KCD11_MOUSE
ID KCD11_MOUSE Reviewed; 232 AA.
AC Q8K485;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=BTB/POZ domain-containing protein KCTD11;
DE AltName: Full=KCASH1 protein {ECO:0000305};
DE AltName: Full=Potassium channel tetramerization domain-containing protein 11;
DE AltName: Full=RING-type E3 ubiquitin transferase subunit KCTD11 {ECO:0000305};
GN Name=Kctd11; Synonyms=Ren;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Swiss Webster;
RX PubMed=12186855; DOI=10.1083/jcb.200202024;
RA Gallo R., Zazzeroni F., Alesse E., Mincione C., Borello U., Buanne P.,
RA D'Eugenio R., Mackay A.R., Argenti B., Gradini R., Russo M.A., Maroder M.,
RA Cossu G., Frati L., Screpanti I., Gulino A.;
RT "REN: a novel, developmentally regulated gene that promotes neural cell
RT differentiation.";
RL J. Cell Biol. 158:731-740(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Head, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and 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 [4]
RP MISCELLANEOUS.
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, AND CHARACTERIZATION OF BTB DOMAIN.
RX PubMed=16148242; DOI=10.1523/jneurosci.2438-05.2005;
RA Argenti B., Gallo R., Di Marcotullio L., Ferretti E., Napolitano M.,
RA Canterini S., De Smaele E., Greco A., Fiorenza M.T., Maroder M.,
RA Screpanti I., Alesse E., Gulino A.;
RT "Hedgehog antagonist REN(KCTD11) regulates proliferation and apoptosis of
RT developing granule cell progenitors.";
RL J. Neurosci. 25:8338-8346(2005).
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 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.
CC {ECO:0000250|UniProtKB:Q693B1, ECO:0000269|PubMed:12186855,
CC ECO:0000269|PubMed:16148242}.
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:0000250|UniProtKB:Q693B1}.
CC -!- TISSUE SPECIFICITY: Weakly expressed in lung. In the cerebellum, higher
CC expression in non proliferating external granule cells layer than in
CC highly proliferating ones. {ECO:0000269|PubMed:12186855,
CC ECO:0000269|PubMed:16148242}.
CC -!- DEVELOPMENTAL STAGE: Detected at 7.5 dpc in neuroectodermal cells, and
CC later in neural crest, in ventral region of the spinal cord and in
CC ventricular epithelium of the neural tube.
CC {ECO:0000269|PubMed:12186855}.
CC -!- DOMAIN: The BTB domain is required for growth-suppressing properties.
CC -!- MISCELLANEOUS: Overexpression of Kctd11 by lentiviral vector injection
CC inhibits xenograft tumor growth in athymic nude mice.
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DR EMBL; AF465352; AAM95915.1; -; mRNA.
DR EMBL; AK039558; BAC30382.1; -; mRNA.
DR EMBL; AK161602; BAE36486.1; -; mRNA.
DR EMBL; AK170258; BAE41666.1; -; mRNA.
DR EMBL; BC052502; AAH52502.1; -; mRNA.
DR EMBL; BC052734; AAH52734.1; -; mRNA.
DR CCDS; CCDS24918.1; -.
DR RefSeq; NP_694783.1; NM_153143.4.
DR AlphaFoldDB; Q8K485; -.
DR SMR; Q8K485; -.
DR STRING; 10090.ENSMUSP00000059107; -.
DR PhosphoSitePlus; Q8K485; -.
DR PaxDb; Q8K485; -.
DR PRIDE; Q8K485; -.
DR ProteomicsDB; 269249; -.
DR Antibodypedia; 11945; 133 antibodies from 25 providers.
DR DNASU; 216858; -.
DR Ensembl; ENSMUST00000238978; ENSMUSP00000159163; ENSMUSG00000046731.
DR GeneID; 216858; -.
DR KEGG; mmu:216858; -.
DR UCSC; uc007jsd.2; mouse.
DR CTD; 147040; -.
DR MGI; MGI:2448712; Kctd11.
DR VEuPathDB; HostDB:ENSMUSG00000046731; -.
DR eggNOG; KOG2723; Eukaryota.
DR GeneTree; ENSGT00940000162799; -.
DR HOGENOM; CLU_088122_0_0_1; -.
DR InParanoid; Q8K485; -.
DR OrthoDB; 1051383at2759; -.
DR PhylomeDB; Q8K485; -.
DR TreeFam; TF315332; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 216858; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Kctd11; mouse.
DR PRO; PR:Q8K485; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8K485; protein.
DR Bgee; ENSMUSG00000046731; Expressed in lip and 202 other tissues.
DR ExpressionAtlas; Q8K485; baseline and differential.
DR Genevisible; Q8K485; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IDA:MGI.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:MGI.
DR GO; GO:0007399; P:nervous system development; IDA:MGI.
DR GO; GO:0014016; P:neuroblast differentiation; IDA:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IDA:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:MGI.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR045763; KCTD11/21_C.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF19329; KCTD11_21_C; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Developmental protein; Growth regulation; Reference proteome;
KW Transferase; Tumor suppressor; Ubl conjugation pathway.
FT CHAIN 1..232
FT /note="BTB/POZ domain-containing protein KCTD11"
FT /id="PRO_0000248592"
FT DOMAIN 1..49
FT /note="BTB"
SQ SEQUENCE 232 AA; 26300 MW; 993C1FFDE8D52943 CRC64;
MLGAMFRADT LMPANLNPQG DGHYFIDRDG KAFRHILNFL RLGRLDLPRG YGETALLKAE
ADFYQIRPLL DALRELEASR GTPASTAALL HADVDVSPRQ VHFSARRGPH HYELSSVQVD
TFRANLFCTD PECLAAMRNR FGVAIGDRAE GGPHFRLEWA SRPQELPEVE YQRLGLQPLW
TGGPEDRREV ANTPTFLEEV LRVALEHGFR LDSVFPDPED LLNSRSLRFV RH