ID   FXL15_HUMAN             Reviewed;         300 AA.
AC   Q9H469; A1L4J8; B1AKX8; B1AKX9; B1AKY0; B1AKY1; C9JWA4; Q0D2Q3; Q49AL7;
AC   Q5JWA5;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   16-JUN-2009, sequence version 2.
DT   10-JUN-2026, entry version 182.
DE   RecName: Full=F-box/LRR-repeat protein 15;
DE   AltName: Full=F-box only protein 37;
GN   Name=FBXL15; Synonyms=FBXO37;
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 GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Hypothalamus, and Lung carcinoma;
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   [3]
RP   FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A SCF PROTEIN LIGASE
RP   COMPLEX, AND INTERACTION WITH SMURF1; SMURF2 AND WWP2.
RX   PubMed=21572392; DOI=10.1038/emboj.2011.155;
RA   Cui Y., He S., Xing C., Lu K., Wang J., Xing G., Meng A., Jia S., He F.,
RA   Zhang L.;
RT   "SCF(FBXL15) regulates BMP signalling by directing the degradation of HECT-
RT   type ubiquitin ligase Smurf1.";
RL   EMBO J. 30:2675-2689(2011).
RN   [4]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC   -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC       protein) E3 ubiquitin-protein ligase complex which mediates the
CC       ubiquitination and subsequent proteasomal degradation of SMURF1,
CC       thereby acting as a positive regulator of the BMP signaling pathway.
CC       Required for dorsal/ventral pattern formation and bone mass
CC       maintenance. Also mediates ubiquitination of SMURF2 and WWP2.
CC       {ECO:0000269|PubMed:21572392}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC       complex SCF(FBXL15) composed of CUL1, SKP1, RBX1 and FBXL15.
CC       {ECO:0000269|PubMed:21572392}.
CC   -!- INTERACTION:
CC       Q9H469; Q9HCE7: SMURF1; NbExp=6; IntAct=EBI-6144096, EBI-976466;
CC       Q9H469; Q9HAU4: SMURF2; NbExp=3; IntAct=EBI-6144096, EBI-396727;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21572392}.
CC   -!- SIMILARITY: Belongs to the FBXL15 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH02912.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAH36120.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AL121928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC002912; AAH02912.1; ALT_INIT; mRNA.
DR   EMBL; BC036120; AAH36120.1; ALT_INIT; mRNA.
DR   EMBL; BC130566; AAI30567.1; -; mRNA.
DR   CCDS; CCDS31273.1; -.
DR   RefSeq; NP_001374223.1; NM_001387294.1.
DR   RefSeq; NP_077302.3; NM_024326.3.
DR   AlphaFoldDB; Q9H469; -.
DR   SMR; Q9H469; -.
DR   BioGRID; 122593; 31.
DR   ComplexPortal; CPX-2492; SCF E3 ubiquitin ligase complex, FBXL15 variant.
DR   FunCoup; Q9H469; 215.
DR   IntAct; Q9H469; 30.
DR   MINT; Q9H469; -.
DR   STRING; 9606.ENSP00000224862; -.
DR   iPTMnet; Q9H469; -.
DR   PhosphoSitePlus; Q9H469; -.
DR   BioMuta; FBXL15; -.
DR   DMDM; 239938631; -.
DR   jPOST; Q9H469; -.
DR   MassIVE; Q9H469; -.
DR   PaxDb; 9606-ENSP00000224862; -.
DR   PeptideAtlas; Q9H469; -.
DR   ProteomicsDB; 80789; -.
DR   Pumba; Q9H469; -.
DR   Antibodypedia; 53264; 88 antibodies from 15 providers.
DR   DNASU; 79176; -.
DR   Ensembl; ENST00000369956.8; ENSP00000358972.3; ENSG00000107872.15.
DR   Ensembl; ENST00000864349.1; ENSP00000534408.1; ENSG00000107872.15.
DR   Ensembl; ENST00000864350.1; ENSP00000534409.1; ENSG00000107872.15.
DR   Ensembl; ENST00000933209.1; ENSP00000603268.1; ENSG00000107872.15.
DR   Ensembl; ENST00000948416.1; ENSP00000618475.1; ENSG00000107872.15.
DR   Ensembl; ENST00000948417.1; ENSP00000618476.1; ENSG00000107872.15.
DR   Ensembl; ENST00000948418.1; ENSP00000618477.1; ENSG00000107872.15.
DR   GeneID; 79176; -.
DR   KEGG; hsa:79176; -.
DR   MANE-Select; ENST00000369956.8; ENSP00000358972.3; NM_024326.4; NP_077302.3.
DR   UCSC; uc001kvk.2; human.
DR   AGR; HGNC:28155; -.
DR   ClinPGx; PA134928704; -.
DR   CTD; 79176; -.
DR   DisGeNET; 79176; -.
DR   GeneCards; FBXL15; -.
DR   HGNC; HGNC:28155; FBXL15.
DR   HPA; ENSG00000107872; Low tissue specificity.
DR   MIM; 610287; gene.
DR   OpenTargets; ENSG00000107872; -.
DR   VEuPathDB; HostDB:ENSG00000107872; -.
DR   eggNOG; KOG1947; Eukaryota.
DR   GeneTree; ENSGT00940000160250; -.
DR   InParanoid; Q9H469; -.
DR   OMA; CHRITER; -.
DR   OrthoDB; 27842at2759; -.
DR   PAN-GO; Q9H469; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; Q9H469; -.
DR   PathwayCommons; Q9H469; -.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q9H469; -.
DR   SIGNOR; Q9H469; -.
DR   UniPathway; UPA00143; -.
DR   Agora; ENSG00000107872; -.
DR   BioGRID-ORCS; 79176; 10 hits in 1194 CRISPR screens.
DR   ChiTaRS; FBXL15; human.
DR   GenomeRNAi; 79176; -.
DR   Pharos; Q9H469; Tbio.
DR   PRO; PR:Q9H469; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q9H469; protein.
DR   Bgee; ENSG00000107872; Expressed in adenohypophysis and 128 other cell types or tissues.
DR   ExpressionAtlas; Q9H469; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR   GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR   GO; GO:0009953; P:dorsal/ventral pattern formation; ISS:UniProtKB.
DR   GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR   GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR   GO; GO:0030510; P:regulation of BMP signaling pathway; NAS:ComplexPortal.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR   CDD; cd22126; F-box_FBXL15; 1.
DR   FunFam; 3.80.10.10:FF:000113; F-box/LRR-repeat protein 15 isoform X1; 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; IPR057207; FBXL15_LRR.
DR   InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   PANTHER; PTHR13318:SF179; F-BOX_LRR-REPEAT PROTEIN 15; 1.
DR   PANTHER; PTHR13318; PARTNER OF PAIRED, ISOFORM B-RELATED; 1.
DR   Pfam; PF00646; F-box; 1.
DR   Pfam; PF25372; LRR_FBXL15; 1.
DR   SMART; SM00367; LRR_CC; 6.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   SUPFAM; SSF52047; RNI-like; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Leucine-rich repeat; Proteomics identification;
KW   Reference proteome; Repeat; Ubl conjugation pathway.
FT   CHAIN           1..300
FT                   /note="F-box/LRR-repeat protein 15"
FT                   /id="PRO_0000119931"
FT   DOMAIN          19..66
FT                   /note="F-box"
FT   REPEAT          141..162
FT                   /note="LRR 1"
FT   REPEAT          167..188
FT                   /note="LRR 2"
FT   REPEAT          194..215
FT                   /note="LRR 3"
FT   REPEAT          220..241
FT                   /note="LRR 4"
FT   REPEAT          246..267
FT                   /note="LRR 5"
FT   REGION          113..269
FT                   /note="Interaction with SMURF1"
FT                   /evidence="ECO:0000269|PubMed:21572392"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CONFLICT        164
FT                   /note="R -> H (in Ref. 2; AAH36120)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   300 AA;  32998 MW;  3AF8CAFDDF75D720 CRC64;
     MEPPMEPSGG EQEPGAVRFL DLPWEDVLLP HVLNRVPLRQ LLRLQRVSRA FRSLVQLHLA
     GLRRFDAAQV GPQIPRAALA RLLRDAEGLQ ELALAPCHEW LSDEDLVPVL ARNPQLRSVA
     LGGCGQLSRR ALGALAEGCP RLQRLSLAHC DWVDGLALRG LADRCPALEE LDLTACRQLK
     DEAIVYLAQR RGAGLRSLSL AVNANVGDAA VQELARNCPE LHHLDLTGCL RVGSDGVRTL
     AEYCPVLRSL RVRHCHHVAE SSLSRLRKRG VDIDVEPPLH QALVLLQDMA GFAPFVNLQV
//