KLH18_HUMAN
ID KLH18_HUMAN Reviewed; 574 AA.
AC O94889; A8K612; Q7Z3E8; Q8N125;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Kelch-like protein 18;
GN Name=KLHL18; Synonyms=KIAA0795; ORFNames=OK/SW-cl.74;
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] (ISOFORM 2).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-reactive
RT CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [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] OF 26-574 (ISOFORM 1).
RC TISSUE=Melanoma;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 110-574 (ISOFORMS 1/2).
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH AURKA AND CUL3.
RX PubMed=23213400; DOI=10.1242/bio.2011018;
RA Moghe S., Jiang F., Miura Y., Cerny R.L., Tsai M.Y., Furukawa M.;
RT "The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-
RT A.";
RL Biol. Open 1:82-91(2012).
RN [9]
RP INTERACTION WITH 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 (PubMed:23213400). 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
CC (PubMed:23213400). Regulates light-and dark-dependent alpha-transducin
CC localization changes in rod photoreceptors through UNC119
CC ubiquitination and degradation (By similarity). Preferentially
CC ubiquitinates the unphosphorylated form of UNC119 over the
CC phosphorylated form (By similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:E9Q4F2, ECO:0000269|PubMed:23213400}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with AURKA (PubMed:23213400). Interacts (via BTB
CC domain) with CUL3 (PubMed:23213400). Interacts (via kelch repeats) with
CC UNC119 (PubMed:31696965). {ECO:0000269|PubMed:23213400,
CC ECO:0000269|PubMed:31696965}.
CC -!- INTERACTION:
CC O94889; P26641-2: EEF1G; NbExp=3; IntAct=EBI-2510096, EBI-10177695;
CC O94889; O60260-5: PRKN; NbExp=3; IntAct=EBI-2510096, EBI-21251460;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O94889-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O94889-2; Sequence=VSP_035974;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32620.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD97920.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB062478; BAB93503.1; -; mRNA.
DR EMBL; AK291477; BAF84166.1; -; mRNA.
DR EMBL; BX537953; CAD97920.1; ALT_INIT; mRNA.
DR EMBL; AC104447; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64819.1; -; Genomic_DNA.
DR EMBL; BC032620; AAH32620.1; ALT_INIT; mRNA.
DR EMBL; AB018338; BAA34515.1; -; mRNA.
DR CCDS; CCDS33749.1; -. [O94889-1]
DR RefSeq; NP_079286.2; NM_025010.4. [O94889-1]
DR AlphaFoldDB; O94889; -.
DR SMR; O94889; -.
DR BioGRID; 116877; 42.
DR IntAct; O94889; 18.
DR MINT; O94889; -.
DR STRING; 9606.ENSP00000232766; -.
DR iPTMnet; O94889; -.
DR PhosphoSitePlus; O94889; -.
DR BioMuta; KLHL18; -.
DR EPD; O94889; -.
DR jPOST; O94889; -.
DR MassIVE; O94889; -.
DR MaxQB; O94889; -.
DR PaxDb; O94889; -.
DR PeptideAtlas; O94889; -.
DR PRIDE; O94889; -.
DR ProteomicsDB; 50527; -. [O94889-1]
DR ProteomicsDB; 50528; -. [O94889-2]
DR Antibodypedia; 29881; 64 antibodies from 19 providers.
DR DNASU; 23276; -.
DR Ensembl; ENST00000232766.6; ENSP00000232766.5; ENSG00000114648.12. [O94889-1]
DR GeneID; 23276; -.
DR KEGG; hsa:23276; -.
DR MANE-Select; ENST00000232766.6; ENSP00000232766.5; NM_025010.5; NP_079286.2.
DR UCSC; uc003crd.4; human. [O94889-1]
DR CTD; 23276; -.
DR DisGeNET; 23276; -.
DR GeneCards; KLHL18; -.
DR HGNC; HGNC:29120; KLHL18.
DR HPA; ENSG00000114648; Low tissue specificity.
DR neXtProt; NX_O94889; -.
DR OpenTargets; ENSG00000114648; -.
DR PharmGKB; PA134920201; -.
DR VEuPathDB; HostDB:ENSG00000114648; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000157026; -.
DR HOGENOM; CLU_004253_14_2_1; -.
DR InParanoid; O94889; -.
DR OMA; HTASWHP; -.
DR OrthoDB; 439290at2759; -.
DR PhylomeDB; O94889; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; O94889; -.
DR SignaLink; O94889; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23276; 5 hits in 1112 CRISPR screens.
DR ChiTaRS; KLHL18; human.
DR GeneWiki; KLHL18; -.
DR GenomeRNAi; 23276; -.
DR Pharos; O94889; Tdark.
DR PRO; PR:O94889; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O94889; protein.
DR Bgee; ENSG00000114648; Expressed in secondary oocyte and 156 other tissues.
DR ExpressionAtlas; O94889; baseline and differential.
DR Genevisible; O94889; HS.
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; IMP:UniProtKB.
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 Alternative splicing; Cell cycle; Cell division; Kelch repeat; Mitosis;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..574
FT /note="Kelch-like protein 18"
FT /id="PRO_0000119122"
FT DOMAIN 66..105
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 140..242
FT /note="BACK"
FT REPEAT 289..336
FT /note="Kelch 1"
FT REPEAT 337..383
FT /note="Kelch 2"
FT REPEAT 384..430
FT /note="Kelch 3"
FT REPEAT 432..477
FT /note="Kelch 4"
FT REPEAT 479..524
FT /note="Kelch 5"
FT REPEAT 525..571
FT /note="Kelch 6"
FT VAR_SEQ 1..65
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_035974"
SQ SEQUENCE 574 AA; 63638 MW; FAD4CD938C962830 CRC64;
MVEDGAEELE DLVHFSVSEL PSRGYGVMEE IRRQGKLCDV TLKIGDHKFS AHRIVLAASI
PYFHAMFTND MMECKQDEIV MQGMDPSALE ALINFAYNGN LAIDQQNVQS LLMGASFLQL
QSIKDACCTF LRERLHPKNC LGVRQFAETM MCAVLYDAAN SFIHQHFVEV SMSEEFLALP
LEDVLELVSR DELNVKSEEQ VFEAALAWVR YDREQRGPYL PELLSNIRLP LCRPQFLSDR
VQQDDLVRCC HKCRDLVDEA KDYHLMPERR PHLPAFRTRP RCCTSIAGLI YAVGGLNSAG
DSLNVVEVFD PIANCWERCR PMTTARSRVG VAVVNGLLYA IGGYDGQLRL STVEAYNPET
DTWTRVGSMN SKRSAMGTVV LDGQIYVCGG YDGNSSLSSV ETYSPETDKW TVVTSMSSNR
SAAGVTVFEG RIYVSGGHDG LQIFSSVEHY NHHTATWHPA AGMLNKRCRH GAASLGSKMF
VCGGYDGSGF LSIAEMYSSV ADQWCLIVPM HTRRSRVSLV ASCGRLYAVG GYDGQSNLSS
VEMYDPETDC WTFMAPMACH EGGVGVGCIP LLTI
