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 27-MAR-2024, entry version 178. 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; P13569: CFTR; NbExp=3; IntAct=EBI-2510096, EBI-349854; 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}; 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; 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; 44. DR ComplexPortal; CPX-8106; CRL3 E3 ubiquitin ligase complex, KLHL18 variant. DR IntAct; O94889; 19. 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; 9606-ENSP00000232766; -. DR PeptideAtlas; O94889; -. DR ProteomicsDB; 50527; -. [O94889-1] DR ProteomicsDB; 50528; -. [O94889-2] DR Pumba; O94889; -. DR Antibodypedia; 29881; 77 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 AGR; HGNC:29120; -. DR CTD; 23276; -. DR DisGeNET; 23276; -. DR GeneCards; KLHL18; -. DR HGNC; HGNC:29120; KLHL18. DR HPA; ENSG00000114648; Low tissue specificity. DR MIM; 619926; gene. 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; FAEAMMC; -. DR OrthoDB; 5472491at2759; -. DR PhylomeDB; O94889; -. DR TreeFam; TF329218; -. DR PathwayCommons; O94889; -. DR SignaLink; O94889; -. DR SIGNOR; O94889; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 23276; 5 hits in 1189 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 157 other cell types or tissues. DR ExpressionAtlas; O94889; baseline and differential. 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; cd18457; BACK_KLHL18; 1. DR CDD; cd18247; BTB_POZ_KLHL18; 1. DR Gene3D; 1.25.40.420; -; 1. DR Gene3D; 2.120.10.80; Kelch-type beta propeller; 2. 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 PANTHER; PTHR24412; KELCH PROTEIN; 1. DR PANTHER; PTHR24412:SF475; RING CANAL KELCH PROTEIN; 1. 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; Kelch motif; 2. DR SUPFAM; SSF54695; POZ domain; 1. DR PROSITE; PS50097; BTB; 1. DR Genevisible; O94889; HS. 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 //