KBTBD_HUMAN
ID KBTBD_HUMAN Reviewed; 458 AA.
AC C9JR72;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Kelch repeat and BTB domain-containing protein 13;
GN Name=KBTBD13;
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 GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
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 [3]
RP FUNCTION, AUTOUBIQUITINATION, INTERACTION WITH CUL3, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22542517; DOI=10.1016/j.bbrc.2012.04.074;
RA Sambuughin N., Swietnicki W., Techtmann S., Matrosova V., Wallace T.,
RA Goldfarb L., Maynard E.;
RT "KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase.";
RL Biochem. Biophys. Res. Commun. 421:743-749(2012).
RN [4]
RP VARIANTS NEM6 SER-248; ASN-390 AND CYS-408, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=21109227; DOI=10.1016/j.ajhg.2010.10.020;
RA Sambuughin N., Yau K.S., Olive M., Duff R.M., Bayarsaikhan M., Lu S.,
RA Gonzalez-Mera L., Sivadorai P., Nowak K.J., Ravenscroft G., Mastaglia F.L.,
RA North K.N., Ilkovski B., Kremer H., Lammens M., van Engelen B.G.,
RA Fabian V., Lamont P., Davis M.R., Laing N.G., Goldfarb L.G.;
RT "Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause
RT nemaline myopathy with cores.";
RL Am. J. Hum. Genet. 87:842-847(2010).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex. {ECO:0000269|PubMed:22542517}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the BCR(KBTBD13) E3 ubiquitin ligase complex, at
CC least composed of CUL3 and KBTBD13 and RBX1. Interacts with CUL3.
CC {ECO:0000269|PubMed:22542517}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21109227,
CC ECO:0000269|PubMed:22542517}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC {ECO:0000269|PubMed:21109227}.
CC -!- DOMAIN: The BCB domain mediates the interaction with CUL3.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:22542517}.
CC -!- DISEASE: Nemaline myopathy 6 (NEM6) [MIM:609273]: A form of nemaline
CC myopathy characterized by childhood onset of slowly progressive
CC proximal muscle weakness, exercise intolerance, and slow movements with
CC stiff muscles. Patients are unable to run or correct themselves from
CC falling over. {ECO:0000269|PubMed:21109227}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
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DR EMBL; AC013553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77711.1; -; Genomic_DNA.
DR CCDS; CCDS45281.1; -.
DR RefSeq; NP_001094832.1; NM_001101362.2.
DR AlphaFoldDB; C9JR72; -.
DR SMR; C9JR72; -.
DR BioGRID; 133620; 1.
DR STRING; 9606.ENSP00000388723; -.
DR iPTMnet; C9JR72; -.
DR PhosphoSitePlus; C9JR72; -.
DR BioMuta; KBTBD13; -.
DR PaxDb; C9JR72; -.
DR PeptideAtlas; C9JR72; -.
DR PRIDE; C9JR72; -.
DR Antibodypedia; 56472; 58 antibodies from 14 providers.
DR DNASU; 390594; -.
DR Ensembl; ENST00000432196.5; ENSP00000388723.2; ENSG00000234438.5.
DR GeneID; 390594; -.
DR KEGG; hsa:390594; -.
DR MANE-Select; ENST00000432196.5; ENSP00000388723.2; NM_001101362.3; NP_001094832.1.
DR UCSC; uc010uis.3; human.
DR CTD; 390594; -.
DR DisGeNET; 390594; -.
DR GeneCards; KBTBD13; -.
DR HGNC; HGNC:37227; KBTBD13.
DR HPA; ENSG00000234438; Tissue enriched (skeletal).
DR MalaCards; KBTBD13; -.
DR MIM; 609273; phenotype.
DR MIM; 613727; gene.
DR neXtProt; NX_C9JR72; -.
DR OpenTargets; ENSG00000234438; -.
DR Orphanet; 171439; Childhood-onset nemaline myopathy.
DR PharmGKB; PA165479144; -.
DR VEuPathDB; HostDB:ENSG00000234438; -.
DR eggNOG; KOG1072; Eukaryota.
DR GeneTree; ENSGT00940000161629; -.
DR HOGENOM; CLU_049036_0_0_1; -.
DR InParanoid; C9JR72; -.
DR OMA; HTPTFEF; -.
DR OrthoDB; 558840at2759; -.
DR PhylomeDB; C9JR72; -.
DR TreeFam; TF328485; -.
DR PathwayCommons; C9JR72; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; C9JR72; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 390594; 6 hits in 1105 CRISPR screens.
DR GenomeRNAi; 390594; -.
DR Pharos; C9JR72; Tbio.
DR PRO; PR:C9JR72; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; C9JR72; protein.
DR Bgee; ENSG00000234438; Expressed in hindlimb stylopod muscle and 39 other tissues.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0051015; F:actin filament binding; IEA:Ensembl.
DR GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0014728; P:regulation of the force of skeletal muscle contraction; IMP:MGI.
DR GO; GO:0090076; P:relaxation of skeletal muscle; IMP:MGI.
DR Gene3D; 2.120.10.80; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
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; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 2.
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; Disease variant; Kelch repeat; Nemaline myopathy;
KW Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..458
FT /note="Kelch repeat and BTB domain-containing protein 13"
FT /id="PRO_0000393906"
FT DOMAIN 7..74
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REPEAT 159..209
FT /note="Kelch 1"
FT REPEAT 210..258
FT /note="Kelch 2"
FT REPEAT 259..305
FT /note="Kelch 3"
FT REPEAT 307..350
FT /note="Kelch 4"
FT REPEAT 352..400
FT /note="Kelch 5"
FT VARIANT 248
FT /note="R -> S (in NEM6; dbSNP:rs200549195)"
FT /evidence="ECO:0000269|PubMed:21109227"
FT /id="VAR_064889"
FT VARIANT 390
FT /note="K -> N (in NEM6; dbSNP:rs1364598710)"
FT /evidence="ECO:0000269|PubMed:21109227"
FT /id="VAR_064890"
FT VARIANT 408
FT /note="R -> C (in NEM6; dbSNP:rs387907090)"
FT /evidence="ECO:0000269|PubMed:21109227"
FT /id="VAR_064891"
SQ SEQUENCE 458 AA; 49485 MW; 4FFD143F16171BCD CRC64;
MARGPQTLVQ VWVGGQLFQA DRALLVEHCG FFRGLFRSGM RETRAAEVRL GVLSAGGFRA
TLQVLRGDRP ALAAEDELLQ AVECAAFLQA PALARFLEHN LTSDNCALLC DAAAAFGLRD
VFHSAALFIC DGERELAAEL ALPEARAYVA ALRPSSYAAV STHTPAPGFL EDASRTLCYL
DEEEDAWRTL AALPLEASTL LAGVATLGNK LYIVGGVRGA SKEVVELGFC YDPDGGTWHE
FPSPHQPRYD TALAGFDGRL YAIGGEFQRT PISSVERYDP AAGCWSFVAD LPQPAAGVPC
AQACGRLFVC LWRPADTTAV VEYAVRTDAW LPVAELRRPQ SYGHCMVAHR DSLYVVRNGP
SDDFLHCAID CLNLATGQWT ALPGQFVNSK GALFTAVVRG DTVYTVNRMF TLLYAIEGGT
WRLLREKAGF PRPGSLQTFL LRLPPGAPGP VTSTTAEL
