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KBTB6_HUMAN
ID   KBTB6_HUMAN             Reviewed;         674 AA.
AC   Q86V97; Q5T6Y8; Q8N8L0; Q8NDM5; Q96MP6;
DT   15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 151.
DE   RecName: Full=Kelch repeat and BTB domain-containing protein 6 {ECO:0000305};
GN   Name=KBTBD6 {ECO:0000312|HGNC:HGNC:25340};
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=Brain;
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 GENOMIC DNA].
RX   PubMed=15057823; DOI=10.1038/nature02379;
RA   Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA   Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA   Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA   Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA   Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA   Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA   Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA   Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA   Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA   Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA   Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA   Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA   Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA   Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA   Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA   Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA   Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA   Rogers J., Ross M.T.;
RT   "The DNA sequence and analysis of human chromosome 13.";
RL   Nature 428:522-528(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Prostate;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 21-674.
RC   TISSUE=Brain;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [5] {ECO:0007744|PDB:4XC2}
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 663-673 IN COMPLEX WITH GABARAP,
RP   FUNCTION, PATHWAY, SUBUNIT, INTERACTION WITH GABARAP; GABARAPL1; GABARAPL2
RP   AND MAP1LC3B, SUBCELLULAR LOCATION, DOMAIN, MOTIF, AND MUTAGENESIS OF
RP   MET-99; 668-TRP--VAL-671 AND TRP-668.
RX   PubMed=25684205; DOI=10.1016/j.molcel.2014.12.040;
RA   Genau H.M., Huber J., Baschieri F., Akutsu M., Doetsch V., Farhan H.,
RA   Rogov V., Behrends C.;
RT   "CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to
RT   spatially restrict TIAM1-RAC1 signaling.";
RL   Mol. Cell 57:995-1010(2015).
CC   -!- FUNCTION: As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex
CC       functions as a substrate adapter for the RAC1 guanine exchange factor
CC       (GEF) TIAM1, mediating its 'Lys-48' ubiquitination and proteasomal
CC       degradation (PubMed:25684205). By controlling this ubiquitination,
CC       regulates RAC1 signal transduction and downstream biological processes
CC       including the organization of the cytoskeleton, cell migration and cell
CC       proliferation (PubMed:25684205). Ubiquitination of TIAM1 requires the
CC       membrane-associated protein GABARAP which may restrict locally the
CC       activity of the complex (PubMed:25684205).
CC       {ECO:0000269|PubMed:25684205}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000269|PubMed:25684205}.
CC   -!- SUBUNIT: Core component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase
CC       complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7),
CC       composed of CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205). Interacts
CC       with GABARAP; the interaction is direct and is required for the
CC       ubiquitination of TIAM1 (PubMed:25684205). Interacts with GABARAPL1,
CC       GABARAPL2 and MAP1LC3B; the interaction is direct (PubMed:25684205).
CC       {ECO:0000269|PubMed:25684205}.
CC   -!- INTERACTION:
CC       Q86V97; O95166: GABARAP; NbExp=3; IntAct=EBI-2514778, EBI-712001;
CC       Q86V97; Q9H0R8: GABARAPL1; NbExp=4; IntAct=EBI-2514778, EBI-746969;
CC       Q86V97; P60520: GABARAPL2; NbExp=2; IntAct=EBI-2514778, EBI-720116;
CC       Q86V97; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-2514778, EBI-373144;
CC       Q86V97; Q9BXW4: MAP1LC3C; NbExp=2; IntAct=EBI-2514778, EBI-2603996;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25684205}. Nucleus
CC       {ECO:0000269|PubMed:25684205}.
CC   -!- DOMAIN: The ATG8 interaction motif (AIM) mediates interaction with
CC       proteins of the ATG8 family including GABARAP.
CC       {ECO:0000269|PubMed:25684205}.
CC   -!- DOMAIN: The BTB domain is required for interaction with CUL3.
CC       {ECO:0000269|PubMed:25684205}.
CC   -!- DOMAIN: The Kelch repeats mediate interaction with TIAM1, a
CC       CUL3(KBTBD6/7) E3 ubiquitin ligase substrate.
CC       {ECO:0000250|UniProtKB:Q8WVZ9}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC04826.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR   EMBL; AK056633; BAB71238.1; -; mRNA.
DR   EMBL; AK096608; BAC04826.1; ALT_SEQ; mRNA.
DR   EMBL; AL354696; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC000560; AAH00560.1; -; mRNA.
DR   EMBL; BC051349; AAH51349.1; -; mRNA.
DR   EMBL; AL833839; CAD38699.1; -; mRNA.
DR   CCDS; CCDS9376.1; -.
DR   RefSeq; NP_690867.3; NM_152903.4.
DR   PDB; 4XC2; X-ray; 1.90 A; E/F/G/H=663-673.
DR   PDBsum; 4XC2; -.
DR   AlphaFoldDB; Q86V97; -.
DR   SMR; Q86V97; -.
DR   BioGRID; 124639; 136.
DR   IntAct; Q86V97; 35.
DR   MINT; Q86V97; -.
DR   STRING; 9606.ENSP00000368799; -.
DR   iPTMnet; Q86V97; -.
DR   PhosphoSitePlus; Q86V97; -.
DR   BioMuta; KBTBD6; -.
DR   DMDM; 45477125; -.
DR   EPD; Q86V97; -.
DR   jPOST; Q86V97; -.
DR   MassIVE; Q86V97; -.
DR   MaxQB; Q86V97; -.
DR   PaxDb; Q86V97; -.
DR   PeptideAtlas; Q86V97; -.
DR   PRIDE; Q86V97; -.
DR   ProteomicsDB; 69981; -.
DR   Antibodypedia; 23388; 66 antibodies from 13 providers.
DR   DNASU; 89890; -.
DR   Ensembl; ENST00000379485.2; ENSP00000368799.1; ENSG00000165572.8.
DR   GeneID; 89890; -.
DR   KEGG; hsa:89890; -.
DR   MANE-Select; ENST00000379485.2; ENSP00000368799.1; NM_152903.5; NP_690867.3.
DR   UCSC; uc001uxu.2; human.
DR   CTD; 89890; -.
DR   GeneCards; KBTBD6; -.
DR   HGNC; HGNC:25340; KBTBD6.
DR   HPA; ENSG00000165572; Low tissue specificity.
DR   MIM; 617738; gene.
DR   neXtProt; NX_Q86V97; -.
DR   OpenTargets; ENSG00000165572; -.
DR   PharmGKB; PA134955690; -.
DR   VEuPathDB; HostDB:ENSG00000165572; -.
DR   eggNOG; ENOG502QWK2; Eukaryota.
DR   GeneTree; ENSGT00940000155175; -.
DR   HOGENOM; CLU_004253_15_1_1; -.
DR   InParanoid; Q86V97; -.
DR   OMA; FISFDLM; -.
DR   OrthoDB; 292881at2759; -.
DR   PhylomeDB; Q86V97; -.
DR   TreeFam; TF332672; -.
DR   PathwayCommons; Q86V97; -.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q86V97; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 89890; 13 hits in 1115 CRISPR screens.
DR   GenomeRNAi; 89890; -.
DR   Pharos; Q86V97; Tdark.
DR   PRO; PR:Q86V97; -.
DR   Proteomes; UP000005640; Chromosome 13.
DR   RNAct; Q86V97; protein.
DR   Bgee; ENSG00000165572; Expressed in cortical plate and 180 other tissues.
DR   Genevisible; Q86V97; HS.
DR   GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0035020; P:regulation of Rac protein signal transduction; IMP:UniProtKB.
DR   GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR   Gene3D; 2.120.10.80; -; 1.
DR   Gene3D; 3.30.710.10; -; 1.
DR   InterPro; IPR011705; BACK.
DR   InterPro; IPR017096; BTB-kelch_protein.
DR   InterPro; IPR000210; BTB/POZ_dom.
DR   InterPro; IPR015915; Kelch-typ_b-propeller.
DR   InterPro; IPR006652; Kelch_1.
DR   InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR   Pfam; PF07707; BACK; 1.
DR   Pfam; PF00651; BTB; 1.
DR   Pfam; PF01344; Kelch_1; 1.
DR   PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR   SMART; SM00875; BACK; 1.
DR   SMART; SM00225; BTB; 1.
DR   SMART; SM00612; Kelch; 1.
DR   SUPFAM; SSF117281; SSF117281; 1.
DR   SUPFAM; SSF54695; SSF54695; 1.
DR   PROSITE; PS50097; BTB; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Kelch repeat; Nucleus; Reference proteome; Repeat;
KW   Signal transduction inhibitor; Unfolded protein response.
FT   CHAIN           1..674
FT                   /note="Kelch repeat and BTB domain-containing protein 6"
FT                   /id="PRO_0000119084"
FT   DOMAIN          63..138
FT                   /note="BTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT   REPEAT          386..435
FT                   /note="Kelch 1"
FT   REPEAT          436..484
FT                   /note="Kelch 2"
FT   REPEAT          486..523
FT                   /note="Kelch 3"
FT   REPEAT          524..564
FT                   /note="Kelch 4"
FT   REPEAT          567..616
FT                   /note="Kelch 5"
FT   REPEAT          642..673
FT                   /note="Kelch 6"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          631..674
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           668..671
FT                   /note="ATG8 interaction motif (AIM)"
FT                   /evidence="ECO:0000269|PubMed:25684205"
FT   COMPBIAS        643..665
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         99
FT                   /note="M->A: Loss of interaction with CUL3. Loss of
FT                   function in TIAM1 ubiquitination and degradation."
FT                   /evidence="ECO:0000269|PubMed:25684205"
FT   MUTAGEN         668..671
FT                   /note="WVRV->AVRA: Decreased interaction with GABARAP and
FT                   GABARAPL2. Loss of function in TIAM1 ubiquitination and
FT                   degradation. No effect on assembly of the CUL3(KBTBD6/7) E3
FT                   ubiquitin ligase complex."
FT                   /evidence="ECO:0000269|PubMed:25684205"
FT   MUTAGEN         668
FT                   /note="W->A: Decreased interaction with GABARAP and
FT                   GABARAPL2. Loss of function in TIAM1 ubiquitination and
FT                   degradation. No effect on assembly of the CUL3(KBTBD6/7) E3
FT                   ubiquitin ligase complex."
FT                   /evidence="ECO:0000269|PubMed:25684205"
FT   CONFLICT        61
FT                   /note="L -> Q (in Ref. 1; BAB71238)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   674 AA;  76138 MW;  5ED49AAEC6350CB5 CRC64;
     MQSREDAPRS RRLASPRGGK RPKKIHKPTV SAFFTGPEEL KDTAHSAALL AQLKSFYDAR
     LLCDVTIEVV TPGSGPGTGR LFPCNRNVLA AACPYFKSMF TGGMYESQQA SVTMHDVDAE
     SFEVLVDYCY TGRVSLSEAN VERLYAASDM LQLEYVREAC ASFLARRLDL TNCTAILKFA
     DAFGHRKLRS QAQSYIAQNF KQLSHMGSIR EETLADLTLA QLLAVLRLDS LDVESEQTVC
     HVAVQWLEAA PKERGPSAAE VFKCVRWMHF TEEDQDYLEG LLTKPIVKKY CLDVIEGALQ
     MRYGDLLYKS LVPVPNSSSS SSSSNSLVSA AENPPQRLGM CAKEMVIFFG HPRDPFLCCD
     PYSGDLYKVP SPLTCLAHTR TVTTLAVCIS PDHDIYLAAQ PRTDLWVYKP AQNSWQQLAD
     RLLCREGMDV AYLNGYIYIL GGRDPITGVK LKEVECYNVK RNQWALVAPL PHSFLSFDLM
     VIRDYLYALN SKRMFCYDPS HNMWLKCVSL KRNDFQEACV FNEEIYCICD IPVMKVYNPV
     RAEWRQMNNI PLVSETNNYR IIKHGQKLLL ITSRTPQWKK NRVTVYEYDI RGDQWINIGT
     TLGLLQFDSN FFCLSARVYP SCLEPGQSFL TEEEEIPSES STEWDLGGFS EPDSESGSSS
     SLSDDDFWVR VAPQ
 
 
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