PR:Q693B1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q693B1; Protein.
DR Bgee; ENSG00000213859; Expressed in lower esophagus mucosa and 97 other cell types or tissues.
DR ExpressionAtlas; Q693B1; baseline and differential.
DR Genevisible; Q693B1; HS.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR InterPro; IPR045763; KCTD11/21_C.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR PANTHER; PTHR14499:SF7; BTB_POZ DOMAIN-CONTAINING PROTEIN KCTD11; 1.
DR PANTHER; PTHR14499; POTASSIUM CHANNEL TETRAMERIZATION DOMAIN-CONTAINING; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF19329; KCTD11_21_C; 1.
DR SUPFAM; SSF54695; POZ domain; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Cell cycle; Developmental protein;
KW Growth regulation; Reference proteome; Transferase; Tumor suppressor;
KW Ubl conjugation pathway.
FT CHAIN 1..232
FT /note="BTB/POZ domain-containing protein KCTD11"
FT /id="PRO_0000248591"
FT DOMAIN 1..49
FT /note="BTB"
FT VAR_SEQ 1
FT /note="M -> MSPPPVPSSPPSFGGPVTLNVGGTLYSTTLETLTRFPDSM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:21237243"
FT /id="VSP_044086"
FT VARIANT 22
FT /note="G -> S (in dbSNP:rs8080182)"
FT /id="VAR_027354"
SQ SEQUENCE 232 AA; 25887 MW; 7F075902E4259B2D CRC64;
MLGAMFRAGT PMPPNLNSQG GGHYFIDRDG KAFRHILNFL RLGRLDLPRG YGETALLRAE
ADFYQIRPLL DALRELEASQ GTPAPTAALL HADVDVSPRL VHFSARRGPH HYELSSVQVD
TFRANLFCTD SECLGALRAR FGVASGDRAE GSPHFHLEWA PRPVELPEVE YGRLGLQPLW
TGGPGERREV VGTPSFLEEV LRVALEHGFR LDSVFPDPED LLNSRSLRFV RH
//
