KBTB7_HUMAN
ID KBTB7_HUMAN Reviewed; 684 AA.
AC Q8WVZ9; B5TZ86; Q5T6Y7; Q8NB99; Q9H0I6;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Kelch repeat and BTB domain-containing protein 7 {ECO:0000305};
GN Name=KBTBD7 {ECO:0000312|HGNC:HGNC:25266};
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].
RA Hu J., Peng X., Yang Z., Yuan W., Wang Y., Li Y., Wu X.;
RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
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 [4]
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 [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
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 Q8WVZ9; Q9BWC9: CCDC106; NbExp=3; IntAct=EBI-473695, EBI-711501;
CC Q8WVZ9; O95166: GABARAP; NbExp=2; IntAct=EBI-473695, EBI-712001;
CC Q8WVZ9; Q9H0R8: GABARAPL1; NbExp=6; IntAct=EBI-473695, EBI-746969;
CC Q8WVZ9; P60520: GABARAPL2; NbExp=3; IntAct=EBI-473695, EBI-720116;
CC Q8WVZ9; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-473695, EBI-2796400;
CC Q8WVZ9; Q9GZQ8: MAP1LC3B; NbExp=4; IntAct=EBI-473695, EBI-373144;
CC Q8WVZ9; Q9BXW4: MAP1LC3C; NbExp=2; IntAct=EBI-473695, EBI-2603996;
CC Q8WVZ9; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-473695, EBI-16439278;
CC Q8WVZ9; Q8IXK0: PHC2; NbExp=3; IntAct=EBI-473695, EBI-713786;
CC Q8WVZ9; P61289: PSME3; NbExp=3; IntAct=EBI-473695, EBI-355546;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:25684205}. Nucleus
CC {ECO:0000305|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:0000269|PubMed:25684205}.
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DR EMBL; AL136782; CAB66716.1; -; mRNA.
DR EMBL; FJ150424; ACH92650.1; -; mRNA.
DR EMBL; AK091344; BAC03641.1; -; mRNA.
DR EMBL; AL354696; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08647.1; -; Genomic_DNA.
DR EMBL; BC022033; AAH22033.1; -; mRNA.
DR CCDS; CCDS9377.1; -.
DR RefSeq; NP_115514.2; NM_032138.5.
DR AlphaFoldDB; Q8WVZ9; -.
DR SMR; Q8WVZ9; -.
DR BioGRID; 123873; 238.
DR IntAct; Q8WVZ9; 143.
DR MINT; Q8WVZ9; -.
DR STRING; 9606.ENSP00000368797; -.
DR iPTMnet; Q8WVZ9; -.
DR PhosphoSitePlus; Q8WVZ9; -.
DR BioMuta; KBTBD7; -.
DR DMDM; 45477155; -.
DR EPD; Q8WVZ9; -.
DR jPOST; Q8WVZ9; -.
DR MassIVE; Q8WVZ9; -.
DR MaxQB; Q8WVZ9; -.
DR PaxDb; Q8WVZ9; -.
DR PeptideAtlas; Q8WVZ9; -.
DR PRIDE; Q8WVZ9; -.
DR ProteomicsDB; 74839; -.
DR Antibodypedia; 23391; 159 antibodies from 22 providers.
DR DNASU; 84078; -.
DR Ensembl; ENST00000379483.4; ENSP00000368797.3; ENSG00000120696.9.
DR GeneID; 84078; -.
DR KEGG; hsa:84078; -.
DR MANE-Select; ENST00000379483.4; ENSP00000368797.3; NM_032138.7; NP_115514.2.
DR UCSC; uc001uxw.2; human.
DR CTD; 84078; -.
DR DisGeNET; 84078; -.
DR GeneCards; KBTBD7; -.
DR HGNC; HGNC:25266; KBTBD7.
DR HPA; ENSG00000120696; Low tissue specificity.
DR MIM; 617739; gene.
DR neXtProt; NX_Q8WVZ9; -.
DR OpenTargets; ENSG00000120696; -.
DR PharmGKB; PA134934036; -.
DR VEuPathDB; HostDB:ENSG00000120696; -.
DR eggNOG; ENOG502QWK2; Eukaryota.
DR GeneTree; ENSGT00940000155175; -.
DR HOGENOM; CLU_004253_15_1_1; -.
DR InParanoid; Q8WVZ9; -.
DR OMA; DLSSQDY; -.
DR OrthoDB; 292881at2759; -.
DR PhylomeDB; Q8WVZ9; -.
DR TreeFam; TF332672; -.
DR PathwayCommons; Q8WVZ9; -.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8WVZ9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 84078; 7 hits in 1119 CRISPR screens.
DR ChiTaRS; KBTBD7; human.
DR GeneWiki; KBTBD7; -.
DR GenomeRNAi; 84078; -.
DR Pharos; Q8WVZ9; Tdark.
DR PRO; PR:Q8WVZ9; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q8WVZ9; protein.
DR Bgee; ENSG00000120696; Expressed in secondary oocyte and 186 other tissues.
DR Genevisible; Q8WVZ9; HS.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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 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; 2.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Kelch repeat; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..684
FT /note="Kelch repeat and BTB domain-containing protein 7"
FT /id="PRO_0000119085"
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 REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..666
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 630..644
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 645..666
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MUTAGEN 99
FT /note="M->A: Loss of interaction with CUL3. Loss of
FT function in TIAM1 degradation."
FT /evidence="ECO:0000269|PubMed:25684205"
FT MUTAGEN 668..671
FT /note="WVQV->AVQA: 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."
FT /evidence="ECO:0000269|PubMed:25684205"
FT CONFLICT 361
FT /note="P -> S (in Ref. 2; CAB66716)"
FT /evidence="ECO:0000305"
FT CONFLICT 602
FT /note="L -> S (in Ref. 3; BAC03641)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="C -> Y (in Ref. 3; BAC03641)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 684 AA; 77163 MW; B2D8B6969A1AE5E9 CRC64;
MQSREDVPRS RRLASPRGGR RPKRISKPSV SAFFTGPEEL KDTAHSAALL AQLKSFYDAR
LLCDVTIEVV TPGSGPGTGR LFSCNRNVLA AACPYFKSMF TGGMYESQQA SVTMHDVDAE
SFEVLVDYCY TGRVSLSEAN VQRLYAASDM LQLEYVREAC ASFLARRLDL TNCTAILKFA
DAFDHHKLRS QAQSYIAHNF KQLSRMGSIR EETLADLTLA QLLAVLRLDS LDIESERTVC
HVAVQWLEAA AKERGPSAAE VFKCVRWMHF TEEDQDYLEG LLTKPIVKKY CLDVIEGALQ
MRYGDLLYKS LVPVPNSSSS SSSSNSLVSA AENPPQRLGM CAKEMVIFFG HPRDPFLCYD
PYSGDIYTMP SPLTSFAHTK TVTSSAVCVS PDHDIYLAAQ PRKDLWVYKP AQNSWQQLAD
RLLCREGMDV AYLNGYIYIL GGRDPITGVK LKEVECYSVQ RNQWALVAPV PHSFYSFELI
VVQNYLYAVN SKRMLCYDPS HNMWLNCASL KRSDFQEACV FNDEIYCICD IPVMKVYNPA
RGEWRRISNI PLDSETHNYQ IVNHDQKLLL ITSTTPQWKK NRVTVYEYDT REDQWINIGT
MLGLLQFDSG FICLCARVYP SCLEPGQSFI TEEDDARSES STEWDLDGFS ELDSESGSSS
SFSDDEVWVQ VAPQRNAQDQ QGSL
