ID   FBXL6_HUMAN             Reviewed;         539 AA.
AC   Q8N531; Q53G43; Q9H5W9; Q9UKC7;
DT   03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 2.
DT   10-JUN-2026, entry version 183.
DE   RecName: Full=F-box/LRR-repeat protein 6 {ECO:0000305};
DE   AltName: Full=F-box and leucine-rich repeat protein 6;
DE   AltName: Full=F-box protein FBL6;
DE   AltName: Full=FBL6A;
GN   Name=FBXL6 {ECO:0000312|HGNC:HGNC:13603}; Synonyms=FBL6;
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), AND VARIANT SER-496.
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 MRNA] (ISOFORM 2), AND VARIANT SER-496.
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-496.
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 90-372 (ISOFORMS 1/2).
RX   PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2;
RA   Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M.,
RA   Pagano M.;
RT   "Identification of a family of human F-box proteins.";
RL   Curr. Biol. 9:1177-1179(1999).
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   -!- INTERACTION:
CC       Q8N531; P63208: SKP1; NbExp=4; IntAct=EBI-2322696, EBI-307486;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8N531-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N531-2; Sequence=VSP_008498;
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DR   EMBL; AK026541; BAB15499.1; -; mRNA.
DR   EMBL; AK223088; BAD96808.1; -; mRNA.
DR   EMBL; BC033066; AAH33066.1; -; mRNA.
DR   EMBL; AF174592; AAF04513.1; -; mRNA.
DR   CCDS; CCDS47942.1; -. [Q8N531-2]
DR   CCDS; CCDS6422.1; -. [Q8N531-1]
DR   RefSeq; NP_036294.2; NM_012162.4. [Q8N531-1]
DR   RefSeq; NP_078831.4; NM_024555.5. [Q8N531-2]
DR   AlphaFoldDB; Q8N531; -.
DR   SMR; Q8N531; -.
DR   BioGRID; 117624; 596.
DR   ComplexPortal; CPX-2516; SCF E3 ubiquitin ligase complex, FBXL6 variant.
DR   FunCoup; Q8N531; 334.
DR   IntAct; Q8N531; 35.
DR   NDEx; MUSIC2-C5190-FBXL6; Osteosarcoma (U2OS) cell map - DNA replication and repair system (48 proteins).
DR   STRING; 9606.ENSP00000330098; -.
DR   GlyGen; Q8N531; 5 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8N531; -.
DR   PhosphoSitePlus; Q8N531; -.
DR   BioMuta; FBXL6; -.
DR   DMDM; 37537803; -.
DR   jPOST; Q8N531; -.
DR   MassIVE; Q8N531; -.
DR   PaxDb; 9606-ENSP00000330098; -.
DR   PeptideAtlas; Q8N531; -.
DR   ProteomicsDB; 71995; -. [Q8N531-1]
DR   ProteomicsDB; 71996; -. [Q8N531-2]
DR   Pumba; Q8N531; -.
DR   Antibodypedia; 28465; 55 antibodies from 18 providers.
DR   DNASU; 26233; -.
DR   Ensembl; ENST00000331890.6; ENSP00000330098.5; ENSG00000182325.12. [Q8N531-1]
DR   Ensembl; ENST00000455319.6; ENSP00000403873.2; ENSG00000182325.12. [Q8N531-2]
DR   Ensembl; ENST00000644788.2; ENSP00000495082.1; ENSG00000285442.2. [Q8N531-1]
DR   Ensembl; ENST00000646393.1; ENSP00000496284.1; ENSG00000285442.2. [Q8N531-2]
DR   GeneID; 26233; -.
DR   KEGG; hsa:26233; -.
DR   MANE-Select; ENST00000331890.6; ENSP00000330098.5; NM_012162.4; NP_036294.2.
DR   UCSC; uc003zca.4; human. [Q8N531-1]
DR   AGR; HGNC:13603; -.
DR   ClinPGx; PA28026; -.
DR   CTD; 26233; -.
DR   DisGeNET; 26233; -.
DR   GeneCards; FBXL6; -.
DR   HGNC; HGNC:13603; FBXL6.
DR   HPA; ENSG00000182325; Low tissue specificity.
DR   MIM; 609076; gene.
DR   OpenTargets; ENSG00000182325; -.
DR   VEuPathDB; HostDB:ENSG00000182325; -.
DR   eggNOG; KOG1947; Eukaryota.
DR   GeneTree; ENSGT00390000009358; -.
DR   HOGENOM; CLU_023545_1_1_1; -.
DR   InParanoid; Q8N531; -.
DR   OMA; WHEAASQ; -.
DR   OrthoDB; 3134645at2759; -.
DR   PAN-GO; Q8N531; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; Q8N531; -.
DR   PathwayCommons; Q8N531; -.
DR   SignaLink; Q8N531; -.
DR   SIGNOR; Q8N531; -.
DR   Agora; ENSG00000182325; -.
DR   BioGRID-ORCS; 26233; 24 hits in 1197 CRISPR screens.
DR   ChiTaRS; FBXL6; human.
DR   GenomeRNAi; 26233; -.
DR   Pharos; Q8N531; Tdark.
DR   PRO; PR:Q8N531; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q8N531; protein.
DR   Bgee; ENSG00000182325; Expressed in mucosa of transverse colon and 96 other cell types or tissues.
DR   GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:ProtInc.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   CDD; cd22119; F-box_FBXL6; 1.
DR   FunFam; 3.80.10.10:FF:000849; F-box and leucine-rich repeat protein 6; 1.
DR   FunFam; 3.80.10.10:FF:000791; F-box/LRR-repeat protein 6 isoform X1; 1.
DR   FunFam; 1.20.1280.50:FF:000035; F-box/LRR-repeat protein 6 isoform X2; 1.
DR   Gene3D; 1.20.1280.50; -; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR047922; FBXL6_F-box.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   PANTHER; PTHR16134; F-BOX/TPR REPEAT PROTEIN POF3; 1.
DR   PANTHER; PTHR16134:SF28; F-BOX_LRR-REPEAT PROTEIN 6; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   Pfam; PF13516; LRR_6; 1.
DR   SMART; SM00367; LRR_CC; 3.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   SUPFAM; SSF52047; RNI-like; 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..539
FT                   /note="F-box/LRR-repeat protein 6"
FT                   /id="PRO_0000119847"
FT   DOMAIN          10..162
FT                   /note="F-box"
FT   REPEAT          177..203
FT                   /note="LRR 1"
FT   REPEAT          204..229
FT                   /note="LRR 2"
FT   REPEAT          230..255
FT                   /note="LRR 3"
FT   REPEAT          281..307
FT                   /note="LRR 4"
FT   REPEAT          312..337
FT                   /note="LRR 5"
FT   REPEAT          341..365
FT                   /note="LRR 6"
FT   REPEAT          368..393
FT                   /note="LRR 7"
FT   REPEAT          394..419
FT                   /note="LRR 8"
FT   REPEAT          423..449
FT                   /note="LRR 9"
FT   REPEAT          453..481
FT                   /note="LRR 10"
FT   REPEAT          482..507
FT                   /note="LRR 11"
FT   REGION          1..27
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          49..111
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        8..17
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        58..68
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        94..104
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         208..213
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT                   /id="VSP_008498"
FT   VARIANT         496
FT                   /note="G -> S (in dbSNP:rs114720164)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT                   /id="VAR_085739"
SQ   SEQUENCE   539 AA;  58558 MW;  8153184415203FB2 CRC64;
     MAAPASRQVR RRARAAPRPR SAEDWWWDRL APRGSGYHLL QSDSMLLVLS EPGPARPRAQ
     RRASRRTPRQ PPRGPSAAAK PKAGLRSEAA AAPAPAPAPT PTPEEGPDAG WGDRIPLEIL
     VQIFGLLVAA DGPMPFLGRA ARVCRRWQEA ASQPALWHTV TLSSPLVGRP AKGGVKAEKK
     LLASLEWLMP NRFSQLQRLT LIHWKSQVHP VLKLVGECCP RLTFLKLSGC HGVTADALVM
     LAKACCQLHS LDLQHSMVES TAVVSFLEEA GSRMRKLWLT YSSQTTAILG ALLGSCCPQL
     QVLEVSTGIN RNSIPLQLPV EALQKGCPQL QVLRLLNLMW LPKPPGRGVA PGPGFPSLEE
     LCLASSTCNF VSNEVLGRLL HGSPNLRLLD LRGCARITPA GLQDLPCREL EQLHLGLYGT
     SDRLTLAKEG SPFLTQKWCH TLRELDLSGQ GFSEKDLEQA LAAFLSTPGG SHPALCSLNL
     RGTRVTPSTV SSVISGCPGL LYLNLESCRC LPRGLKRAYR GLEEVQWCLE QLLTSPSPS
//