ID   FXL18_HUMAN             Reviewed;         718 AA.
AC   Q96ME1; A0A024R857; B3KTC9; B4DH63; H0Y6I6; Q9BR90; Q9BTC7; Q9HAK7;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2023, sequence version 3.
DT   10-JUN-2026, entry version 179.
DE   RecName: Full=F-box/LRR-repeat protein 18;
DE   AltName: Full=F-box and leucine-rich repeat protein 18;
GN   Name=FBXL18; Synonyms=FBL18;
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 2 AND 5), NUCLEOTIDE
RP   SEQUENCE [LARGE SCALE MRNA] OF 424-718 (ISOFORM 1), AND VARIANTS CYS-696
RP   AND ILE-723 (ISOFORM 5).
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=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
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-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 476-718 (ISOFORM 4).
RC   TISSUE=Skin;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box
CC       protein)-type E3 ubiquitin ligase complex. {ECO:0000250}.
CC   -!- SUBUNIT: Directly interacts with SKP1 and CUL1. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=4;
CC         IsoId=Q96ME1-4; Sequence=Displayed;
CC       Name=1;
CC         IsoId=Q96ME1-1; Sequence=VSP_061756;
CC       Name=2;
CC         IsoId=Q96ME1-2; Sequence=VSP_061758, VSP_061759;
CC       Name=3;
CC         IsoId=Q96ME1-3; Sequence=VSP_061754, VSP_061755;
CC       Name=5;
CC         IsoId=Q96ME1-5; Sequence=VSP_061757;
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB13838.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAG53041.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AK021529; BAB13838.1; ALT_INIT; mRNA.
DR   EMBL; AK057042; BAB71354.1; -; mRNA.
DR   EMBL; AK095394; BAG53041.1; ALT_INIT; mRNA.
DR   EMBL; AK294949; BAG58024.1; -; mRNA.
DR   EMBL; AC006483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC092171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471144; EAW87338.1; -; Genomic_DNA.
DR   EMBL; CH471144; EAW87339.1; -; Genomic_DNA.
DR   EMBL; BC004228; AAH04228.1; -; mRNA.
DR   EMBL; BC006426; AAH06426.2; -; mRNA.
DR   EMBL; BC024256; AAH24256.1; -; mRNA.
DR   CCDS; CCDS43546.1; -. [Q96ME1-4]
DR   RefSeq; NP_001308142.1; NM_001321213.2. [Q96ME1-5]
DR   RefSeq; NP_079239.3; NM_024963.5. [Q96ME1-4]
DR   AlphaFoldDB; Q96ME1; -.
DR   SMR; Q96ME1; -.
DR   BioGRID; 123080; 66.
DR   ComplexPortal; CPX-2553; SCF E3 ubiquitin ligase complex, FBXL18 variant.
DR   FunCoup; Q96ME1; 427.
DR   IntAct; Q96ME1; 21.
DR   MINT; Q96ME1; -.
DR   STRING; 9606.ENSP00000371805; -.
DR   GlyGen; Q96ME1; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q96ME1; -.
DR   MetOSite; Q96ME1; -.
DR   PhosphoSitePlus; Q96ME1; -.
DR   SwissPalm; Q96ME1; -.
DR   BioMuta; FBXL18; -.
DR   DMDM; 61213731; -.
DR   jPOST; Q96ME1; -.
DR   MassIVE; Q96ME1; -.
DR   PaxDb; 9606-ENSP00000371805; -.
DR   PeptideAtlas; Q96ME1; -.
DR   ProteomicsDB; 35218; -.
DR   ProteomicsDB; 77339; -. [Q96ME1-1]
DR   ProteomicsDB; 77340; -. [Q96ME1-2]
DR   ProteomicsDB; 77341; -. [Q96ME1-3]
DR   ProteomicsDB; 77342; -. [Q96ME1-4]
DR   Pumba; Q96ME1; -.
DR   Antibodypedia; 24615; 99 antibodies from 20 providers.
DR   Ensembl; ENST00000382368.8; ENSP00000371805.3; ENSG00000155034.22. [Q96ME1-4]
DR   Ensembl; ENST00000415009.5; ENSP00000415064.1; ENSG00000155034.22. [Q96ME1-2]
DR   GeneID; 80028; -.
DR   KEGG; hsa:80028; -.
DR   MANE-Select; ENST00000382368.8; ENSP00000371805.3; NM_024963.6; NP_079239.3.
DR   UCSC; uc003son.5; human. [Q96ME1-4]
DR   UCSC; uc064beg.1; human.
DR   AGR; HGNC:21874; -.
DR   ClinPGx; PA134949446; -.
DR   CTD; 80028; -.
DR   GeneCards; FBXL18; -.
DR   HGNC; HGNC:21874; FBXL18.
DR   HPA; ENSG00000155034; Tissue enhanced (brain).
DR   MIM; 609084; gene.
DR   OpenTargets; ENSG00000155034; -.
DR   VEuPathDB; HostDB:ENSG00000155034; -.
DR   eggNOG; ENOG502QVW9; Eukaryota.
DR   GeneTree; ENSGT00390000015109; -.
DR   HOGENOM; CLU_758549_0_0_1; -.
DR   InParanoid; Q96ME1; -.
DR   OMA; VLYSECR; -.
DR   OrthoDB; 9856535at2759; -.
DR   PAN-GO; Q96ME1; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; Q96ME1; -.
DR   PathwayCommons; Q96ME1; -.
DR   Reactome; R-HSA-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q96ME1; -.
DR   SIGNOR; Q96ME1; -.
DR   Agora; ENSG00000155034; -.
DR   BioGRID-ORCS; 80028; 31 hits in 1196 CRISPR screens.
DR   CD-CODE; 804901D1; Nuclear speckle.
DR   ChiTaRS; FBXL18; human.
DR   Pharos; Q96ME1; Tdark.
DR   PRO; PR:Q96ME1; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q96ME1; protein.
DR   Bgee; ENSG00000155034; Expressed in lateral globus pallidus and 164 other cell types or tissues.
DR   ExpressionAtlas; Q96ME1; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0042981; P:regulation of apoptotic process; NAS:ComplexPortal.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal.
DR   CDD; cd22128; F-box_FBXL18; 1.
DR   FunFam; 3.80.10.10:FF:000187; F-box and leucine rich repeat protein 18; 1.
DR   FunFam; 3.80.10.10:FF:000222; F-box and leucine rich repeat protein 18; 1.
DR   FunFam; 3.80.10.10:FF:000749; F-box and leucine rich repeat protein 18; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 3.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR047948; FBXL18_F-box.
DR   InterPro; IPR045627; FBXL18_LRR.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   PANTHER; PTHR16134:SF19; F-BOX AND LEUCINE-RICH REPEAT PROTEIN 18; 1.
DR   PANTHER; PTHR16134; F-BOX/TPR REPEAT PROTEIN POF3; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   Pfam; PF19729; LRR_FBXL18; 1.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   SUPFAM; SSF52047; RNI-like; 1.
DR   PROSITE; PS50181; FBOX; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Leucine-rich repeat; Proteomics identification;
KW   Reference proteome; Repeat; Ubl conjugation pathway.
FT   CHAIN           1..718
FT                   /note="F-box/LRR-repeat protein 18"
FT                   /id="PRO_0000119867"
FT   DOMAIN          25..72
FT                   /note="F-box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT   REPEAT          77..103
FT                   /note="LRR 1"
FT   REPEAT          104..128
FT                   /note="LRR 2"
FT   REPEAT          129..153
FT                   /note="LRR 3"
FT   REPEAT          177..201
FT                   /note="LRR 4"
FT   REPEAT          324..352
FT                   /note="LRR 5"
FT   REPEAT          367..392
FT                   /note="LRR 6"
FT   REPEAT          393..422
FT                   /note="LRR 7"
FT   REPEAT          468..492
FT                   /note="LRR 8"
FT   REPEAT          516..540
FT                   /note="LRR 9"
FT   REPEAT          542..567
FT                   /note="LRR 10"
FT   REPEAT          572..597
FT                   /note="LRR 11"
FT   REPEAT          599..623
FT                   /note="LRR 12"
FT   VAR_SEQ         364..365
FT                   /note="RK -> CR (in isoform 3)"
FT                   /id="VSP_061754"
FT   VAR_SEQ         366..718
FT                   /note="Missing (in isoform 3)"
FT                   /id="VSP_061755"
FT   VAR_SEQ         667..718
FT                   /note="SFQAERPALNVVIFPLLHEGLTDVIRDVPLVHLDEITLFKSRVAEEPPNLWW
FT                   -> RWGEVTGRRPQLFTELREEPSARTSRATGRRQPCLPDSGVVCCPCGRPLAVSGIIL
FT                   VGVSPSLVVKTTCVYRVLFKNLDYASIFFLVCLFETESHSVVQAGVQWRDLSSLQPLLS
FT                   GLQPQPPEQLENELEIGFSYCFVI (in isoform 1)"
FT                   /id="VSP_061756"
FT   VAR_SEQ         667..718
FT                   /note="SFQAERPALNVVIFPLLHEGLTDVIRDVPLVHLDEITLFKSRVAEEPPNLWW
FT                   -> RWGEVTGRRPQLFTELREEPSARTSRATGRRQPCLPDSGVVCCPCGRPLAVSGIIL
FT                   VGVSPSLVVKTTCVYRVLFKNLDYASIFFLVCLFETESHSVVQAGVQWRDLSSLQPLLS
FT                   GLQPQPPEQLGLQVCTTIPG (in isoform 5)"
FT                   /id="VSP_061757"
FT   VAR_SEQ         668
FT                   /note="F -> R (in isoform 2)"
FT                   /id="VSP_061758"
FT   VAR_SEQ         669..718
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_061759"
FT   VARIANT         552
FT                   /note="N -> K (in dbSNP:rs33941092)"
FT                   /id="VAR_055800"
FT   CONFLICT        128
FT                   /note="G -> D (in Ref. 1; BAG58024)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        349
FT                   /note="N -> G (in Ref. 1; BAG53041)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        494
FT                   /note="N -> H (in Ref. 1; BAG58024)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        555
FT                   /note="L -> P (in Ref. 1; BAB13838)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         Q96ME1-5:696
FT                   /note="R -> C (in dbSNP:rs28566736)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_087450"
FT   VARIANT         Q96ME1-5:723
FT                   /note="V -> I (in dbSNP:rs148642174)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_087451"
SQ   SEQUENCE   718 AA;  78919 MW;  A4BB27A1195DE07B CRC64;
     MASSGEDISN DDDDMHPAAA GMADGVHLLG FSDEILLHIL SHVPSTDLIL NVRRTCRKLA
     ALCLDKSLIH TVLLQKDYQA SEDKVRQLVK EIGREIQQLS MAGCYWLPGS TVEHVARCRS
     LVKVNLSGCH LTSLRLSKML SALQHLRSLA IDVSPGFDAS QLSSECKATL SRVRELKQTL
     FTPSYGVVPC CTSLEKLLLY FEILDRTREG AILSGQLMVG QSNVPHYQNL RVFYARLAPG
     YINQEVVRLY LAVLSDRTPQ NLHAFLISVP GSFAESGATK NLLDSMARNV VLDALQLPKS
     WLNGSSLLQH MKFNNPFYFS FSRCTLSGGH LIQQVINGGK DLRSLASLNL SGCVHCLSPD
     SLLRKAEDDI DSSILETLVA SCCNLRHLNL SAAHHHSSEG LGRHLCQLLA RLRHLRSLSL
     PVCSVADSAP RADRAPAQPA MHAVPRGFGK KVRVGVQSCP SPFSGQACPQ PSSVFWSLLK
     NLPFLEHLEL IGSNFSSAMP RNEPAIRNSL PPCSRAQSVG DSEVAAIGQL AFLRHLTLAQ
     LPSVLTGSGL VNIGLQCQQL RSLSLANLGM MGKVVYMPAL SDMLKHCKRL RDLRLEQPYF
     SANAQFFQAL SQCPSLQRLC LVSRSGTLQP DAVLAFMARC LQVVMCHLFT GESLATCKSL
     QQSLLRSFQA ERPALNVVIF PLLHEGLTDV IRDVPLVHLD EITLFKSRVA EEPPNLWW
//