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 24-JAN-2024, entry version 161. 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; Q8NFY9: KBTBD8; NbExp=4; IntAct=EBI-473695, EBI-21328977; 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}. 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; 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; 241. DR IntAct; Q8WVZ9; 145. 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; 9606-ENSP00000368797; -. DR PeptideAtlas; Q8WVZ9; -. DR ProteomicsDB; 74839; -. DR Pumba; Q8WVZ9; -. DR Antibodypedia; 23391; 184 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 AGR; HGNC:25266; -. 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; 5472491at2759; -. 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; 9 hits in 1199 CRISPR screens. DR ChiTaRS; KBTBD7; human. DR GeneWiki; KBTBD7; -. DR GenomeRNAi; 84078; -. DR Pharos; Q8WVZ9; Tbio. DR PRO; PR:Q8WVZ9; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q8WVZ9; Protein. DR Bgee; ENSG00000120696; Expressed in secondary oocyte and 188 other cell types or tissues. 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 CDD; cd18482; BACK_KBTBD6_7; 1. DR CDD; cd18273; BTB_POZ_KBTBD6_7; 1. DR Gene3D; 1.25.40.420; -; 1. DR Gene3D; 2.120.10.80; Kelch-type beta propeller; 1. DR InterPro; IPR011705; BACK. DR InterPro; IPR017096; BTB-kelch_protein. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR046790; KBTB_W-LIR. DR InterPro; IPR047931; KBTBD6_7_BACK. DR InterPro; IPR047933; KBTBD6_7_BTB_POZ. DR InterPro; IPR015915; Kelch-typ_b-propeller. DR InterPro; IPR006652; Kelch_1. DR InterPro; IPR011333; SKP1/BTB/POZ_sf. DR PANTHER; PTHR24412; KELCH PROTEIN; 1. DR PANTHER; PTHR24412:SF23; KELCH REPEAT AND BTB DOMAIN-CONTAINING PROTEIN 7; 1. DR Pfam; PF07707; BACK; 1. DR Pfam; PF00651; BTB; 1. DR Pfam; PF20165; KBTB_W-LIR; 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; Kelch motif; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR PROSITE; PS50097; BTB; 1. DR Genevisible; Q8WVZ9; HS. 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 //