ID   KCD21_HUMAN             Reviewed;         260 AA.
AC   Q4G0X4; B4DTR0;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2005, sequence version 1.
DT   10-FEB-2021, entry version 112.
DE   RecName: Full=BTB/POZ domain-containing protein KCTD21;
DE   AltName: Full=KCASH2 protein {ECO:0000303|PubMed:21472142};
DE   AltName: Full=Potassium channel tetramerization domain-containing protein 21;
GN   Name=KCTD21;
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].
RC   TISSUE=Placenta;
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].
RC   TISSUE=Brain;
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   [3]
RP   SUBUNIT, FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF 85-ASP--TYR-87.
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
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. Can function as antagonist of the Hedgehog
CC       pathway by affecting the nuclear transfer of transcription factor GLI1;
CC       the function probably occurs via HDAC1 down-regulation, keeping GLI1
CC       acetylated and inactive. Inhibits cell growth and tumorigenicity of
CC       medulloblastoma (MDB) (PubMed:21472142). {ECO:0000269|PubMed:21472142}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Homopentamer (By similarity). Interacts with KCTD11; KCTD21
CC       and KCTD11 may associate in pentameric assemblies. Interacts (via BTB
CC       domain) with CUL3; indicative for a participation in a BCR (BTB-CUL3-
CC       RBX1) E3 ubiquitin-protein ligase complex (PubMed:21472142).
CC       {ECO:0000250|UniProtKB:Q693B1, ECO:0000250|UniProtKB:Q8NC69,
CC       ECO:0000269|PubMed:21472142, ECO:0000305}.
CC   -!- INTERACTION:
CC       Q4G0X4; Q8WYQ4-2: C22orf15; NbExp=3; IntAct=EBI-11976683, EBI-12030460;
CC       Q4G0X4; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-11976683, EBI-2872414;
CC       Q4G0X4; Q4G0X4: KCTD21; NbExp=4; IntAct=EBI-11976683, EBI-11976683;
CC       Q4G0X4; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-11976683, EBI-2341787;
CC       Q4G0X4; Q9NWW6: NMRK1; NbExp=3; IntAct=EBI-11976683, EBI-10315485;
CC       Q4G0X4; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-11976683, EBI-741158;
CC       Q4G0X4; O60437: PPL; NbExp=3; IntAct=EBI-11976683, EBI-368321;
CC       Q4G0X4; Q96BH1: RNF25; NbExp=3; IntAct=EBI-11976683, EBI-2129220;
CC       Q4G0X4; P61960: UFM1; NbExp=3; IntAct=EBI-11976683, EBI-1045061;
CC       Q4G0X4; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-11976683, EBI-746595;
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; AK300320; BAG62072.1; -; mRNA.
DR   EMBL; BC036058; AAH36058.1; -; mRNA.
DR   CCDS; CCDS31645.1; -.
DR   RefSeq; NP_001025030.1; NM_001029859.2.
DR   RefSeq; XP_005273985.1; XM_005273928.1.
DR   RefSeq; XP_006718580.1; XM_006718517.2.
DR   RefSeq; XP_006718581.1; XM_006718518.3.
DR   RefSeq; XP_011543257.1; XM_011544955.2.
DR   SMR; Q4G0X4; -.
DR   BioGRID; 129500; 24.
DR   IntAct; Q4G0X4; 20.
DR   STRING; 9606.ENSP00000339340; -.
DR   iPTMnet; Q4G0X4; -.
DR   PhosphoSitePlus; Q4G0X4; -.
DR   BioMuta; KCTD21; -.
DR   DMDM; 121943921; -.
DR   EPD; Q4G0X4; -.
DR   jPOST; Q4G0X4; -.
DR   MassIVE; Q4G0X4; -.
DR   MaxQB; Q4G0X4; -.
DR   PaxDb; Q4G0X4; -.
DR   PeptideAtlas; Q4G0X4; -.
DR   PRIDE; Q4G0X4; -.
DR   ProteomicsDB; 62137; -.
DR   Antibodypedia; 31300; 100 antibodies.
DR   Ensembl; ENST00000340067; ENSP00000339340; ENSG00000188997.
DR   GeneID; 283219; -.
DR   KEGG; hsa:283219; -.
DR   UCSC; uc001ozb.4; human.
DR   CTD; 283219; -.
DR   DisGeNET; 283219; -.
DR   GeneCards; KCTD21; -.
DR   HGNC; HGNC:27452; KCTD21.
DR   HPA; ENSG00000188997; Low tissue specificity.
DR   MIM; 618790; gene.
DR   neXtProt; NX_Q4G0X4; -.
DR   OpenTargets; ENSG00000188997; -.
DR   PharmGKB; PA145148689; -.
DR   VEuPathDB; HostDB:ENSG00000188997.7; -.
DR   eggNOG; KOG2723; Eukaryota.
DR   GeneTree; ENSGT00940000160906; -.
DR   HOGENOM; CLU_088122_0_0_1; -.
DR   InParanoid; Q4G0X4; -.
DR   OMA; QNIHFTV; -.
DR   OrthoDB; 1426852at2759; -.
DR   PhylomeDB; Q4G0X4; -.
DR   TreeFam; TF315332; -.
DR   PathwayCommons; Q4G0X4; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 283219; 8 hits in 873 CRISPR screens.
DR   ChiTaRS; KCTD21; human.
DR   GenomeRNAi; 283219; -.
DR   Pharos; Q4G0X4; Tbio.
DR   PRO; PR:Q4G0X4; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q4G0X4; protein.
DR   Bgee; ENSG00000188997; Expressed in substantia nigra and 205 other tissues.
DR   ExpressionAtlas; Q4G0X4; baseline and differential.
DR   Genevisible; Q4G0X4; HS.
DR   GO; GO:0097602; F:cullin family protein binding; IDA:UniProtKB.
DR   GO; GO:0042826; F:histone deacetylase 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   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.
DR   PROSITE; PS50097; BTB; 1.
PE   1: Evidence at protein level;
KW   Coiled coil; Growth regulation; Reference proteome; Tumor suppressor;
KW   Ubl conjugation pathway.
FT   CHAIN           1..260
FT                   /note="BTB/POZ domain-containing protein KCTD21"
FT                   /id="PRO_0000281151"
FT   DOMAIN          3..72
FT                   /note="BTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT   COILED          88..112
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        135..140
FT                   /note="Poly-Ser"
FT   MUTAGEN         85..87
FT                   /note="DFY->KKK: Abolishes interaction with CUL3."
FT                   /evidence="ECO:0000269|PubMed:21472142"
FT   CONFLICT        152
FT                   /note="S -> P (in Ref. 1; BAG62072)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   260 AA;  29643 MW;  E94BAD422C106070 CRC64;
     MSDPITLNVG GKLYTTSLAT LTSFPDSMLG AMFSGKMPTK RDSQGNCFID RDGKVFRYIL
     NFLRTSHLDL PEDFQEMGLL RREADFYQVQ PLIEALQEKE VELSKAEKNA MLNITLNQRV
     QTVHFTVREA PQIYSLSSSS MEVFNANIFS TSCLFLKLLG SKLFYCSNGN LSSITSHLQD
     PNHLTLDWVA NVEGLPEEEY TKQNLKRLWV VPANKQINSF QVFVEEVLKI ALSDGFCIDS
     SHPHALDFMN NKIIRLIRYR
//