ID   KLH18_MOUSE             Reviewed;         574 AA.
AC   E9Q4F2;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   03-AUG-2022, entry version 82.
DE   RecName: Full=Kelch-like protein 18;
GN   Name=Klhl18;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INTERACTION WITH
RP   UNC119.
RX   PubMed=31696965; DOI=10.15252/embj.2018101409;
RA   Chaya T., Tsutsumi R., Varner L.R., Maeda Y., Yoshida S., Furukawa T.;
RT   "Cul3-Klhl18 ubiquitin ligase modulates rod transducin translocation during
RT   light-dark adaptation.";
RL   EMBO J. 2019:E101409-E101409(2019).
CC   -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC       ubiquitin-protein ligase complex required for mitotic progression and
CC       cytokinesis (By similarity). The BCR(KLHL18) E3 ubiquitin ligase
CC       complex mediates the ubiquitination of AURKA leading to its activation
CC       at the centrosome which is required for initiating mitotic entry (By
CC       similarity). Regulates light- and dark-dependent alpha-transducin
CC       localization changes in rod photoreceptors through UNC119
CC       ubiquitination and degradation (PubMed:31696965). Preferentially
CC       ubiquitinates the unphosphorylated form of UNC119 over the
CC       phosphorylated form (PubMed:31696965). In the presence of UNC119, under
CC       dark-adapted conditions alpha-transducin mislocalizes from the outer
CC       segment to the inner part of rod photoreceptors which leads to
CC       decreased photoreceptor damage caused by light (PubMed:31696965).
CC       {ECO:0000250|UniProtKB:O94889, ECO:0000269|PubMed:31696965}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000250|UniProtKB:O94889}.
CC   -!- SUBUNIT: Interacts with AURKA (By similarity). Interacts (via BTB
CC       domain) with CUL3 (By similarity). Interacts (via kelch repeats) with
CC       UNC119 (PubMed:31696965). {ECO:0000250|UniProtKB:O94889,
CC       ECO:0000269|PubMed:31696965}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in maturing and mature
CC       retinal photoreceptor cells. {ECO:0000269|PubMed:31696965}.
CC   -!- DISRUPTION PHENOTYPE: Retina-specific gene disruption leads to
CC       decreased light response in rod photoreceptor cells and mislocalization
CC       of alpha-transducin from the outer segment to the inner part of rod
CC       photoreceptors. {ECO:0000269|PubMed:31696965}.
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DR   EMBL; AC132103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC160104; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS23567.1; -.
DR   RefSeq; NP_808439.2; NM_177771.5.
DR   AlphaFoldDB; E9Q4F2; -.
DR   SMR; E9Q4F2; -.
DR   STRING; 10090.ENSMUSP00000069674; -.
DR   PhosphoSitePlus; E9Q4F2; -.
DR   MaxQB; E9Q4F2; -.
DR   PaxDb; E9Q4F2; -.
DR   PRIDE; E9Q4F2; -.
DR   ProteomicsDB; 361007; -.
DR   Antibodypedia; 29881; 64 antibodies from 19 providers.
DR   DNASU; 270201; -.
DR   Ensembl; ENSMUST00000068025; ENSMUSP00000069674; ENSMUSG00000054792.
DR   GeneID; 270201; -.
DR   KEGG; mmu:270201; -.
DR   UCSC; uc009rua.1; mouse.
DR   CTD; 23276; -.
DR   MGI; MGI:2143315; Klhl18.
DR   VEuPathDB; HostDB:ENSMUSG00000054792; -.
DR   eggNOG; KOG4441; Eukaryota.
DR   GeneTree; ENSGT00940000157026; -.
DR   TreeFam; TF329218; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 270201; 7 hits in 73 CRISPR screens.
DR   ChiTaRS; Klhl18; mouse.
DR   PRO; PR:E9Q4F2; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   Bgee; ENSMUSG00000054792; Expressed in retinal neural layer and 221 other tissues.
DR   ExpressionAtlas; E9Q4F2; baseline and differential.
DR   Genevisible; E9Q4F2; MM.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:1901992; P:positive regulation of mitotic cell cycle phase transition; ISO:MGI.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR   CDD; cd18247; BTB_POZ_KLHL18; 1.
DR   Gene3D; 2.120.10.80; -; 2.
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; IPR030603; KLHL18_BTB/POZ.
DR   InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR   Pfam; PF07707; BACK; 1.
DR   Pfam; PF00651; BTB; 1.
DR   Pfam; PF01344; Kelch_1; 6.
DR   PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR   SMART; SM00875; BACK; 1.
DR   SMART; SM00225; BTB; 1.
DR   SMART; SM00612; Kelch; 6.
DR   SUPFAM; SSF117281; SSF117281; 2.
DR   SUPFAM; SSF54695; SSF54695; 1.
DR   PROSITE; PS50097; BTB; 1.
PE   1: Evidence at protein level;
KW   Cell cycle; Cell division; Kelch repeat; Mitosis; Reference proteome;
KW   Repeat; Ubl conjugation pathway.
FT   CHAIN           1..574
FT                   /note="Kelch-like protein 18"
FT                   /id="PRO_0000449196"
FT   DOMAIN          38..105
FT                   /note="BTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT   DOMAIN          140..242
FT                   /note="BACK"
FT                   /evidence="ECO:0000255"
FT   REPEAT          289..336
FT                   /note="Kelch 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          337..383
FT                   /note="Kelch 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          384..430
FT                   /note="Kelch 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          432..477
FT                   /note="Kelch 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          479..524
FT                   /note="Kelch 5"
FT                   /evidence="ECO:0000255"
FT   REPEAT          525..571
FT                   /note="Kelch 6"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   574 AA;  63686 MW;  5C2D5F5F55ECFC5A CRC64;
     MVEDGAEELE DLVHFSVSEL PSRGYGVMEE IRRQGKLCDV TLKIGDHKFS AHRIVLAASI
     PYFHAMFTND MMECKQDEIV MQGMDPSALE ALINFAYNGN LAIDQQNVQS LLMGASFLQL
     QSIKDACCTF LRERLHPKNC LGVRQFAETM MCAVLYDAAN SFIHQHFVEV SLSEEFLALP
     LEDVLELVSR DELNVKSEEQ VFEAALAWVR YDREQRGPCL PELLSNIRLP LCRPQFLSDR
     VQQDDLVRCC HKCRDLVDEA KDYHLMPERR PHLPAFRTRP RCCTSIAGLI YAVGGLNSAG
     DSLNVVEVFD PIANRWEKCH PMTTARSRVG VAVVNGLLYA IGGYDGQLRL STVEAYNPET
     DTWTRVGSMN SKRSAMGTVV LDGQIYVCGG YDGNSSLNSV ETYSPETDKW TVVTPMSSNR
     SAAGVTVFEG RIYVSGGHDG LQIFSSVEHY NHHTATWHPA ASMLNKRCRH GAASLGSKMF
     VCGGYDGSGF LSIAEMYSSV ADQWCLIVPM HTRRSRVSLV ASCGRLYAVG GYDGQSNLSS
     VEMYDPETDR WTFMAPMACH EGGVGVGCIP LLTI