KBTB8_HUMAN
ID KBTB8_HUMAN Reviewed; 601 AA.
AC Q8NFY9; B4DTW6; Q96JI5;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Kelch repeat and BTB domain-containing protein 8;
DE AltName: Full=T-cell activation kelch repeat protein;
DE Short=TA-KRP;
GN Name=KBTBD8; Synonyms=KIAA1842, TAKRP;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Fetal brain, and 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 GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-601 (ISOFORM 1).
RC TISSUE=T-cell;
RA Mao M., Biery M.C., Kobayashi S.V., Schimmack G.A., Ward T.R.,
RA Schelter J.M., Burchard J., He Y.D., Dai H., Leonardson A., Coffey E.,
RA Stoughton R., Linsley P.S.;
RT "T lymphocyte activation gene discovery using ink-jet microarrays.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-601 (ISOFORM 1).
RC TISSUE=Lung;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 76-575 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [6]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=23578279; DOI=10.1186/1747-1028-8-3;
RA Luhrig S., Kolb S., Mellies N., Nolte J.;
RT "The novel BTB-kelch protein, KBTBD8, is located in the Golgi apparatus and
RT translocates to the spindle apparatus during mitosis.";
RL Cell Div. 8:3-3(2013).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-198 AND LYS-405.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [9]
RP FUNCTION, IDENTIFICATION IN THE BCR(KBTBD8) COMPLEX, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF TYR-74 AND TRP-579.
RX PubMed=26399832; DOI=10.1038/nature14978;
RA Werner A., Iwasaki S., McGourty C.A., Medina-Ruiz S., Teerikorpi N.,
RA Fedrigo I., Ingolia N.T., Rape M.;
RT "Cell-fate determination by ubiquitin-dependent regulation of
RT translation.";
RL Nature 525:523-527(2015).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex that acts as a regulator of neural crest
CC specification (PubMed:26399832). The BCR(KBTBD8) complex acts by
CC mediating monoubiquitination of NOLC1 and TCOF1: monoubiquitination
CC promotes the formation of a NOLC1-TCOF1 complex that acts as a platform
CC to connect RNA polymerase I with enzymes responsible for ribosomal
CC processing and modification, leading to remodel the translational
CC program of differentiating cells in favor of neural crest specification
CC (PubMed:26399832). {ECO:0000269|PubMed:26399832}.
CC -!- SUBUNIT: Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at
CC least composed of CUL3, KBTBD8 and RBX1 (PubMed:26399832).
CC {ECO:0000269|PubMed:26399832}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:23578279}. Golgi apparatus
CC {ECO:0000269|PubMed:23578279}. Note=Translocates to the spindle
CC apparatus during mitosis. {ECO:0000269|PubMed:23578279}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NFY9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NFY9-2; Sequence=VSP_056107;
CC -!- DEVELOPMENTAL STAGE: Down-regulated in differentiating embryonic stem
CC cells (ESCs) (at protein level). {ECO:0000269|PubMed:26399832}.
CC -!- SIMILARITY: Belongs to the KBTBD8 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI17488.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAM43839.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK096640; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK300397; BAG62128.1; -; mRNA.
DR EMBL; AC020655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF385438; AAM43839.1; ALT_INIT; mRNA.
DR EMBL; BC117487; AAI17488.1; ALT_INIT; mRNA.
DR EMBL; AB058745; BAB47471.1; -; mRNA.
DR CCDS; CCDS2906.2; -. [Q8NFY9-1]
DR RefSeq; NP_115894.2; NM_032505.2. [Q8NFY9-1]
DR AlphaFoldDB; Q8NFY9; -.
DR SMR; Q8NFY9; -.
DR BioGRID; 124128; 19.
DR IntAct; Q8NFY9; 5.
DR STRING; 9606.ENSP00000401878; -.
DR iPTMnet; Q8NFY9; -.
DR PhosphoSitePlus; Q8NFY9; -.
DR BioMuta; KBTBD8; -.
DR DMDM; 126215728; -.
DR EPD; Q8NFY9; -.
DR MassIVE; Q8NFY9; -.
DR MaxQB; Q8NFY9; -.
DR PaxDb; Q8NFY9; -.
DR PeptideAtlas; Q8NFY9; -.
DR PRIDE; Q8NFY9; -.
DR ProteomicsDB; 5133; -.
DR ProteomicsDB; 73392; -. [Q8NFY9-1]
DR Antibodypedia; 51228; 70 antibodies from 15 providers.
DR DNASU; 84541; -.
DR Ensembl; ENST00000417314.2; ENSP00000401878.2; ENSG00000163376.11. [Q8NFY9-1]
DR Ensembl; ENST00000460576.5; ENSP00000419738.1; ENSG00000163376.11. [Q8NFY9-2]
DR GeneID; 84541; -.
DR KEGG; hsa:84541; -.
DR MANE-Select; ENST00000417314.2; ENSP00000401878.2; NM_032505.3; NP_115894.2.
DR UCSC; uc003dmy.4; human. [Q8NFY9-1]
DR CTD; 84541; -.
DR DisGeNET; 84541; -.
DR GeneCards; KBTBD8; -.
DR HGNC; HGNC:30691; KBTBD8.
DR HPA; ENSG00000163376; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 616607; gene.
DR neXtProt; NX_Q8NFY9; -.
DR OpenTargets; ENSG00000163376; -.
DR PharmGKB; PA142671641; -.
DR VEuPathDB; HostDB:ENSG00000163376; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000158653; -.
DR HOGENOM; CLU_1660073_0_0_1; -.
DR InParanoid; Q8NFY9; -.
DR OMA; AAVYNDS; -.
DR OrthoDB; 398028at2759; -.
DR PhylomeDB; Q8NFY9; -.
DR TreeFam; TF332672; -.
DR PathwayCommons; Q8NFY9; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8NFY9; -.
DR BioGRID-ORCS; 84541; 8 hits in 1118 CRISPR screens.
DR ChiTaRS; KBTBD8; human.
DR GenomeRNAi; 84541; -.
DR Pharos; Q8NFY9; Tbio.
DR PRO; PR:Q8NFY9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8NFY9; protein.
DR Bgee; ENSG00000163376; Expressed in secondary oocyte and 159 other tissues.
DR ExpressionAtlas; Q8NFY9; baseline and differential.
DR Genevisible; Q8NFY9; HS.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0014032; P:neural crest cell development; IMP:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; 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; IPR028764; KBTBD8.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF433; PTHR24412:SF433; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 3.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 3.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Cytoskeleton; Golgi apparatus;
KW Kelch repeat; Reference proteome; Repeat; Translation regulation;
KW Ubl conjugation pathway.
FT CHAIN 1..601
FT /note="Kelch repeat and BTB domain-containing protein 8"
FT /id="PRO_0000278220"
FT DOMAIN 49..117
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 153..252
FT /note="BACK"
FT /evidence="ECO:0000255"
FT REPEAT 336..390
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 391..441
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 443..481
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 483..532
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 542..588
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 6..447
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056107"
FT VARIANT 198
FT /note="S -> C (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036082"
FT VARIANT 405
FT /note="R -> K (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036083"
FT VARIANT 420
FT /note="C -> R (in dbSNP:rs13096789)"
FT /id="VAR_030694"
FT MUTAGEN 74
FT /note="Y->A: Abolishes CUL3-binding and ability to mediate
FT monoubiquitination of NOLC1 and TCOF1."
FT /evidence="ECO:0000269|PubMed:26399832"
FT MUTAGEN 579
FT /note="W->A: Abolishes substrate-binding and ability to
FT mediate monoubiquitination of NOLC1 and TCOF1."
FT /evidence="ECO:0000269|PubMed:26399832"
SQ SEQUENCE 601 AA; 68823 MW; E5DC921FD9C10BBA CRC64;
MAASADLSKS SPTPNGIPSS DPASDAMDPF HACSILKQLK TMYDEGQLTD IVVEVDHGKT
FSCHRNVLAA ISPYFRSMFT SGLTESTQKE VRIVGVEAES MDLVLNYAYT SRVILTEANV
QALFTAASIF QIPSIQDQCA KYMISHLDPQ NSIGVFIFAD HYGHQELGDR SKEYIRKKFL
CVTKEQEFLQ LTKDQLISIL DSDDLNVDRE EHVYESIIRW FEHEQNEREV HLPEIFAKCI
RFPLMEDTFI EKIPPQFAQA IAKSCVEKGP SNTNGCTQRL GMTASEMIIC FDAAHKHSGK
KQTVPCLDIV TGRVFKLCKP PNDLREVGIL VSPDNDIYIA GGYRPSSSEV SIDHKAENDF
WMYDHSTNRW LSKPSLLRAR IGCKLVYCCG KMYAIGGRVY EGDGRNSLKS VECYDSRENC
WTTVCAMPVA MEFHNAVEYK EKIYVLQGEF FLFYEPQKDY WGFLTPMTVP RIQGLAAVYK
DSIYYIAGTC GNHQRMFTVE AYDIELNKWT RKKDFPCDQS INPYLKLVLF QNKLHLFVRA
TQVTVEEHVF RTSRKNSLYQ YDDIADQWMK VYETPDRLWD LGRHFECAVA KLYPQCLQKV
L
