KCD21_HUMAN
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 03-AUG-2022, entry version 118.
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}.
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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 AlphaFoldDB; Q4G0X4; -.
DR SMR; Q4G0X4; -.
DR BioGRID; 129500; 33.
DR IntAct; Q4G0X4; 21.
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; 101 antibodies from 19 providers.
DR DNASU; 283219; -.
DR Ensembl; ENST00000340067.4; ENSP00000339340.3; ENSG00000188997.8.
DR GeneID; 283219; -.
DR KEGG; hsa:283219; -.
DR MANE-Select; ENST00000340067.4; ENSP00000339340.3; NM_001029859.3; NP_001025030.1.
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; -.
DR eggNOG; KOG2723; Eukaryota.
DR GeneTree; ENSGT00940000160906; -.
DR HOGENOM; CLU_088122_0_0_1; -.
DR InParanoid; Q4G0X4; -.
DR OMA; SQGHCFI; -.
DR OrthoDB; 1426852at2759; -.
DR PhylomeDB; Q4G0X4; -.
DR TreeFam; TF315332; -.
DR PathwayCommons; Q4G0X4; -.
DR SignaLink; Q4G0X4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 283219; 15 hits in 1078 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 cardiac muscle of right atrium and 170 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 Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
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 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 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
